bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study on the Prediction of Damage Ranges by Leakages of Seaport-Stored Substances
Authors: Hwang Woonyong
Published: April 2021

In order to check the risk of hydrogen peroxide leakage from the seaport, the leakage amount was changed from 1.0 ton to 10.0 tons, with the maximum and minimum diffusion distances per month in 2020 being subsequently calculated. A total of 82 scenarios were created to confirm the change in the diffusion distance according to the amount of leakage. The scenario was analyzed based on the distance at which the risk concentration was maintained through the ALOHA Air Dispersion Models. As indicated by the analysis, when the amount of leakage is relatively large, the temperature is also high and the wind speed is fast - resulting in the maximum spread. However, when the amount of leakage was relatively minimal, the temperature was low and the wind speed remained fast - this kept diffusion to the minimum. Concerning characteristics of fast wind speeds, the dispersion length changed based on amounts of leakages where PAC-1 contains 2.0 tons, PAC-2 contains 4.0 tons, and PAC-3 contains 5.0 tons. In addition, when the amount of leakage equaled 10.0 tons, and the wind speed was high, the dispersion length reached up to 10 kms. In light of this, it was confirmed that even adjacent administrative districts were affected. Therefore, it is necessary to establish appropriate measures to prevent damage by utilizing the diffusion distance caused by chemical leakages.
Application of Facebook’s Prophet Model for Forecasting Meteorological Data
Authors: Kim Junsuk , Kim Tae Jin
Published: April 2021

The wildfire risk index was calculated based on current meteorological information, for example, temperature, humidity, and wind speed. Thus, meteorological data forecasting could help estimate the probability of fire occurrence or spreading speed to prevent large wildfires. This study predicts meteorological data (e.g., temperature, humidity, and wind speed) using Facebook's Prophet library. We trained the Prophet model using meteorological data between 2016 and 2018 in Goseong, Gangwon-do (where the wildfire occurred in 2019) and predicted meteorological data for the first four months in 2019. We obtained that Facebook's Prophet model was effective in computing speed and predicting the overall trend. However, it could not predict sudden irregular changes satisfactorily. Considering its rapidity, these results could play an important role in future research, especially as a basic research for time-series forecasting.
Angiotensin‐Converting Enzyme Inhibitors
Authors: Petrillo Edward W.
Published: April 2021

The discovery of captopril, the first orally active angiotensin‐converting enzyme inhibitor, showed that blockade of the renin‐angiotensin system effectively lowers blood pressure in a wide spectrum of patients with hypertension. Captopril was designed using a hypothetical model of the enzyme active site that subsequently guided the design of new classes of inhibitors. Because ACE inhibitors retard the progression of cardiovascular disease and the complications of diabetes, leading to an overall reduction in mortality, they have become one of the most widely used drug classes in cardiovascular medicine. New genetic and structural evidence has revealed that ACE has two functional catalytic domains with differences that may be exploited in the future to design inhibitors with superior properties.
Antiplatelet Agents
Authors: Chackalamannil Samuel
Published: April 2021

In addition to their life‐sustaining role in hemostasis and wound healing, platelets play a central role in the pathogenesis of coronary artery, cerebrovascular, and peripheral vascular diseases. Under pathologic conditions such as rupture of an atherosclerotic plaque, the platelet activation mechanism and coagulation mechanism synergize in the formation of an occlusive thrombus leading to ischemic disorders such as acute coronary syndrome and stroke. Antiplatelet agents are the mainstay of pharmacological approach for the treatment of ischemic vascular disorders. Platelets have multiple cell‐surface receptors that, upon activation by specific ligands, trigger a cascade of cellular events resulting in the activation of the integrin glycoprotein (GP) IIb/IIIa receptors. Activated GP IIb/IIIa receptors cross‐link with fibrinogen causing platelet to aggregate. Aggregated platelets get trapped by fibrin meshwork, produced by the proteolysis of fibrinogen by thrombin. Cell‐surface platelet receptors have been the target of antiplatelet therapy. For example, aspirin, the most widely used antiplatelet agent, inhibit the biosynthesis of thromboxane A2, the endogenous agonist that activates thromboxane receptors. The ADP antagonists such as clopidogrel and ticlopidine inhibit ADP‐mediated activation of purinergic P2Y12receptors. Glycoprotein IIb/IIIa antagonists such as abciximab, eptifibatide, and tirofiban inhibit GP IIb/IIIa receptors, which involve the final common pathway of platelet aggregation. Phosphodiesterase inhibitors are less widely used antiplatelet agents that potentiate intracellular cyclic AMP levels. Promising newer antiplatelet agents such as thrombin receptor antagonists with reduced bleeding liability, third‐generation thienopyridine ADP antagonists with improved potency and reversible ADP antagonists are at advanced stage of development.
Anticoagulants
Authors: Quan Mimi L. , Glunz Peter W. , Luettgen Joseph M.
Published: April 2021

