bluuebunny/crossref_metadata_2025 huggingface dataset:
A Visible‐Blind Photodetector and Artificial Optoelectronic Synapse Using Liquid‐Metal Exfoliated ZnO Nanosheets
Authors: Krishnamurthi Vaishnavi , Ahmed Taimur , Mohiuddin Md , Zavabeti Ali , Pillai Naresh , McConville Christopher F. , Mahmood Nasir , Walia Sumeet
Published: May 2021

Atomically thin 2D materials are highly sought for high‐performance electronic and optoelectronic devices. Despite being a widely recognized functional material for a plethora of applications, ultra‐thin nanosheets of zinc oxide (ZnO) at a millimeter‐scale for developing high‐performance electronic/optoelectronic devices have not been reported. This has prevented the exploration of electronic and optical properties of ZnO when it is only a few atoms thick. Here, a liquid metal exfoliation technique is used that takes advantage of the van der Waals forces between the interfacial oxide and the chosen substrate to obtain ZnO nanosheets with lateral dimensions in the millimeter scale and thickness down to 5 nm. Their suitability for applications is shown by demonstrating a visible‐blind photodetector with high figures of merit as compared to other ZnO morphologies. At extremely low operating bias of 50 mV and low optical intensity of 0.5 mW cm−2, the ZnO photodetector demonstrates an external quantum efficiency (EQE), responsivity (R), and detectivity (D*) of 4.3 × 103%, 12.64 A W−1, and 5.81 × 1015 Jones at a wavelength of 365 nm. The trap‐mediated photoresponse in the ZnO nanosheets is further utilized to demonstrate optoelectronic synapses. Versatile synaptic functions of the nervous systems are optically emulated with the ultra‐thin ZnO nanosheets.
High‐Performance Nondoped Organic Light‐Emitting Diode Based on a Thermally Activated Delayed Fluorescence Emitter with 1D Intermolecular Hydrogen Bonding Interactions
Authors: Shi Yi‐Zhong , Wang Kai , Fan Xiao‐Chun , Chen Jia‐Xiong , Ou Xue‐Mei , Yu Jia , Jie Jian‐Sheng , Lee Chun‐Sing , Zhang Xiao‐Hong
Published: May 2021

Nondoped organic light‐emitting diodes (OLEDs) have drawn enormous attention for their merits of process simplicity, reduced fabrication cost, and phase stability. Herein, a novel approach of utilizing intermolecular hydrogen bonding for enhancing performance of nondoped OLEDs with a new thermally activated delayed fluorescence (TADF) emitter 10‐(4‐(2,6‐di(pyrimidin‐5‐yl)pyridin‐4‐yl)phenyl)‐10H‐phenoxazine (DPmP‐PXZ) is investigated. Endowing with suitable intermolecular hydrogen bonds linking the ends of neighboring DPmP‐PXZ molecules, the molecules tend to form extended 1D molecular chain in solid. This 1D structure effectively keeps the electron‐rich PXZ cores in neighboring molecules apart from each other such that triplet‐related exciton quenching can be well suppressed. In addition, it also improves the balance of carrier mobilities and the optical out‐coupling from the emitting layer. With these merits, OLEDs using DPmP‐PXZ as a dopant emitter, from 10 to 100 wt%, can maintain high external quantum efficiencies (EQEs) of over 20%. More importantly, its nondoped OLED shows a yellow emission and an excellent maximum EQE of 21.8% with little efficiency roll‐off which is even comparable with state‐of‐the‐art yellow OLEDs. These results provide new insight on the role of hydrogen bonding in molecular packing and its subsequent influences on the performance of OLEDs.
Manganese‐Based Materials for Rechargeable Batteries beyond Lithium‐Ion
Authors: Li Huangxu , Zhang Wei , Sun Kena , Guo Jun , Yuan Kuo , Fu Jiaju , Zhang Tao , Zhang Xiankun , Long Huiwu , Zhang Zhian , Lai Yanqing , Sun Hongyan
Published: May 2021

The newly emerging rechargeable batteries beyond lithium‐ion, including aqueous and nonaqueous Na‐/K‐/Zn‐/Mg‐/Ca‐/Al‐ion batteries, are rapidly developing toward large‐scale energy storage application. The properties of electrode materials are determinant for electrochemical performance of the batteries. By virtue of the prominent features of low cost, non‐toxicity, high voltage, and rich valence states, Mn‐based electrode materials have attracted increasing attention. The big family of Mn‐based materials with rich composition and polymorphs, provides great possibilities for exploring and designing advanced electrode materials for these emerging rechargeable batteries. In this review, three main categories of Mn‐based materials, including oxides, Prussian blue analogous, and polyanion type materials, are systematically introduced to offer a comprehensive overview about the development and applications of Mn‐based materials in various emerging rechargeable battery systems. Their crystal structure, electrochemical performance, and reaction mechanism are highlighted. In addition, the key issues encountered by many Mn‐based materials, including Jahn–Teller distortion, Mn dissolution, crystal water, impact of electrolyte, etc., are also discussed. Finally, challenges and perspectives on the future development of manganese‐based materials are provided as well. It is believed this review is timely and important to further promote exploration and applications of Mn‐based materials in both aqueous and nonaqueous rechargeable battery systems beyond lithium‐ion.
Root anatomy helps to reconcile observed root trait syndromes in tropical tree species
Authors: Valverde‐Barrantes Oscar J. , Authier Louise , Schimann Heidy , Baraloto Christopher
Published: May 2021

Premise

Studying the organization of functional traits in plant leaves and stems has revealed notable patterns linking function and form; however, evidence of similarly robust organization in root tissues remains controversial. We posit that anatomical traits in roots can provide insight on the overall organization of the root system. We hypothesized that size variation in the tissue outside the stele is related in a nonlinear fashion with functional traits associated with direct resource uptake, including a negative relationship with root architectural traits, and that similar relationships detected in tropical areas also hold true in other biomes.

