bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing a Strategy Trial for the Management of Gout: The Use of a Modified Delphi Panel
Authors: Solomon Daniel H. , Weissman Joel S. , Choi Hyon , Atlas Steven J. , Berardinelli Cesar , Dedier Julien , Fischer Michael A. , Fitzgerald John , Hinteregger Erica , Johnsen Brianne , Marini Diana D. , McLean Robert , Murray Fred , Neogi Tuhina , Oertel Lynn B. , Pillinger Michael H. , Riggs Kevin R. , Saag Ken , Suh Dong , Watkins James , Barry Michael J.
Published: May 2021

Objective

Disagreement exists between rheumatology and primary care societies regarding gout management. This paper describes a formal process for gathering input from stakeholders in the planning of a trial to compare gout management strategies.

Methods

We recruited patients, nurses, physician assistants, primary care clinicians, and rheumatologists to participate in a modified Delphi panel (mDP) to provide input on design of a trial focused on optimal management for primary care patients with gout. The 16 panelists received a plain‐language briefing document that discussed the rationale for the trial, key clinical issues in gout, and aspects of trial design. The panelists also received information and considerations on nine voting questions (VQs), judged to be the key design questions. Cognitive interviews with panelists ensured that the VQs were understood by the range of panelists involved in the mDP. Panelists were asked to score all VQs from 1 (definitely no) to 9 (definitely yes). Two voting rounds were conducted—round 1 by email and round 2 by video conference.

Results

The VQs were modified through the cognitive interviews. The round 1 voting resulted in consensus on eight items, with consensus defined as median voting score in the same tercile (1‐3, 4‐6 or 7‐9). Re‐voting at the meeting (round 2) reached consensus on the remaining item.

Conclusion

An mDP with various stakeholders facilitated consensus on the design of a trial of different management strategies for chronic gout. This method may be useful for designing trials of clinical questions with substantial disagreement across stakeholders.
Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
Authors: Giles Jon T. , Rist Pamela M. , Liao Katherine P. , Tawakol Ahmed , Fayad Zahi A. , Mani Venkatesh , Paynter Nina P. , Ridker Paul M. , Glynn Robert J. , Lu Fengxin , Broderick Rachel , Murray Meredith , Vanni Kathleen M. M. , Solomon Daniel H. , Bathon Joan M.
Published: May 2021

Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18‐Fluorodeoxyglucose [18F‐FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full‐body 18F‐FDG–labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat‐to‐target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target‐to‐background ratio of arterial 18F‐FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease‐modifying antirheumatic drugs.
ABHW: Federal court overstepped bounds in rejecting insurer guidelines in Wit
Authors: Enos Gary
Published: May 2021

The national association representing managed behavioral health care companies has formally weighed in on the appeal of the landmark Wit v. United Behavioral Health court ruling, arguing in a filing that the U.S. District Court overstepped its authority in ruling that UBH's coverage guidelines were contrary to generally accepted standards of care.
HHS exempts bupe prescribers with 30 patients from training
Authors: Knopf Alison
Published: May 2021

Last week, the Department of Health and Human Services (HHS) announced new “practice guidelines” allowing prescribers of buprenorphine for opioid use disorder an exemption from the x‐waiver's training requirements, as long as they have 30 patients or fewer.
White House nominates Delphin‐Rittmon, for SAMHSA head
Authors: Knopf Alison
Published: May 2021

Miriam E. Delphin‐Rittmon, M.D., since 2015 the commissioner of the Connecticut State Department of Mental Health and Addiction Services, was nominated to be assistant secretary for mental health and substance use at the federal Department of Health and Human Services by the White House last week. In her role as SSA (Single State Authority), Delphin‐Rittmon has been committed to promoting recovery‐oriented, integrated and culturally responsive services and systems that foster dignity, respect and meaningful community inclusion. In addition, through her 20‐year career in the behavioral health field, Delphin‐Rittmon has extensive experience in the design, evaluation and administration of mental health, substance use and prevention services and programs, and has received several awards for advancing policy in these areas. Most recently, she received the 2019 State Service Award from the National Association of State Drug and Alcohol Directors and the 2016 Mental Health Award for Excellence from the United Nations Committee on Mental Health.
1D p–n Junction Electronic and Optoelectronic Devices from Transition Metal Dichalcogenide Lateral Heterostructures Grown by One‐Pot Chemical Vapor Deposition Synthesis
Authors: Najafidehaghani Emad , Gan Ziyang , George Antony , Lehnert Tibor , Ngo Gia Quyet , Neumann Christof , Bucher Tobias , Staude Isabelle , Kaiser David , Vogl Tobias , Hübner Uwe , Kaiser Ute , Eilenberger Falk , Turchanin Andrey
Published: May 2021

