bluuebunny/crossref_metadata_2025 huggingface dataset:
Oligosaccharyltransferase complex‐congenital disorders of glycosylation: A novel congenital disorder of glycosylation
Authors: Bryant Emily M. , Millichap John J. , Spinelli Egidio , Calhoun Jeffrey D. , Miller Christopher , Giannelli Jessica , Wolak Jacqueline , Sanders Victoria , Carvill Gemma L. , Charrow Joel
Published: April 2020

Congenital disorders of glycosylation (CDG) are metabolic disorders that affect the glycosylation of proteins and lipids. Since glycosylation affects all organs, CDG show a wide spectrum of phenotypes. We present a patient with microcephaly, dysmorphic facies, congenital heart defect, focal epilepsy, infantile spasms, skeletal dysplasia, and a type 1 serum transferrin isoelectrofocusing due to a novel CDG caused by a homozygous variant in the oligosaccharyltransferase complex noncatalytic subunit (OSTC) gene involved in glycosylation and confirmed by serum transferrin electrophoresis.
Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation
Authors: Abdel‐Salam Ghada M. H. , Sayed Inas S. M. , Afifi Hanan H. , Abdel‐Ghafar Sherif F. , Abouzaid Maha R. , Ismail Samira I. , Aglan Mona S. , Issa Mahmoud Y. , EL‐Bassyouni Hala T. , El‐Kamah Ghada , Effat Laila K. , Eid Maha , Zaki Maha S. , Temtamy Samia A. , Abdel‐Hamid Mohamed S.
Published: April 2020

PCNT encodes a large coiled‐ protein localizing to pericentriolar material and is associated with microcephalic osteodysplastic primordial dwarfism type II syndrome (MOPD II). We report our experience of nine new patients from seven unrelated consanguineous Egyptian families with the distinctive clinical features of MOPD II in whom a customized NGS panel showed homozygous truncating variants of PCNT. The NGS panel results were validated thereafter using Sanger sequencing revealing three previously reported and three novel PCNT pathogenic variants. The core phenotype appeared homogeneous to what had been reported before although patients differed in the severity showing inter and intra familial variability. The orodental pattern showed atrophic alveolar ridge (five patients), rootless tooth (four patients), tooth agenesis (three patients), and malformed tooth (three patients). In addition, mesiodens was a novel finding found in one patient. The novel c.9394‐1G>T variant was found in two sibs who had tooth agenesis. CNS anomalies with possible vascular sequelae were documented in two male patients (22.2%). Simplified gyral pattern with poor development of the frontal horns of lateral ventricles was seen in four patients and mild thinning of the corpus callosum in two patients. Unilateral coronal craniosynstosis was noted in one patient and thick but short corpus callosum was an unusual finding noted in another. The later has not been reported before. Our results refine the clinical, neuroradiological, and orodental features and expand the molecular spectrum of MOPD II.
Real‐World Effectiveness of Initial Disease‐Modifying Therapies in Pediatric Multiple Sclerosis
Authors: Krysko Kristen M. , Graves Jennifer S. , Rensel Mary , Weinstock‐Guttman Bianca , Rutatangwa Alice , Aaen Gregory , Belman Anita , Benson Leslie , Chitnis Tanuja , Gorman Mark , Goyal Manu S. , Harris Yolanda , Krupp Lauren , Lotze Timothy , Mar Soe , Moodley Manikum , Ness Jayne , Rodriguez Moses , Rose John , Schreiner Teri , Tillema Jan‐Mendelt , Waltz Michael , Casper T. Charles , Waubant Emmanuelle ,   the US Network of Pediatric MS Centers
Published: April 2020

Objective

To assess real‐world effectiveness of initial treatment with newer compared to injectable disease‐modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS).

Methods

This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon‐β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS‐quintile. Time to new/enlarging T2‐hyperintense and gadolinium‐enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS‐quintile.

Results

A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS‐quintile–adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29–0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14–0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person‐years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36–0.72, p < 0.001) and gadolinium‐enhancing lesions (HR = 0.38, 95% CI = 0.23–0.63, p < 0.001) than those on injectables.

Interpretation

Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long‐term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42–55
Catalytic Coherence Transformation and Distillation for Special Mixed States
Authors: Xing Hai‐Bo , Yang Ming
Published: April 2020

The coherence transformation and distillation for a class of special mixed coherent states of rank‐2 under incoherent operations (IO) is discussed. Similar to the entanglement transformation for mixed entangled states, the catalytic coherence transformation for this class of special mixed coherent states is analyzed. On the one hand, it is found that some of the mixed coherent states can be converted into other mixed coherent states under IO. But for those mixed coherent states which fail in the coherence conversion under IO, the catalytic coherence manipulation can solve this problem. In this case, a mixed coherent state cannot be converted into another under IO, while the coherence transformation can be realized with the help of coherence‐assisted incoherent operations, that is, catalytic coherence transformation. On the other hand, these special mixed coherent states can be distilled into the maximally pure coherent states or mixed states of arbitrary dimensions by strictly incoherent operations with certain probabilities. Finally, the coherence transformation of this type of mixed states can be generalized to the case of higher rank in a similar way, which is discussed at the end of this paper.
Generation of Near‐Circularly Polarized Attosecond Pulse with Tunable Helicity by Unidirectionally Rotating Laser Field
Authors: Yuan Hua , He Lixin , Njoroge Stephen Maina , Wang Dian , Shao Renzhi , Lan Pengfei , Lu Peixiang
Published: April 2020