Methods

We addressed our hypotheses using empirical data from 24 tropical tree species in French Guiana, including anatomical measurements in first order roots and functional trait description for the entire fine root system. In addition, we compiled a global meta‐analysis of root traits for 500+ forest species across tropical, subtropical, and temperate forests.

Results

Our results supported the expected nonlinear relationships between cortical size and morphological traits and a negative linear trend with architectural traits. We confirmed a global negative relationship among specific root length (SRL), diameter, and tissue density, suggesting similar anatomical constraints in root systems across woody plants. However, the importance of factors varies across biomes, possibly related to the unequal phylogenetic representation across latitudes.

Conclusions

Our findings imply that the rhizocentric hypothesis can be a valuable approach to understand fine root trait syndromes and the evolution of absorptive roots in vascular plants.
Modulating the Efficacy of Carbonic Anhydrase Inhibitors through Fluorine Substitution
Authors: Berrino Emanuela , Michelet Bastien , Martin‐Mingot Agnès , Carta Fabrizio , Supuran Claudiu T. , Thibaudeau Sébastien
Published: May 2021

The insertion of fluorine atoms and/or fluoroalkyl groups can lead to many beneficial effects in biologically active molecules, such as enhanced metabolic stability, bioavailability, lipophilicity, and membrane permeability, as well as a strengthening of protein–ligand binding interactions. However, this “magic effect” of fluorine atom(s) insertion can often be meaningless. Taking advantage of the wide range of data coming from the quest for carbonic anhydrase (CA) fluorinated inhibitors, this Minireview attempts to give “general guidelines” on how to wisely insert fluorine atom(s) within an inhibitor moiety to precisely enhance or disrupt ligand–protein interactions, depending on the target location of the fluorine substitution in the ligand. Multiple approaches such as ITC, kinetic and inhibition studies, X‐ray crystallography, and NMR spectroscopy are useful in dissecting single binding contributions to the overall observed effect. The exploitation of innovative directions made in the field of protein and ligand‐based fluorine NMR screening is also discussed to avoid misconduct and finely tune the exploitation of selective fluorine atom insertion in the future.
Constructing the single‐site of pyridine‐based organic compounds for acetylene hydrochlorination: From theory to experiment
Authors: Zhao Chaoyue , Yi Zenghuimin , Xue Yinan , Guan Qingxin , Li Wei
Published: May 2021

Acetylene hydrochlorination reaction requires toxic mercuric chloride catalyst, which caused serious environmental pollution by mercury in recent years. Though Au‐based catalysts show the best catalytic activity and high rates of acetylene conversion, much work still needs to be done to reduce the cost before their large‐scale applications. Here, a pure pyridine‐based organic polymer was successfully designed and assembled, which contains only one nitrogen species and exhibits a high activity with acetylene conversion reaching 88% and the selectivity of vinyl chloride above 99%. Both experimental and density functional theory (DFT) studies directly demonstrate that the pyridinic N atom in pyridine ring is the active site of the catalyst and the insertion of acetylene to HCl might be the rate‐determining step. Different from traditional carbonization and aminating treatment at high temperature, the pyridine‐based polymers were obtained by polymerization in liquid phase. Besides, the activity of the catalyst may be determined by these combined effects of surface area, pores structure, and the amount of pyridinic N.
Unveiling the dermatological potential of marine fungal species components: Antioxidant and inhibitory capacities over tyrosinase
Authors: Agrawal Shivankar , Barrow Colin J. , Adholeya Alok , Deshmukh Sunil Kumar
Published: May 2021

Marine fungi are a rich source of biologically active molecules, but a poorly explored bioresource for cosmeceutical products. This study evaluates the phytochemistry, antioxidant, and antityrosinase effects of the organic extracts of marine fungi isolated from various marine environments in India. Out of 35 screened fungal strains, methanol extracts of strains P2, Talaromyces stipitatus, and D4, Aspergillus terreus exhibited antityrosinase activity of 45% and 43%, respectively, at the lowest concentration of 0.5 mg/mL. The highest free radicals scavenging activity of 94% and 97% was observed at 500 mg/mL, respectively, of the same fungal extracts. The total phenolic content ranged from 8.20 to 20.30 mg/g of the dry weight of extract, expressed as gallic acid equivalent. GC–MS analysis of T. stipitatus and A. terreus extract identified seven and 10 major compounds, respectively. Some of the major compounds included azetidine, (3E)‐3‐[(3,5‐dimethoxybenzoyl)hydrazono]‐N‐isobutyl butanamide, aziridine, and 3‐methylcyclopentanone, 1,1‐dimethylcyclohexane, cyclopentane carboxylic acid, N‐allyl‐4,5,6,7‐tetrahydro‐2‐benzothiophene‐1‐carboxamide, cyclo(l‐Pro‐l‐Val), and 3‐phenylpropionitrile. In conclusion, this study showed abundant fungal resources in Indian marine environments. A correlation between total phenolic contents of the extracts confirmed that phenolic compounds play an important role in antioxidant as well as antityrosinase activity of the marine fungal extracts and can be viewed as new potential antityrosinase and antioxidant resources.
Longitudinal observations call into question the scientific consensus that humans are unaffected by lunar cycles
Authors: Wehr Thomas A. , Helfrich‐Förster Charlotte
Published: May 2021