Lateral heterostructures of dissimilar monolayer transition metal dichalcogenides provide great opportunities to build 1D in‐plane p–n junctions for sub‐nanometer thin low‐power electronic, optoelectronic, optical, and sensing devices. Electronic and optoelectronic applications of such p–n junction devices fabricated using a scalable one‐pot chemical vapor deposition process yielding MoSe2‐WSe2 lateral heterostructures are reported here. The growth of the monolayer lateral heterostructures is achieved by in situ controlling the partial pressures of the oxide precursors by a two‐step heating protocol. The grown lateral heterostructures are characterized structurally and optically using optical microscopy, Raman spectroscopy/microscopy, and photoluminescence spectroscopy/microscopy. High‐resolution transmission electron microscopy further confirms the high‐quality 1D boundary between MoSe2 and WSe2 in the lateral heterostructure. p–n junction devices are fabricated from these lateral heterostructures and their applicability as rectifiers, solar cells, self‐powered photovoltaic photodetectors, ambipolar transistors, and electroluminescent light emitters are demonstrated.
Mimicking the Human Tympanic Membrane: The Significance of Scaffold Geometry
Authors: Anand Shivesh , Stoppe Thomas , Lucena Mónica , Rademakers Timo , Neudert Marcus , Danti Serena , Moroni Lorenzo , Mota Carlos
Published: May 2021

The human tympanic membrane (TM) captures sound waves from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations is attributed to the unique architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important for fabricating functional TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue‐engineered TM scaffolds. Three test designs along with a plain control are chosen to decouple some of the dominant structural elements, such as the radial and circumferential alignment of the collagen fibrils. In silico models suggest a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers is observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing has been optimized to manufacture biomimetic scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macroindentation and laser Doppler vibrometry corroborate the computational findings. Finally, biological studies with human dermal fibroblasts and human mesenchymal stromal cells reveal a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition.
Bloch Oscillations of Hybrid Light‐Matter Particles in a Waveguide Array
Authors: Beierlein J. , Egorov O. A. , Harder T. H. , Gagel P. , Emmerling M. , Schneider C. , Höfling S. , Peschel U. , Klembt S.
Published: May 2021

Bloch oscillations are a phenomenon well known from quantum mechanics where electrons in a lattice experience an oscillatory motion in the presence of an electric field gradient. Here, the authors report on Bloch oscillations of hybrid light−matter particles, called exciton‐polaritons (polaritons), being confined in an array of coupled microcavity waveguides. To this end, the waveguide widths and their mutual couplings are carefully designed such that a constant energy gradient is induced perpendicular to the direction of motion of the propagating polaritons. This technique allows us to directly observe and study Bloch oscillations in real‐ and momentum‐space. Furthermore, the experimental findings are supported by numerical simulations based on a modified Gross–Pitaevskii approach. This work provides an important transfer of basic concepts of quantum mechanics to integrated solid state devices, using quantum fluids of light.
Self‐Powered and Spectrally Distinctive Nanoporous Ga2O3/GaN Epitaxial Heterojunction UV Photodetectors
Authors: Chen Tiwei , Zhang Xiaodong , Ma Yongjian , He Tao , Wei Xing , Tang Wenbo , Tang Wenxin , Zhou Xin , Fu Houqiang , Zhang Li , Xu Kun , Zeng Chunhong , Fan Yaming , Cai Yong , Zhang Baoshun
Published: May 2021

