bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 1 trial of olaratumab monotherapy and in combination with chemotherapy in pediatric patients with relapsed/refractory solid and central nervous system tumors
Authors: Mascarenhas Leo , Ogawa Chitose , Laetsch Theodore W. , Weigel Brenda J. , Bishop Michael W. , Krystal Julie , Borinstein Scott C. , Slotkin Emily K. , Muscal Jodi A. , Hingorani Pooja , Levy Donna E. , Mo Gary , Shahir Ashwin , Wright Jennifer , DuBois Steven G.
Published: January 2021

Olaratumab is a monoclonal antibody that specifically binds to platelet‐derived growth factor receptor alpha (PDGFRα) and blocks receptor activation. We conducted a phase 1 trial to evaluate the safety of olaratumab and determine a recommended dose in combination with three different chemotherapy regimens in children. Patients <18 years with relapsed/refractory solid or central nervous system tumors were enrolled to two dose levels of olaratumab. Patients received olaratumab monotherapy at 15 mg/kg (Part A) or 20 mg/kg (Part B) on Days 1 and 8 of the first 21‐day cycle, followed by olaratumab combined with standard fixed doses of chemotherapy with doxorubicin, vincristine/irinotecan, or high‐dose ifosfamide by investigator choice for subsequent 21‐day cycles. In Part C, patients received olaratumab 20 mg/kg plus assigned chemotherapy for all cycles. Parts A‐C enrolled 68 patients across three chemotherapy treatment arms; olaratumab in combination with doxorubicin (N = 16), vincristine/irinotecan (N = 26), or ifosfamide (N = 26). Three dose‐limiting toxicities (DLTs) occurred during olaratumab monotherapy (at 15 mg/kg, grade [G] 4 alanine aminotransferase [ALT]; at 20 mg/kg, G3 lung infection and G3 gamma‐glutamyl transferase). One DLT occurred during vincristine/irinotecan with olaratumab 20 mg/kg therapy (G3 ALT). Treatment‐emergent adverse events ≥G3 in >25% of patients included neutropenia, anemia, leukopenia, lymphopenia, and thrombocytopenia. Pharmacokinetic profiles of olaratumab with chemotherapy were within the projected range based on adult data. There was one complete response (rhabdomyosarcoma [Part B vincristine/irinotecan arm]) and three partial responses (two rhabdomyosarcoma [Part A doxorubicin arm and Part C doxorubicin arm]; one pineoblastoma [Part B vincristine/irinotecan arm]). Olaratumab was tolerable and safely administered in combination with chemotherapy regimens commonly used in children and adolescents.
Synergistic Nanostructured MnOx/TiO2 Catalyst for Highly Selective Synthesis of Aromatic Imines
Authors: Sudarsanam Putla , Köckritz Angela , Atia Hanan , Amin Mohamad Hassan , Brückner Angelika
Published: January 2021

This work reports the development of a synergistic nanostructured MnOx/TiO2 catalyst, with highly dispersed MnOx nanoparticles (4.5±1 nm) on shape‐controlled TiO2 nanotubes (8–11 nm width and 120–280 nm length), for selective synthesis of valuable aromatic imines at industrially important conditions. Pristine TiO2 nanotubes exhibited 97 % imine selectivity at a 38.3 % benzylamine conversion, whereas very low imine selectivity was obtained over commercial TiO2 materials, indicating the catalytic significance of shape‐controlled TiO2 nanotubes. The MnOx nanoparticle/TiO2 nanotube (10 wt% Mn) catalyst calcined at 400 °C showed the best activity with 95.6 % benzylamine conversion and 99.9 % imine selectivity. This catalyst exhibited good recyclability for four times and is effective for converting numerous benzylamines into higher yields of imines. The high catalytic performance of MnOx/TiO2 nanotubes was attributed to higher number of redox sites (Mn3+), high dispersion of Mn species, and shape‐controlled structure of TiO2, indicating that this catalyst could be a promising candidate for selective oxidation reactions.
Simple RuCl3‐catalyzed N‐Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol
Authors: Sarki Naina , Goyal Vishakha , Tyagi Nitin Kumar , Puttaswamy  , Narani Anand , Ray Anjan , Natte Kishore
Published: January 2021

Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost‐competitive method with the use of methanol as both C1 synthon and H2 source for selective N‐methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand‐free catalyst. This readily available catalyst tolerates various amines comprising electron‐deficient and electron‐donating groups and allows them to transform into corresponding N‐methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late‐stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N‐methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N‐methylated amines using MeOH under H2‐free conditions including transfer hydrogenation of nitroarenes‐to‐anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one‐shot selective and green syntheses of 1‐methylbenzimidazole using ortho‐phenylenediamine (OPDA) and methanol as coupling partners.
A Durable Metalloporphyrin 2D‐Polymer for Photocatalytic Hydrogen and Oxygen Evolution from River and Sea Waters
Authors: Ranjeesh Kayaramkodath Chandran , George Leena , Maibam Ashakiran , Krishnamurty Sailaja , Babu Sukumaran Santhosh
Published: January 2021