Recent longitudinal observations show that human menstrual cycles, sleep‐wake cycles and manic‐depressive cycles can become synchronized with lunar cycles, but do so in uniquely complex and heterogeneous ways that are unlikely to have been detected by past studies. Past studies’ negative results have given rise to a scientific consensus that human biology and behavior are unaffected by lunar cycles. The recent observations show that synchrony can be temporary, and can occur with more than one type of lunar cycle, more than one phase of a lunar cycle and more than one resonant frequency of a lunar cycle. Given the variability of human responses to lunar cycles, aggregate analyses used in almost all previous studies would likely have cancelled out individuals’ responses and led to false negative results. In light of these observations, the question of lunar influence should be investigated further, with longitudinal observations and case‐by‐case analyses of individuals’ data.
Chitosan and silver nanoparticles are attractive auxin carriers: A comparative study on the adventitious rooting of microcuttings in apple rootstocks
Authors: Korpayev Serdar , Karakeçili Ayşe , Dumanoğlu Hatice , Ibrahim Ahmed Osman Salwa
Published: May 2021

Nanocarriers for encapsulation and sustained release of agrochemicals such as auxins have emerged as an attractive strategy to provide enhanced bioavailability and efficacy for improved crop yields and nutrition quality. Here, a comparative study was conducted on the effectiveness of chitosan‐as a biopolymeric nanocarrier‐ and silver‐as a metallic nanocarrier‐ on in vitro adventitious rooting potential of microcuttings in apple rootstocks, for the first time. Auxins indole‐3‐acetic acid (IAA) and indole‐3‐butyric acid (IBA) loaded silver (nAg) or chitosan nanoparticles (nChi) were synthesized. Scanning electron microscopy and transmission electron microscopy studies showed the spherical shape of the nanoparticles. The average particle size of IAA‐nChi was 167.5 ± 0.1 nm while that of IBA‐nChi was 123.2 ± 2.6 nm. The hydrodynamic diameter of the nAg‐IAA and nAg‐IBA particles were measured as 93.66 ± 5 nm and 71.41 ± 3 nm, respectively. Fourier transform infrared spectroscopy analyses confirmed the encapsulation of IAA or IBA in the chitosan nanoparticles. Meanwhile, the characteristic peaks of IAA or IBA were detected on silver nanoparticles. In‐vitro adventitious rooting of microcuttings of Malling Merton 106 (MM 106) was significantly higher both in chitosan and silver nanoparticles loaded with IAA or IBA (91.7%–62.5%) compared to free IAA or IBA applications (50.0%–33.3%), except for 2.0 mg L–1 IBA (66.7%). However, the application of 2 mg L–1 IBA and IBA‐nChi at all concentrations caused an undesirable large callus development.
Drawing up a collaborative contract: Amino acid cross‐feeding between interspecies bacterial pairs
Authors: Kelly Erin E. , Fischer Alexandria M. , Collins Cynthia H.
Published: May 2021

Synthetic microbial communities have the potential to enable new platforms for bioproduction of biofuels and biopharmaceuticals. However, using engineered communities is often assumed to be difficult because of anticipated challenges in establishing and controlling community composition. Cross‐feeding between microbial auxotrophs has the potential to facilitate coculture growth and stability through a mutualistic ecological interaction. We assessed cross‐feeding between 13 Escherichia coli amino acid auxotrophs paired with a leucine auxotroph of Bacillus megaterium. We developed a minimal medium capable of supporting the growth of both bacteria and used the media to study coculture growth of the 13 interspecies pairs of auxotrophs in batch and continuous culture, as well as on semi‐solid media. In batch culture, 8 of 13 pairs of auxotrophs were observed to grow in coculture. We developed a new metric to quantify the impact of cross‐feeding on coculture growth. Six pairs also showed long‐term stability in continuous culture, where coculture growth at different dilution rates highlighted differences in cross‐feeding amongst the pairs. Finally, we found that cross‐feeding‐dependent growth on semi‐solid media is highly stringent and enables identification of the most efficient pairs. These results demonstrate that cross‐feeding is a viable approach for controlling community composition within diverse synthetic communities.
Very‐Long‐Chain Wax Constituents from Primula veris and P. acaulis: Does the Paradigm of Non‐Branched vs. Branched Chain Dominance Universally Hold in all Plant Taxa?
Authors: Živković Stošić Milena Z. , Radulović Niko S. , Genčić Marija S. , Ranđelović Vladimir N.
Published: May 2021

Herein n‐, iso‐ and anteiso‐series of very‐long‐chained (VLC) alkanes (C21–C35), fatty acid benzyl esters (FABEs; C20–C32), and 2‐alkanones (C23–C35) were identified in the wax of Primula veris L. and P. acaulis (L.) L. (Primulaceae). For the very first time in a sample of natural origin, the presence of iso‐ and anteiso‐VLC FABEs and 2‐alkanones was unequivocally confirmed by synthetic work, derivatization, and NMR. It should be noted that the studied species produced unusually high amounts of branched wax constituents (e. g., >50 % of 2‐alkanones were branched isomers). The domination of iso‐isomers, probably biosynthesized from leucine‐derived starters, is a unique feature in the Plant Kingdom. The plant organ distribution of these VLC compounds in P. acaulis samples (different habitats and phenological phases) pointed to their possible ecological value. This was supported by a eutectic behavior of binary blends of FABEs and alkanes, as well as by high UV‐C absorption by FABEs.
Short term outcomes of Impella circulatory support for high‐risk percutaneous coronary intervention a systematic review and meta‐analysis
Authors: Elia Edoardo , Iannaccone Mario , D'Ascenzo Fabrizio , Gallone Guglielmo , Colombo Francesco , Albani Stefano , Attisani Matteo , Rinaldi Mauro , Boccuzzi Giacomo , Conrotto Federico , Noussan Patrizia , De Ferrari Gaetano Maria
Published: May 2021

Objective

Aim of this study is to evaluate short term safety and efficacy of Impella in high risk percutaneous coronary intervention (HR‐PCI) population.