Herein, self‐powered spectrally distinctive UV photodetectors (PDs) based on nanoporous epitaxial Ga2O3/GaN heterojunctions grown by metalorganic chemical vapor deposition (MOCVD) are reported. The nanoporous structures are formed by a novel self‐reactive etching (SRE) method, which significantly enhances the device performance. PDs with different porosities are fabricated and compared. In the self‐powered mode, the PD with the highest nanopore porosity exhibits the best performance, with an ultralow dark current of 0.04 nA, a fast photoresponse speed, and a high responsivity of 43.9 mA W−1 (35.8 mA W−1) under 254 nm (365 nm) illumination, which is 800% higher than that of the reference device without the porous structure. Furthermore, opposite current polarities are observed in the PDs under different illumination spectra, the mechanism of which is explained by the carrier transportation using the device band diagrams. This phenomenon can be used to distinguish different incident spectra, opening the door to more new applications. This work represents one of the first spectrally distinctive self‐powered UV PDs based on nanoporous Ga2O3/GaN heterojunctions and significantly benefits the development of multifunctional UV PDs.
Circularly Polarized Transmissive Meta‐Holograms with High Fidelity
Authors: Li Xiaofeng , Hou Haisheng , Liu Kaiyue , Lou Jing , Wang Guangming , Cai Tong
Published: May 2021

Holography has attracted considerable interest because of its excellent capacity of recording and perfectly reconstructing the target information. The emergence of metasurfaces provides a new medium to code holograms in the subwavelength scale. Phase‐based holograms reported so far intrinsically decrease the image fidelity, because the amplitude information is ignored, especially for circularly polarized (CP) holograms. Herein, a novel strategy is proposed to achieve complex‐amplitude (CA) meta‐holography for CP transmissive waves with high fidelity and high polarization purity. Two cascaded patches are used to realize an amplitude modulation of 0–0.97 and a 2π phase shift in the microwave region. To verify and prove the concept, two CA meta‐holograms are designed, fabricated, and measured. The theoretical structural similarity index is 0.94 for the meta‐hologram reconstructing the letter “L” and 0.89 for the meta‐hologram reconstructing the Chinese character “”. It is experimentally demonstrated that the proposed CA method performs better, yielding higher‐accuracy reconstructed images than the phase‐only method. The polarization purity in the reconstructed images can be higher than 20 dB. The finding paves the way for synthesizing arbitrary wave‐front shapes and can find several applications in communication systems, imaging construction, and information processing.
Construction of Oxepino[3,2‐b]indoles via [4+3] Annulation of 2‐Ylideneoxindoles with Crotonate‐Derived Sulfur Ylides
Authors: Fei Xing‐Hai , Zhao Yong‐Long , Yang Fen‐Fen , Guan Xiang , Li Zong‐Qin , Wang Da‐Peng , Zhou Meng , Yang Yuan‐Yong , He Bin
Published: May 2021

A [4+3] annulation of 2‐ylideneoxindoles with crotonate‐derived sulfur ylides has been developed. A series of oxepino[3,2‐b]indoles were prepared in moderate to excellent yields (62‐93%) under mild conditions. Moreover, the synthetic oxepino[3,2‐b] indoles can be further transformed into more complex cyclopropa[5,6]oxepino[3,2‐b]indoles via a [2+1] cyclopropanation. In addition, the synthetic compounds show certain antiproliferative activity against K562 and MCF‐7 cells, and its IC50 values for these two kinds of tumor cells up to 5.40±0.88 μM and 18.41±0.50 μM, respectively.

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Molecular Structure Effects on the Aggregation Motif of Porphyrins: Computational Insights
Authors: Politi Antiope T. , Politis Achilleas , Seton Linda
Published: May 2021

The latest advancements in semiempirical Hamiltonians have inspired new confidence for the supramolecular computational predictivity. The advanced accuracy of newly developed semiempirical methods is offered for computations of what can provide a valuable database of molecular tuning recommendations for the synthesis of new supramolecular materials. In this work the very versatile and impactful porphyrin is employed for examination of the first basic chemical tuning factors that may drive specific aggregation motifs. The 1D motifs are examined as a function of peripheral substituent steric bulk. Subsequently, a 1D‐wire versus a 3D‐square motif is investigated as a function of the metal–ligand effect. For the first time, an interesting effect of misprediction of semiempirical computations is encountered for a small class of these aggregates and is briefly examined with a conformational search analysis. These findings encourage further in silico work which is greatly required for diminishing the current discovery bottleneck in supramolecular chemistry.
Ultrahigh‐Uptake Capacity‐Enabled Gas Separation and Fruit Preservation by a New Single‐Walled Nickel–Organic Framework
Authors: Li Yong‐Peng , Zhao Yong‐Ni , Li Shu‐Ni , Yuan Da‐Qiang , Jiang Yu‐Cheng , Bu Xianhui , Hu Man‐Cheng , Zhai Quan‐Guo
Published: May 2021