A method to produce circularly polarized attosecond pulses with tunable helicity from CO molecule by using an unidirectionally rotating laser field is proposed. It is found that broadband harmonic supercontinuum with circular polarization can be generated from the oriented CO molecule. This enables the production sub‐100 attosecond isolated pulse with the ellipticity as high as 0.9 at the macroscopic level. Moreover, the helicity of the generated high‐order harmonics and the attosecond pulse can be tuned by adjusting the orientation of the CO molecule. This method will be beneficial for the studies on chiral‐specific dynamics and magnetic circular dichroism on an attosecond time scale.
Continuous‐Variable Entanglement and Wigner‐Function Negativity via Adding or Subtracting Photons
Authors: Meng Xiang‐Guo , Li Kai‐Cai , Wang Ji‐Suo , Zhang Xiao‐Yan , Zhang Zhen‐Tao , Yang Zhen‐Shan , Liang Bao‐Long
Published: April 2020

The performance of adding or subtracting photons on two‐mode squeezed thermal states via examining the Einstein–Podolsky–Rosen (EPR) correlation, the Hillery–Zubairy (HZ) correlation, the fidelity of teleportation, and the negativity of Wigner function is theoretically investigated. The normalization factors and the teleportation fidelity are related to Jacobi polynomials, and the (evolved) Wigner functions are simply associated with two‐variable Hermite polynomials. Compared with the original squeezed thermal states, the EPR correlation and the teleportation fidelity can be enhanced by photon subtraction and basically weakened by photon addition symmetric operations, but they cannot be enhanced for both photon addition and subtraction asymmetric cases. Also, HZ correlation can provide a better option relative to the EPR correlation in detecting the entanglement, and the fidelity for teleporting a squeezed state with a large squeezing can also be enhanced via photon addition symmetric operations, in contrast to teleporting a coherent state. Additionally, the nonclassicality is discussed in terms of the negativity of the (evolved) Wigner functions, which shows that photon addition and subtraction and the squeezing cannot restrain the deteriorate of nonclassicality, and the evolved Wigner functions become Gaussian (corresponding to vacuum) with long decay times as a result of amplitude decay.
Surface organo‐modification of hydroxyapatites to improvePLA/HAcompatibility
Authors: Rocha Carmen R. , Chávez‐Flores David , Zuverza‐Mena Nubia , Duarte Alma , Rocha‐Gutiérrez Beatriz A. , Zaragoza‐Contreras Erasto Armando , Flores‐Gallardo Sergio
Published: April 2020

Polylactide/hydroxyapatite (PLA/HA) composites are promising tissue engineering materials because of the PLA biodegradability and HA as a natural bone component. PLA/HA composites without HA modification lead to mechanical failure due to the interfacial immiscibility. In this study, an effective chemical surface methodology is used to modify HA to obtain PLA/HA composites with superior mechanical properties. The HA particles are modified with fatty acids (adipic, sebacic, lauric, and linoleic) and incorporated into a PLA matrix by polymer solution casting, using chloroform as the solvent. After the HA modification, the films exhibited an improvement in tensile strength, elongation at break, and elastic modulus. Yet, the best results observed are by sebacic and adipic acid modification. These increments are attributed to a higher affinity of the organo‐modified HA particles within the PLA matrix. Therefore, the development of materials for osteo‐regeneration engineering based on these systems is quite promising.
Study on high‐temperature composite properties of fluorosilicone rubber with nano‐Sb2O3
Authors: Xu Zehua , Zhang Yanbin , Zhou Jin , Qi Ming , Shi Jianyong , Zhang Jiaqi
Published: April 2020

This article studied the influence of nano‐Sb2O3 on the high‐temperature composite performance of fluorosilicone rubber (FVMQ). FVMQ with 4% mass of nano‐Sb2O3 content was prepared by mechanical blending method. The friction properties of FVMQ and Sb2O3/FVMQ composites at different temperatures were analyzed by means of three‐dimensional profilometer and scanning electron microscopy. The results showed that nano‐Sb2O3 can enhance the matrix strength of FVMQ, and this effect was obvious at high temperature. The elongation of Sb2O3/FVMQ composites was increased by 10.7% at 25°C. The tear strength of Sb2O3/FVMQ composites was increased by 53.1%. While the friction coefficient and the wear amount, respectively, were decreased by 20 and 48.53% at 200°C. Sb2O3/FVMQ composite showed excellent anti‐wear, antifriction, anti‐tear, and other characteristics in the high‐temperature test. The enhancement of the cross‐linking density of matrix caused by adding Sb2O3 into FVMQ can lead to the softening of rubber, and the type of wear changed from abrasive wear to adhesive wear. Thus, the composite showed good wear resistance.
Retracted: Increasing Prevalence of Antinuclear Antibodies in the United States
Authors: Dinse Gregg E. , Parks Christine G. , Weinberg Clarice R. , Co Caroll A. , Wilkerson Jesse , Zeldin Darryl C. , Chan Edward K. L. , Miller Frederick W.
Published: April 2020