Background

While several studies demonstrated the clinical significance of Impella in HR‐PCI, few data exist about its impact on short term outcome.

Methods

All studies reporting short term outcomes of PCI with any Impella device were included. The primary endpoint was either in‐hospital or 30‐day mortality, while vascular complications, post‐procedural stroke, post‐procedural dialysis and bleeding complications were assessed as secondary outcomes.

Results

Nine studies with 7448 patients were included. Median age was 69.5 years old (67–73), with a mean ejection fraction of 29.7% (20%–39%) and a Syntax score of 30.2 (25. 5–33, interquartile [IQR]). Impella 2.5 was the most commonly used axial flow pump used to support these PCIs (88.7%). In‐hospital death was observed in 5.09% of patients (95% confidence interval [CI] 3.69–6.49, I2 = 78%), while vascular complications in 2.53% of patients (1.07–4.00, I2 = 89%) and post‐procedural stroke in 2.77% of patients (0.50–6.05, I2 = 98%). Major bleeding occurred in 5.98% of patients (3.66–8.31, I2 = 90%) and post‐procedural dialysis in 4.44% of patients (1.50–7.37, I2 = 93% all CI 93%).

Conclusion

Use of Impella in high risk PCI appears to have an acceptable rate of complication, especially regarding vascular complications and major bleedings.
Fracture of the tibia after a fibula graft for mandibular reconstruction: A rare complication, report of a case
Authors: Goey Ru‐shan , van Drunen Bert , van der Linden Enrike , van Merkesteyn J.P. Richard
Published: May 2021

A tibia fracture after a fibula harvest is a rare and serious condition; however, when treated adequately, it has a good outcome. The possibility of a fracture should be kept in mind and other pathology and/or metastasis should be ruled out.
Clozapine‐induced gastroesophageal rumination in 22q11.2 Deletion Syndrome. A case report on gastroesophageal side effects management without renouncing clozapine's effectiveness
Authors: Accinni Tommaso , Frascarelli Marianna , Ghezzi Francesco , Panzera Alessia , Buzzanca Antonino , Fanella Martina , Di Bonaventura Carlo , Carlone Luca , Girardi Nicoletta , Pasquini Massimo , Di Fabio Fabio
Published: May 2021

Despite entailing more severe and uncommon side effects in 22q11.2DS compared to idiopathic schizophrenia, we strongly believe that clozapine should continue to be considered the gold standard for all treatment‐resistant schizophrenia, even in 22qDS.
Mixed medullary—papillary thyroid carcinoma with mixed lymph node metastases: A case report
Authors: Guerreiro Vanessa , Costa Cláudia , Oliveira Joana , Santos Ana Paula , Farinha Mónica , Jácome Manuel , Freitas Paula , Carvalho Davide , Torres Isabel
Published: May 2021

Mixed medullary‐follicular‐derived carcinoma is a very rare event. It is extremely important to make the correct diagnosis, due to prognostic and treatment implications. A genetic study of these patients is advisable to exclude the presence of MEN 2.
Low back pain in beta thalassemia major revealing sacral extramedullay hematopoeisis: A case report
Authors: Ahmad Rita W. , Okar Lina A. , Elhiday Abdelhaleem , Almasri Hussam , Ata Fateen , Ahmed Mounir Elsayed , Barah Ali , Abdelrazek Mohamed , Gamil Amna , Sharaf Eldean Mouhammad Z. , Yassin Mohamed A.
Published: May 2021

Extramedullary hematopoiesis (EMH) is a well‐known complication of beta thalassemia major and frequently occurs in typical sites such as liver or spleen. However, when presenting in unusual sites as sacrum, other diagnosis should be excluded by histopathology prior to deciding on treatment plan.
Ectopic pregnancy in noncommunicating horn of unicornuate uterus: 3D‐ultrasound and primary laparoscopic management
Authors: Dhanawat Juhi , Pape Julian , Stuhlmann‐Laeisz Christiane , Maass Nicolai , Freytag Damaris , Gitas Georgios , Alkatout Ibrahim
Published: May 2021

Unicornuate uterus with pregnancy in the noncommunicating rudimentary horn is extremely rare. Diagnosis requires awareness, high suspicion index, 3D ultrasound, and MRI. If missed, it can be catastrophic. Treatment varies across literature. We present a case where detection was done by 3D ultrasound and primary laparoscopic surgery done for treatment.
The Promiscuous Activity of the Radical SAM Enzyme NosL toward Two Unnatural Substrates
Authors: Yin Yue , Ji Xinjian , Zhang Qi
Published: May 2021

