bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19 Pandemic Prompts a Paradigm Shift in Global Emergency Medicine: Multidirectional Education and Remote Collaboration
Authors: Karim Naz , Rybarczyk Megan M. , Jacquet Gabrielle A. , Pousson Amelia , Aluisio Adam R. , Bilal Saadiyah , Moretti Katelyn , Douglass Katherine A , Henwood Patricia C. , Kharel Ramu , Lee J. Austin , MenkinSmith Lacey , Moresky Rachel T. , Gonzalez Marques Catalina , Myers Justin G. , O’Laughlin Kelli N. , Schmidt Jessica , Kivlehan Sean M.
Published: October 2020

To date, the practice of global emergency medicine (GEM) has involved being “on the ground” supporting in‐country training of local learners, conducting research, and providing clinical care. This face‐to‐face interaction has been understood as critically important for developing partnerships and building trust. The COVID‐19 pandemic has brought significant uncertainty worldwide, including international travel restrictions of indeterminate permanence. Following the 2020 Society for Academic Emergency Medicine meeting, the Global Emergency Medicine Academy (GEMA) sought to enhance collective understanding of best practices in GEM training with a focus on multidirectional education and remote collaboration in the setting of COVID‐19. GEMA members led an initiative to outline thematic areas deemed most pertinent to the continued implementation of impactful GEM programming within the physical and technologic confines of a pandemic. Eighteen GEM practitioners were divided into four workgroups to focus on the following themes: advances in technology, valuation, climate impacts, skill translation, research/scholastic projects, and future challenges. Several opportunities were identified: broadened availability of technology such as video conferencing, Internet, and smartphones; online learning; reduced costs of cloud storage and printing; reduced carbon footprint; and strengthened local leadership. Skills and knowledge bases of GEM practitioners, including practicing in resource‐poor settings and allocation of scarce resources, are translatable domestically. The COVID‐19 pandemic has accelerated a paradigm shift in the practice of GEM, identifying a previously underrecognized potential to both strengthen partnerships and increase accessibility. This time of change has provided an opportunity to enhance multidirectional education and remote collaboration to improve global health equity.
Seasonal nutrient partitioning and uptake in hybrid carrot seed production
Authors: Moore Amber D. , Spring John F. , Jeliazkova Ekaterina A. , Wilson Tracy L.
Published: October 2020

Central Oregon is an important production region for hybrid carrot (Daucus carota L.) seed. Hybrid carrots are favored by the fresh vegetable market, but often produce lower and less consistent seed yields than traditional open‐pollinated varieties. Understanding how hybrid carrots use nutrients to support seed production for hybrid varieties can help growers manage soil fertility for optimal seed yield. The objective of this research was to evaluate seasonal nutrient partitioning and uptake in a modern Nantes‐type hybrid carrot grown for seed. Plants from four randomized replicated plots in two commercial fields were destructively sampled throughout the growing season, separated into roots, tops, and umbels; seed samples were collected at harvest. Plant samples were weighed and dried for biomass content and analyzed for N, P, K, S, Ca, Mg, Na, Zn, Fe, Mn, Cu, and B concentration. Mean whole plant nutrient uptake at crop maturity for N, P2O5, K2O, S, Ca, Mg, and Na was 137, 35, 229, 16, 105, 38, and 25 kg ha−1, respectively; Zn, Fe, Mn, Cu, and B uptake was 156, 1,984, 414, 35, and 305 g ha−1, respectively. Our findings highlighted the critical need for Cu in initial crop establishment, for N, K, Zn, and Fe in crown development, and for P and Zn in seed development, based on nutrient uptake proportion relative to the other nutrients taken up during that period. This information is available as a resource to agronomists, crop advisors, and growers who are interested in optimizing nutrient management practices for hybrid carrot seed production.
Structural insights into peptide self‐assembly using photo‐induced crosslinking experiments and discontinuous molecular dynamics
Authors: Bunce Samuel J. , Wang Yiming , Radford Sheena E. , Wilson Andrew J. , Hall Carol K.
Published: October 2020

Determining the structure of the (oligomeric) intermediates that form during the self‐assembly of amyloidogenic peptides is challenging because of their heterogeneous and dynamic nature. Thus, there is need for methodology to analyze the underlying molecular structure of these transient species. In this work, a combination of fluorescence quenching, photo‐induced crosslinking (PIC) and molecular dynamics simulation was used to study the assembly of a synthetic amyloid‐forming peptide, Aβ16‐22. A PIC amino acid containing a trifluormethyldiazirine (TFMD) group—Fmoc(TFMD)Phe—was incorporated into the sequence (Aβ*16–22). Electrospray ionization ion‐mobility spectrometry mass‐spectrometry (ESI‐IMS‐MS) analysis of the PIC products confirmed that Aβ*16–22 forms assemblies with the monomers arranged as anti‐parallel, in‐register β‐strands at all time points during the aggregation assay. The assembly process was also monitored separately using fluorescence quenching to profile the fibril assembly reaction. The molecular picture resulting from discontinuous molecule dynamics simulations showed that Aβ16‐22 assembles through a single‐step nucleation into a β‐sheet fibril in agreement with these experimental observations. This study provides detailed structural insights into the Aβ16‐22 self‐assembly processes, paving the way to explore the self‐assembly mechanism of larger, more complex peptides, including those whose aggregation is responsible for human disease.
Optimal loading for injection
Authors: Swan James W. , Winslow Samuel W. , Tisdale William A.
Published: October 2020