Retraction: Dinse G.E. et al., Increasing Prevalence of Antinuclear Antibodies in the United States, Arthritis & Rheumatology 2020, 72(6), 1026–1035 (https://onlinelibrary.wiley.com/doi/10.1002/art.41214). The above article, published online on April 7, 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement among the authors, the journal Editor‐in‐Chief Daniel H. Solomon, MD, PhD, the American College of Rheumatology, and Wiley Periodicals LLC. The retraction was agreed upon due to the many corrections required because the Centers for Disease Control and Prevention removed some of the publicly released National Health and Nutrition Examination Survey (NHANES) data used in the original study and then released revised data; the retraction was not the result of any author wrongdoing or error. The corrections do not change the conclusions of the paper but are necessary for accuracy. The text, figure, and tables have been updated to reflect the currently available NHANES data and the paper republished here: https://doi.org/10.1002/art.42330.
Metal‐Free Facile Synthesis of Multisubstituted 1‐Aminoisoquinoline Derivatives with Dual‐State Emissions
Authors: Zhang Xinyu , Zhou Yibin , Wang Mengzhu , Chen Yating , Zhou Yunbing , Gao Wenxia , Liu Miaochang , Huang Xiaobo , Wu Huayue
Published: April 2020

Although isoquinoline is a good traditional fluorescent structural unit, most of its derivatives emit fluorescence in solution and a few of them can emit solid‐state fluorescence as well. Herein, a series of multisubstituted 1‐aminoisoquinoline derivatives were synthesized by a simple reaction of a readily available 4H‐pyran derivative and secondary amines. The reaction had advantages of metal‐free, mild conditions, simple operation, and good yields, which was realized by a ring‐opening and sequential ring‐closing mechanism. These 1‐aminoisoquinoline derivatives were found to exhibit interesting dual‐state emissions. In the solution, they emitted strong blue fluorescence at about 458 nm. In the solid state, they emitted solid‐state blue fluorescence at 444–468 nm with high fluorescence quantum yields of 40.3–98.1%. Crystal structural analyses indicated that solid‐state emissions of these compounds originated from twisted molecular conformations and the resultant loose stacking arrangements. Furthermore, their solid‐state fluorescence wavelengths were demonstrated to depend on molecular conformations rather than stacking arrangements. The discovery of these 1‐aminoisoquinolines with multiple reaction sites provides new possibilities for the development of solid‐state fluorescent materials based on the traditional isoquinoline skeleton.
Postsurgical pyoderma gangrenosum and flap necrosis in a head and neck cancer patient following neck dissection
Authors: Arebro Julia , Palmgren Björn
Published: April 2020

Postsurgical pyoderma gangrenosum (PSPG) develops in the skin after surgery without known cause. Immunosuppression constitutes first‐line therapy and increases the likelihood of successful surgery when needed. PSPG should be considered when a flap necrosis occurs.
Computational Analysis of the Solid‐State and Solvation Properties of Carbamazepine in Relation to its Polymorphism
Authors: Rosbottom Ian , Cheng Thomas Nok Hin , Heng Jerry Y. Y.
Published: April 2020

The solvent‐dependent polymorphism of the active pharmaceutical ingredient (API) carbamazepine is interpreted from calculations of the solid‐state and API‐solvent intermolecular interactions. These simulations suggested that apolar solute‐solute interactions could be disrupted by apolar solvents. In contrast, the polar solute‐solute interactions were found to be easily disrupted by polar and protic solvents. This is consistent with experimental observations that the crystallization of the metastable form II is more dominant in apolar solvents. The Mercury program remains the gold standard in terms of usability; however, further expansion into more complex simulation techniques could make this package of even greater use in pharmaceutical manufacturing workflows.
Perovskite Oxides Prepared by Hydrothermal and Solvothermal Synthesis: A Review of Crystallisation, Chemistry, and Compositions
Authors: Walton Richard I.
Published: April 2020