It is highly imaginary that the outcome of a combination of two complementary resources leads to answer an alarming global issue. One such possible example is the solar seawater splitting for ‘clean fuel’ H2 generation. Since the catalytic activity and stability of the photocatalysts are substantially challenged in seawater, the design of an efficient and stable photocatalyst is highly desirable. Herein, we demonstrate the solar seawater splitting by a two‐dimensional polymer catalyst derived from metalloporphyrin bearing multi‐hydroxyl groups. A bimetallic (Co and Ni) porphyrin 2D‐polymer exhibits excellent long‐term durability of 15 cycles of H2 and O2 generation in 200 days from pure water without a considerable decrease in efficiency. Detailed studies using river and seawaters also show the reliable performance of the catalyst over repeated cycles. Here the deactivation modes of catalytic activity have been nullified by the layered metalloporphyrin polymer structure through stable π−π stacking, signifying the molecular design of 2D‐polymer photocatalyst.
Experimental study on the flow field characteristics of the two‐layer impinging stream mixer
Authors: Zhang Jianwei , Ding Changwei , Dong Xin , Feng Ying , Ma Fanrong
Published: January 2021

The impinging stream mixer is an efficient equipment for fluid mixing with potential for many chemical engineering and industrial applications. In this paper, the flow field characteristics of symmetrical and asymmetrical flow field in the two‐layer impinging stream mixer were investigated. The concentration field was obtained by planar laser induced fluorescence (PLIF) and the velocity field was obtained by time resolved particle image velocimetry (TR‐PIV). The velocity field was reconstructed by proper orthogonal decomposition (POD) to extract dominant coherent structures from the perspective of energy. The influence of Reynolds number, nozzle diameter, and nozzle spacing on flow field energy and mixing rate were investigated. The results show that in the symmetrical flow field, the flow field energy and mixing rate increased with the Reynolds number. With the increase of nozzle diameter, the flow field energy and mixing rate increased firstly and then decreased. In the asymmetrical flow field, the flow field energy was higher than that of the symmetrical flow field, while the mixing rate was smaller than that of the symmetrical flow field.
Electrocatalytic CO2 Reduction with Re‐Based Spiro Bipyridine Complexes: Effects of the Local Proton in the Second Coordination Sphere†
Authors: Yang Yong , Zhang Ziyun , Zhang Zhenyu , Tang Chao , Chang Xiaoyong , Duan Lele
Published: January 2021

Main observation and conclusion

We report herein a Re‐based tricarbonyl catalyst [fac‐Re(L1)(CO)3Cl] (Re1) bearing a spiro center and a phenol group as a local proton source in the second coordination sphere. Due to the large steric spiro group, dimerization of one‐electron reduced species was completely eliminated, improving the stability of Re1. Simultaneously, the phenol group in the second coordination sphere improves the formation of an H‐bonding chain that promotes the protonation of CO2 reduction intermediates, boosting the electrocatalytic CO2 reduction activity of Re1. Mechanistic studies reveal that the doubly reduced complex Re1b is active for CO2 addition.
Enhanced Removal of Pb(II) from Aqueous Solution using EDTA‐Modified Magnetic Graphene Oxide
Authors: Xing Cuijuan , Xia Aiqing , Yu Ling , Dong Lili , Hao Yongchao , Qi Xingcun
Published: January 2021

Ethylenediaminetetraacetic acid (EDTA) groups are successfully linked to magnetic graphene oxide (MGO) by a silanization reaction between N‐(trimethoxysilylpropyl) ethylenediaminetriacetic acid and OH on the surface of MGO. The EDTA‐modification enhances the adsorption capacity of MGO because of the chelating ability of EDTA. The adsorption behavior of Pb(II) and the effects of solution conditions such as contact time, initial Pb(II) concentration, and pH (1–9) are investigated. The adsorption capacity for Pb(II) removal is found to be 211.3 mg g−1 and the adsorption process is completed at pH 6.8 within 50 min. The process is shown to follow a pseudo‐second‐order kinetic rate. The isothermal data reveal that the adsorption process of Pb(II) is well‐matched with the Freundlich model. In addition, the magnetic composite can be effectively and simply separated by an external magnetic field. Therefore, MGO‐EDTA can potentially serve as an adsorbent for the separation and removal of Pb(II) from water.
Smoothed particle hydrodynamic modelling of the cerebrospinal fluid for brain biomechanics: Accuracy and stability
Authors: Duckworth Harry , Sharp David J. , Ghajari Mazdak
Published: January 2021

The Cerebrospinal Fluid (CSF) can undergo shear deformations under head motions. Finite Element (FE) models, which are commonly used to simulate biomechanics of the brain, including traumatic brain injury, employ solid elements to represent the CSF. However, the limited number of elements paired with shear deformations in CSF can decrease the accuracy of their predictions. Large deformation problems can be accurately modelled using the mesh‐free Smoothed Particle Hydrodynamics (SPH) method, but there is limited previous work on using this method for modelling the CSF. Here we explored the stability and accuracy of key modelling parameters of an SPH model of the CSF when predicting relative brain/skull displacements in a simulation of an in vivo mild head impact in human. The Moving Least Squares (MLS) SPH formulation and Ogden rubber material model were found to be the most accurate and stable. The strain and strain rate in the brain differed across the SPH and FE models of CSF. The FE mesh anchored the gyri, preventing them from experiencing the level of strains seen in the in vivo brain experiments and predicted by the SPH model. Additionally, SPH showed higher levels of strains in the sulci compared to the FE model. However, tensile instability was found to be a key challenge of the SPH method, which needs to be addressed in future. Our study provides a detailed investigation of the use of SPH and shows its potential for improving the accuracy of computational models of brain biomechanics.
Gamma — General Abstract Model for Multiset mAnipulation and dynamic dataflow model: An equivalence study
Authors: Mello Rui R. , de Araújo Leandro S. , Alves Tiago A. O. , Marzulo Leandro A. J. , Paillard Gabriel A. L. , França Felipe M. G.
Published: January 2021