The injection of fluids loaded with a precise number of particles, polymers, and other solutes is common in many areas of chemical engineering. By definition, injection of these fluids is meant to occur over the shortest possible duration. This raises the question that is answered in this note: At what concentration should a fluid be loaded in order to inject that fluid fastest? A similar question has been addressed for flows of Newtonian fluids in biophysical and physiological studies. We generalize that analysis. We show for Newtonian fluids containing a single suspended component that the optimal loading is determined from a common tangent construction for the viscosity as a function of concentration. We extend this formulation to describe optimal injection of a multicomponent Newtonian fluid. Additionally, we study the injection problem for a simple, model non‐Newtonian fluid carrying a single suspended component. Finally, we discuss applications for optimally loaded injections.
Promoted absorption of CO at high temperature by cuprous‐based ternary deep eutectic solvents
Authors: Tao Duan‐Jian , Qu Feng , Li Zhang‐Min , Zhou Yan
Published: October 2020

Achieving efficient dissolution of carbon monoxide (CO) in the solvent is very helpful for the implementation of carbonylation reaction at ambient pressure. However, almost all of common solvents show very low solubilities of CO at high temperature. Herein, a series of cuprous‐based ternary deep eutectic solvent (DES) was prepared by mixing imidazolium hydrochloride with CuCl and ZnCl2. The ternary DES [BimH]Cl‐CuCl‐1.0ZnCl2 exhibited very large CO absorption capacity (0.075 mol mol−1, 1 bar) even at a high temperature (353.2 K), which is superior to all of the reported absorbents. Moreover, the ternary DES [BimH]Cl‐CuCl‐1.0ZnCl2 could further promote the reactive absorption of CO to conduct the aminocarbonylation reaction effortlessly at ambient pressure, and thus the targeted products benzamides were obtained in 70–97 yields. We believe that this finding opens a new way to design advanced solvents for efficient capture of CO at high temperature.
Specialized cockroach pollination in the rare and endangered plant Vincetoxicum hainanense in China
Authors: Xiong Wujian , Ollerton Jeff , Liede‐Schumann Sigrid , Zhao Wanyi , Jiang Qiancai , Sun Hongmei , Liao Wenbo , You Wenhui
Published: October 2020

Premise

Species of Apocynaceae are pollinated by a diverse assemblage of animals. Here we report the first record of specialized cockroach pollination in the family, involving an endangered climbing vine species, Vincetoxicum hainanense in China. Experiments were designed to provide direct proof of cockroach pollination and compare the effectiveness of other flower visitors.

Methods

We investigated the reproductive biology, pollination ecology, pollinaria removal, pollinia insertion, and fruit set following single visits by the most common insects. In addition, we reviewed reports of cockroaches as pollinators of other plants and analyzed the known pollination systems in Vincetoxicum in a phylogenetic context.

Results

The small, pale green flowers of V. hainanense opened during the night. The flowers were not autogamous, but were self‐compatible. Flower visitors included beetles, flies, ants and bush crickets, but the most effective pollinator was the cockroach Blattella bisignata, the only visitor that carried pollen between plants. Less frequent and effective pollinators are ants and Carabidae. Plants in this genus are predominantly pollinated by flies, moths and wasps.

Conclusions

Globally, only 11 plant species are known to be cockroach‐pollinated. Because their range of floral features encompass similarities and differences, defining a “cockroach pollination syndrome” is difficult. One commonality is that flowers are often visited by insects other than cockroaches, such as beetles, that vary in their significance as pollinators. Cockroach pollination is undoubtedly more widespread than previously thought and requires further attention.
Inherited intragenic PBX1 deletion: Expanding the phenotype
Authors: Fitzgerald Kristi K. , Powell‐Hamilton Nina , Shillingford Amanda J. , Robinson Bradley , Gripp Karen W.
Published: October 2020

PBX1 encodes the pre‐B cell leukemia homeobox transcription factor, a three amino acid loop extension (TALE) homeodomain transcription factor, which forms nuclear complexes with other TALE class homeodomain proteins that ultimately regulate target genes controlling organ patterning during embryogenesis. Heterozygous de novo pathogenic variants in PBX1 resulting in haploinsufficiency are associated with congenital anomalies of the kidneys and urinary tract, most commonly renal hypoplasia, as well as anomalies involving the external ear, branchial arch, heart, and genitalia, and they cause intellectual disability and developmental delay. Affected individuals described thus far have had de novo variants. Here, we report three related individuals with an inherited pathogenic intragenic PBX1 deletion with variable clinical features typical for this syndrome.
A new case of osteogenesis imperfecta type VIII and retinal detachment
Authors: de Souza Liliane Todeschini , Nunes Ricardo Rodrigues , de Azevedo Magalhães Otavio , Maria Félix Têmis
Published: October 2020