Perovskite oxides with general composition ABO3 are a large group of inorganic materials that can contain a variety of cations from all parts of the Periodic Table and that have diverse properties of application in fields ranging from electronics, energy storage to photocatalysis. Solvothermal synthesis routes to these materials have become increasingly investigated in the past decade as a means of direct crystallisation of the solids from solution. These methods have significant advantages leading to adjustment of crystal form from the nanoscale to the micron‐scale, the isolation of compositions not possible using conventional solid‐state synthesis and in addition may lead to scalable processes for producing materials at moderate temperatures. These aspects are reviewed, with examples taken from the past decade's literature on the solvothermal synthesis of perovskites with a systematic survey of B‐site cations, from transition metals in Groups 4–8 and main group elements in Groups 13, 14 and 15, to solid solutions and heterostructures. As well as hydrothermal reactions, the use of various solvents and solution additives are discussed and some trends identified, along with prospects for developing control and predictability in the crystallisation of complex oxide materials.
Direct, Enantioselective, and Nickel(II) Catalyzed Reactions of N‐Azidoacetyl Thioimides with Trimethyl Orthoformate: A New Combined Methodology for the Rapid Synthesis of Lacosamide and Derivatives
Authors: Teloxa Saul F. , Kennington Stuart C. D. , Camats Marc , Romea Pedro , Urpí Fèlix , Aullón Gabriel , Font‐Bardia Mercè
Published: April 2020

A direct and highly enantioselective reaction of N‐azidoacetyl‐1,3‐thiazolidine‐2‐thione with trimethyl orthoformate catalyzed by Tol‐BINAPNiCl2 in the presence of TESOTf and 2,6‐lutidine is reported. The heterocyclic scaffold can be easily removed by addition of a wide array of amines to give the corresponding enantiomerically pure 2‐azido‐3,3‐dimethoxypropanamides in high yields. Appropriate manipulation of the N‐benzyl amide derivative provides an efficient access to the antiepileptic agent lacosamide through a new enantioselective C−C bond‐forming process. DFT computational studies uncover clues for the understanding of the remarkable stereocontrol of the addition of a nickel(II) enolate to a putative oxocarbenium intermediate from trimethyl orthoformate.
Cytologic grading of primary malignant salivary gland tumors: A blinded review by an international panel
Authors: Johnson Daniel N. , Onenerk Mine , Krane Jeffrey F. , Rossi Esther Diana , Baloch Zubair , Barkan Güliz , Bongiovanni Massimo , Callegari Fabiano , Canberk Sule , Dixon Glen , Field Andrew , Griffith Christopher C. , Jhala Nirag , Jiang Sara , Kurtycz Daniel , Layfield Lester , Lin Oscar , Maleki Zahra , Perez‐Machado Miguel , Pusztaszeri Marc , Vielh Philippe , Wang He , Zarka Matthew A. , Faquin William C.
Published: April 2020

Background

Fine needle aspiration (FNA) is commonly used for the preoperative evaluation of salivary gland tumors. Tumor grade is a key factor influencing clinical management of salivary gland carcinomas (SGCs). To assess the ability to grade nonbasaloid SGCs in FNA specimens, an international panel of cytopathologists convened to review and score SGC cases.

Methods

The study cohort included 61 cases of primary SGC from the pathology archives of 3 tertiary medical centers. Cases from 2005 to 2016 were selected, scanned, and digitized. Nineteen cytopathologists blinded to the histologic diagnosis reviewed the digitized cytology slides and graded them as low, high, or indeterminate. The panelists' results were then compared to the tumor grades based on histopathologic examination of the corresponding resection specimens.

Results

All but 2 of the 19 (89.5%) expert panelists review more than 20 salivary gland FNAs per year; 16 (84.2%) of the panelists work at academic medical centers, and 13 (68.4%) have more than 10 years' experience. Participants had an overall accuracy of 89.4% in the grading of SGC cases, with 90.2% and 88.3% for low‐ and high‐grade SGC, respectively. Acinic cell carcinoma and mucoepidermoid carcinoma had the highest degree of accuracy, while epithelial‐myoepithelial carcinoma and salivary duct carcinoma had the lowest degree of accuracy. As expected, the intermediate‐grade SGC cases showed the greatest variability (high‐grade, 42.1%; low‐grade, 37.5%, indeterminate, 20.4%).

Conclusion

This study confirms the high accuracy of cytomorphologic grading of primary SGC by FNA as low‐ or high‐grade. However, caution should be exercised when a grade cannot be confidently assigned.
Resting‐state networks of the neonate brain identified using independent component analysis
Authors: Rajasilta Olli , Tuulari Jetro J. , Björnsdotter Malin , Scheinin Noora M. , Lehtola Satu J. , Saunavaara Jani , Häkkinen Suvi , Merisaari Harri , Parkkola Riitta , Lähdesmäki Tuire , Karlsson Linnea , Karlsson Hasse
Published: April 2020

Resting‐state functional magnetic resonance imaging (rs‐fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6‐min resting‐state data set acquired from 21 naturally sleeping term‐born (age 26 ± 6.7 d), healthy neonates to investigate the emerging functional resting‐state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default‐mode‐network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA‐based denoising of fMRI data increased the number of networks identified with group‐ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth.
Dimensional Control of Assembling Metal Chalcogenide Clusters
Authors: Gadjieva Natalia A. , Champsaur Anouck M. , Steigerwald Michael L. , Roy Xavier , Nuckolls Colin
Published: April 2020