With the increase of the search for computational models where the expression of parallelism occurs naturally, some paradigms arise as options for the current generation of computers. In this context, dynamic dataflow and Gamma—GeneralAbstractModel forMultiset mAnipulation—emerge as interesting computational model choices. In dynamic dataflow model, operations are performed as soon as their associated operands are available, without rely on a Program Counter to dictate the execution order of instructions. The Gamma paradigm is based on a parallel multiset rewriting scheme. It provides a nondeterministic execution model inspired by anabstract chemical machinemetaphor, where operations are formulated as reactions that occur freely among matching elements belonging to the multiset. In this work, equivalence relations between the dynamic dataflow and Gamma paradigms are exposed and explored, while methods to convert from dataflow to Gamma paradigm and vice versa are provided. It is shown that vertices and edges of a dynamic dataflow graph can correspond, respectively, to reactions and multiset elements in the Gamma paradigm. This work provides the scientific community with the possibility of taking profit of both parallel programming models, contributing with a versatility component to researchers and developers.
Genetic diversity and agronomic performance of wheat landraces currently grown in Tajikistan
Authors: Husenov Bahromiddin , Muminjanov Hafiz , Dreisigacker Susanne , Otambekova Munira , Akin Beyhan , Subasi Kemal , Rasheed Awais , Shepelev Sergey , Morgounov Alexey
Published: January 2021

Tajikistan is rich in genetic resources and one of a few countries where farmers still grow wheat (Triticum spp) landraces, which are important for production and breeding. This study undertook morphological description and agronomic and genomic characterization of wheat landraces collected in Tajikistan in 2013 and 2014 to develop opportunities for their use in breeding and on‐farm maintenance. In total, 60 wheat landraces were collected from 40 villages in 14 administrative districts and four regions. They were evaluated for agronomic traits in field trials in Turkey. The study identified six distinct regions where landraces are still grown. The villages growing the landraces were remote, with the distance to the nearest market being 30–100 km. The area allocated to wheat landraces varied from 0.01 to 2 ha. The main reason for maintaining the wheat landraces was their suitability for homemade bread and specific adaptation to high altitude. Overall, 68 distinct lines originating from landraces were identified using morphological and genomic descriptions. A core set of 30 lines was selected and field phenotyped under rain‐fed conditions. Several landraces (Joydori, Safedak, Surkhaki besuk, Shukhak, Surkh‐suk, and Kilaki bartang) that exceeded local check for grain yield and size were identified. Cluster analysis using single nucleotide polymorphism (SNP) array kinship matrix demonstrated relatedness between the landraces from different regions of Tajikistan and from neighboring regions of Uzbekistan. The value of this study for the international community is in conservation of rare and unique wheat landraces that could have been lost in the future.
Investigation of Voltage Range and Self‐Discharge in Aqueous Zinc‐Ion Hybrid Supercapacitors
Authors: Yang Jie , Bissett Mark A. , Dryfe Robert A. W.
Published: January 2021

Aqueous zinc‐ion hybrid supercapacitors are a promising energy storage technology, owing to their high safety, low cost, and long‐term stability. At present, however, there is a lack of understanding of the potential window and self‐discharge of this aqueous energy storage technology. This study concerns a systematic investigation of the potential window of this device by cyclic voltammetry and galvanostatic charge–discharge. Hybrid supercapacitors based on commercial activated carbon (AC) demonstrate a wide and stable potential window (0.2 V to 1.8 V), high specific capacitances (308 F g−1 at 0.5 A g−1 and 110 F g−1 at 30 A g−1), good cycling stability (10000 cycles with 95.1 % capacitance retention), and a high energy density (104.8 Wh kg−1 at 383.5 W kg−1), based on the active materials. The mechanism involves simultaneous adsorption–desorption of ions on the AC cathode and zinc ion plating/stripping on the Zn anode. This work leads to better understanding of such devices and will aid future development of practical high‐performance aqueous zinc‐ion hybrid supercapacitors based on commercial carbon materials, thus accelerating the deployment of these hybrid supercapacitors and filling the gap between supercapacitors and batteries.
A Complementary Co−Ni Phosphide/Bimetallic Alloy‐Interspersed N‐Doped Graphene Electrocatalyst for Overall Alkaline Water Splitting
Authors: Arunkumar Paulraj , Gayathri Sampath , Han Jong Hun
Published: January 2021