Main observation and conclusion

The radical S‐adenosylmethionine (SAM) enzyme NosL catalyzes the conversion of L‐tryptophan (L‐Trp, 1) to 3‐methyl‐2‐indolic acid (MIA, 2), a key intermediate in the biosynthesis of the peptide antibiotic nosiheptide. Previous study showed that this remarkable recombination reaction starts from the cleavage of the Cα—COO– bond to result in a •CO2− radical migration. In contrast to the radical SAM tyrosine lyases, NosL appears unable to cleave the Cα—Cβ bond, which is intrinsically more favorable to be cleaved than the Cα—COO– bond. In this study, we investigate the NosL activity with tryptamine (11) and tryptophol (12), two L‐Trp analogues lacking a carboxylate moiety. We showed that NosL cleaves the C1—C2 bond of these two substrates to produce 3‐methylindole (7), suggesting that the enzyme can still catalyze a β‐scission when the carboxyl group of Trp is absent. We also showed the enzyme exhibits a promiscuous activity, initiating the reaction by abstracting hydrogen atoms from two different sites to produce two sets of products.
Epigenetic age acceleration, fatigue, and inflammation in patients undergoing radiation therapy for head and neck cancer: A longitudinal study
Authors: Xiao Canhua , Beitler Jonathan J. , Peng Gang , Levine Morgan E. , Conneely Karen N. , Zhao Hongyu , Felger Jennifer C. , Wommack Evanthia C. , Chico Cynthia E. , Jeon Sangchoon , Higgins Kristin A. , Shin Dong M. , Saba Nabil F. , Burtness Barbara A. , Bruner Deborah W. , Miller Andrew H.
Published: May 2021

Background

The authors measured epigenetic age acceleration (EAA) during and after cancer treatment and its association with inflammation and fatigue, which is a debilitating symptom in patients with cancer.

Methods

Patients who had head and neck cancer without distant metastases were assessed before, immediately after, and at 6 months and 12 months postradiotherapy. Blood DNA methylation was assessed using a proprietary bead chip (the Illumina MethylationEPIC BeadChip). EAA was calculated using the Levine epigenetic clock (DNAmPhenoAge), adjusted for chronological age. Fatigue was assessed using the Multidimensional Fatigue Inventory‐20. Inflammatory markers were measured using standard techniques.

Results

Most patients (N = 133) were men, White, had advanced disease, and received concurrent chemoradiation. EAA changes over time were significant, with the largest increase (4.9 years) observed immediately after radiotherapy (P < .001). Increased EAA was associated with elevated fatigue (P = .003) over time, and patients who had severe fatigue experienced 3.1 years higher EAA than those who had low fatigue (P < .001), which was more prominent (5.6 years; P = .018) for patients who had human papillomavirus‐unrelated disease at 12 months posttreatment. EAA was also positively associated with inflammatory markers, including C‐reactive protein (CRP) and interleukin‐6 (IL‐6), over time (P < .001), and patients who had high CRP and IL‐6 levels exhibited increases of 4.6 and 5.9 years, respectively, in EAA compared with those who had low CRP and IL‐6 levels (P < .001). CRP and IL‐6 mediated the association between EAA and fatigue (CRP: 95% CI, 0.060‐0.279; IL‐6: 95% CI, 0.024‐0.220).

Conclusions

Patients with head and neck cancer experienced increased EAA, especially immediately after treatment completion. EAA was associated with greater fatigue and inflammation, including 1 year after treatment. Inflammation may be a target to reduce the impact of age acceleration on poor functional outcomes.
Inclusion of Infants and Neonates in Pediatric Orphan Product Approvals
Authors: Park Kyunghun , Virparia Riddhi , Green Dionna J. , Epps Carla , Wharton Gerold T. , McCune Susan K. , Burckart Gilbert J.
Published: May 2021

The Orphan Drug Act (ODA) of 1983 was enacted to provide financial incentives to drug sponsors to develop therapies for rare diseases. Although this act increased the number of orphan products approved, there are still a limited number of products available for the pediatric population because orphan drug products are exempt from the Pediatric Research Equity Act. The objectives of this study were (i) to evaluate the pediatric orphan drug studies submitted to the US Food and Drug Administration (FDA) in the period of 2007–2018 and (ii) to examine whether orphan drug products were fully labeled with a pediatric indication in infants and neonates. Out of the 468 indications evaluated, 171 (37%) were FDA‐labeled for use in the pediatric population. Labeling for the 12 to < 18 years age group was most common (98%). Fifty‐two percent of FDA‐labeled pediatric indications included the newborn to < 2 years of age group. In this newborn to < 2 years age group, the indication was labeled without pivotal clinical trials in 43% of the programs. Of the 60 new indications not labeled down to birth, 50% were found to have an age of onset and diagnosis that occurs earlier than the age approved for use of the product for that indication. In summary, although the ODA has been successful in improving pediatric access to medications for rare diseases, our analysis identified the incomplete labeling for pediatric patients under 2 years of age. Strategies to include the birth to < 2 years old group of pediatric patients in orphan drug development programs should be explored.
Simulation modeling accounts for uncertainty while quantifying ecological effects of development alternatives
Authors: Fullman Timothy J. , Sullender Benjamin K. , Cameron Matthew D. , Joly Kyle
Published: May 2021