Although blood circulation is highly regulated, dysfunctional activities resulting from either deficient or excessive coagulation have serious health consequences. Insufficient clotting can lead to prolonged bleeding and hemophilia‐related conditions. Over activation of coagulation can lead to thrombosis‐related disorders, such as deep venous thrombosis, pulmonary embolism, and stroke, which together are a major cause of morbidity and mortality. Studies of the biological pathways leading to coagulation, and the resultant development and refinement of the coagulation cascade, have identified many potential biological targets for therapeutic intervention. The major challenge regarding the treatment and prevention of thromboembolic diseases is the requirement for effective anticoagulant therapy without exposing patients to an increased risk of bleeding. Preclinical and clinical evaluations of anticoagulant agents highlight this efficacy/bleeding dichotomy. This article presents the medicinal chemistry efforts leading to the discovery of inhibitors of the coagulation cascade, resulting in marketed thrombin and Factor Xa inhibitors. Also reported is the progress toward identifying emerging anticoagulants.
Ion Channels as Therapeutic Drug Targets
Authors: Garcia Maria L. , Kaczorowski Gregory J.
Published: April 2021

Ion channels comprise a large and diverse family of proteins that control many physiological functions. For this reason, a number of inherited diseases result from mutations in specific genes that alter the functions of given ion channels. Drugs used to treat a variety of pathophysiological conditions derive their benefits from interacting with specific ion channel(s), and efforts to develop novel ion channel drugs that would address unmet clinical needs are ongoing in pharmaceutical, biotech, and academic institutions. During the past period of time, major developments in functional screening technologies have afforded the study of these proteins in high‐density formats. In addition, a large body of information concerning the structure of different ion channels has become available. In some cases, intimate details of the interactions between drugs and ion channels have been obtained, which may help with designing more potent and selective ion channel modulators. Although a number of ion channel modulators have entered clinical development, lack of therapeutic efficacy or toxicity issues have caused termination of the development of many of these agents. Nonetheless, with all accumulated experience and new technological advancements, expectations are high for the successful development of novel ion channel modulators in the future.
Drug Discovery Beyond the Rule of Five
Authors: DeGoey David A. , Cox Philip B.
Published: April 2021

Approximately 6% of orally administered drugs have physicochemical properties that are beyond Lipinski's rule of five (bRo5). However, in the past five years, there have been 22 new oral bRo5 drugs approved by the FDA, which account for 21% of new oral drug approvals. The significant increase in the percentage of bRo5 drug approvals represents a shift in the types of drug targets undertaken by medicinal chemists including a larger number of protein–protein interaction (PPI) inhibitors, such as BCL‐2 inhibitors, and nontraditional drug targets such as NS5A inhibitors for the treatment of hepatitis C (HCV). The shift away from more druggable enzyme and GPCR targets has resulted in the development of larger molecules that have physicochemical properties that far exceed those previously expected to yield adequate solubility and permeability for oral absorption. Due to frequently lower solubility and permeability, conducting drug discovery research in bRo5 chemical space is difficult and represents a challenge for medicinal chemists to move away from the more well‐understood Ro5 chemical space. In this article, we review the current state of the art for drug discovery bRo5 including a review of the literature, an analysis of physicochemical properties and case studies of the approved classes of bRo5 drugs.
Fragment‐Based Lead Discovery
Authors: Hubbard Roderick E.
Published: April 2021

Fragment‐based discovery is an effective approach to finding hit compounds that bind to a target. Fragments can be found that bind to most sites on most proteins, providing a rich source of chemical ideas for the medicinal chemist to develop into hits and leads. There are two distinctive activities in fragment‐based discovery: (i) finding fragments that bind and (ii) evolving the fragments to hit compounds which can then be progressed using conventional (structure‐guided) optimization. A wide variety of methods have been developed for screening, many based on biophysical approaches to identify and then characterize the binding of the relatively low affinity (but efficient) compounds – a separate section summarizes the key features of the methods. Perhaps the most difficult aspect of fragment‐based discovery is deciding which fragments to evolve – another section describes some recent projects to highlight the key strategies that are used. The article concludes with some summary statements on the main features and advantages of the approach and a discussion about future directions.
Clinical Development – A Primer
Authors: Chachad Siddharth
Published: April 2021

Objective
: Clinical development of a drug product is a long and complex process, so it is rather impossible to capture all the aspects of this process in details in this article. Accordingly, the key objective of this article is to present an overview of how a new medicinal product undergoes clinical evaluation to ensure that ultimately quality medicine with proven safety and efficacy is delivered to the end user, i.e. patient who consumes it for health benefit. An attempt is also made to briefly cover clinical development of biological drugs, which can require a different approach to supporting the dose justification and assessing immunogenicity risks as compared to chemically synthesized drug products.

Method
: The information covered in this article is based on personal experience in the area of clinical development for regulatory submissions worldwide, regulatory guidance documents and legislations, as well as extensive literature surveillance using key terms such as clinical research, phases of development, efficacy, safety, new drug product, new chemical entity, new therapeutic entity, generics, biologics and biosimilars, oncology trials, modeling, and simulation. Clinical development is a process driven not only by science and regulations but also significantly by cost and time. The interested reader is encouraged to review clinical trial guidelines on the Food and Drug Administration (FDA) website and websites of other regulatory authorities such as European Medicines Agency (EMA), Therapeutic Goods Administration (TGA), and Health Canada. Those with further interest may also visit Clinical Trial Registry websites including
www.clinicaltrials.gov
to get familiar to different types of clinical study designs across phases of development carried out by sponsors as research studies or in pursuance of their marketing authorization applications.
Recent Advances in Chemistry Technologies and Applications to Medicinal Chemistry
Authors: Bogdan Andrew R. , Gesmundo Nathan J. , Webster Matthew P. , Wang Ying , Vasudevan Anil
Published: April 2021