Echinops‐like bimetallic CoNiP−CoNi alloy is synthesized from a metal−organic framework (MOF) and serves as an efficient catalyst for the oxygen evolution reaction (OER), with a low overpotential of 300 mV in 1 M KOH at 10 mA cm−2 (η10). The cooperative effect of Ni and Co metal, as well as the interfacial properties of the integrated semiconducting phosphide/metallic alloy and electronic conductivity of the MOF‐derived carbon regulate the performance of the catalyst. Moreover, the bimetallic CoNiP/CoNi alloy catalyst is interspersed with N‐doped graphene, forming a triad catalyst that demonstrates superior activity towards the hydrogen evolution reaction (η10=150 mV) and excellent durability, owing to interfacial effects of the triad catalyst, large electrochemical active surface area, and enhanced conductivity from N‐doped graphene. The stability of the carbon‐containing catalyst during OER (oxidation) is altered by the high reactivity of heteroatom dopant. The assembled CoNiP/CoNi/N−RGO||CoNiP/CoNi water electrolyzer delivers a reasonable cell potential of 1.76 V at 10 mA cm−2. The synthesized bimetallic CoNiP/CoNi alloy‐based triad catalyst thus demonstrates excellent electrocatalytic activity and high durability suitable for efficient alkaline water splitting.
Simulations of filamentary structure in an edge‐localized mode burst on EAST using BOUT++ code
Authors: Wu Y.B. , Xia T.Y. , Zhong F.C. ,   EAST Team
Published: January 2021

In this paper, simulation on the filamentary structure for the low‐hybrid wave heating H‐mode on experimental advanced superconducting tokamak (EAST) is carried out for the first time using BOUT++, and the speed and width of edge localized mode (ELM) filaments have been evaluated during the simulation. The evolutions of the ELM filaments are illustrated temporally and spatially. Then the results are compared with the experimental observations. It is found that at the peak gradient region in the outer midplane, the radial speed of the filaments is changed frequently and varied from 0.016 to 0.38 km/s. For the contrast, the poloidal speed oscillates in a narrower range of 0.68–0.88 km/s. The calculation results show the width of ELM filaments oscillates during the simulation, the minimum width is around 8.3 mm, and the maximum value is 41.24 mm. The distributions of the ELM filament widths with the radial position indicate the width is decreased with the radial position. Furthermore, by tracing one single filament, the radial width is decreased gradually when the filament is moving outward, which is also consistent with experiment conclusion. The consistencies also indicate the availability and practicability of the six‐field two‐fluid model of BOUT++ on the study of ELMs.
Undue financial burden and the dog that never barked
Authors: Masinter Michael R.
Published: January 2021

Both Section 504 of the Rehabilitation Act and the Americans with Disabilities Act treat an undue financial burden as a defense for claiming nondiscrimination if a college or university does not meet its obligation to provide a student with a disability an auxiliary aid necessary for equal access. The Supreme Court wrote the undue financial burden defense into Section 504 in its seminal decision in Southeastern Community College v. Davis, and the Department of Justice formalized its application to the ADA with regulations under Titles II and III. Yet despite its long pedigree, the undue financial burden defense has not been the basis for adjudication in Office for Civil Rights auxiliary aid determinations or by courts in comparable Title II or III litigation. As Sherlock Holmes might say, the undue financial burden defense is the dog that didn't bark.
Better boundaries: identifying the upper extent of fish distributions in forested streams using eDNA and electrofishing
Authors: Penaluna Brooke E. , Allen Jennifer M. , Arismendi Ivan , Levi Taal , Garcia Tiffany S. , Walter Jason K.
Published: January 2021

The management of species that occur in low densities is a conservation concern worldwide across taxa with consequences for managers and policymakers. The distribution boundary at the upper extent of fish in North America receives extra attention because stream reaches with fish are managed differently and often have more protections than fishless reaches. Here, we examine the relative reliability of water environmental DNA (eDNA), polymerase chain reaction (PCR)‐amplified for Coastal Cutthroat Trout (Oncorhynchus clarkii clarkii) to detect the upper extent of fish across streams as a potential management tool compared to standard electrofishing methods. We provide estimates of fish detection probabilities from eDNA analyses, and probabilities of detection for both eDNA field samples and quantitative PCR (qPCR) given covariates of habitat characteristics and fish densities from electrofishing. We present a primer and probe based on the cytochrome oxidase I gene using qPCR to detect trout DNA across water samples from 60 forested streams in the Pacific Northwest, USA using high‐resolution spatial sampling. In 28% of streams, the upper extent of fish matches between methods. In over half of the streams, Coastal Cutthroat Trout eDNA was detected above the electrofishing last‐fish boundary. Although some detections could be attributed to false‐positive errors, eDNA results extend the upstream, leading edge of fish by 50–250 m from the electrofishing boundary. In 20% of the streams, detections of last‐fish occurred higher in the stream network with electrofishing rather than eDNA, but generally by only 50 m. Modeled results revealed that the occurrence of trout eDNA was higher in wider‐stream locations and that eDNA detections occurred at lower electrofishing densities (<5 trout per 50 linear m). We also showed that three replicate eDNA samples were sufficient to capture trout eDNA when eDNA was present. Although eDNA constitutes an effective addition to approaches to delimit the upper extent of fish, its effectiveness depends on previous knowledge of the last‐fish boundary to apprise where to start sampling and targeting fish species anticipated to be last‐fish. We present evidence that eDNA is a valuable tool in investigating fish distributions taking its place alongside traditional high‐effort catch–release tools.
Nitrogen acquisition strategies of mature Douglas‐fir: a case study in the northern Rocky Mountains
Authors: Qubain Claire A. , Yano Yuriko , Hu Jia
Published: January 2021

