bluuebunny/crossref_metadata_2025 huggingface dataset:
Seed longevity and germination in response to changing drought and heat conditions on four populations of the invasive weed African Lovegrass (Eragrostis curvula)
Authors: Roberts Jason , Florentine Singarayer , van Etten Eddie , Turville Christopher
Published: April 2021

African lovegrass [Eragrostis curvula (Schrad.) Nees] is an invasive weed that is threatening biodiversity around the world and will continue to do so unless its efficient management is achieved. Consequently, laboratory and field-based experiments were performed to analyse several measures of germination to determine the effect of drought stress, radiant heat stress and burial depth and duration (longevity) on E. curvula seeds. This study investigated seeds from four spatially varied populations across Australia: Maffra and Shepparton, Victoria; Tenterfield, New South Wales; and Midvale, Western Australia. Results showed that increasing drought stress reduced and slowed germination for all populations. Maffra (24% vs. 83%) and Shepparton (41% vs. 74%) were reduced at the osmotic potential of ≤-0.4 MPa, whilst Tenterfield (35% vs. 98.6%) and Midvale (32% vs. 91%) were reduced at ≤-0.6 MPa, compared to the mean of all other osmotic potentials. Radiant heat at 100 C significantly reduced and slowed germination compared to 40 C for Tenterfield (62% vs. 100%), Shepparton (15% vs. 89%) and Midvale (41% vs. 100%); whilst Maffra (75% vs. 86%) had consistent germination. For the effect of burial depth and duration (longevity), there was no significant difference across the fourteen-month period, however, the 0 cm burial depth had a significantly lower final germination percentage compared to depths of 3, 5 and 10 cm (24% vs. 55%). Although each trial was conducted independently, their results can be used to help identify efficient control measures to reduce infesting populations. Such measures recommended include using soil moisture monitoring to detect which conditions will promote germination, as germination is encouraged when the osmotic potential is >-0.6 MPa; exposing seeds to radiant heat (>100 C) using methods such as prescribed burning; and limiting soil disturbance over time to reduce seed establishment.
The Three‐Dimensional Internal Tide Radiation and Dissipation in the Mariana Arc‐Trench System
Authors: Zhao Chen , Xu Zhenhua , Robertson Robin , Li Qun , Wang Yang , Yin Baoshu
Published: April 2021

Internal tides are energetic in the Mariana arc, but their three‐dimensional radiation and dissipation remain unexplored, particularly the trench‐arc‐basin impacts. Here, the generation, propagation and dissipation of M2 internal tides over the Mariana area are examined using a series of observation‐supported high‐resolution simulations. The M2 barotropic to baroclinic conversion rate amounts to 8.35 GW, of which two arc‐shaped ridges contribute ∼81% of the generated energy. The contributions to generation by the Mariana basin and deep trench are weak. Nevertheless, they are important in modulating the energy radiation and dissipation, since tidal beams can spread to these areas. The Mariana ridges radiate the westward‐focused and eastward‐spreading tidal beams. This is very consistent with the altimetric measurements. The resonance in the ridge center enhances the westward converging beam, which can travel across the Palau Ridge, 800 km away. In contrast, the eastward beams propagate over a limited lateral range, but can radiate and dissipate significant energy in the deep water column, reaching even to the abyssal Mariana trench. The direct estimation from the model results reveals the dissipation's multilayer vertical profile in the entire water column, and is well consistent with the finescale parameterization estimate based on vertical strain. However, the estimate of an oft‐used energy balance method, which typically assumes an exponentially decaying vertical structure function for the dissipation rate based on distance above the seafloor, is largely inconsistent with the measurements. Our findings highlight the complexity of three‐dimensional radiation paths and dissipation map of internal tides in the Mariana area.
High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses
Authors: Hammarsjö Anna , Pettersson Maria , Chitayat David , Handa Atsuhiko , Anderlid Britt-Marie , Bartocci Marco , Basel Donald , Batkovskyte Dominyka , Beleza-Meireles Ana , Conner Peter , Eisfeldt Jesper , Girisha Katta M. , Chung Brian Hon-Yin , Horemuzova Eva , Hyodo Hironobu , Korņejeva Liene , Lagerstedt-Robinson Kristina , Lin Angela E. , Magnusson Måns , Moosa Shahida , Nayak Shalini S. , Nilsson Daniel , Ohashi Hirofumi , Ohashi-Fukuda Naoko , Stranneheim Henrik , Taylan Fulya , Traberg Rasa , Voss Ulrika , Wirta Valtteri , Nordgren Ann , Nishimura Gen , Lindstrand Anna , Grigelioniene Giedre
Published: April 2021

Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes:DYNC2H1,KIAA0753, WDR19,C2CD3,TTC21B,EVC, andEVC2. Four variants located in non-canonical splice sites ofDYNC2H1,EVC, andKIAA0753led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion ofDYNC2H1in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant inPRKACAand in another we found a homozygous intragenic deletion ofIFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establishIFT74as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.
Diagnostic and therapeutic pitfalls in NPM1-mutated AML: notes from the field
Authors: Falini Brunangelo , Sciabolacci Sofia , Falini Lorenza , Brunetti Lorenzo , Martelli Maria Paola
Published: April 2021