Successful drug discovery is a team sport, wherein several disciplines contribute customized scholarship toward the common goal of delivering medications that can have a remarkable impact on patients' lives. In the realm of medicinal chemistry, there have been significant advances in molecular‐/structure‐based design, organic synthesis, and chemistry technologies, the interplay of all of which can have a significant impact on reducing cycle times, cost of goods, and improving the probability of technical success of drug discovery. This article covers the evolution and application of some of the newer chemistry technologies in medicinal chemistry.
Function of Proteins Identified as Part of the Nuclear Matrix
Authors: Zhang Yuwen , Huo Xiangru , Wen Bo
Published: April 2021

Nuclear matrix (NM) is an intranuclear protein network originally found after high‐salt or lithium diiodosalicylate extraction and nuclease treatment. Proteins identified as part of the NM comprise a multifunctional platform for various nuclear functions. NM contains proteins involved in chromatin packaging, deoxyribonucleic acid (DNA) replication, transcription, ribonucleic acid (RNA) splicing, DNA repair and cell signalling. Dysfunction of NM proteins may result in defective cell functions, abnormal organogenesis and disorders such as progeria and some cancers.

Key Concepts

Some NM proteins bind to chromatin via its scaffold/matrix‐attached regions (S/MARs), help chromatin loop formation or organise higher order chromatin architecture.

The deoxyribonucleic acid (DNA) replication machinery can be attached to certain nuclear matrix (NM) proteins.

Some NM proteins are associated with transcription factories and regulate gene expression.

The abnormal expression or genetic variants of NM genes may cause development abnormalities and diseases.
Strongly Luminescent Dion–Jacobson Tin Bromide Perovskite Microcrystals Induced by Molecular Proton Donors Chloroform and Dichloromethane
Authors: Wang Shixun , Popović Jasminka , Burazer Sanja , Portniagin Arsenii , Liu Fangzhou , Low Kam‐Hung , Duan Zonghui , Li Yanxiu , Xiong Yuan , Zhu Yuanming , Kershaw Stephen V. , Djurišić Aleksandra B. , Rogach Andrey L.
Published: April 2021

Lead‐free 2D perovskites based on tin halide octahedron slabs with Dion–Jacobson (DJ) phases have drawn attention due to their improved stability; still, reports on light‐emitting DJ lead‐free perovskites are scarce. Herein, a room‐temperature ligand assisted re‐precipitation method is used to produce ODASnBr4 perovskite microcrystals (ODA denotes protonated 1,8‐octanediamine). After incorporating molecular dopants chloroform and dichloromethane, not only the crystallinity of the DJ perovskite phase improves, but their emission becomes much stronger due to the formation of hydrogen bonds between [SnBr6]4− octahedra and acidic CH proton donors. ODASnBr4 microcrystals doped with these molecules show a high photoluminescence quantum yield (PLQY) approaching 90%, and their emission remains stable under a continuous UV irradiation, with less than 10% loss in intensity over 6 h. Moreover, by tuning the pristine ODASnBr4 with various degrees of exposure to the molecular dopants, the maximum of their self‐trapped exciton emission can be fine‐tuned over a spectral range of 570–608 nm while maintaining high PLQYs of 83–88%. This provides a convenient way to adjust the spectral position of DJ perovskite emission without changing halides or A‐site spacers. Thus, stable and strongly emitting lead‐free DJ perovskite materials have been developed.
A Versatile Cationic Organic Network Adsorbent for the Highly Efficient Removal of Diverse Water Contaminants
Authors: Li Zhi‐Jun , Zhang Qi , Xue Hua‐Dong , Zheng Xu‐Dong , Qi Hui‐Li , Li Hui‐Cheng
Published: April 2021

Water decontamination is of great importance to address the increasing shortage of water resources, ion‐exchange‐driven adsorption being one of the most efficient approaches to this aim. Despite the advances achieved in this field, particularly with the emergence of ionic organic networks as a new class of adsorbents for water treatment, the development of adsorbents with high performance is still highly desired. This paper describes the facile preparation of a new cationic organic network, denoted as CON‐LDU3, via a quaternization reaction between 1,2,4,5‐tetra(pyridin‐4‐yl)benzene and 1,4‐bis(bromomethyl)benzene. The cationic framework and abundant exchangeable Br− anions render CON‐LDU3 as a suitable adsorbent to capture anionic contaminants from water. CON‐LDU3 displays fast kinetics and high capacity for the removal of CrO42−, reaching the kinetic constant and maximum capacity values of 0.0539 g mg−1 min−1 and 232 mg g−1, respectively. Moreover, this adsorbent can be regenerated by simple washing with KBr solution, and it can be recycled for at least eight times. CON‐LDU3 also exhibits excellent performance in the adsorption of some emerging organic water contaminants such as orange G and diclofenac sodium. Therefore, this study demonstrates the high potential of CON‐LDU3 as a versatile adsorbent for water remediation.
Multiplexing Liquid Biopsy with Surface‐Enhanced Raman Scattering Spectroscopy
Authors: Abalde‐Cela Sara , Wu Lei , Teixeira Alexandra , Oliveira Kevin , Diéguez Lorena
Published: April 2021