Nitrogen (N) limits plant growth in temperate ecosystems, yet many evergreens exhibit low photosynthetic N use efficiency, which can be explained in part by their tendency to store more N than to use it in photosynthesis. However, it remains uncertain to what extent mature conifers translocate internal N reserves or take up N from soils to support new growth. In this study, we explored N dynamics within mature Douglas‐fir (Pseudotsuga menziesii var. glauca) trees by linking N uptake in field‐grown trees with seasonal soil available N. We used a branch‐level mass balance approach to infer seasonal changes in total N among multiple needle and stem cohorts and bole tissue, and used foliar δ15N to evaluate N translocation/uptake from soils. Soil resin‐exchangeable N and net N transformation rates were measured to assess whether soils had sufficient N to support new needle growth. We estimated that after bud break, new needle biomass in Douglas‐fir trees accumulated an average of 0.20 ± 0.03 mg N/branch and 0.17 ± 0.03 mg N/branch in 2016 and 2017, respectively. While we did find some evidence of translocation of N from older stems to buds prior to bud break, we did not detect a significant drawdown of N from previous years’ growth during needle expansion. This suggests that the majority of N used for new growth was not reallocated from aboveground storage, but originated from the soils. This finding was further supported by the δ15N data, which showed divergent δ15N patterns between older needles and buds prior to leaf flushing (indicative of translocation), but similar patterns of depletion and subsequent enrichment following leaf expansion (indicative of N originating from soils). Overall, in order to support new growth, our study trees obtained the majority of N from the soils, suggesting tight coupling between soil available N and N uptake in the ecosystem.
Impacts of a drought and hurricane on tropical bird and frog distributions
Authors: Campos‐Cerqueira Marconi , Aide T. Mitchell
Published: January 2021

During the last few decades, much attention has focused on how global change is affecting the environment and species distributions. Land‐use change is still the major cause of species declines worldwide, but changes in species distributions have been documented even in pristine and protected areas. Here, we document the distribution dynamics of 26 species of frogs and birds within a Caribbean protected area between 2015 and 2019. Specifically, we document species occupancy and detectability in 59 sites along three elevational transects within the El Yunque National Forest in Puerto Rico. Species were sampled using acoustic recorders, species identification algorithms, and post‐classification validation. The study period included a severe drought (2015–2016) and a category 4 hurricane (2017). The distribution of most frog species did not change significantly during the study period. In contrast, the distributions of the bird species contracted between the 2015 and 2016 pre‐hurricane surveys. This contraction coincides with a severe drought that peaked after the 2015 survey. The response of bird species after H. Maria was heterogeneous. Our results suggest that for many species, particularly birds, the 2015–2016 drought in Puerto Rico had a greater negative effect than H. Maria. The difference in the response of the bird and frog communities is likely related to their abundance at the site level, their ability to disperse, and temporal patterns of reproduction. If a site is occupied by a frog species, it could easily include 100s of individuals, and even if condition worsens, over a relatively short period the species will continue to occupy the site. In contrast, a site may only be occupied by one or a few individuals of birds. Birds have also higher dispersal abilities than frogs. Furthermore, Puerto Rican frogs reproduce year‐round, whereas birds concentrate their reproduction during a few months in the wet season. Future climate scenarios predict a decrease in total precipitation and an increase in droughts for the region, which emphasizes the need to consider the diversity of changes that will be associated with future climate change.
Hospitalization for hypoglycaemia in people with diabetes in Denmark, 1997–2017: Time trends in incidence and HbA1c and glucose‐lowering drug use before and after hypoglycaemia
Authors: Bengtsen Mads Bisgaard , Knudsen Jakob Schöllhammer , Bengtsen Maria Bisgaard , Møller Niels , Thomsen Reimar Wernich
Published: January 2021

Objective

To assess incidence trends of first hospitalization for hypoglycaemia in Denmark and to examine HbA1c levels and glucose‐lowering drug use before and after hospitalization among individuals with type 1 or type 2 diabetes.

Research Design and Methods

We performed a population‐based study linking diagnosis, prescription and laboratory data. Standardized incidence of first hospitalization for hypoglycaemia in Denmark was assessed for each calendar year 1997–2017. HbA1c and glucose‐lowering drug use was compared with age‐ and sex‐matched diabetes comparisons without hospitalization for hypoglycaemia.

Results

The annual age‐ and sex‐standardized incidence rate of first hospitalization for hypoglycaemia per 100,000 person‐years increased during 1997–2003 (from 17.7 to 30.3 per 100,000 person‐years), remained stable until 2010 (30.4) and gradually declined until 2017 (22.0). During this period, we identified 3,479 people with type 1 diabetes and 15,329 people with type 2 diabetes experiencing first hospitalization for hypoglycaemia. Both diabetes groups experienced a mean HbA1c decrease of ~12%–15% in the months preceding first hospitalization, followed by a gradually increasing HbA1c afterwards. People with type 1 diabetes and hospitalization used similar insulin therapies as those without hospitalization. People with type 2 diabetes and hospitalization more often received insulin (55%) than comparisons (45%), and 45% discontinued insulin or stopped all glucose‐lowering therapy after first hospitalization.