Mutations of Nucleophosmin (NPM1) are the most common genetic abnormalities in adult acute myeloid leukaemia (AML), accounting for about 30% of cases. NPM1-mutated AML has been recognized as distinct entity in the 2017 World Health Organization (WHO) classification of lympho-haematopoietic neoplasms. WHO criteria allow recognition of this leukaemia entity and its distinction from AML with myelodysplasia-related changes, AML with BCR-ABL1 rearrangement and AML with RUNX1 mutations. Nevertheless, controversial issues include the percentage of blasts required for the diagnosis of NPM1-mutated AML and whether cases of NPM1-mutated myelodysplasia and chronic myelomonocytic leukaemia do exist. Evaluation of NPM1 and FLT3 status represents a major pillar of the European LeukemiaNet (ELN) genetic-based risk stratification model. Moreover, NPM1 mutations are particularly suitable for assessing measurable residual disease (MRD) since they are frequent, stable at relapse and do not drive clonal haematopoiesis. Ideally, combining monitoring of MRD with the ELN prognostication model can help to guide therapeutic decisions. Here, we provide examples of instructive cases of NPM1-mutated AML, in order to provide criteria for the appropriate diagnosis and therapy of this frequent leukaemia entity.
Multichannel EEG abnormalities during the first 6 hours in infants with mild hypoxic–ischaemic encephalopathy
Authors: Garvey Aisling A. , Pavel Andreea M. , O’Toole John M. , Walsh Brian H. , Korotchikova Irina , Livingstone Vicki , Dempsey Eugene M. , Murray Deirdre M. , Boylan Geraldine B.
Published: April 2021

Background

Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants.

Methods

Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003–2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups.

Results

Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups.

Conclusions

Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE.

Impact

Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up.

In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value.

72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment.

Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants.

Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.
Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
Authors: Parkes Linden , Moore Tyler M. , Calkins Monica E. , Cook Philip A. , Cieslak Matthew , Roalf David R. , Wolf Daniel H. , Gur Ruben C. , Gur Raquel E. , Satterthwaite Theodore D. , Bassett Danielle S.
Published: April 2021

Psychopathology is rooted in neurodevelopment. However, clinical and biological heterogeneity, together with a focus on case-control approaches, have made it difficult to link dimensions of psychopathology to abnormalities of neurodevelopment. Here, using the Philadelphia Neurodevelopmental Cohort, we built normative models of cortical volume and tested whether deviations from these models better predicted psychiatric symptoms compared to raw cortical volume. Specifically, drawing on thep-factorhypothesis, we distilled 117 clinical symptom measures into six orthogonal psychopathology dimensions: overall psychopathology, anxious-misery, externalizing disorders, fear, positive psychosis symptoms, and negative psychosis symptoms. We found that multivariate patterns of deviations yielded improved out-of-sample prediction of psychopathology dimensions compared to multivariate patterns of raw cortical volume. We also found that correlations between overall psychopathology and deviations in ventromedial prefrontal, inferior temporal, and dorsal anterior cingulate cortices were stronger than those observed for specific dimensions of psychopathology (e.g., anxious-misery). Notably, these same regions are consistently implicated in a range of putatively distinct disorders. Finally, we performed conventional case-control comparisons of deviations in a group of individuals with depression and a group with attention-deficit hyperactivity disorder (ADHD). We observed spatially overlapping effects between these groups that diminished when controlling for overall psychopathology. Together, our results suggest that modeling cortical brain features as deviations from normative neurodevelopment improves prediction of psychiatric symptoms in out-of-sample testing, and thatp-factormodels of psychopathology may assist in separating biomarkers that are disorder-general from those that are disorder-specific.
Cross-sectional investigation of insulin resistance in youths with autism spectrum disorder. Any role for reduced brain glucose metabolism?
Authors: Manco Melania , Guerrera Silvia , Ravà Lucilla , Ciofi degli Atti Marta , Di Vara Silvia , Valeri Giovanni , Vicari Stefano
Published: April 2021

The autism spectrum disorder (ASD) is an etiologically heterogeneous disorder. Dysfunctions of the intermediate metabolism have been described in some patients. We speculate these metabolic abnormalities are associated with brain insulin resistance (IR), i.e., the reduced glucose metabolism at the level of the nervous central system. The Homeostasis model assessment of insulin resistance (HOMA-IR) is very often used in population studies as estimate of peripheral IR and it has been recently recognized as proxy of brain IR. We investigated HOMA-IR in 60 ASD patients aged 4–18 years and 240 healthy controls, also aged 4–18 years, but unmatched for age, sex, body weight, or body mass index (BMI). At multivariable linear regression model, the HOMA-IR was 0.31 unit higher in ASD individuals than in controls, after having adjusted for sex, age, BMI z-score category, and lipids that are factors known to influence HOMA-IR. Findings of this preliminary study suggest it is worth investigating brain glucose metabolism in larger population of patients with ASD by using gold standard technique. The recognition of a reduced glucose metabolism in some areas of the brain as marker of autism might have tremendous impact on our understanding of the pathogenic mechanisms of the disease and in terms of public health.
Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis
Authors: Rocha Mariana , Wang Daniel , Avila-Quintero Victor , Bloch Michael H. , Kaffman Arie
Published: April 2021