Among the main challenges faced in cancer research, early detection, metastatic pathways and biomarker discovery are being tackled both by researchers and technology‐based companies. The development of novel technologies that can advance the state‐of‐the‐art for those defined challenges is critical in order to enhance the survival rates as well as to significantly lower cancer associated costs, not to mention social and human impact. In the recent years, the field of liquid biopsy has grown tremendously due to its capacity to obtain and study tumor material in a non‐invasive way. Liquid biopsy arises as an alternative diagnostic tool based on the analysis of biomarkers present in body fluids. The characterization of those biomarkers is commonly made by already well‐established standard technologies, usually limited in terms of sensitivity, selectivity, multiplexing, high‐throughput, and/or speed of analysis. Unfortunately, highly sensitive molecular diagnostic technologies still have high associated costs preventing their universal application. In this review, the authors aim to provide the reader with a general comprehension on how surface‐enhanced Raman scattering (SERS) spectroscopy can overcome those bottlenecks. The combination of SERS and liquid biopsy may fulfill the holy grail of the so‐called precision medicine, ultimately contributing to the dream of cancer chronification.
Thinking outside “The Box”: Case‐based didactics for medical education and the instructional legacy of Dr John M. Graham, Jr
Authors: Sanchez‐Lara Pedro A. , Grand Katheryn , Haanpää Maria K. , Curry Cynthia J. , Wang Raymond , Ezgü Fatih , Rose Catherine M. , D'Cunha Burkardt Deepika , Conway Robert L. , Relan Anju , Carey John C.
Published: April 2021

The increasing demand for advanced genomic services has finally come to the attention of healthcare systems and stakeholders who are now eager to find creative solutions to increase the pool of genomic literate providers. Training in genetics and dysmorphology has historically been conducted as a self‐driven practice in pattern recognition, ideally within a formal or informal apprenticeship supervised by a master diagnostician. In recent times, case‐based learning, framed by flipped classroom pedagogy have become the preferred teaching methods for complex medical topics such as genetics and genomics. To illuminate this perspective, our article was written in honor of the teaching style and pedagogy of Dr John M. Graham Jr and his lifelong commitment to medical education and mentoring.
Green synthesis of palladium nanoparticles: Preparation, characterization, and investigation of antioxidant, antimicrobial, anticancer, and DNA cleavage activities
Authors: Gulbagca Fulya , Aygün Ayşenur , Gülcan Mehmet , Ozdemir Sadin , Gonca Serpil , Şen Fatih
Published: April 2021

Green synthesis is considered to be one of the most suitable method because it enhances the therapeutic effects of palladium nanoparticles (Pd NPs). In this study, various biological activities such as antimicrobial, anticancer, antioxidant, and DNA cleavage activities of Urtica‐mediated green synthesizing Pd NPs were investigated. The synthesized Pd NPs were characterized by using UV‐vis, XPS, FT‐IR, TEM, and XRD analyses. As a result of the TEM analysis of Pd NPs, the mean particle size was found to be 7.44 ± 1.94 nm, and this result was supported by XRD analysis. The maximum DPPH scavenging activity was determined as 79.6% at 500 mg/L. The newly green synthesized Pd NPs exhibited high antimicrobial activity to gram‐negative bacteria than gram‐positive bacteria. Urtica‐mediated green synthesized Pd NPs also showed double strain DNA cleavage activity. For the cytotoxic effects of Pd NPs, the MDA‐MB‐231 breast cancer cell line, HT‐29 colon cancer cell line, Mia Paca‐2 human pancreatic cancer cell line, and healthy cell line L929‐Murine fibroblast cell line were used. IC50 values of Pd NPs against MDA‐MB‐231, HT‐29, and MIA PaCa‐2 cancer cell lines were calculated as 31.175, 20.383, and 29.335 μg/ml, respectively. No significant cytotoxic effect was observed in the healthy lines L929.
Elaboration of porosity for the alumina particle surfaces/ bimodal PP composite cast films under continuous stretching
Authors: MohammadKarimi Shiva , Morshedian Jalil , Morshedian Hamed
Published: April 2021

Efforts have been focused on developing an interrelationship between machine direction orientation (MDO)/material variables and the porosity of Al2O3 particulate‐filled orientable PP for various applications. Composite films were prepared by cast‐extrusion followed by stretching up to 100% and 200% by the MDO machine. Cavitation could occur during film stretching when the adhesion between dispersed alumina and continuous polypropylene phase failed. Composite films with modified micro‐particles and also nano ones could not generate any voids. On the other hand, composite specimens of unmodified micro‐alumina particles generated micro‐pores in the joint between dispersed particles and polymer during the hot stretching. Beta nucleation in these films, plays an important role in the generated ductility of the specimens. Cavitation effectiveness (no. of voids) or film permeability depended on the size and amount of alumina particles, in addition to the ratio and temperature of stretching. Cavitation particles with a size range of 0.7–3 μm, create cavities of about 3–7 μm. Generation of voids, by drawing environmentally friendly and antimicrobial active alumina particles, can be utilized in the fabrication of sustainable hygiene polypropylene films with desirable separation abilities for gases or small molecules. Furthermore, the polypropylene/alumina composite films have the potential for microwaveable packaging.
Synthesis and properties of magnetite nanoparticles with peroxide‐containing polymer shell and nanocomposites based on them
Authors: Serdiuk Vitalii , Shevchuk Oleh , Bukartyk Natalya , Kovalenko Tetiana , Borysiuk Anatolii , Tokarev Viktor
Published: April 2021