Invited for the cover of this issue is the group of Colin Nuckolls from Columbia University, New York, USA. The cover image shows the metal chalcogenide core building block and its 1D, 2D, and 3D extensions.
Commercial Copper‐Catalyzed Aerobic Oxidative Synthesis of Quinazolinones from 2‐Aminobenzamide and Methanol
Authors: Kerdphon Sutthichat , Sanghong Patthadon , Chatwichien Jaruwan , Choommongkol Vachira , Rithchumpon Puracheth , Singh Thishana , Meepowpan Puttinan
Published: April 2020

The focus of this study was the development of a new synthetic method for quinazolinones based on the principles of Green Chemistry. Quinazolinones were synthesized from 2‐aminobenzamide using methanol as both the C1 source and a green solvent in the presence of base Cs2CO3. Additionally, a commercially available, economical copper complex was used as a catalyst in the reaction. The desired products were achieved in moderate to high yield with up to 99 % isolated yield.
Acute and subchronic toxicity study of nonpolar extract of licorice roots in mice
Authors: Kim Hyun‐Yong , Zuo Guanglei , Lee Soo Kyeong , Lim Soon Sung
Published: April 2020

Licorice is used as a medicinal plant, and several studies have shown that licorice has beneficial effects. The objective of this study was to evaluate the safety of nonpolar licorice extract using toxicity experiments. Nonpolar extract from the root of Glycyrrhiza uralensis (NERG) was analyzed by high‐performance liquid chromatography (HPLC). Antioxidant ability was determined by method of TPC and DPPH. Blood pressure was monitored by using blood pressure meter. In the acute study, a single dose (2,000 mg/kg) was orally administered to mice. In the subchronic study, mice were treated with extract at doses (50, 100, 500, and 1,000 mg/kg) for 120 days. Significantly difference was not shown at blood pressure, hematological, and biochemical parameters, and histopathology on mice. The results suggested that at acute and subchronic toxicity, each levels of nonpolar licorice extract administration in experiments did not cause toxicity effects or death on mice.
Mortality and Hepatic Decompensation in Patients With Cirrhosis and Atrial Fibrillation Treated With Anticoagulation
Authors: Serper Marina , Weinberg Ethan M. , Cohen Jordana B. , Reese Peter P. , Taddei Tamar H. , Kaplan David E.
Published: April 2020

Background and Aims

Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all‐cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF).

Approach and Results

This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time‐dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow‐up. All‐cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55‐0.76; MSM models: HR, 0.54; 95% CI, 0.40‐0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50‐0.93; MSM models: HR, 0.50; 95% CI, 0.31‐0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09‐0.90) and DOACs (HR, 0.23; 95% CI, 0.07‐0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26‐0.94).

Conclusions

Warfarin and DOACs were associated with reduced all‐cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.
Vegetation‐groundwater dynamics at a former uranium mill site following invasion of a biocontrol agent: A time series analysis of Landsat normalized difference vegetation index data
Authors: Jarchow Christopher J. , Waugh William J. , Didan Kamel , Barreto‐Muñoz Armando , Herrmann Stefanie , Nagler Pamela L.
Published: April 2020

Because groundwater recharge in dry regions is generally low, arid and semiarid environments have been considered well‐suited for long‐term isolation of hazardous materials (e.g., radioactive waste). In these dry regions, water lost (transpired) by plants and evaporated from the soil surface, collectively termed evapotranspiration (ET), is usually the primary discharge component in the water balance. Therefore, vegetation can potentially affect groundwater flow and contaminant transport at waste disposal sites. We studied vegetation health and ET dynamics at a Uranium Mill Tailings Radiation Control Act (UMTRCA) disposal site in Shiprock, New Mexico, where a floodplain alluvial aquifer was contaminated by mill effluent. Vegetation on the floodplain was predominantly deep‐rooted, non‐native tamarisk shrubs (Tamarix sp.). After the introduction of the tamarisk beetle (Diorhabda sp.) as a biocontrol agent, the health of the invasive tamarisk on the Shiprock floodplain declined. We used Landsat normalized difference vegetation index (NDVI) data to measure greenness and a remote sensing algorithm to estimate landscape‐scale ET along the floodplain of the UMTRCA site in Shiprock prior to (2000–2009) and after (2010–2018) beetle establishment. Using groundwater level data collected from 2011 to 2014, we also assessed the role of ET in explaining seasonal variations in depth to water of the floodplain. Growing season scaled NDVI decreased 30% (p < .001), while ET decreased 26% from the pre‐ to post‐beetle period and seasonal ET estimates were significantly correlated with groundwater levels from 2011 to 2014 (r2 = .71; p = .009). Tamarisk greenness (a proxy for health) was significantly affected by Diorhabda but has partially recovered since 2012. Despite this, increased ET demand in the summer/fall period might reduce contaminant transport to the San Juan River during this period.
Drug excipients, food additives, and cosmetic ingredients probably not carcinogenic to humans reveal a functional specificity for the 2‐year rodent bioassay
Authors: Suarez‐Torres Jose D. , Jimenez‐Orozco Fausto A. , Ciangherotti Carlos E.
Published: April 2020