Exposure to early life stress (ELS) causes abnormal hippocampal development and functional deficits in rodents and humans, but no meta-analysis has been used yet to quantify the effects of different rodent models of ELS on hippocampal-dependent memory. We searched PubMed and Web of Science for publications that assessed the effects of handling, maternal separation (MS), and limited bedding and nesting (LBN) on performance in the Morris water maze (MWM), novel object recognition (NOR), and contextual fear conditioning (CFC). Forty-five studies met inclusion criteria (n = 451–763 rodents per test) and were used to calculate standardized mean differences (Hedge’s g) and to assess heterogeneity, publication bias, and the moderating effects of sex and species (rats vs. mice). We found significantly lower heterogeneity in LBN compared to handling and MS with no consistent effects of sex or species across the three paradigms. LBN and MS caused similar cognitive deficits in tasks that rely heavily on the dorsal hippocampus, such as MWM and NOR, and were significantly different compared to the improved performance seen in rodents exposed to handling. In the CFC task, which relies more on the ventral hippocampus, all three paradigms showed reduced freezing with moderate effect sizes that were not statistically different. These findings demonstrate the utility of using meta-analysis to quantify outcomes in a large number of inconsistent preclinical studies and highlight the need to further investigate the possibility that handling causes different alterations in the dorsal hippocampus but similar outcomes in the ventral hippocampus when compared to MS and LBN.
The transcriptional activator of the bfp operon in EPEC (PerA) interacts with the RNA polymerase alpha subunit
Authors: Lara-Ochoa Cristina , González-Lara Fabiola , Romero-González Luis E. , Jaramillo-Rodríguez Juan B. , Vázquez-Arellano Sergio I. , Medrano-López Abraham , Cedillo-Ramírez Lilia , Martínez-Laguna Ygnacio , Girón Jorge A. , Pérez-Rueda Ernesto , Puente José Luis , Ibarra J. Antonio
Published: April 2021

Enteropathogenic E. coli virulence genes are under the control of various regulators, one of which is PerA, an AraC/XylS-like regulator. PerA directly promotes its own expression and that of the bfp operon encoding the genes involved in the biogenesis of the bundle-forming pilus (BFP); it also activates PerC expression, which in turn stimulates locus of enterocyte effacement (LEE) activation through the LEE-encoded regulator Ler. Monomeric PerA directly binds to the per and bfp regulatory regions; however, it is not known whether interactions between PerA and the RNA polymerase (RNAP) are needed to activate gene transcription as has been observed for other AraC-like regulators. Results showed that PerA interacts with the alpha subunit of the RNAP polymerase and that it is necessary for the genetic and phenotypic expression of bfpA. Furthermore, an in silico analysis shows that PerA might be interacting with specific alpha subunit amino acids residues highlighting the direction of future experiments.
Learning future terrorist targets through temporal meta-graphs
Authors: Campedelli Gian Maria , Bartulovic Mihovil , Carley Kathleen M.
Published: April 2021

In the last 20 years, terrorism has led to hundreds of thousands of deaths and massive economic, political, and humanitarian crises in several regions of the world. Using real-world data on attacks occurred in Afghanistan and Iraq from 2001 to 2018, we propose the use of temporal meta-graphs and deep learning to forecast future terrorist targets. Focusing on three event dimensions, i.e., employed weapons, deployed tactics and chosen targets, meta-graphs map the connections among temporally close attacks, capturing their operational similarities and dependencies. From these temporal meta-graphs, we derive 2-day-based time series that measure the centrality of each feature within each dimension over time. Formulating the problem in the context of the strategic behavior of terrorist actors, these multivariate temporal sequences are then utilized to learn what target types are at the highest risk of being chosen. The paper makes two contributions. First, it demonstrates that engineering the feature space via temporal meta-graphs produces richer knowledge than shallow time-series that only rely on frequency of feature occurrences. Second, the performed experiments reveal that bi-directional LSTM networks achieve superior forecasting performance compared to other algorithms, calling for future research aiming at fully discovering the potential of artificial intelligence to counter terrorist violence.
Trienone analogs of curcuminoids induce fetal hemoglobin synthesis via demethylation at Gγ-globin gene promoter
Authors: Nuamsee Khanita , Chuprajob Thipphawan , Pabuprapap Wachirachai , Jintaridth Pornrutsami , Munkongdee Thongperm , Phannasil Phatchariya , Vadolas Jim , Chaichompoo Pornthip , Suksamrarn Apichart , Svasti Saovaros
Published: April 2021