Osteogenesis imperfecta (OI) type VIII (OMIM: 610915) is a rare autosomal recessive disorder characterized by white sclerae, severe growth deficiency, and bone fragility. This condition results from pathogenic variants of P3H1, a gene that codes for P3H1, an important protein involved in the prolyl‐3‐hydroxylation complex required for collagen type I folding. Here, we described a woman with OI type VIII due to a homozygous mutation of c.1914+1G>C (NM_001243246.1) in P3H1 and retinal detachment. We compared our case to five severe OI and retinal detachment cases reported in the literature. The only case previously reported with a molecular diagnosis had a similar mutation in P3H1 c.1914+1G>A and a giant retinal detachment. We suggest that individuals with OI type VIII should be submitted to careful fundoscopic examination.
Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease
Authors: Murueta‐Goyena Ane , Del Pino Rocío , Galdós Marta , Arana Begoña , Acera Marian , Carmona‐Abellán Mar , Fernández‐Valle Tamara , Tijero Beatriz , Lucas‐Jiménez Olaia , Ojeda Natalia , Ibarretxe‐Bilbao Naroa , Peña Javier , Cortes Jesus , Ayala Unai , Barrenechea Maitane , Gómez‐Esteban Juan Carlos , Gabilondo Iñigo
Published: October 2020

Objective

This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD).

Methods

Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K‐SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell–inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs.

Results

GCIPL thickness in the parafoveal region (1‐ to 3‐mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63μm in iPD patients and 0.23μm in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10–11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03–10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration.

Interpretation

Our results provide evidence of the potential use of optical coherence tomography–measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD. ANN NEUROL 2021;89:165–176
Autonomous Transient pH Flips Shaped by Layered Compartmentalization of Antagonistic Enzymatic Reactions
Authors: Fan Xinlong , Walther Andreas
Published: October 2020

Transient signaling orchestrates complex spatiotemporal behaviour in living organisms via (bio)chemical reaction networks (CRNs). Compartmentalization of signal processing is an important aspect for controlling such networks. However, artificial CRNs mostly focus on homogeneous solutions to program autonomous self‐assembling systems, which limits their accessible behaviour and tuneability. Here, we introduce layered compartments housing antagonistic pH‐modulating enzymes and demonstrate that transient pH signals in a supernatant solution can be programmed based on spatial delays. This overcomes limitations of activity mismatches of antagonistic enzymes in solution and allows to flexibly program acidic and alkaline pH lifecycles beyond the possibilities of homogeneous solutions. Lag time, lifetime, and the pH minima and maxima can be precisely programmed by adjusting spatial and kinetic conditions. We integrate these spatially controlled pH flips with switchable peptides, furnishing time‐programmed self‐assemblies and hydrogel material system.
A Design Principle for Polar Assemblies with C3‐Sym Bowl‐Shaped π‐Conjugated Molecules
Authors: Zhang Cheng , Guo Yuan , He Dan , Komiya Jouji , Watanabe Go , Ogaki Takuya , Wang Chengyuan , Nihonyanagi Atsuko , Inuzuka Hiroyuki , Gong Hao , Yi Yuanping , Takimiya Kazuo , Hashizume Daisuke , Miyajima Daigo
Published: October 2020

Polar materials attract wide research interest due to their unique properties, such as ferroelectricity and the bulk photovoltaic effect (BPVE), which are not accessible with nonpolar materials. However, in general, rationally designing polar materials is difficult because nonpolar materials are more favorable in terms of dipole‐dipole interactions. Here, we report a rational strategy to form polar assemblies with bowl‐shaped π‐conjugated molecules and a molecular design principle for this strategy. We synthesized and thoroughly characterized 12 single crystals with the help of various theoretical calculations. Furthermore, we demonstrated that it can be possible to predict whether polar assemblies become more favorable or not by estimating their lattice energies. We believe that this study contributes to the development of organic polar materials and their related studies.
Ionization–liquid‐crystalline polymer synergistically reinforced poly(ethylene terephthalate) due to interfacial compatibilization by ion–dipole interactions
Authors: Tian Yuanfu , Yang Yehua , Tan Jinqiang , Ding Dachuan , Song Zhiyuan , Tao Qian , Zheng Xuan , Hu Tao , Gong Xinghou , Wu Chonggang
Published: October 2020

To enhance the compatibility of poly(ethylene terephthalate) (PET)/liquid crystalline polymer (LCP) composite, thereby mechanically strengthening the PET matrix, an optimally compatibilized composite of chain‐extended and ‐carboxylated PET ionomer and poly(4‐hydroxybenzoic acid–ran–6‐hydroxy‐2‐naphthoic acid) (HBA–HNA) was successfully prepared. Upon PET carboxylated chain extension with pyromellitic dianhydride and subsequent ionization with Zn(OH)2, the compatibility of the composite was distinctly improved, as verified by the refined dispersed‐phase morphology, increased number of refined HBA–HNA fibrils, reduced crystallinity, and improved complex viscosity. Compared with PET, the optimally compatibilized composite displayed a 70.1 and 148.7% increase in Young's modulus and tensile strength, respectively. Tentatively mechanistically, the interfacial interaction may change from weak hydrogen bonding to strong ion–dipole interactions due to the introduction of ionic groups, which remarkably boosts the interfacial compatibility, thereby achieving synergistic effects of the ionization and HBA–HNA inclusion to maximally strengthen PET. It seems that the synergistic ionization/LCP inclusion by a one‐pot method establishes a promising preparation approach to commercial PET engineering resins.
Multiwalled carbon nanotubes filled thermoplastic vulcanizate dielectric elastomer with excellent resilience properties via inhibiting MWCNT network formation
Authors: Ma Lifeng , Hu Jiajia , Dou Rui
Published: October 2020