Conclusions

Incidence of hospitalizations for hypoglycaemia has declined by one fourth the last decade in the Danish population. A HbA1c decrease precedes first hospitalization for hypoglycaemia in individuals with diabetes, and profound changes in glucose‐lowering drug therapy for type 2 diabetes occur after hospitalization.
Influence of abutment straight backwall fracture on the seismic response of bridges
Authors: Zheng Qiu , Yang Chuang‐Sheng Walter , Xie Yazhou , Padgett Jamie , DesRoches Reginald , Roblee Cliff
Published: January 2021

Field reconnaissance reports reveal the seismic vulnerability of bridge abutment foundations. To reduce the time and cost of postearthquake repair, modern seismic design specifications allow abutment backwalls to fracture before the supporting abutment foundations reach their maximum strength. This design strategy enables abutment backwalls to function as a fuse, thus protecting the abutment foundations from experiencing excessive forces and damage. This paper introduces a new abutment modeling scheme to capture the shear fracture mechanism of straight backwalls in seat abutments. To this end, a backwall connection spring is developed and incorporated into a spring system that simulates the behavior of various abutment components. The importance of considering the backwall fracture is examined by reviewing conventional modeling methodologies for abutments and building companion numerical models. Static pushover and incremental dynamic analyses (IDAs) were conducted for two bridges (single‐ and two‐span) modeled by both the proposed and conventional abutment modeling schemes. Moreover, component‐level fragility curves are developed using IDA results. The comparisons show that the conventional abutment modeling schemes significantly overestimate abutment foundation damage and underestimate the likelihood of deck unseating, column damage, and bearing displacement in the passive direction. Conversely, the proposed modeling scheme is able to capture the essential seismic responses of various components in seat abutment bridges. The consideration of backwall fracture in the modeling of abutment components enables a more rational seismic response assessment of bridges with backwalls, which are likely to be damaged during earthquakes, particularly for bridges which are seismically designed to protect abutment foundations.
Testing bias in professional forecasts
Authors: Franses Philip Hans
Published: January 2021

Professional forecasters can rely on econometric models, on their personal expertise or on both. To accommodate for adjustments to model forecasts, this paper proposes to use two stage least squares (TSLS) (and not ordinary least squares [OLS]) for the familiar Mincer–Zarnowitz regression when examining bias in professional forecasts, where the instrumental variable is the consensus forecast. An illustration for 15 professional forecasters with their quotes for real gross domestic product (GDP) growth, inflation and unemployment for the United States documents the usefulness of this new estimation method. It also shows that TSLS suggests less bias than OLS does.
Digitalization and globalization in a turbulent world: Centrifugal and centripetal forces
Authors: Autio Erkko , Mudambi Ram , Yoo Youngjin
Published: January 2021

Research Summary

Digitalization has three fundamental characteristics, reprogrammability infrastructural elementality, and intangibility. Based on these characteristics, it is transforming how firms organize for value creation, delivery, and capture. Its intangibility and infrastructural character largely free economic and business activities from the constraints of physical geography like those imposed by transportation and collocation. Digital communication technologies typically reinforce the centrifugal forces that favor dispersing the firm's high knowledge activities. Digital in situ technologies strengthen the centripetal forces toward concentrating the firm's low knowledge activities. Location dependence and product modularity are crucial moderators for tangible products, while institutional barriers are important for intangible ones. Finally, digital technologies increase the resilience of firms during disruptive events that impose restrictions on the movements of people and goods, as during the COVID‐19 pandemic.

Managerial Summary

Digitalization is a general purpose technology on the scale of the steam engine and electricity, and affects every aspect of business and society. It is transforming how firms organize for value creation, delivery, and capture. Freeing businesses from the constraints of transportation and collocation, it increases their resiliency in the face of global disruptions like those associated with the COVID‐19 pandemic. Digital communication technologies typically reinforce the centrifugal forces that favor dispersing the firm's high knowledge activities. Digital in situ technologies like advanced robotics strengthen the centripetal forces toward concentrating the firm's low knowledge activities. Location dependence and product modularity are crucial moderators for tangible products, while institutional barriers are important for intangible ones.
Association of outdoor air pollution with the medical expense of ischemic stroke: The case study of an industrial city in western China
Authors: Zeng Siyu , luo Li , Chen Fang , Li Yue , Chen Mei , He Xiaozhou
Published: January 2021