The reactivation of γ-globin chain synthesis to combine with excess free α-globin chains and form fetal hemoglobin (HbF) is an important alternative treatment for β-thalassemia. We had reported HbF induction property of natural curcuminoids, curcumin (Cur), demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), in erythroid progenitors. Herein, the HbF induction property of trienone analogs of the three curcuminoids in erythroleukemic K562 cell lines and primary human erythroid progenitor cells from β-thalassemia/HbE patients was examined. All three trienone analogs could induce HbF synthesis. The most potent HbF inducer in K562 cells was trienone analog of BDMC (T-BDMC) with 2.4 ± 0.2 fold increase. In addition, DNA methylation at CpG − 53, − 50 and + 6 of Gγ-globin gene promoter in K562 cells treated with the compounds including T-BDMC (9.3 ± 1.7%, 7.3 ± 1.7% and 5.3 ± 0.5%, respectively) was significantly lower than those obtained from the control cells (30.7 ± 3.8%, 25.0 ± 2.9% and 7.7 ± 0.9%, respectively P < 0.05). The trienone compounds also significantly induced HbF synthesis in β-thalassemia/HbE erythroid progenitor cells with significantly reduction in DNA methylation at CpG + 6 of Gγ-globin gene promoter. These results suggested that the curcuminoids and their three trienone analogs induced HbF synthesis by decreased DNA methylation at Gγ-globin promoter region, without effect on Aγ-globin promoter region.
Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan
Authors: Lu Ming-Ying , Chen Chun-Ting , Shih Yu-Lueng , Tsai Pei-Chien , Hsieh Meng-Hsuan , Huang Chung-Feng , Yeh Ming-Lun , Huang Ching-I , Wang Shu-Chi , Tsai Yi-Shan , Ko Yu-Min , Lin Ching-Chih , Chen Kuan-Yu , Wei Yu-Ju , Hsu Po-Yao , Hsu Cheng-Ting , Jang Tyng-Yuan , Liu Ta-Wei , Liang Po-Cheng , Hsieh Ming-Yen , Lin Zu-Yau , Chen Shinn-Cherng , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung , Chang Wen-Yu
Published: April 2021

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.
Association among extracellular superoxide dismutase genotype, plasma concentration, and comorbidity in the very old and centenarians
Authors: Sasaki Takashi , Abe Yukiko , Takayama Michiyo , Adachi Tetsuo , Okano Hideyuki , Hirose Nobuyoshi , Arai Yasumichi
Published: April 2021

Superoxide dismutase 3 (SOD3), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85–99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98–3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39–0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.
Enhanced inter-regional coupling of neural responses and repetition suppression provide separate contributions to long-term behavioral priming
Authors: Gotts Stephen J. , Milleville Shawn C. , Martin Alex
Published: April 2021

Stimulus identification commonly improves with repetition over long delays (“repetition priming”), whereas neural activity commonly decreases (“repetition suppression”). Multiple models have been proposed to explain this brain-behavior relationship, predicting alterations in functional and/or effective connectivity (Synchrony and Predictive Coding models), in the latency of neural responses (Facilitation model), and in the relative similarity of neural representations (Sharpening model). Here, we test these predictions with fMRI during overt and covert naming of repeated and novel objects. While we find partial support for predictions of the Facilitation and Sharpening models in the left fusiform gyrus and left frontal cortex, the data were most consistent with the Synchrony model, with increased coupling between right temporoparietal and anterior cingulate cortex for repeated objects that correlated with priming magnitude across participants. Increased coupling and repetition suppression varied independently, each explaining unique variance in priming and requiring modifications of all current models.
Optimal, near-optimal, and robust epidemic control
Authors: Morris Dylan H. , Rossine Fernando W. , Plotkin Joshua B. , Levin Simon A.
Published: April 2021

In the absence of drugs and vaccines, policymakers use non-pharmaceutical interventions such as social distancing to decrease rates of disease-causing contact, with the aim of reducing or delaying the epidemic peak. These measures carry social and economic costs, so societies may be unable to maintain them for more than a short period of time. Intervention policy design often relies on numerical simulations of epidemic models, but comparing policies and assessing their robustness demands clear principles that apply across strategies. Here we derive the theoretically optimal strategy for using a time-limited intervention to reduce the peak prevalence of a novel disease in the classic Susceptible-Infectious-Recovered epidemic model. We show that broad classes of easier-to-implement strategies can perform nearly as well as the theoretically optimal strategy. But neither the optimal strategy nor any of these near-optimal strategies is robust to implementation error: small errors in timing the intervention produce large increases in peak prevalence. Our results reveal fundamental principles of non-pharmaceutical disease control and expose their potential fragility. For robust control, an intervention must be strong, early, and ideally sustained.
Changes in the Gulf Stream preceded rapid warming of the Northwest Atlantic Shelf
Authors: Gonçalves Neto Afonso , Langan Joseph A. , Palter Jaime B.
Published: April 2021