Multiwalled carbon nanotubes (MWCNTs) filled thermoplastic vulcanizate (TPV) dielectric elastomer based on polypropylene (PP)/ethylene‐propylene‐diene monomer blends were fabricated via a simple melt compounding. MWCNT could be selectively distributed in PP matrix which induced by the dynamic vulcanization reaction. By reducing the rotor speed of melting blending to 60 rpm, the MWCNT network formation can be effectively inhibited, which have been verified by a higher volume resistivity (above 109 Ω cm). With increasing the MWCNTs loading to 4.1 vol%, a maximum increase, 423.4% (from 3.04 to 12.87), of the dielectric constant have been achieved for TPV/MWCNTs elastomer at 103 Hz, while the dielectric loss is still lower than 0.072 at 101–103 Hz. Meanwhile, with various MWCNTs loading, the tensile recovery of these series TPV elastomer does not change anymore, resulting an excellent rebound resistance. The TPV elastomer exhibits an enhanced dielectric performance and balanced elastic recovery performance, providing a simple and scalable melt compounding approach to fabricate high‐performance dielectric elastomer.
Preparation of hyperbranch‐structured polyester fiber via thiol‐ene click reaction under UV light irradiation for asphalt binder modification
Authors: Meng Fei , Muhammad Yaseen , Ye Yuting , Ji Jiaqi , Tao Hua , Huang Junxian , Zhu Zhaorong , Li Jing
Published: October 2020

This study reports the application of UV induced “thiol‐ene click reaction” by coupling the covalent bonds of venyl‐terminated dendritic polyester (VTDP) and polyester (PET) fiber and resulting in the fabrication of hyperbranch‐structured PET named as VTDP‐PET fiber. The PET fiber or VTDP‐PET fiber as additives were blended with styrene‐butadiene‐styrene modified asphalt (SBSMA) to prepare fiber/SBSMAs. Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectrometry, and X‐ray photoelectron spectroscopy characterizations indicated that VTDP‐PET fiber was linked with spherical three‐dimensional dendritic molecular structure. Cone penetration, dynamic shear rheometer, multistress creep recovery, and thermogravimetric analysis tests showed that VTDP‐PET/SBSMA exhibited enhanced resistance to flow, viscoelasticity, resistance against rutting, and thermal stability as compared to those of PET/SBSMA. The newly designed PET fiber and VTDP‐PET fiber can be envisioned as effective alternative candidate for the fabricated of modified SBSMA with enhanced performances for practical applications in construction and highway industries.
Inner defects elimination and significant reinforcement of rice straw/high‐density polyethylene composites by extractives removal process
Authors: Lin Fazhi , Wang Huanbo , Yue Tianqi , Qiu Pingping , Liu Tian
Published: October 2020

The effects on the internal defects of the rice straw (RS)/high‐density polyethylene (HDPE) composites are investigated by removing the extractives with cold water (CW), hot water (HW), and 1% alkaline (AL) solution. The characteristics of the RSs are measured by chemical composition, Fourier transform infrared, X‐ray diffractometry, scanning electron microscopy, thermogravimetric analysis, and bulk density testing. The three extractive removal methods change the surface features of the RS and increase the interphase adhesion between the RS and the HDPE matrix. As a result, the inner defects of the RS/HDPE composites are eradicated and the die swell phenomenon disappear. The flexural modulus, flexural strength, and impact strength of the final composites increase by 95.59, 83.29, and 154.79% in the HW extraction method. The CW and the AL extraction also significantly improve the static mechanical properties of the obtained RS/HDPE composites.
Variation of internal structure and performance of polyethylene‐ and polypropylene‐modified bitumen during blending process
Authors: Desidery Luca , Lanotte Michele
Published: October 2020

Linear‐viscoelastic characteristics and performance are evaluated throughout the blending process of polyethylene and polypropylene with bitumen. Results indicate that type, form and percentage of polyolefin play a significant role in the time evolution of the composite's mechanical response. Toluene extraction of modified bitumen revealed, for the first time, the formation of a sponge‐like polymer network. Visual inspection and Fourier transform infrared analysis of the polyolefins recovered after extraction indicates higher affinity of the polyethylene with bitumen in agreement with the rheological test results. The use of polypropylene is discouraged if rutting performance is a concern, and polyethylene in both pellets and powder form at 4%, and after 210 min of blending produces a modified bitumen with acceptable performance.
Development of a novel composite film based on polyurethane and defatted Chlorella biomass: Physical and functional characterization
Authors: Saha Pathikrit , Aloui Hajer , Yun Jin‐Ho , Kim Hee‐Sik , Kim Beom Soo
Published: October 2020