Wildlife management often involves trade‐offs between protecting species and allowing human activities and development. Ideally, these decisions are guided by scientific studies that quantify the impacts of proposed actions on the environment. However, critical information to assess impacts of proposed activities may be lacking, such as certainty in where actions will take place, which may hinder a robust impact assessment. To address this issue, we present the Development Impacts Analysis (DIA), which employs Monte Carlo simulation modeling to quantify the environmental consequences of proposed development scenarios, while accounting for uncertainty in the exact location of future development. We applied the DIA to five proposed oil leasing management scenarios under a revised management plan for the National Petroleum Reserve—Alaska. For each management scenario with differing levels of proposed development (“alternatives”), oil production pads and roads were randomly simulated in proportion to estimated undiscovered oil and following alternative‐specific restrictions. We assessed habitat displacement for two caribou (Rangifer tarandus) herds, eight shorebird species, and black brant (Branta bernicla) based on reported responses to development, repeating the process 100 times for each alternative. Some habitat loss was reported for each proposed alternative, but the amount of impact varied by alternative and species. One caribou herd and most bird species indicated greatest effects in the alternative with the least restrictions on development and lesser impacts under more protective alternatives. Our results emphasized the importance of considering spatial variation in development effects and species‐specific differences when evaluating management proposals. The DIA quantified potential impacts on a suite of species under proposed management alternatives, while accounting for uncertainty in where development will occur and providing confidence intervals on estimated impacts. This illustrates that uncertainty need not preclude management decisions about establishment of broad land use restrictions prior to submission of project‐level proposals but can instead be explicitly incorporated into decision making. While no single management approach will likely benefit all species, use of tools such as the DIA allows managers to quantify trade‐offs among species and pursue approaches that balance the needs of various taxa and other management objectives.
Approaching Superior Potassium Storage of Carbonaceous Anode Through a Combined Strategy of Carbon Hybridization and Sulfur Doping
Authors: Yao Qianqian , Gan Yanmei , Ma Zuju , Qian Xiangying , Cai Suzhi , Zhao Yi , Guan Lunhui , Huang Wei
Published: May 2021

Carbonaceous materials are promising anode candidates for potassium‐ion batteries (PIBs) given its high conductivity, stable property, and abundant resource, while its practical implementation is still hampered by its limited capacity and inferior rate behavior. Herein, we report a superior carbonaceous anode through a combined strategy of carbon hybridization and heteroatom doping. In this composite, hollow carbon spindles (HCS) were anchored on the surface of graphene (G) followed with sulfur doping treatment, aiming to integrate the high conductivity of graphene, the good structure stability of HCS, and the S doping‐induced ample active sites. As a PIB anode, the S‐G@HCS composite can display high capacity (301 mA h g−1 at 0.1 A g−1 after 500 cycles) and long‐term cyclability up to 1800 cycles at 2 A g−1. Impressively, it can deliver an outstanding rate capacity of 215 mA h g−1 at 10 A g−1, which is superior to most carbon anodes as‐reported so far for PIBs. Experimental and theoretical analysis manifests that the construction of graphene/amorphous carbon interface as well as S doping enables the regulation of electronic structure and ion adsorption/transportation properties of carbonaceous material, thus accounting for the high capacity and superior rate capability of S‐G@HCS composite.
Work Function and Electron Affinity of Semiconductors: Doping Effect and Complication due to Fermi Level Pinning
Authors: Shao Guosheng
Published: May 2021

Semiconductors are a major category of functional materials essential to various applications to sustain the modern society. Most applied materials or devices utilizing semiconductors are enabled by interfaces or junctions, such as solar cells, electronic/photonic devices, environmental sensors, and redox hetero‐catalysts. Herein, the author provides a critical commentary on photoemission measurement of the work function and, more importantly, the electron affinity of semiconductors essential for energy band diagram of heterojunctions. Particular effort is made towards addressing complications associated with Fermi level pinning due to surficial states of doped semiconductors.
Luminescent Imidazolium Salts as Bright Multi‐Faceted Tools for Biology
Authors: Berthiot Romain , del Giudice Nicolas , Douce Laurent
Published: May 2021

Light and cognate phenomena, e. g., luminescence are powerful tools endowed with great sensitivity to explore the infinitely small. Molecular salts, especially those based on imidazolium units, are granted with original properties and structural versatility. Associated with fluorophores, they constitute highly bioavailable platforms. Their interactions with negatively charged species and biological membranes as well as their controllable cytotoxicity imparted their applications as anion receptors, but also a promising potential as antibacterial and anticancer agents whose mechanism of action can be observed using luminescence, opening the possibility of theranostics (therapy and diagnosis). One of the other assets of imidazolium salts is their flexible amphipathic character which promotes their self‐organizations into liquid‐crystal mesophases and their ability to mimic lipids. Combining luminescence to these amphipathic properties opens new prospects, e. g., following gene or drug delivery inside cells. These salts, all‐in‐one, should lead to new tools for biologists, as well as active theranostic molecules.
Synthesis of 2‐Substituted Cyclobutanones by a Suzuki Reaction and Dephosphorylation Sequence
Authors: Koudelka Jakub , Tobrman Tomáš
Published: May 2021

We report a novel process for the preparation of 2‐substituted cyclobutanones. Such a method relies on the cross‐coupling reaction of bromocyclobutenyl diethyl phosphate with either boronic acids or organozinc reagents. Dephosphorylation of the prepared 2‐substituted cyclobutenyl phosphates affords 2‐substituted cyclobutanones. We observed that the course of the dephosphorylation reaction depends on the properties of the substituents found on the cyclobutene nucleus. The presence of groups capable of stabilizing the negative charge is necessary for ring opening of cyclobutanones. The scope of the reported process for the preparation of 2‐substituted cyclobutanones has also been extended to the preparation of cyclobutenyl sulfides.
The opioid antagonist naltrexone decreases seizure‐like activity in genetic and chemically induced epilepsy models
Authors: Sturgeon Morgan L. , Langton Rachel , Sharma Shaunik , Cornell Robert A. , Glykys Joseph , Bassuk Alexander G.
Published: May 2021

Objective

A significant number of epileptic patients fail to respond to available anticonvulsive medications. To find new anticonvulsive medications, we evaluated FDA‐approved drugs not known to be anticonvulsants. Using zebrafish larvae as an initial model system, we found that the opioid antagonist naltrexone exhibited an anticonvulsant effect. We validated this effect in three other epilepsy models and present naltrexone as a promising anticonvulsive candidate.