The Northwest Atlantic Shelf provides ecological and economic benefits along the heavily populated North American coastline and beyond. In 2009-2010, abrupt warming prompted an ecosystem shift with consequences for fisheries, yet the cause of this event is unclear. Here we use satellite altimetry and in situ measurements to show that, in 2008, the Gulf Stream migrated closer to the Tail of the Grand Banks, a shift that has persisted ever since. This change reduced the westward connectivity of the Labrador Current that otherwise supplies cold, fresh, oxygen-rich waters to the shelf. Within one year after the appearance of anomalously warm and saline water at the Tail of Grand Banks, subsurface warming progressed south-westwards. Historical observations suggest a similar sequence of events may have occurred in the 1970s. Therefore, monitoring water properties at the Tail of Grand Banks may offer predictability for shelf properties and ecosystem perturbations with substantial lead time.
External-oxidant-free amino-benzoyloxylation of unactivated alkenes of unsaturated ketoximes with O-benzoylhydroxylamines
Authors: Chen Jiangfei , Zhu Yan-Ping , Li Jin-Heng , Wang Qiu-An
Published: April 2021

Radical-mediated aminobenzoyloxylation of alkenyl ketoximes using O-benzoylhydroxylamines as the benzoyloxyl radical precursors and internal oxidants is presented.
Design and perspective of amorphous metal nanoparticles from laser synthesis and processing
Authors: Liang Shun-Xing , Zhang Lai-Chang , Reichenberger Sven , Barcikowski Stephan
Published: April 2021

Pulsed laser strategies (i.e.pulsed laser ablation and fragmentation in liquid) have been reviewed with a focus on the synthesis and processing of amorphous metal nanoparticles. The possible formation criteria and mechanism have been discussed.
Spiers Memorial Lecture: Introduction to ultrafast spectroscopy and imaging of photochemical reactions
Authors: Suzuki Toshinori
Published: April 2021

A brief overview is presented on ultrafast spectroscopy and imaging of photochemical reactions by highlighting several experimental studies reported in the last five years.
LED-driven controlled deposition of Ni onto TiO2 for visible-light expanded conversion of carbon dioxide into C1–C2 alkanes
Authors: Sanz-Marco Arturo , Hueso José L. , Sebastian Víctor , Nielsen David , Mossin Susanne , Holgado Juan P. , Bueno-Alejo Carlos J. , Balas Francisco , Santamaria Jesus
Published: April 2021

Photodeposited 5 nm Ni nanoparticles on TiO2 P25 catalysts promote the photocatalytic hydrogenation of CO2 under visible light to CH4 and C2H6.
High-efficiency synthesis of enhanced-titanium and anatase-free TS-1 zeolite by using a crystallization modifier
Authors: Zhang Jiani , Shi Huaizhong , Song Yue , Xu Wenjing , Meng Xianyu , Li Jiyang
Published: April 2021

A high-efficiency strategy to rapidly synthesize enhanced-titanium TS-1 zeolite without extra-framework anatase TiO2by using 1,3,5-benzenetricarboxylic acid (H3BTC) as a crystallization modifier.
Eu-doped ZnO quantum dots with solid-state fluorescence and dual emission for high-performance luminescent solar concentrators
Authors: Gong Xiao , Jiang Hang , Cao Mengyan , Rao Zhihui , Zhao Xiujian , Vomiero Alberto
Published: April 2021

Eu-doped ZnO quantum dots with strong solid-state fluorescence and dual emission are synthesized via a simple sol–gel method, which can be used for fabrication of high-performance luminescent solar concentrators.
Bioinspired modified graphene oxide/polyurethane composites with rapid self-healing performance and excellent mechanical properties
Authors: Liu Yahao , Zheng Jian , Zhang Xiao , Du Yongqiang , Yu Guibo , Li Ke , Jia Yunfei , Zhang Yu
Published: April 2021

We successfully modified graphene oxide with amino-terminated hyperbranched polyamide(MGO), and obtained novel mussel-inspired MGO/polyurethane composites with outstanding self-healing and mechanical performances via rational molecular design.
A carrier-free nanoparticle with dual NIR/acid responsiveness by co-assembly of enediyne and IR820 for combined PTT/chemotherapy
Authors: Lu Haotian , Wang Wenbo , Li Xiaoxuan , Zhang Mengsi , Cheng Xiaoyu , Sun Ke , Ding Yun , Li Xinxin , Hu Aiguo
Published: April 2021

Combined photothermal therapy/chemotherapy by co-delivery of a photosensitizer (PS) and a chemotherapeutic drug has demonstrated great potential for cancer treatment.
Experimental and numerical investigation of geometric effect on cavitation flow through orifice
Authors: Davoudi Mohammad Reza , Mahdi Miralam
Published: April 2021