Magnetite nanoparticles (Fe3O4 NPs) with peroxide‐containing polymer shell have been synthesized using the method of coprecipitation from the mixture solutions of Fe (II) and Fe (III) salts in the presence of peroxide‐containing copolymer (PCC). Polymer shell presence has been proved by elemental and complex thermal analysis. Synthesized Fe3O4 NPs possess superparamagnetic properties. Their specific saturation magnetization decreases gradually from 65 to 54 A·m2·kg−1 with increasing PCC concentration owing to the surface spin pinning effect caused by a polymer shell. The average sizes of Fe3O4 NPs estimated from the data of XRD analysis and magnetic measurements are in the range of 9–12 nm. The NP sizes determined by the DLS method lie in the range of 150–270 nm; this result is significantly larger than the sizes estimated by the two aforementioned methods evidencing a tendency for Fe3O4 NPs toward self‐association. Cross‐linked composite films based on polyvinyl alcohol have been obtained via radical curing initiated by the PCC shell of nanoparticles. The resulting composite films are magnetically sensitive films with rather high physico‐mechanical properties (tensile strength reaches 48–67 MPa and relative elongation – 4%–21% depending on cross‐linking degree), a priori non‐toxic and biocompatible, which makes them promising materials for various applications.
Downstream processing for influenza vaccines and candidates: An update
Authors: B. Carvalho Sofia , Peixoto Cristina , T. Carrondo Manuel J. , S. Silva Ricardo J.
Published: April 2021

Seasonal and pandemic influenza outbreaks present severe health and economic burdens. To overcome limitations on influenza vaccines' availability and effectiveness, researchers chase universal vaccines providing broad, long‐lasting protection against multiple influenza subtypes, and including pandemic ones.

Novel influenza vaccine designs are under development, in clinical trials, or reaching the market, namely inactivated, or live‐attenuated virus, virus‐like particles, or recombinant antigens, searching for improved effectiveness; all these bring downstream processing (DSP) new challenges. Having to deal with new influenza strains, including pandemics, requires shorter development time, driving the development of faster bioprocesses. To cope with better upstream processes, new regulatory demands for quality and safety, and cost reduction requirements, new unit operations and integrated processes are increasing DSP efficiency for novel vaccine formats.

This review covers recent advances in DSP strategies of different influenza vaccine formats. Focus is given to the improvements on relevant state‐of‐the‐art unit operations, from harvest and clarification to purification steps, ending with sterile filtration and formulation. The development of more efficient unit operations to cope with biophysical properties of the new candidates is discussed: emphasis is given to the design of new stationary phases, 3D printing approaches, and continuous processing tools, such as continuous chromatography. The impact of the production platforms and vaccine designs on the downstream operations for the different influenza vaccine formats approved for this season are highlighted.
Ultra‐rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities
Authors: Stacchiotti Silvia , Frezza Anna Maria , Blay Jean‐Yves , Baldini Elizabeth H. , Bonvalot Sylvie , Bovée Judith V. M. G. , Callegaro Dario , Casali Paolo G. , Chiang RuRu Chun‐ju , Demetri George D. , Demicco Elisabeth G. , Desai Jayesh , Eriksson Mikael , Gelderblom Hans , George Suzanne , Gounder Mrinal M. , Gronchi Alessandro , Gupta Abha , Haas Rick L. , Hayes‐Jardon Andrea , Hohenberger Peter , Jones Kevin B. , Jones Robin L. , Kasper Bernd , Kawai Akira , Kirsch David G. , Kleinerman Eugene S. , Le Cesne Axel , Lim Jiwon , Chirlaque López María Dolores , Maestro Roberta , Marcos‐Gragera Rafael , Martin Broto Javier , Matsuda Tomohiro , Mir Olivier , Patel Shreyaskumar R. , Raut Chandrajit P. , Razak Albiruni R. A. , Reed Damon R. , Rutkowski Piotr , Sanfilippo Roberta G. , Sbaraglia Marta , Schaefer Inga‐Marie , Strauss Dirk C. , Sundby Hall Kirsten , Tap William D. , Thomas David M. , van der Graaf Winette T. A. , van Houdt Winan J. , Visser Otto , von Mehren Margaret , Wagner Andrew J. , Wilky Breelyn A. , Won Young‐Joo , Fletcher Christopher D. M. , Dei Tos Angelo P. , Trama Annalisa
Published: April 2021

Background

Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra‐rare cancers has not been established. The problem of ultra‐rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies.

Methods

The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra‐rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra‐rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical‐pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan.

Results

It was agreed that the best criterion for a definition of ultra‐rare sarcomas would be incidence. Ultra‐rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra‐rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types.

conclusions

Altogether, the incidence of ultra‐rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra‐rare sarcomas affect large numbers of patients.
Highly Efficient All‐Polymer Solar Cells Processed from Nonhalogenated Solvents
Authors: Li Zuojia , Feng Kui , Wang Jingwei , Li Min , Xu Qianqian , Li Xiaochang , Guo Xugang
Published: April 2021