Methods

Candidate anticonvulsant drugs, determined by our prior transcriptomics analysis of hippocampal tissue, were evaluated in a larval zebrafish model of human Dravet syndrome (scn1Lab mutants), in wild‐type zebrafish larvae treated with the pro‐convulsant drug pentylenetetrazole (PTZ), in wild‐type C57bl/6J acute brain slices exposed to PTZ, and in wild‐type mice treated with PTZ in vivo. Abnormal locomotion was determined behaviorally in zebrafish and mice and by field potential in neocortex layer IV/V and CA1 stratum pyramidale in the hippocampus.

Results

The opioid antagonist naltrexone decreased abnormal locomotion in the larval zebrafish model of human Dravet syndrome (scn1Lab mutants) and wild‐type larvae treated with the pro‐convulsant drug PTZ. Naltrexone also decreased seizure‐like events in acute brain slices of wild‐type mice, and the duration and number of seizures in adult mice injected with PTZ.

Significance

Our data reveal that naltrexone has anticonvulsive properties and is a candidate drug for seizure treatment.
The effect of asymmetric dune roughness on tidal asymmetry in the Weser estuary
Authors: Herrling Gerald , Becker Marius , Lefebvre Alice , Zorndt Anna , Krämer Knut , Winter Christian
Published: May 2021

The bed of estuaries is often characterized by ripples and dunes of varying size. Whereas smaller bedforms adapt their morphological shape to the oscillating tidal currents, large compound dunes (here: asymmetric tidal dunes) remain stable for periods longer than a tidal cycle. Bedforms constitute a form roughness, that is, hydraulic flow resistance, which has a large‐scale effect on tidal asymmetry and, hence, on hydrodynamics, sediment transport, and morphodynamics of estuaries and coastal seas. Flow separation behind the dune crest and recirculation on the steep downstream side result in turbulence and energy loss. Since the energy dissipation can be related to the dune lee slope angle, asymmetric dune shapes induce variable flow resistance during ebb and flood phases. Here, a noncalibrated numerical model has been applied to analyze the large‐scale effect of symmetric and asymmetric dune shapes on estuarine tidal asymmetry evaluated by residual bed load sediment transport at the Weser estuary, Germany. Scenario simulations were performed with parameterized bed roughness of symmetric and asymmetric dune shapes and without dune roughness. The spatiotemporal interaction of distinct dune shapes with the main drivers of estuarine sediment and morphodynamics, that is, river discharge and tidal energy, is shown to be complex but substantial. The contrasting effects of flood‐ and ebb‐oriented asymmetric dunes on residual bed load transport rates and directions are estimated to be of a similar importance as the controls of seasonal changes of discharge on these net sediment fluxes at the Lower Weser estuary. This corroborates the need to consider dune‐induced directional bed roughness in numerical models of estuarine and tidal environments.
Enzymatic browning in relation to permeation of oxygen into the kernel of postharvest areca nut under different storage temperatures
Authors: Pan Yonggui , Guo Yuting , Huang Qun , Zhang Weimin , Zhang Zhengke
Published: May 2021

Previous study indicates that kernel of areca nut is susceptible to enzymatic browning caused by phenolic oxidation, which involves the ingression of oxygen into interior tissue. However, the reason for permeation of oxygen into the interior of areca nut and its possible influencing factors (e.g., temperatures) are little known. In the present study, we set three storage temperatures (25, 10, and 5°C) and investigated the effects on kernel browning and related physic‐biochemical and tissue morphological changes. The results showed that the most severe kernel browning was observed in areca nut stored at 25°C, followed by 5°C. Comparatively, a slower browning development was found in areca nut stored at 10°C. More serious kernel browning at 25 and 5°C might be attributed to increased membrane permeability and aggravated tissue damage in view of morphological observations on pericarp, mesocarp, and kernel shell. Higher lignin content and phenylalanine ammonia‐lyase activity were observed in mesocarp of areca nuts stored at 25 and 5°C as compared to 10°C, indicating that mesocarp lignification could facilitate the permeability of oxygen. Furthermore, the data showed that storage at 25 and 5°C induced the higher polyphenol oxidase activity while accelerating the decline in total phenolic content in areca nut kernel, which could contribute to higher occurrence of enzymatic browning reaction compared to that at 10°C. These results suggest that natural senescence at 25°C and severe chilling stress at 5°C could be influencing factors triggering the permeation of oxygen, leading to internal kernel browning in areca nut.
Does price deregulation increase drug price in China? An interrupted time series analysis
Authors: Xiong Yao , Xu Judy , Gao Yuexia
Published: May 2021

Background

The Chinese government removed the price ceiling of most drugs in June 2015 to establish a market‐driven pricing system. The purpose of this study is to examine the impact of the elimination of drug ceiling price (EDCP) policy on drug prices.

Methods

Using a national macro‐level dataset, we employed an interrupted time series method to study the abrupt level and gradual trend changes of Chinese and Western medicine consumer price index (CPI) between June 2014 and June 2017.

Results

The policy exerted level change on Chinese medicine CPI, increasing 0.201% (95% CI 0.026% to 0.376%, p = 0.026). And the trend in Chinese medicine CPI was still decreased nonsignificantly after the EDCP policy. However, there was no significant price change in Western medicine.