Due to the set of factors and conditions, the stream pressure through the orifice decreases, which can lead to the occurrence of the cavitation phenomenon. The most important factor in this regard is the geometry of orifice. In the first part of this study, the flow through two types of single-hole orifice and a multi-hole orifice were experimentally studied. The results showed that the single hole orifice with a two-sided sloped edge caused less pressure drop, which in order to control the cavitation phenomenon is more efficient compared to the single-hole and multi-hole orifices with one-sided sloped edges and the same equal diameter ratio. Additionally, all experiments were simulated in the second part of this research using finite volume methods. Considering the complexity of the problem, several numerical solutions were investigated to approach the experimental results. Finally, it was determined that the type of gridding, turbulence method, and cavitation model have a great influence on the accuracy of the obtained numerical results.
Seltene Erkrankungen in der Rheumatologie
Authors: Bauhammer Jutta , Fiehn Christoph
Published: April 2021

Aus der Rheumatologie sind seltene entzündliche Erkrankungen nicht wegzudenken. Ihre Therapie stellt den Rheumatologen/die Rheumatologin vor besondere Herausforderungen, da oft keine zugelassenen Medikamente existieren. Um aber im Off-Label-Einsatz zu behandeln, ist es notwendig, die Evidenz in der Behandlung der verschiedenen Erkrankungen gut zu kennen. In der folgenden Arbeit werden die Therapieoptionen sowohl zu In- wie auch Off-Label-Therapie der wichtigsten seltenen rheumatischen Erkrankungen der Erwachsenen dargestellt. Dies sind die systemische Sklerose, die idiopathischen inflammatorischen Myopathien, der Morbus Behçet, das familiäre Mittelmeerfieber, der Morbus Still, die idiopathische rekurrierende Perikarditis, das SAPHO-Syndrom, die chronisch rekurrierende multifokale und chronisch nicht bakterielle Osteomyelitis, die IgG4-Syndrome, die Mischkollagenose (Sharp-Syndrom) sowie die undifferenzierte und Overlap-Kollagenosen. Die klinischen Studien und aktuellen Empfehlungen zur Therapie dieser Erkrankungen, bezogen auch auf die jeweiligen Krankheitsmanifestationen, werden tabellarisch aufgelistet und die Referenzen genannt. Das Ziel des Artikels ist es, dem praktisch tätigen Rheumatologen eine Hilfestellung zur Auswahl der Therapie und unter Umständen auch der Beantragung einer Kostenübernahme für Off-Label-Therapien zu geben.
In-/Off-Label-Therapie bei rheumatoider Arthritis
Authors: Krüger Klaus
Published: April 2021

Labelgerechter Einsatz von Medikamenten ist formaljuristisch und in Bezug auf Erstattungsfähigkeit einer Therapie wichtig – Off-Label-Therapie bedarf besonderer Aufklärungspflicht und birgt ein hohes Regress-Risiko. In der Rheumatologie ist vor allem bei Verschreibung kostenintensiver Medikamente wie Biologika und JAK-Inhibitoren auf labelgerechten Einsatz zu achten. Hierbei stehen – neben der Voraussetzung einer Zulassung für die rheumatoide Arthritis (RA) – 3 Risikobereiche im Mittelpunkt: Richtiger Zeitpunkt des Einsatzes, korrekte Dosierung und Mono- bzw. Kombinationstherapie. Der Zeitpunkt betrifft die Frage, ob eine Substanz im Therapie-Algorithmus als First-, Second- oder sogar Third-Line-Therapie (Rituximab) zugelassen ist. Bei der Dosierung ist darauf zu achten, dass die oberste zugelassene Dosis nicht überschritten wird. Zwar stellt formell auch Unterschreitung der Zulassungsdosis einen Off-Label-Einsatz dar, bleibt jedoch in der Regel ohne Konsequenzen. Da DMARD z. T. nur in Kombination mit Methotrexat (Mtx) zugelassen sind, liegt auch hier ein Fallstrick, ebenso bei Verwendung anderer Kombinationspartner als Mtx. Die vorliegende Übersicht bemüht sich, dem Verordner Hilfestellung für eine sichere Anwendung vor allem der DMARD-Therapie zu geben.
Disparities in Trial of Labor among Women with Twin Gestations in the United States
Authors: Mo Gina N. , Cheng Yvonne W. , Caughey Aaron B. , Yee Lynn M.
Published: April 2021

Objective The aim of the study is to examine clinical and demographic factors associated with trial of labor (TOL) among women with twin gestations eligible for a vaginal delivery.

Study Design This was a population-based cohort study of women giving birth to twin gestations in the United States (2012–2014). Inclusion criteria for the analysis included live births greater than 23 weeks' gestation and a cephalic presenting twin. Women with prior cesarean delivery were excluded. Women were categorized by whether they underwent a TOL. Clinical and demographic characteristics associated with TOL status were evaluated using multivariable logistic regression analyses. Secondary analyses with stratification by parity and by second twin presentation were performed.