The remarkable advance of all‐polymer solar cells (all‐PSCs) achieved in the past decades is primarily powered by the innovation of polymer acceptors. However, most of high‐performance all‐PSCs are dominantly fabricated with halogenated solvents, which are detrimental to human bodies and the environment. Herein, eco‐friendly solvent‐processed all‐PSCs were developed, based on wide‐bandgap polymer poly[4,8‐bis(5‐(2‐ethylhexylthio)thiophen‐2‐yl)‐benzo‐[1,2‐b;4,5‐b’]dithiophene‐alt‐2,5‐di(butyloctylthiophen‐2‐yl) ‐thiazolo[5,4‐d]thiazole] (PSTZ) as donor and newly synthesized narrow‐bandgap polymer 5,6‐dicyano‐2,1,3‐benzothiadiazole indacenodithiophene (DCNBT‐IDT) as acceptor. When processed with o‐xylene and THF, PSTZ : DCNBT‐IDT‐based all‐PSCs yielded remarkable power conversion efficiencies of 7.23 and 8.77 % with high short‐circuit currents of 12.94 and 14.12 mA cm−2, respectively. The results indicated that the utilization of an all‐polymer blend based on narrow polymer acceptor and compatible polymer donor is an effective strategy for advancing eco‐friendly solvent‐processed all‐PSCs.
The role of Cairns–Gurevich distributed electrons on obliquely propagating ion‐acoustic waves
Authors: Bouziane H. , Annou K.
Published: April 2021

We used a new distribution of electrons in a two‐component magnetized plasma to study the non‐linear ion‐acoustic solitary structures. The distribution called “Cairns–Gurevich distribution” describes simultaneously the evolution of the energetic electrons and those trapped in the plasma potential well. A modified KdV equation describing the non‐linear comportment of the ion‐acoustic wave (IAW) was found by using the standard reductive perturbation technique and the appropriate independent variables. The behaviour of the soliton by changing the plasma parameters has been investigated, and we demonstrated that by decreasing the non‐thermality parameter, the soliton solution amplitude is enhanced. In addition, we have discussed the growth rate of the solitary waves by calculating the instability criterion. Through discussion, we have conferred how different plasma parameters, such as the trapping, non‐thermality, Mach number, obliqueness via the angle of propagation, and magnetic field via the ion‐cyclotron frequency, can affect the solitary wave structures. This kind of theoretical studies can be relevant to understand the non‐linear propagation of IA solitary waves plasmas of electrons and particles in laser‐plasma interaction, pulsar magnetosphere, the auroral zone, and the upper ionosphere, where plasma with trapped and energetic electrons are often present.
Cellular mechanisms of frontal bone development in spotted gar (Lepisosteus oculatus)
Authors: Enny Alyssa , Shanabag Anusha , Thompson Andrew W. , Racicot Brett , Braasch Ingo , Nakamura Tetsuya
Published: April 2021

Background

The cellular and molecular mechanisms initiating vertebrate cranial dermal bone formation is a conundrum in evolutionary and developmental biology. Decades of studies have determined the developmental processes of cranial dermal bones in various vertebrates and identified possible inducers of dermal bone. However, evolutionarily derived characters of current experimental model organisms, such as non‐homologous frontal bones between teleosts and sarcopterygians, hinder investigations of ancestral and conserved mechanisms of vertebrate cranial dermal bone induction. Thus, investigating such mechanisms with animals diverging at evolutionarily informative phylogenetic nodes is imperative.

Results

We investigated the cellular foundations of skull frontal bone formation in the spotted gar Lepisosteus oculatus, a basally branching non‐teleost actinopterygian. Whole‐mount bone and cartilage staining and hematoxylin‐eosin section staining revealed that mesenchymal cell condensations in the frontal bone of spotted gar develop in close association with the underlying cartilage. We also identified novel aspects of frontal bone formation: enrichment of F‐actin, cellular membranes, and E‐cadherin in condensing cells, and extension of podia‐like structures from osteoblasts to the frontal bone, which may be responsible for bone mineral transport.

Conclusion

This study highlights the process of frontal bone formation with dynamic architectural changes of mesenchymal cells in spotted gar, an emerging non‐teleost fish model system, illuminating supposedly ancestral and likely conserved developmental mechanisms of skull bone formation among vertebrates.
Dental students’ attitudes and hesitancy toward COVID‐19 vaccine
Authors: Mascarenhas Ana Karina , Lucia Victoria C. , Kelekar Arati , Afonso Nelia M.
Published: April 2021

Background

Dentists are a group of providers who have been identified by CDC at high risk of exposure to COVID‐19 through their contact with patients. This would apply to dental students as well. Thus, it is important to achieve high COVID‐19 vaccination rates in this group. Further, as healthcare providers, they are entrusted with providing health recommendations and advocating for their patients, community, and profession, including vaccinations.

Methods

Using ualtricsXM an online platform, in 2020, a survey was administered anonymously to dental students at three dental schools to assess the attitudes of dental students to the novel COVID‐19 vaccine. Factors and reasons associated with vaccine hesitancy and acceptance toward the COVID‐19 vaccine and likelihood of recommending and giving the vaccination to patients were assessed.

Results

Nearly, all participants had positive attitudes toward vaccines in general, agreed they would likely be exposed to COVID‐19, and personally knew someone who had COVID‐19; however, only 56% are willing to take a COVID‐19 vaccine as soon as an FDA‐approved vaccine was available. Of those unwilling to take the vaccine, 63% reported they would take it if mandated by the health systems/dental school; however, 16.3% of the overall respondents would not take the COVID‐19 vaccine even if mandated. Several factors are associated with vaccine acceptance and the likelihood of recommending the vaccination, such as trusting public health experts, concerns about side effects, and agreeing with vaccine mandates.