Ischemic stroke, the most frequent cause of severe disability, imposes a significant mental and economic burden on patients and their families. There is increasing evidence to indicate that air pollution contributes to the risk of ischemic stroke. This study aimed to examine the correlation between air pollution and the expense imposed by an ischemic stroke. Data were obtained from hospitals and environmental monitoring stations in an industry city, Longspring, in western China. We used a generalized additive model to estimate the associations between the two factors, measured during 2015–2017. Counter‐intuitively, the medical expenses arising from ischemia were negatively associated with the level of air pollution. The corresponding ER for per interquartile range increase of PM2.5, PM10, SO2, and NO2 in lag10 was −0.17% (95% confidence interval (95% CI −0.31%, −0.03%), −0.11% (95% CI −0.2%, −0.02%), −1.04% (95% CI −1.92%, −0.17%) and −0.44% (95% CI −0.66%, −0.22%), respectively (p < 0.05). Subgroups based on gender, age, and season were considered in the analysis. The results indicated that pollutants had significant effects on ischaemia's medical expenses, which were stronger for older people, patients who survived, and warm seasons. This study is the first step in optimizing medical resources, which are essential for policymaking and service planning.
Estimation of mass and energy balance of glaciers using a distributed energy balance model over the Chandra river basin (Western Himalaya)
Authors: Patel Akansha , Goswami Ajanta , Dharpure Jaydeo K. , Thamban Meloth , Sharma Parmanand , Kulkarni Anil V. , Oulkar Sunil
Published: January 2021

The ongoing glacier shrinking in the Himalayan region causes a significant threat to freshwater sustainability and associated future runoff. However, data on the spatial climatic contribution of glacier retreat is scanty in this region. To investigate the spatially distributed glacier surface energy and mass fluxes, a two‐dimensional mass balance model was developed and applied to the selected glaciers of the Chandra basin, in the Upper Indus Basin, Western Himalaya. This model is driven by the remote sensing data and meteorological variables measured in the vicinity of the Chandra basin for six hydrological years (October 2013 to September 2019). The modelled variables were calibrated/validated with the in‐situ observation from the Himansh station in the Chandra basin. We have derived air temperature (Ta) spatially using the multivariate statistical approach, which indicates a relative error of 0.02–0.05°C with the observed data. Additionally, the relative error between the modelled and observed radiation fluxes was <10.0 W m−2. Our study revealed that the Chandra basin glaciers have been losing its mass with a mean annual mass balance of −0.59 ± 0.12 m w.e.a−1for the six hydrological years. Results illustrated that the mean surface melt rate of the selected glaciers ranged from −5.1 to −2.5 m w.e.a−1that lies between 4500 and 5000 m a.s.l. The study revealed that the net radiation(RN)contributes ~75% in total energy (FM) during the melt season while sensible heat(HS), latent heat(Hl), and ground heat(HG)fluxes shared 15%, 8%, and 2%, respectively. Sensitivity analysis of the energy balance components suggested that the mass balance is highly sensitive to albedo and surface radiations in the study area. Overall, the proposed model performed well for glacier‐wide energy and mass balance estimation and confirms the utility of remote sensing data, which may help in reducing data scarcity in the upper reaches of the Himalayan region.
Jump volatility spillover network based measurement of systemic importance of Chinese financial institutions
Authors: Yang Xin , Chen Shan , Liu Hong , Yang Xiaoguang , Huang Chuangxia
Published: January 2021

The identification of systemically important financial institutions (SIFIs) is an important measure to deal with systemic risks. To achieve this goal, we first use generalized variance decomposition method and granger causality test to construct jump volatility spillover networks of Chinese financial institutions based on the 5‐min high‐frequency data. Then, out‐strength and in‐strength are adopted to analyze the SIFI. Finally, we use panel data regression model to investigate the determinant of the SIFIs. The empirical results show that: (a) The network density reaches a peak when the financial system under pressure during the China's stock market disaster of 2015. (b) Large banks and insurances usually display systemic importance, while some small financial institutions are also SIFIs due to their high value of out‐strength and in‐strength. (c) There are obvious differences in the factors that affect the out‐strength and in‐strength based on panel data regression model, but turnover rate, jump volatility, firm size and growth rate of total assets are the common driving factors.
Colloidal stability, cytotoxicity, and cellular uptake of HfO2 nanoparticles
Authors: McGinnity Tracie L. , Sokolova Viktoriya , Prymak Oleg , Nallathamby Prakash D. , Epple Matthias , Roeder Ryan K.
Published: January 2021

The colloidal stability, cytotoxicity, and cellular uptake of hafnium oxide (HfO2) nanoparticles (NPs) were investigated in vitro to assess safety and efficacy for use as a deliverable theranostic in nanomedicine. Monoclinic HfO2 NPs, ~60–90 nm in diameter and ellipsoidal in shape, were directly prepared without calcination by a hydrothermal synthesis at 83% yield. The as‐prepared, bare HfO2 NPs exhibited colloidal stability in cell culture media for at least 10 days without significant agglomeration or settling. The viability (live/dead assay) of human epithelial cells (HeLa) and monocyte‐derived macrophages (THP‐1) did not fall below 95% of untreated cells after up to 24 h exposure to HfO2 NPs at concentrations up to 0.80 mg/ml. Similarly, the mitochondrial activity (MTT assay) of HeLa and THP‐1 cells did not fall below 80% of untreated cells after up to 24 h exposure to HfO2 NPs at concentrations up to 0.40 mg/ml. Cellular uptake was confirmed and visualized in both HeLa and THP‐1 cells by fluorescence microscopy of HfO2 NPs labeled with Cy5 and transmission electron microscopy (TEM) of bare HfO2 NPs. TEM micrographs provided direct observation of macropinocytosis and endosomal compartmentalization within 4 h of exposure. Thus, the HfO2 NPs in this study exhibited colloidal stability, cytocompatibility, and cellular uptake for potential use as a deliverable theranostic in nanomedicine.
Osteoinductive effect of soluble transforming growth factor beta receptor 3 on human osteoblast lineage
Authors: Amanso Angelica Mastandrea , Kamalakar Archana , Bitarafan Sara , Abramowicz Shelly , Drissi Hicham , Barnett Joey Victor , Wood Levi Benjamin , Goudy S. L.
Published: January 2021