Results Of 90,000 women eligible for inclusion, a minority (39.3%) underwent TOL. Women who had a greater gestational age at delivery were more likely to have a TOL. In contrast, several demographic factors were associated with decreased likelihood of TOL, including maternal age >35 years and identifying as Hispanic or Asian compared with non-Hispanic White. No differences in odds of TOL were observed for women who were identified as non-Hispanic Black versus non-Hispanic White, nor were other demographic factors such as marital status, insurance status, or educational attainment associated with undergoing TOL. Clinical factors associated with decreased odds of TOL included nulliparity, obesity, and hypertensive disorders of pregnancy. Results did not substantively change when stratified by parity or second twin presentation, nor did findings differ in the subgroup who delivered at 32 weeks of gestation or greater.

Conclusion In this large population of women with twins who were eligible for a TOL, a minority of individuals attempted a vaginal delivery. Demographic and clinical factors such as older maternal age, Asian or Hispanic racial or ethnic identification, nulliparity, and obesity are associated with decreased odds of undergoing TOL.

Key Points
Innovating Evaluation and Treatment of Intrapartum Fevers: Where Do We Go from Here?
Authors: Wilkie Gianna L. , James Kaitlyn , Ona Samsiya , Easter Sarah Rae , Chou Joseph , Roberts Drucilla , Sahin Zehra Ordulu , Tuomala Ruth , Diouf Khady , Riley Laura , Prabhu Malavika
Published: April 2021

As intrapartum fevers are not always infectious in origin, determining whether antibiotics are indicated is challenging. We previously sought to create a point-of-care calculator using clinical data available at the time of an intrapartum fever to identify the subset of women who require antibiotic treatment to avoid maternal and neonatal morbidity. Despite the use of a comprehensive dataset from our institutions, we were unable to propose a valid and highly predictive model. In this commentary, we discuss why our model failed, as well as future research directions to identify and treat true intraamniotic infection. Developing a risk-stratification model is paramount to minimizing maternal and neonatal exposure to unnecessary antibiotics while allowing for early identification of women and babies at risk for infectious morbidity.

Key Points
Research on hydrodynamics of high velocity regions in a water-jet pump based on experimental and numerical calculations at different cavitation conditions
Authors: Long Yun , An Ce , Zhu Rongsheng , Chen Jianping
Published: April 2021

Cavitation is a common phenomenon and continues to be a primary concern in the fields of hydraulic machinery. To provide a reference for cavitation flow and cavitation performance improvement, this paper presents the experimental study on the cavitation flow structures of the water-jet pump. High-speed photography technology is used to capture the cavitation flow structures and reveal the physical process of cavitation evolution in the water-jet pump. Cavitation–vortex interaction was further explored by numerical simulations. By extracting 24 m/s water velocity isosurface and analyzing the water superficial velocity on the isosurface, the flow characteristics in the high-velocity fluid area under different cavitation stages are revealed. Then, by analyzing the vortex structure on the isosurface, the main factors affecting the development of the vortex structure on the high-velocity fluid area are summarized.
Temperature measurements in cerium shocked from 8.4 to 23.5 GPa
Authors: Hixson R. S. , La Lone B. M. , Staska M. D. , Stevens G. D. , Turley W. D. , Veeser L. R.
Published: April 2021

Shock temperature, stress, and dynamic emissivity for cerium shocked from 8.4 to 23.5 GPa were measured. In addition, the isentropic shock release temperature as a function of release stress was determined at a window interface. Cerium samples were shock compressed by plate impact on a single-stage gun. We made time-resolved measurements of thermal radiance, reflectance, and interface velocity of samples glued to lithium fluoride windows. Reflectance was measured with an integrating sphere and velocity with photonic Doppler velocimetry. From these measurements, we determined the temperature, emissivity, and stress at the interface. For shock stresses below 10.24 GPa, the samples were shocked from the γ phase into the α phase; at higher stresses, the cerium presumably melted or entered a mixed phase upon shock. The shock Hugoniot temperature as a function of stress follows a straight line over the entire range of our measurements, disagreeing with previously published predictions that the Hugoniot would follow the melt boundary from 10.24 up to around 16–18 GPa. Between 11.9 and 16.8 GPa, all the release isentropes converged (within experimental uncertainty) to a point around 4 GPa and 900 K, near the published melt curve. For experiments shocked above ∼16 GPa, the release isentropes behave differently. This suggests that within this 12–16 GPa range, there is a phase transition taking place, probably melt, and that it is occurring somewhere along the shock and release path. We could not identify a single-valued phase boundary from our experiments. Potential reasons for this are discussed.
Effect of vortex and entropy sources in sound generation for compressible cavity flow
Authors: Arya Nitish , De Ashoke
Published: April 2021