Conclusion

Our results highlight the need for an educational curriculum about the safety and effectiveness to promote the uptake of COVID‐19 vaccine.
Prevalence of high‐risk human papillomavirus and cervical lesion risk factors: A population‐based study in Zhejiang, China 2010–2019
Authors: Lu Wei , Chen Tingting , Yao Yimin , Chen Ping
Published: April 2021

This study investigates the epidemiological characteristics of high‐risk human papillomavirus (hrHPV) and analyzes the risk of cervical lesions among women in Zhejiang province, China. HPV data were collected retrospectively from a cohort of 67 742 women who underwent routine cervical cancer screening from 2010 to 2019. Precancerous and cervical cancer cases (n = 980) were histologically diagnosed as a low‐grade squamous intraepithelial lesion (LSIL; n = 341) or a high‐grade squamous intraepithelial lesion (HSIL; n = 499) and invasive cervical cancer (ICC) (n = 140) groups. Disordered logistic regression analysis was used to test the relationship between different degrees of cervical lesions, HPV16/18 infection status, positive rate of p16INK4a (p16), Ki‐67 expression, and patient's age in SIL and ICC (270/980 cases) patients. HPV52 (4.7%) was the most prevalent HPV type, followed by HPV16 (3.3%) and HPV58 (2.6%). HPV16 was the most common HPV in SIL, peaking at the age of 30–39. The HPV16 infection rate was significantly higher in HSIL than in LSIL patients; moreover, HPV16, HPV18, and HPV51 infection rates were significantly higher in ICC patients than in HSIL (Bonferroni‐adjusted p < 0.0167). The presence of HPV16/18 was also associated with a higher risk of developing HSIL from LSIL (odds ratio [OR] = 9.198, 95% confidence interval [CI]: 2.76–127.49). The increased p16 expression and HPV16/18 were associated with the increased risk of cancer progression (OR = 1.092, 95% CI: 1.03–1.36; OR = 1.495, 95% CI: 1.23–2.19, respectively). The identified hrHPV genotypes in cervical lesions can serve as a baseline indicator for future vaccine assessment in Zhejiang, China.
Spatiotemporal differences and uncertainties in projections of precipitation and temperature in South Korea from CMIP6 and CMIP5 general circulation models
Authors: Song Young Hoon , Chung Eun‐Sung , Shahid Shamsuddin
Published: April 2021

This study compared the historical simulations and future projections of precipitation and temperature of Coupled Model Intercomparison Project (CMIP)5 and CMIP6 general circulation models (GCMs) to quantify the differences in the projections due to differences in scenarios. Five performance indicators were used to quantify the model reproducibility of the observed precipitation levels at 22 stations for the historical period of 1970–2005. The percentages of change in precipitation and temperature were estimated for the near (2025–2060) and far future (2065–2100) for two Representative Concentration Pathway (RCP)4.5 and RCP8.5 scenarios of CMIP5 and two Shared Socioeconomic Pathway (SSP)2–4.5 and SSP5‐8.5 scenarios of CMIP6. The uncertainty in the projection in each case was calculated using the reliability ensemble average (REA) method. As a result, the CMIP6 GCMs showed an improvement compared with the CMIP5 GCMs with regard to the ability to simulate the historical climate. The uncertainty in the precipitation projections was higher for SSPs than that in RCPs. With regard to the temperature, the uncertainty was higher for RCPs than for SSPs. The ensemble means of the precipitation and temperature showed higher changes in the far future compared with the near future for both RCPs and SSPs. This study contributes to improvement in the confidence of future projections using CMIP6 GCMs and bolsters our understanding of the relative uncertainty in SSPs and RCPs.
The 20th century global warming signature on the ocean at global and basin scales as depicted from historical reanalyses
Authors: Storto Andrea , Balmaseda Magdalena A. , de Boisseson Eric , Giese Benjamin S. , Masina Simona , Yang Chunxue
Published: April 2021

More than 90% of excess energy trapped by greenhouse gases is accumulated in the oceans. Ocean heat content (OHC) and its changes are therefore fundamental metrics to monitor climate change. However, due to sparse observation sampling before the 1950s, accurate observation‐based estimations only exist for the second half of the 20th century. A 16‐member ensemble of historical ocean reanalyses is used for the first time to compile a unique estimate of 20th century oceanic warming rates. The reanalyses combine dynamical ocean general circulation models with historical observations and observation‐based atmospheric forcing. Ocean heat content tendencies (OHCT) from the multireanalysis ensemble (MRE) agree well with independent estimates of ocean heat content, and show a coherent evolution with records of Earth's energy imbalance from atmospheric reanalyses and atmospheric CO2concentration at a range of timescales. OHCT from reanalyses proves to be a more effective climate change proxy, that is, more closely related to independent climate indexes, than observed surface warming tendencies that contain high‐frequency variability not related to the climate change signature, or historical coupled model simulations, which neglect interannual fluctuations. The ensemble mean estimate of the century‐long ocean warming rate is 0.26 ± 0.08 W m−2. The warming rate of 0.84 ± 0.21 W m−2estimated from 1993 onwards is unprecedented. The global decadal warming rate is persistently positive from about 1925 onwards, except for two neutral periods. The Indian Ocean exhibits the highest relative contribution to centennial heat accumulation, while the Atlantic Ocean plays an increasingly prominent role, especially during the 1995–2004 decade. These findings are in agreement with previous studies.
Bilateral asymmetry of bone density adjacent to pelvic sarcomas: A retrospective study using computed tomography
Authors: Baines Andrew J. , Babazadeh‐Naseri Ata , Dunbar Nicholas J. , Lewis Valerae O. , Fregly Benjamin J.
Published: April 2021