Regarding carcinogenicity testing, the long‐term rodent bioassay (RCB) has been the test required by most regulatory agencies across the world. Nonetheless, due to the lack of knowledge about its specificity, it has been argued that the RCB is unspecific or even invalid. Because of the substantial limitations of epidemiology to identify chemicals probably not carcinogenic to humans (PNCH), it has been very difficult to address the specificity of the RCB. Nevertheless, because mechanistic/pharmacological data are currently recognized as a valid stream of evidence for the identification of chemical hazards, the road is now open to gain insight into the specificity of the RCB. Based on sound mechanistic/pharmacological data that support the classification of chemicals as PNCH, 100 PNCH substances were gathered in this investigation. Contrary to what was previously forecast, in this study, the RCB exhibited a functional specificity that ranged from 83% to 91%, depending on the settings of the testing (2‐species vs. rats only, and the nominal maximum tolerated dose). Other contributions of this work were: (a) enabling the comparison, in terms of specificity, between the RCB and the alternative methods that could replace it (eg, Tg.AC mouse, rasH2 mouse); (b) disclosing what the specificity is for alternative methods that were developed using the RCB as the reference standard; and (c) expanding the previous narrow (only seven substances) set of chemicals identified as not likely to be carcinogenic to humans by hazard identification programs.
Encapsulation of Mg2inside a C60cage forms an electride
Authors: Das Prasenjit , Saha Ranajit , Chattaraj Pratim K.
Published: April 2020

Density functional theory (DFT) based calculations have been carried out for the endohedral encapsulation of magnesium dimer inside fullerene, that is, Mg2@C60. It is observed that the minimum energy structure of the Mg2@C60system isC2hsymmetry. The MgMg bond distance in the Mg2@C60system is much shorter than that in the free Mg2and Mg22+ion. The formation of the endohedral Mg2@C60system is thermochemically spontaneous in nature. The natural bond orbital (NBO) analysis showed the presence of an Mg22+fragment with an MgMg bond inside the C60cage. The electron density descriptors have identified the covalency in the MgMg bond. A non‐nuclear attractor (NNA) is present in the middle of the two Mg‐atoms. The bonding interaction between the Mg2and C60fragments is ionic in nature and the [Mg22+] and [C602−] represent the bonding pattern in the Mg2@C60system. The designed endohedrally encapsulated system behaves as an electride.
Revision of serum ALT upper limits of normal facilitates assessment of mild liver injury in obese children with non‐alcoholic fatty liver disease
Authors: Lu Yutian , Wang Qiongdan , Yu Lisha , Yin XueRui , Yang Huijie , Xu Xi , Xia Ying , Luo Yue , Peng Ying , Yu Qigui , Chen Zhanguo , Yu Jian , Lai Meimei , Wu Nan , Pan Xiao‐Ben , Zheng Xiaoqun
Published: April 2020

Background

The serum alanine aminotransferase (ALT) level is a critical parameter for evaluating liver injury in non‐alcoholic fatty liver disease (NAFLD). However, the currently accepted upper limits of normal (ULN) for serum ALT (ULN‐ALT) are debated, as they may be excessively high.

Methods

A total of 1638 children aged 6‐16 years, comprising 507 children with normal BMI (500 healthy children and 7 children with NAFLD), 199 overweight children, and 932 obese children, were included in the analysis. We re‐evaluated the ULN‐ALT in 500 healthy Chinese children using the 95th percentiles of serum ALT levels as revised ULN‐ALT. Fatty liver was identified by ultrasound examination.

Results

Significant positive correlations between serum ALT levels and body mass index (BMI) were detected in overweight boys (r = .399, P < .001), obese boys (r = .398, P < .001), and obese girls (r = .392, P < .001). The prevalence percentages of NAFLD were 93.6%, 75.8%, and 37.9% in obese boys with serum ALT levels of >50, 25‐50, and ≤25 U/L and were 81.6%, 67.9%, and 20.6% in obese girls with serum ALT levels of >40, 20‐40, and ≤20 U/L, respectively.

Conclusion

Serum ALT levels significantly correlated with abnormal BMI values in children, suggesting a rigorous BMI threshold is needed to establish the cutoffs for serum ULN‐ALT in children. Besides, the revised serum ULN‐ALT can uncover mild liver injury in obese children with NAFLD.
Clinical experience regarding the accuracy of NIPT in the detection of sex chromosome abnormality
Authors: Zheng Yunyun , Wan Shanning , Dang Yinghui , Song Tingting , Chen Biliang , Zhang Jianfang
Published: April 2020

Background

The present study aimed to determine the accuracy (Z‐value) of non‐invasive prenatal testing (NIPT) results for sex chromosome aneuploidy (SCA) in routine clinical practice.