The present study reports the effect of different source terms on the near and far-field acoustic characteristics of compressible flow over a rectangular cavity using hybrid computational aeroacoustics methodology. We use a low dispersive and dissipative compressible fluid flow solver in conjunction with an acoustic perturbation equation solver based on the spectral/hp element method. The hybrid approach involves calculating the base fields and the acoustic sources from a fluid simulation in the first step. In the next step, the acoustic solver utilizes the variables to predict the acoustic propagation due to the given sources. The validation of the methodology against benchmark cases provides quite accurate results while compared against the existing literature. The study is then extended to assess the importance of the entropy source term for the flow over a rectangular cavity. The predictions of hybrid simulations with vortex and entropy source terms reproduce the perturbation pressure values very close to the existing direct numerical simulation results. Moreover, the results suggest that the use of just the vortex source terms over-predicts the perturbation pressure near the source region. Finally, we have carried out detailed simulations with all the source terms to investigate the noise sources for compressible flow over the cavity for different Mach number ranges (M=0.4,0.5,0.6,0.7,1.5). The obtained acoustic spectra and the sound directivity are in close agreement with the reference experiment.
How real are liquid groundstates? Ultra-fast crystal growth and the susceptibility of energy minima in liquids
Authors: Sun Gang , Harrowell Peter
Published: April 2021

We calculate the degree to which the final structure of the local groundstate in a liquid is a function of the strength of a perturbing potential applied during energy minimization. This structural susceptibility is shown to correlate well with the observed tendency of the liquid adjacent to a crystal interface to exhibit a crystalline groundstate, a feature that has been strongly linked to the observation of ultra-fast crystal growth in pure metals and ionic melts. It is shown that the structural susceptibility increases dramatically as the interaction potential between atoms is softened.
Bandgap engineering of layered mono-chalcogenides via pressure
Authors: Xiong Heqi , Li Ruiping , Cheng Yingchun , Xing Guichuan , Huang Wei
Published: April 2021

The layered mono-chalcogenide semiconductors MX (M = In, Ga; X = Se, S) have attracted considerable attention due to their high carrier mobility and tunable bandgap, which gives them potential applications in the development of new optoelectronic devices. We have systematically studied the effect of pressure on the band structure evolution and electronic properties of monolayer indium selenide (InSe) using first-principles calculations. The bandgap of monolayer InSe first increases and then decreases with increasing pressure. In addition, monolayer InSe undergoes an indirect to direct bandgap transition at 6.8 GPa. Increasing the pressure further to 10.4 GPa leads to recovery of the indirect bandgap. This indirect-direct bandgap transition is absent in other monolayer MX compounds. The continuous tuning of band structure of monolayer InSe gives them potential applications for pressure-response optoelectronic devices.
β-arrestin–dependent PI(4,5)P2synthesis boosts GPCR endocytosis
Authors: Jung Seung-Ryoung , Jiang Yifei , Seo Jong Bae , Chiu Daniel T. , Hille Bertil , Koh Duk-Su
Published: April 2021

Significance

Stimulation of protease-activated receptor 2 (PAR2) at the plasma membrane triggers a branching cascade of interrelated events in several cellular compartments. In one branch, the G protein Gqcouples to phospholipase C, and the membrane phosphoinositide lipids PI(4,5)P2and PI(4)P are depleted. In another branch, the receptor becomes desensitized by becoming phosphorylated, bound to β-arrestin, and internalized by clathrin-coated pits. This second branch needs PI(4,5)P2at several steps. We found that β-arrestin in complex with receptors stably binds to clathrin-coated pits and increases transient binding of the PI(4,5)P2synthetic enzyme PIP5K-Iγ. Then, this complex in clathrin-coated pits boosts the rate of PI(4,5)P2synthesis from Golgi and plasma membrane PI(4)P, so that PI(4,5)P2becomes elevated. The new PI(4,5)P2allows receptor internalization.
A unique AtSar1D-AtRabD2a nexus modulates autophagosome biogenesis in
Arabidopsis thaliana
Authors: Zeng Yonglun , Li Baiying , Ji Changyang , Feng Lei , Niu Fangfang , Deng Cesi , Chen Shuai , Lin Youshun , Cheung Kenneth C. P. , Shen Jinbo , Wong Kam-Bo , Jiang Liwen
Published: April 2021

Significance

In addition to mediating protein traffic from the endoplasmic reticulum to the Golgi apparatus, coat protein complex II (COPII) vesicles also act constructively as a membrane source for autophagosome biogenesis during autophagy to maintain cellular homeostasis in eukaryotes. Nonetheless, the participation and underlying mechanism of the COPII machinery in the autophagic pathway and autophagosome biogenesis remain elusive in plants. Here, we identified and characterized a distinct population of COPII vesicles consisting of a unique AtSar1d-AtRabD2a nexus, which is required for autophagosome biogenesis through mechanistic connection with autophagy-related (ATG) machinery in
Arabidopsis
. Our results broadened the understandings of the mechanism underlying COPII function in eukaryotic autophagy and manifested the functional diversity of specific COPII paralogs in plant autophagy and autophagosome biogenesis.