Limb‐salvaging hemipelvectomy surgeries involving allograft or custom prosthesis reconstruction require high quality remaining pelvic bone for adequate device fixation. Modeling studies of custom pelvis prosthesis designs typically mirror contralateral pelvic bone material properties to the ipsilateral pelvis. However, the extent of bone material property and geometric symmetry, and thus the appropriateness of mirroring, remains unknown and should be considered when designing or analyzing the performance of pelvic prostheses. This study investigates preoperative differences between ipsilateral and contralateral pelvic bone for patients with a pelvic sarcoma. Computed tomography (CT) data were obtained retrospectively from eight patients with a pelvic sarcoma. Subject‐specific computational models of the pelvic bones were constructed from the CT data. Bilateral asymmetry of bone material properties and cross‐sectional areas between the ipsilateral and contralateral hemipelvis were quantified at points adjacent to the pelvic sarcoma. Large bilateral asymmetry (>20%) in trabecular but not cortical bone density was observed within 20 mm of the tumor location. Differences in trabecular bone density typically declined with increased distance from the tumor. The greatest bilateral difference in cross‐sectional area occurred within 10 mm of the tumor boundary for three patients and within 40 mm from the tumor site for four patients. Our results suggest that pelvic sarcomas can cause significant bilateral asymmetries in trabecular bone density for patients with a pelvic sarcoma. These differences should be taken into account when designing custom implants for this patient population.
The cervical spine demonstrates less postoperative bone loss than the lumbar spine
Authors: Salzmann Stephan N. , Okano Ichiro , Miller Courtney Ortiz , Chiapparelli Erika , Reisener Marie‐Jacqueline , Amini Dominik Adl , Winter Fabian , Shue Jennifer , Carrino John A. , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: April 2021

The objective of this study is to determine the bone mineral density (BMD) changes in adjacent vertebra following anterior cervical discectomy and fusion (ACDF). Consecutive patients undergoing ACDF with available preoperative and postoperative computed tomography (CT) imaging were included. Quantitative CT measurements of screw‐free cervical and first thoracic vertebra were performed. Comparisons between pre‐ and postoperative BMD in the vertebrae one or two levels above the upper instrumented vertebra (UIV + 1, UIV + 2) and one level below the lowest instrumented vertebra (LIV + 1) were assessed. Seventy‐two patients (men, 66.7%) met the inclusion criteria. The patient population was 91.7% Caucasian with a mean age of 55.0 years. The mean interval (±SD) between surgery and secondary CT was 157 ± 23 days. Preoperative BMD (±SD) in UIV + 1 was 300.6 ± 66.2 mg/cm3. There was a significant BMD loss of 1.5% at UIV + 1 after surgery, resulting in a postoperative BMD of 296.2 ± 64.8 mg/cm3 (p = .029). At UIV + 2 and LIV + 1, no significant differences between pre‐ and postoperative BMD (304.7 ± 75.7 mg/cm3 vs. 299.8 ± 74.3 mg/cm3, 197.3 ± 50.4 mg/cm3 vs. 200.8 ± 48.7 mg/cm3, p = .113 and p = .078, respectively) were observed.

Clinical significance

Our results demonstrate a small BMD decrease of 1.5% at UIV + 1. This suggests that the effect of ACDF surgery on the adjacent levels might be smaller compared to the previously described lumbar BMD loss of 10%–20% following posterior lumbar fusion procedures.
Smokeless tobacco analysis: Simultaneous extraction and purification of alkaloids, volatile N‐nitrosamines, and polycyclic hydrocarbons for GC‐MS/MS
Authors: Wang Xiaoyu , Qin Yaqiong , Nie Cong , Guo Junwei , Pan Lining , Xie Fuwei , Wang Sheng , Wang Bing , Zhao Xiaodong , Wang Baolin , Jia Guotao
Published: April 2021

Several smokeless tobacco products are available in the market and comprise complex chemical matrices. Sample preparation for analysis of the multiple classes of harmful compounds in smokeless tobacco products is highly cumbersome. In this study, a simultaneous extraction scheme was developed for three toxic analyte classes in smokeless tobacco products using a two‐phase solution consisting of 5% aqueous NaOH and dichloromethane in a 1:4 ratio. The dichloromethane extract was used to analyze four alkaloids directly at levels greater than parts per million; however, passing the layer through a silica cartridge for further purification and concentration was necessary for determining 18 polycyclic aromatic hydrocarbons and four volatile N‐nitrosoamines at the ppt level. The multitargets were determined by using gas chromatography with tandem mass spectrometry. The limits of detection for the 18 polycyclic aromatic hydrocarbons, four volatile N‐nitrosoamines, three minor alkaloids, and nicotine were 0.2‐1.2, 0.2‐0.4, 0.6‐1.0, and 10.2 μg/g, respectively. Four different smokeless tobacco substrates were fortified with three levels of mixed standards, and the recoveries ranged between 83 and 110%. The method was highly efficient, reduced the sample amounts, solvents, and the time required by approximately 60%. The method was used to assay 18 smokeless tobacco products, and showed potentials in assaying drugs and other plant‐based substrates.