Novel composite films made of polyurethane (PU) and defatted Chlorella biomass (DCB) at different mass proportions (10–70 wt%) were prepared using polyethylene glycol (PEG) as a model polyol and hexamethylene diisocyanate (HMDI) as a coupling agent. Increasing DCB content led to a respective increase in tensile strength and elongation at break of the composites in the range of 33.9–116% and 69.6–248%, compared to the neat PU‐PEG film. As confirmed by Fourier transform infrared and scanning electron microscopy analysis, such improvement in mechanical properties can be attributed to the establishment of hydrogen bonds and other molecular interactions between isocyanate groups of PEG‐HMDI prepolymer and hydroxyl groups of DCB biofiller along with the uniform distribution of the incorporated DCB into the PU‐PEG based matrix. DCB incorporation at the highest content of 70% increased both antioxidant activity and bulk hydrophilicity of the composites by more than 69.3 and 85.0%, respectively, compared to the neat PU‐PEG.
The dog–human connection
Authors: Smith Timothy D. , Van Valkenburgh Blaire
Published: October 2020

This special issue of The Anatomical Record is the end result of a rare convergence of researchers scattered around the globe who came together to explore the mystery of the dog–human connection. Many of the discussions at the 12th International Congress of Vertebrate Morphology in Prague (July 23, 2019) are echoed within this issue. The enigmatic origins of dog domestication (as well as feralized descendants such as the dingo) are discussed, including phases of domestication that we might infer, and our historical knowledge of dog breeding. Emphasized by the morphological and genetic data are the forces of selection, both unintentional and intentional. In our modern life with dogs, we enjoy their companionship and benefit from the utility of many breeds, but we encounter unintended health care issues that are often breed‐specific. Dogs are so different in their sensory specializations (especially olfaction), but have uniquely (among other domestic mammals) developed highly sophisticated means of interspecific communication with humans. In sum, the manuscripts within this issue discuss anatomical, paleontological, genetic, and behavioral evidence bearing on the antiquity of the domestic dog, the process of domestication, and the many ways in which dogs continue to affect human life.
Identifying Children and Youth With Autism Spectrum Disorder in Electronic Medical Records: Examining Health System Utilization and Comorbidities
Authors: Brooks Jennifer D. , Bronskill Susan E. , Fu Longdi , Saxena Farah E. , Arneja Jasleen , Pinzaru Virgiliu Bogdan , Anagnostou Evdokia , Nylen Kirk , McLaughlin John , Tu Karen
Published: October 2020

Autism spectrum disorder (ASD) is a neurodevelopmental disorder requiring significant health and educational resources for affected individuals. A reference standard for ASD was generated from an existing population‐based cohort of 10,000 children and youth aged 1–24 years who were randomly selected for chart abstraction from 29,256 patients from 119 family physicians. We developed and validated an algorithm to identify children and youth with ASD within an electronic medical record system (N = 80,237, aged 1–24 years) in order to examine the prevalence of comorbidities and quantify health system utilization within the cohort. We identified 1,062 children and youth with ASD representing a prevalence of 1.32%. Compared to individuals without ASD, those with ASD had a higher prevalence of asthma, were more likely to visit a specialist, undergo surgery, and be hospitalized for psychiatric reasons. Children and youth with ASD in Ontario have complex health system needs, illustrated through a significant burden of comorbidities and increased health system utilization.

Lay Summary

Our paper generates population‐based estimates of health system use by children and youth with ASD, who have a higher burden of comorbidities than the general population. We developed a case‐finding algorithm and applied it in electronic medical records to create a cohort of children and youth with ASD, thereby generating an important resource to further study the health care needs of individuals with ASD.
Evaluation of an active population‐based surveillance system for major birth defects in South Carolina
Authors: Samson Marsha E. , Leedom Vinita , Mai Cara T. , Humphries Brian , Yeung Lorraine F.
Published: October 2020

Introduction

Birth defects are common, costly, and contribute substantially to infant mortality. The South Carolina Birth Defects Program (SCBDP) employs active population‐based surveillance to monitor major birth defects statewide. We evaluated SCBDP's system attributes using published CDC guidelines.

Methods

To determine timeliness, completeness, and accuracy of birth defects information, we examined SCBDP's reports, program and education materials, advisory group meeting minutes, and strategic plan. We also met with program staff and stakeholders (n = 10) to discuss program goals and data utilization. We calculated the percentage of birth defects cases found 6 months after a birth cohort year for 2016–2018.

Results

SCBDP identifies 900–1,200 birth defects cases for a birth population of approximately 55,000 live births annually through active case reviews. SCBDP uses trained medical staff to abstract detailed information from maternal and infant medical records; SCBDP also has established auto‐linkage with state vital statistics to capture demographic and birth data. SCBDP is timely and captures 97.1% (range 96.7–97.6%) of birth defects cases within 6 months after the birth cohort year closes. Active case identification using medical records as the primary data source improves quality assurance and completeness, while prepopulating demographic information improves timeliness.