The development of bone requires carefully choregraphed signaling to bone progenitors to form bone. Our group recently described the requirement of transforming growth factor beta receptor 3 (TGFβR3), a receptor involved in TGFβ pathway signaling, during osteoblast lineage commitment in mice. The TGFβ pathway is known to play multiple osteo‐inductive and osteo‐inhibitory roles during osteoblast development and TGFβR3 human mutations are associated with reduced bone mineral density, making TGFβR3 a unique target for bone inductive therapy. In this article, we demonstrated increased mineralization of human pediatric bone‐derived osteoblast‐like cells (HBO) when treated with soluble TGFβR3 (sR3) using Alizarin Red staining. Osteogenic commitment of HBO cells was demonstrated by induction of osteogenic genes RUNX2, osteocalcin, osteopontin, and osterix. Evaluation of the canonical TGFβ pathway signaling demonstrated that sR3 was able to induce bone formation in HBO cells, mainly through activation of noncanonical targets of TGFβ pathway signaling including AKT, ERK, and p38 MAP kinases. Inhibition of these osteogenic noncanonical pathways in the HBO cells also inhibited mineralization, suggesting they are each required. Although no induction of SMAD1, 5, and 9 was observed, there was the activation of SMAD2 and 3 suggesting that sR3 is primarily signaling via the noncanonical pathways during osteogenic induction of the HBO. Our results highlight the important role of TGFβR3 in osteoblast induction of mineralization in human bone cells through noncanonical targets of TGFβ signaling. Future studies will focus on the ability of sR3 to induce bone regeneration in vivo using animal models.
Development and functionalization of DNA nanostructures for biomedical applications
Authors: Baig Mirza Muhammad Faran Ashraf , Zou Ting , Neelakantan Prasanna , Zhang Chengfei
Published: January 2021

Nanomaterials are excellent drug delivery systems, yet, they must be functionalized in a manner compatible with the biological environment. Regarding delivery of the payloads, it is critical to monitor the nanocarrier's biocompatibility and the ability to control its drug encapsulation and release, as well as targeting. The current challenges include avoiding negative host immune responses, optimizing stability in biological environments, and achieving precise interactions with the targets. Contemporary advances in structural DNA nanotechnology, DNA origami, and supramolecular DNA assembly make it possible to produce complex multi‐functional DNA nanostructures, wherein precise control of the size, geometry, and appearance of the ligands is feasible. DNA nanostructures offer ease of synthesis and conjugation of functional moieties to target the release of cargo or to analyze important biomarkers for diagnostics. Furthermore, the biocompatibility, programmability, responsiveness to biomolecules, cell‐surfaces, and organisms make such DNA nanomaterials highly suitable for potential translational applications. This overview summarizes the recent developments in functionalizing, stabilizing, and applying DNA nanostructures for potential biomedical applications.
Alliance rupture‐repair processes in intensive short‐term dynamic psychotherapy: Working with resistance
Authors: Abbass Allan A. , Town Joel M.
Published: January 2021

Intensive short‐term dynamic psychotherapy (ISTDP) was developed to manage treatment impasses preventing the experiencing of feelings related to childhood attachment interruptions, such as parental loss. According to ISTDP theory, certain categories of patients will exhibit habitual patterns of responding within the treatment relationship (called defenses) to certain anxiety‐provoking thoughts and feelings. Such defensive behaviors interrupt awareness of one's own feelings, self‐directed compassion and engagement in close human attachments, including the bond with the therapist. Rupture‐repair sequences in ISTDP are primarily considered in the context of a patient's defenses and the responses a therapist has to these defenses. By understanding and clarifying these defenses, this risk of subsequent misalliance, that is negative shifts or ruptures in the alliance, are minimized. In this paper we summarize ISTDP theory and technique through the use of clinical vignettes to illustrate defense management as a rupture‐repair equivalent in ISTDP.
Everybody Thinks We Should but Nobody Does: How Combined Injunctive and Descriptive Norms Motivate Organ Donor Registration
Authors: Habib Rishad , White Katherine , Hoegg JoAndrea
Published: January 2021

The potential for deceased‐donor organ transplants to save lives is severely limited by the number of people registered as donors around the world. Various national and regional health organizations often emphasize low registration rates (i.e., low descriptive norms) in an effort to demonstrate need and encourage registration. However, we predict and find that combining low descriptive norms with high injunctive norms, making salient the discrepancy between what people think they should do and what they actually do, results in greater organ donor registrations than communicating either descriptive or injunctive norms separately. We demonstrate these effects across three focal studies and two follow‐up studies conducted online, in the laboratory, and in the field, and show that the findings are mediated by feelings of responsibility. We also demonstrate that making the situation feel psychologically close increases responsibility and intentions to register for low descriptive and high injunctive norms, to the level of combined norms. Our research contributes to the literature on norms and responsibility and can help policymakers and marketers design more effective communication strategies.