Methods

Among a cohort of 12505 pregnant females, maternal plasma samples collected from our hospital were utilized for SCA analysis by NIPT detection. The positive samples were validated through an invasive procedure and karyotyping analysis. The predictive value from positive samples in sex chromosomes was compared to analyze the accuracy of the Z‐value.

Results

There were 65 females with sex chromosome abnormalities within 12,505 pregnant females in the NIPT detection, which was validated by karyotype analysis of amniotic fluid puncture through sequencing, as well as bioinformatics analysis, with 18 true‐positive samples. The true‐positive results with 45,X, 47,XXY, 47,XXX and 47,XYY karyotypes predicted by NIPT were 14.29%, 50.00%, 66.67% and 71.43%, respectively. Among sex chromosome cases, the findings indicated that positive NIPT results with Z ≥ 9 show a higher accuracy.

Conclusions

The findings of the present study demonstrate that the positive predictive value of NIPT for sex chromosome abnormalities is distinctive. The positive predictive value was highest for 47,XYY and lowest for 45,X. Additionally, the Z‐value results are considered to be correlated with the accuracy of NIPT, although further studies need to be made.
Consensus guideline for the diagnosis and management of mannose phosphate isomerase‐congenital disorder of glycosylation
Authors: Čechová Anna , Altassan Ruqaiah , Borgel Delphine , Bruneel Arnaud , Correia Joana , Girard Muriel , Harroche Annie , Kiec‐Wilk Beata , Mohnike Klaus , Pascreau Tiffany , Pawliński Łukasz , Radenkovic Silvia , Vuillaumier‐Barrot Sandrine , Aldamiz‐Echevarria Luis , Couce Maria Luz , Martins Esmeralda G. , Quelhas Dulce , Morava Eva , de Lonlay Pascale , Witters Peter , Honzík Tomáš
Published: April 2020

Mannose phosphate isomerase‐congenital disorder of glycosylation (MPI‐CDG) deficiency is a rare subtype of congenital disorders of protein N‐glycosylation. It is characterised by deficiency of MPI caused by pathogenic variants in MPI gene. The manifestation of MPI‐CDG is different from other CDGs as the patients suffer dominantly from gastrointestinal and hepatic involvement whereas they usually do not present intellectual disability or neurological impairment. It is also one of the few treatable subtypes of CDGs with proven effect of oral mannose. This article covers a complex review of the literature and recommendations for the management of MPI‐CDG with an emphasis on the clinical aspect of the disease. A team of international experts elaborated summaries and recommendations for diagnostics, differential diagnosis, management, and treatment of each system/organ involvement based on evidence‐based data and experts' opinions. Those guidelines also reveal more questions about MPI‐CDG which need to be further studied.
Comparison of a VLP‐based and GST‐L1‐based multiplex immunoassay to detect vaccine‐induced HPV‐specific antibodies in first‐void urine
Authors: Pattyn Jade , Panicker Gitika , Willhauck‐Fleckenstein Martina , Van Keer Severien , Téblick Laura , Pieters Zoë , Tjalma Wiebren A. A. , Matheeussen Veerle , Van Damme Pierre , Waterboer Tim , Unger Elizabeth R. , Vorsters Alex
Published: April 2020

Vaccine‐induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first‐void (FV) urine. This presents a novel opportunity for noninvasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared the measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus‐like particles (VLP)‐based ELISA (M4ELISA) with previously reported results using a glutathione S‐transferase (GST)‐L1‐based immunoassay (GST‐L1‐MIA). We tested 53 paired FV urine and serum samples from 19‐ to 26‐year‐old healthy women, unvaccinated (n = 17) or vaccinated with either the bivalent or quadrivalent HPV‐vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST‐L1‐MIA results. Inter‐assay and inter‐specimen correlations were examined using the Spearman's rank test (rs). As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine P = .0003; serum P ≤ .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti‐HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, P ≤ .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST‐L1‐MIA (FV urine anti‐HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, P ≤  .0001; serum anti‐HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, P ≤ .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine‐induced HPV antibody detection.
Whole‐school antibullying interventions: A systematic review of 20 years of publications
Authors: Valle Jessica E. , Williams Lucia C. A. , Stelko‐Pereira Ana C.
Published: April 2020