Conclusions

Given that birth defects significantly contribute to infant morbidity and mortality, monitoring these conditions is important to understand their impact on communities and to drive public health actions. SCBDP active surveillance and rigorous data quality practices provide the program with timely, complete, and accurate birth defects data.
An assessment of poly (ADP‐ribose) polymerase‐1 role in normal and cancer cells
Authors: Kumar Manoj , Jaiswal Rishi Kumar , Yadava Pramod K. , Singh Rana P.
Published: October 2020

Poly (ADP‐ribose) polymerase (PARP) is a superfamily of 18 proteins characterized by the PARP homology domain, the catalytic domain. This catalytic domain helps in the ADP‐ribosylation of various acceptor proteins using nicotinamide adenine dinucleotide (NAD+) as a donor for ADP‐ribose. PARP‐1 and PARP‐2 carry out 80% of poly‐ADP‐ribosylation of cellular protein. Hence, their combined knockout results in embryonic lethality of mice. PARP‐1 consists of three major domains, namely, DNA binding domain, automodification domain, and a catalytic domain. These domains further consist of subdomains and motifs, which helps PARP‐1 in a diverse function. PARP‐1 is mainly involved in DNA damage detection and repair, but emerging evidence suggests its role in many other functions such as DNA synthesis, replication, apoptosis, necrosis, and cancer progression. Herein, we review the current state of the PARP‐1 role in DNA damage repair and other biological processes including epithelial to mesenchymal transition (EMT). We have also observed the role of PARP‐1 in modulating EMT regulators like E‐cadherin, Vimentin, Claudin‐1, Snail, Smad‐4, Twist‐1, and β‐catenin. Here, we have also attempted to relate the role of PARP‐1 in EMT of cancer cells.
Disrupted topological properties of functional networks in epileptic children with generalized tonic‐clonic seizures
Authors: Li Yongxin , Chen Qian , Huang Wenhua
Published: October 2020

Introduction

Generalized tonic‐clonic seizure (GTCS) is a condition that is characterized by generalized spike‐wave discharge in bilateral cerebral hemispheres during the seizure. Although previous neuroimaging studies revealed functional abnormalities in the brain activities of children with GTCS, the topological alterations in whole‐brain networks remain poorly understood.

Methods

The present study used graph theory to investigate the topological organization of functional networks in 13 GTCS children and 30 age‐matched healthy controls.

Results

We found that both groups exhibited a small‐world topology of the functional network. However, children with GTCS showed a significant decrease in nodal local efficiency and clustering coefficient in some key nodes compared with the controls. The connections within the default mode network (DMN) were decreased significantly, and the internetwork connections were increased significantly. The altered topological properties may be an effect of chronic epilepsy. As a result, the optimal topological organization of the functional network was disrupted in the patient group. Notably, clustering coefficient and nodal local efficiency in the bilateral temporal pole of the middle temporal gyrus negatively correlated with the epilepsy duration.

Conclusion

These results suggest that the bilateral temporal pole plays an important role in reflecting the effect of chronic epilepsy on the topological properties in GTCS children. The present study demonstrated a disrupted topological organization in children with GTCS. These findings provide new insight into our understanding of this disorder.
Modified J‐CAPRA scoring system in predicting treatment outcomes of metastatic prostate cancer patients undergoing androgen deprivation therapy
Authors: Lim Jasmine , Hinotsu Shiro , Onozawa Mizuki , Malek Rohan , Sundram Murali , Teh Guan C. , Ong Teng‐Aik , Thevarajah Shankaran , Zainal Rohana , Khoo Say C. , Omar Shamsuddin , Nasuha Noor A. , Akaza Hideyuki
Published: October 2020

The J‐CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate‐specific antigen, Gleason score, and clinical TNM staging. Here, we aimed to assess the generalisability of this tool in multi‐ethnic Asians. Performance of J‐CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M‐CaP) and Japan Study Group of Prostate Cancer (J‐CaP) databases, respectively. Using the original J‐CAPRA, 69.6% metastatic (M1) cases without T and/or N staging were stratified as intermediate‐risk disease in the M‐CaP database. To address this, we first omitted clinical T and N stage variables, and calculated the score on a 0–8 scale in the modified J‐CAPRA scoring system for M1 patients. Notably, treatment decisions of M1 cases were not directly affected by both T and N staging. The J‐CAPRA score threshold was adjusted for intermediate (modified J‐CAPRA score 3–5) and high‐risk (modified J‐CAPRA score ≥6) groups in M1 patients. Using J‐CaP database, validation analysis showed that overall survival, prostate cancer‐specific survival, and progression‐free survival of modified intermediate and high‐risk groups were comparable to those of original J‐CAPRA (p > 0.05) with Cohen's coefficient of 0.65. Around 88% M1 cases from M‐CaP database were reclassified into high‐risk category. Modified J‐CAPRA scoring system is instrumental in risk assessment and treatment outcome prediction for M1 patients without T and/or N staging.
Alterations of DNA damage response genes correlate with response and overall survival in anti‐PD‐1/PD‐L1‐treated advanced urothelial cancer
Authors: Joshi Monika , Grivas Petros , Mortazavi Amir , Monk Paul , Clinton Steven K. , Sue‐Ann Woo Michele , Holder Sheldon L. , Drabick Joseph J. , Yin Ming
Published: October 2020