Conclusion

The EDCP policy has different effects on the prices of Chinese and Western medicines. Therefore, we need to pay more attention to the drug pricing mechanism in the future.
Testing the ‘two water worlds’ hypothesis under variable preferential flow conditions
Authors: Radolinski Jesse , Pangle Luke , Klaus Julian , Stewart Ryan D.
Published: May 2021

Widespread observations of ecohydrological separation are interpreted by suggesting that water flowing through highly conductive soil pores resists mixing with matrix storage over periods of days to months (i.e., two ‘water worlds’ exist). These interpretations imply that heterogeneous flow can produce ecohydrological separation in soils, yet little mechanistic evidence exists to explain this phenomenon. We quantified the separation between mobile water moving through preferential flow paths versus less mobile water remaining in the soil matrix after free‐drainage to identify the amount of preferential flow necessary to maintain a two water world's scenario. Soil columns of varying macropore structure were subjected to simulated rainfall of increasing rainfall intensity (26 mm h−1, 60 mm h−1, and 110 mm h−1) whose stable isotope signatures oscillated around known baseline values. Prior to rainfall, soil matrix water δ2H nearly matched the known value used to initially wet the pore space whereas soil δ18O deviated from this value by up to 3.4‰, suggesting that soils may strongly fractionate 18O. All treatments had up to 100% mixing between rain and matrix water under the lowest (26 mm h−1) and medium (60 mm h−1) rainfall intensities. The highest rainfall intensity (110 mm h−1), however, reduced mixing of rain and matrix water for all treatments and produced significantly different preferential flow estimates between columns with intact soil structure compared to columns with reduced soil structure. Further, artificially limiting exchange between preferential flow paths and matrix water reduced bypass flow under the most intense rainfall. We show that (1) precipitation offset metrics such as lc‐excess and d‐excess may yield questionable interpretations when used to identify ecohydrological separation, (2) distinct domain separation may require extreme rainfall intensities and (3) domain exchange is an important component of macropore flow.
Improving pretend play for children with autism through experiencing the stimulus properties of real objects
Authors: Lee Gabrielle T. , Hu Xiaoyi , Liu Yanhong , Yang Zijin
Published: May 2021

Children with autism spectrum disorder (ASD) often lack symbolic play skills. Attribution of pretend properties (APP) is a type of symbolic play in which a child tacts pretend properties of an object (e.g., smelling a toy flower and saying, “It smells like a rose!”). Three Chinese boys (5‐6 years of age) with ASD served as participants. A multiple‐probe design across 5 objects was used to determine the effects of an intervention that involved having the child experience and tact sensory properties of real objects (e.g., rose). Corresponding test objects, including mock (e.g., a toy flower) and arbitrary objects (e.g., a stick), were used to evaluate whether tact responses for sensory properties were transferred. Results indicated that all 3 children emitted tacts of stimulus properties for test objects and maintained the skill for 7 to 10 weeks following the intervention. Two participants also tacted novel (nontarget) properties for test objects.
Association between SP‐A rs1965708 gene polymorphism and allergic rhinitis risk in Chinese population
Authors: Yin Xinghong , Wang Bo , Yan Zhiqiang , Hu Lulu , Zhang Xinhai
Published: May 2021

Background

Pulmonary surfactant protein A (SP‐A) in the respiratory tract plays an important role in host. In the present, we assessed the association between SP‐A gene polymorphism and allergic rhinitis.

Methods

Using a case–control design, we compared the genotype frequencies of SP‐A rs1965708 between allergic rhinitis patients and healthy control group. Genotyping was performed using real‐time quantitative PCR‐based molecular identification methods. Univariate and multivariate logistic regression were performed to quantitatively assess the association between rs1965708 polymorphism and allergic rhinitis, and the odds ratio (OR) and 95% confidence interval (CI) were also calculated.

Results

500 patients with allergic rhinitis and 500 healthy controls were included in the study. Compared with the CC genotype, we found that AA genotype of rs1965708 could increase the allergic rhinitis risk in the univariate analysis (OR = 2.63, 95% CI: 1.56–4.54, p = 0.000). For dominant model, we found no significant difference in the dominant model (OR = 1.14, 95% CI: 0.86–1.52, p = 0.367). In the recessive model, the CC genotype could elevate the risk of allergic rhinitis compared with CC + AA genotype (OR = 2.70, 95% CI: 1.61–4.54, p = 0.000). Similar results were also found in the allele model (OR = 1.28, 95% CI: 1.07–1.54, p = 0.008). Interactions between rs1965708 AA or AC and smoking increased the allergic rhinitis risk.

Conclusions

The rs1965708 variants of SP‐A gene polymorphism are associated with allergic rhinitis, and the A allele could increase the allergic rhinitis risk. The AA SNP variants that interact with smoking may alter the susceptibility to allergic rhinitis.
Intersection between macrophages and periodontal pathogens in periodontitis
Authors: Wang Wenzhe , Zheng Chenxi , Yang Jianhua , Li Bei
Published: May 2021

Periodontitis is a chronic infectious disease characterized by loss of periodontal attachment and resorption of alveolar bone. Dysregulated oral microbial community is the initial factor of periodontitis and causes excessive infiltration of immune cells in periodontal tissues. Macrophage, as an important part of the innate immune system, interacts continually with oral pathogens. Macrophages can recognize and phagocytize pathogens and apoptotic neutrophils and produce the specialized pro-resolving mediators (SPMs) playing an important role in maintaining the homeostasis of tissue microenvironment. However, macrophages may also induce abnormal immune responses with the overstimulation from pathogens, leading to the destruction of periodontal tissues and alveolar bone. Looking for targeted drugs that can regulate the activities of oral pathogens and the functions of macrophages provides a new idea for periodontitis treatment. This review summarizes the interaction between macrophages and periodontal pathogens in periodontitis, focusing on the pro-inflammation and anti-inflammation phenotypes of macrophages, and briefly concludes potential new methods of periodontitis therapy targeted at oral pathogens and macrophages.