A systematic literature review on whole‐school antibullying interventions was conducted. Twelve databases were consulted, considering as inclusion criteria: scientific article, published between 1998 and June 2018, in English or Portuguese, describing empirical studies on whole‐school antibullying interventions. Seventeen studies were analyzed, indicating that the interventions had the reduction of bullying prevalence as main goal, and secondary goals as improvements in reporting bullying occurrences, bullying identification, and attitudes toward bullying. Six interventions had experimental designs, five were quasiexperimental, and six were preexperimental. Data collection in 14 studies involved exclusively students, in two studies measurements also encompassed teachers, and one study applied questionnaires to parents only. Intervention effects on bullying prevalence were inconsistent, with eight studies finding significant decreases in bullying involvement, while seven studies did not show significant effects on bullying prevalence or found negative results, such as an increase of its prevalence. However, the interventions had significant positive effects on increasing the reporting of bullying occurrences, attitudes toward bullying, and perceived peer and teacher intervention. Thus, whole‐school antibullying interventions, incorporating multiple strategies and targeting multiple individuals, should be encouraged to address the complexity of bullying.
The Age of Data‐Driven Proteomics: How Machine Learning Enables Novel Workflows
Authors: Bouwmeester Robbin , Gabriels Ralf , Van Den Bossche Tim , Martens Lennart , Degroeve Sven
Published: April 2020

A lot of energy in the field of proteomics is dedicated to the application of challenging experimental workflows, which include metaproteomics, proteogenomics, data independent acquisition (DIA), non‐specific proteolysis, immunopeptidomics, and open modification searches. These workflows are all challenging because of ambiguity in the identification stage; they either expand the search space and thus increase the ambiguity of identifications, or, in the case of DIA, they generate data that is inherently more ambiguous. In this context, machine learning‐based predictive models are now generating considerable excitement in the field of proteomics because these predictive models hold great potential to drastically reduce the ambiguity in the identification process of the above‐mentioned workflows. Indeed, the field has already produced classical machine learning and deep learning models to predict almost every aspect of a liquid chromatography‐mass spectrometry (LC‐MS) experiment. Yet despite all the excitement, thorough integration of predictive models in these challenging LC‐MS workflows is still limited, and further improvements to the modeling and validation procedures can still be made. Therefore, highly promising recent machine learning developments in proteomics are pointed out in this viewpoint, alongside some of the remaining challenges.
Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design
Authors: Shukla Shashank , Favata Joseph , Srivastava Vikas , Shahbazmohamadi Sina , Tripathi Anubhav , Shukla Anita
Published: April 2020

Developing optimized hydrogel products requires an in‐depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl2concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl2concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power‐law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl2concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.
Permafrost research in China related to express highway construction
Authors: Wang Shuangjie , Niu Fujun , Chen Jianbing , Dong Yuanhong
Published: April 2020

Express highways are roads of high speed, large capacity, and transportation flexibility. The network of express highways in China has been developed over the last 30 years to accommodate the needs of a growing population and to facilitate economic development. Part of the network is in permafrost regions, where the construction and maintenance of these roads present significant engineering challenges due to permafrost degradation induced by climate warming and by construction. This paper summarizes the engineering problems encountered in the construction and maintenance of these express highways, and the mitigation techniques used to overcome them on new transportation projects in permafrost regions. Ten types of engineering problems along the Qinghai‐Tibet Highway, the oldest and longest highway in the permafrost regions of China are identified. Their main cause is related to permafrost degradation in the subgrade beneath the road subbase. Settlement of the highway embankment due to thaw consolidation of degrading permafrost is the dominant mechanical distress observed. Mitigation techniques, mainly for enhancing heat convection beneath express highways, are discussed along with their effects. Research in China related to transportation projects may provide a reference for future express highway design and construction in permafrost regions around the world.
Applicability of free drug hypothesis to drugs with good membrane permeability that are not efflux transporter substrates: A microdialysis study in rats
Authors: Chen Chun , Zhou Hongyu , Guan Chi , Zhang Huanhuan , Li Yingying , Jiang Xue , Dong Zheng , Tao Yuanyuan , Du Juan , Wang Shuyao , Zhang Teng , Du Na , Guo Junyang , Wu Yaqiong , Song Zehai , Luan Haofei , Wang Yu , Du Hongwen , Zhang Shaofeng , Li Chen , Chang Hang , Wang Tao
Published: April 2020

In clinical pharmacology, the free drug hypothesis has been widely applied in the interpretation of the relationship between pharmacokinetics and pharmacodynamics (PK/PD). The free drug hypothesis assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state. The objective of this study is to demonstrate whether the free drug hypothesis is universally applicable for all drugs. The unbound concentrations of the 18 compounds in blood and in brain interstitial fluids (ISF) at steady state following constant intravenous infusion were simultaneously monitored up to 6 hours via in vivo microdialysis technique. Based on the permeability and efflux ratio (ER), the test compounds can be divided into two classes. Class I includes the compounds with good membrane permeability that are not substrates of efflux transporters (eg, P‐gp, BCRP, and MRPs), whereas Class II includes the compounds that are substrates of efflux transporters. The steady‐state unbound drug concentrations in blood, brain, and CSF are quantitatively very similar for Class I compounds, whereas the steady‐state unbound concentrations in the brain and CSF are significantly lower than those in blood for Class II compounds. These results strongly suggest that the free drug hypothesis is not universal for all drugs but is only applicable for drugs with good permeability that are not substrates of efflux transporters.