DNA damage response (DDR) gene alterations in cancer are associated with a higher tumor mutational burden (TMB) and may impact clinical outcomes of urothelial cancer (UC). Here, we explore the prognostic role of DDR alterations in advanced UC treated with anti‐PD‐1/PD‐L1 agents. The study included 53 patients who had FoundationOne genomic sequencing and received anti‐PD‐1/PD‐L1 therapy. Fisher exact test and trend test were used to assess differences in objective response rate (ORR). Overall survival (OS) was measured from the time of initial UC diagnosis and Cox proportional hazard regression analysis was performed to calculate hazard ratio (HR) and 95% confidence interval (CI). The cohort had a median age of 66 with 64% receiving platinum‐based chemotherapy. DDR alterations (including ATM) were associated with a non‐significantly higher ORR to PD‐1/PD‐L1 blockade (41% vs. 21%, p = 0.136). Patients with DDR alterations (excluding ATM) had non‐significantly longer OS, likely due to a small sample size (HR = 0.53, 95% CI 0.20–1.38, p = 0.19). ATM alterations were associated with a non‐significantly higher ORR (40% vs. 29%, p = 0.6), but also with significantly shorter OS (HR = 5.7, 95% CI 1.65–19.74, p = 0.006). Patients with ≥ 3 DDR alterations (including ATM) had substantially higher TMB (p = 0.01) and higher ORR (80%) with PD‐1/PD‐L1 blockade versus 24% ORR in patients with <3 DDR alterations. In summary, DDR alterations were associated with non‐significantly higher ORR and longer OS for patients with advanced UC receiving anti‐PD‐1/PD‐L1 agents. ATM alterations were associated with shorter OS.
Blockade of IL‐33 signalling attenuates osteoarthritis
Authors: He Zengliang , Song Yan , Yi Yongxiang , Qiu Fengzhuo , Wang Junhua , Li Junwei , Jin Qingwen , Sacitharan Pradeep Kumar
Published: October 2020

Objectives

Osteoarthritis (OA) is the most common form of arthritis characterised by cartilage degradation, synovitis and pain. Disease modifying treatments for OA are not available. The critical unmet need is to find therapeutic targets to reduce both disease progression and pain. The cytokine IL‐33 and its receptor ST2 have been shown to play a role in immune and inflammatory diseases, but their role in osteoarthritis is unknown.

Methods

Non‐OA and OA human chondrocytes samples were examined for IL‐33 and ST2 expression. Novel inducible cartilage specific knockout mice (IL‐33Acan CreERT2) and inducible fibroblast‐like synoviocyte knockout mice (IL‐33Col1a2 CreERT2) were generated and subjected to an experimental OA model. In addition, wild‐type mice were intra‐articularly administered with either IL‐33‐ or ST2‐neutralising antibodies during experimental OA studies.

Results

IL‐33 and its receptor ST2 have increased expression in OA patients and a murine disease model. Administering recombinant IL‐33 increased OA and painin vivo. Synovial fibroblast‐specific deletion of IL‐33 decreased synovitis but did not impact disease outcomes, whilst cartilage‐specific deletion of IL‐33 improved disease outcomesin vivo. Blocking IL‐33 signalling also reduced the release of cartilage‐degrading enzymes in human and mouse chondrocytes. Most importantly, we show the use of monoclonal antibodies against IL‐33 and ST2 attenuates both OA and painin vivo.

Conclusion

Overall, our data reveal blockade of IL‐33 signalling as a viable therapeutic target for OA.
Comprehensive Phenotyping of Peripheral Blood T Lymphocytes in Healthy Mice
Authors: Del Zotto Genny , Principi Elisa , Antonini Francesca , Baratto Serena , Panicucci Chiara , Bruno Claudio , Raffaghello Lizzia
Published: October 2020

T lymphocytes play a central role in antigen‐specific immune responses. They modulate the function of different immune cells both through a direct contact (receptor binding) and through the secretion of cytokines. At the same time, they are deeply involved in the direct killing of aberrant target cells. T lymphocytes derive from a bone marrow precursor that migrates in the thymus where the main differentiation steps take place. Mature CD4 and CD8 single‐positive cells, then, leave the thymus to reach the secondary lymphoid organs. T‐cell subsets and their maturation steps can be identified mainly based on the expression of extracellular markers, intracellular transcription factors and cytokine production profiles. In this review, we report, from a cytometric point of view, an overview of the most important T‐cell subpopulations and their differentiation state. © 2020 International Society for Advancement of Cytometry
A practical approach to the clinical challenges in initiation of basal insulin therapy in people with type 2 diabetes
Authors: Forst Thomas , Choudhary Pratik , Schneider Doron , Linetzky Bruno , Pozzilli Paolo
Published: October 2020

Initiating insulin therapy with a basal insulin analogue has become a standard of care in the treatment of type 2 diabetes mellitus (T2DM). Despite increasing choices in pharmacological approaches, intensified glucose monitoring and improvements in quality of care, many patients do not achieve the desired level of glycaemic control. Although insulin therapy, when optimized, can help patients reach their glycaemic goals, there are barriers to treatment initiation on both the side of the patient and provider. Providers experience barriers based on their perceptions of patients' capabilities and concerns. They may lack the confidence to solve the practical problems of insulin therapy and avoid decisions they perceive as risky for their patients. In this study, we review recommendations for basal insulin initiation, focussing on glycaemic targets, titration, monitoring, and combination therapy with non‐insulin anti‐hyperglycaemic medications. We provide practical advice on how to address some of the key problems encountered in everyday clinical practice and give recommendations where there are gaps in knowledge or guidelines. We also discuss common challenges faced by people with T2DM, such as weight gain and hypoglycaemia, and how providers can address and overcome them.
Examining academic confidence and study support needs for university students with dyslexia and/or developmental coordination disorder
Authors: Sumner Emma , Crane Laura , Hill Elisabeth L.
Published: October 2020

Higher education providers are seeing a shift from externally funded support for students with specific learning difficulties (SpLD), to a need to develop more inclusive practices generally. However, the precise needs of students with different SpLD diagnoses is unknown. A total of 367 students in England and Wales (163 students with dyslexia, 50 students with developmental coordination disorder [DCD/“dyspraxia”], 62 students with dyslexia and DCD, and 92 non‐SpLD students) completed an online questionnaire to determine: (a) how confident they are with their study‐related capabilities, (b) the types of support they access, and (c) their views on current inclusive practices. Students with dyslexia and students with dyslexia/DCD reported lower confidence in their grades and studying than non‐SpLD students, and accessed more technology‐related support than students with DCD only. Examination accommodations supporting writing were common for all SpLD students. Inclusive practices were perceived positively, although different priorities were seen across groups. The findings demonstrate the complexities inherent in providing effective support for all students at university, with the varied profiles across and within SpLD groups suggesting that an individualized approach is necessary. Practical implications are discussed.
Evaluating multiple historical climate products in ecological models under current and projected temperatures
Authors: Sadoti Giancarlo , McAfee Stephanie A. , Nicklen E. Fleur , Sousanes Pamela J. , Roland Carl A.
Published: October 2020

Gridded historical climate products (GHCPs) are employed with increasing frequency when modeling ecological phenomena across large scales and predicting ecological responses to projected climate changes. Concurrently, there is an increasing acknowledgement of the need to account for uncertainty when employing climate projections from ensembles of global circulation models (GCMs) and emissions scenarios. Despite the growing usage and documented differences among GHCPs, uncertainty characterization has primarily focused on GCM and emissions scenario choice, while the consequences of using a single GHCP to make predictions over space and time have received less attention. Here we employ average July temperature data from observations and seven GHCPs to model plant canopy cover and tree basal area across central Alaska, USA. We first compare the fit of, and support for, models employing observed temperatures, GHCP temperatures, and GHCP temperatures with an elevation adjustment, finding (1) greater support for, and better fit using, elevation‐adjusted vs. raw temperature models and (2) overall similar fits of elevation‐adjusted models employing temperatures from observations or GHCPs. Focusing on basal area, we next compare predictions generated by elevation‐adjusted models employing GHCP data under current conditions and a warming scenario of current temperatures plus 2°C, finding good agreement among GHCPs though with between‐GHCP differences and variation primarily at middle elevations (~1,000 m). These differences were amplified under the warming scenario. Finally, using pooled indices of prediction variation and difference across GHCP models, we identify characteristics of areas most likely to exhibit prediction uncertainty under current and warming conditions. Despite (1) overall good performance of GHCP data relative to observations in models and (2) positive correlation among model predictions, variation in predictions across models, particularly in mid‐elevation areas where the position of treeline may be changing, suggests researchers should exercise caution if selecting a single GHCP for use in models. We recommend the use of multiple GHCPs to provide additional uncertainty information beyond standard estimated prediction intervals, particularly when model predictions are employed in conservation planning.
Environment shapes the spatial organization of tree diversity in fragmented forests across a human‐modified landscape
Authors: Krishnadas Meghna , Osuri Anand M.
Published: October 2020

Biodiversity patterns are shaped by the combination of dispersal, environment, and stochasticity, but how the influence of these drivers changes in fragmented habitats remains poorly understood. We examined patterns and relationships among total (γ) and site‐level (α) diversity, and site‐to‐site variation in composition (β‐diversity) of tree communities in structurally contiguous and fragmented tropical rainforests within a human‐modified landscape in India's Western Ghats. First, for the entire landscape, we assessed the extent to which habitat type (fragment or contiguous forest), space and environment explained variation in α‐diversity and composition. Next, within fragments and contiguous forest, we assessed the relative contribution of spatial proximity, environmental similarity, and their joint effects in explaining β‐diversity. We repeated these assessments with β‐diversity values corrected for the confounding effects of α‐ and γ‐diversity using null models (β‐deviation). Lower γ‐diversity of fragments resulted from both lower α‐ and β‐diversity compared to contiguous forests. However, β‐deviation did not differ between contiguous forests and fragments. Fragmented and contiguous forest clearly diverged in floristic composition, which was attributable to β‐diversity being driven by differences in elevation and MAP. Within fragmented forest, neither space nor environment explained β‐diversity, but β‐deviation increased with greater elevational differences. In contiguous forests by comparison, environment alone (mainly elevation) explained the most variation in β‐diversity and β‐deviation of both species' occurrences and abundances. Spatial gradients in environmental conditions played a larger role than dispersal limitation in shaping diversity and composition of tree communities across forest fragments. Thus, location of remnant patches at different elevations was a key factor underlying site‐to‐site variability in species abundances across fragments. Understanding the environmental characteristics of remnant forests in human‐modified landscapes, combined with knowledge of species–environment relationships across different functional groups, would therefore be important considerations for management and restoration planning in human‐modified landscapes.