High gas‐uptake capacity is desirable for many reasons such as gas storage and sequestration. Moreover, ultrahigh capacity can enable a practical separation process by mitigating the selectivity factor that sometimes compromises separation efficiency. Herein, a single‐walled nickel–organic framework with an exceptionally high gas capture capability is reported. For example, C2H4 and C2H6 uptake capacities are at record‐setting levels of 224 and 289 cm3 g−1 at 273 K and 1 bar (169 and 110 cm3 g−1 at 298 K and 1 bar), respectively. Such ultrahigh capacities for both gases give rise to an excellent separation performance, as shown for C2H6/C2H4 with breakthrough times of 100, 60 and 30 min at 273, 283 and 298 K and under 1 atm. This new material is also shown to readily remove ethylene released from fruits, and once again, its ultrahigh capacity plays a key role in the extraordinary length of time achieved in the preservation of the fruit freshness.
Physiology‐Based Stretchable Electronics Design Method for Accurate Surface Electromyography Evaluation
Authors: Wang Shengming , Dong Shurong , Li Wenjuan , Cen Jin , Zhu Huimin , Fu Congyi , Jin Hao , Li Yucong , Feng Xue , Luo Jikui , Xie Zhenwei
Published: May 2021

Stretchable electronics‐based surface electromyography (sEMG) evaluation devices are expected to play a big role in clinical diagnosis. However, the stability and quality of the signals collected by existing stretchable electronics are too poor, especially when muscle movement is involved, making them inappropriate for high standard clinical diagnosis. Here, a physiology‐based design method for stretchable electronics and a novel airbag‐type stretchable electrode array (ASEA) device for assessment of the complex female pelvic floor muscle (PFM) is proposed. Clinical trials show that the ASEA device is able to provide stable contact interface and multi‐channel accurate data acquisition. The stability and quality of the sEMG signal are much better than those obtained by the existing stretchable electronics‐based PFM electrode devices. Furthermore, a muscle‐unit evaluation method (MUEM) to assess the PFM complex state is proposed, especially its cross‐interaction between muscles. Clinical trials show that MUEM can accurately and comprehensively assess PFM state and the correlations between main muscles, which unveils the mechanisms of some special muscle states that are not possible using traditional methods. This proof of concept research holds the promise for the development of new diagnostic strategies for muscle pathological research, and has the potential for clinical application and general implication.
N,P‐Codoped, Low‐Density, Amorphous Carbon Foam for High‐Performance Supercapacitors: Polymer‐Based Scalable Production at Low Cost
Authors: Paul Rajib , Price Erik J. , Roy Ajit K. , Wnek Gary E.
Published: May 2021

Herein, a large‐scale production of low‐dense (1.7–2.0 mg cc−1) amorphous carbon foam (char) is demonstrated by simple combustion of an epoxy‐based intumescent composite followed by annealing in argon at 600–900 ºC. It is observed that a balance among physical, chemical, and structural characteristics results in highest electrochemical energy storage performance. For example, the char annealed at 700 ºC (ATA 700) has a specific surface area of 970.55 m2 g−1, a highest pore width diversity (1.87–212.26 nm), moderate sp2‐C and N,P heteroatom contents, highest graphitic‐N, and moderate C–P binding networks. These characteristics promote 1109.7 and 310.4 F g−1 specific capacitances in ATA 700 char with 1 m H2SO4 for three and two electrode cell configurations, respectively, at 0.1 A g−1 specific current. Importantly, the cell demonstrates 97.25% coulombic efficiency and 86.3% capacitance retention after 20 000 charge–discharge cycles (8 A g−1). A highest energy density of 43.1 Wh kg−1 and 20 kW kg−1 peak power density are attained. Such performances are attributed to the hierarchically distributed mesopores and micropores for efficient charge and mass transports along with suitable heteroatoms contents. Therefore, this study brings enormous promise for low‐cost and scalable production of efficient electrodes for electrochemical energy storage.
Convolutional neural nets in chemical engineering: Foundations, computations, and applications
Authors: Jiang Shengli , Zavala Victor M.
Published: May 2021

In this article, we review the mathematical foundations of convolutional neural nets (CNNs) with the goals of: (i) highlighting connections with techniques from statistics, signal processing, linear algebra, differential equations, and optimization, (ii) demystifying underlying computations, and (iii) identifying new types of applications. CNNs are powerful machine learning models that highlight features from grid data to make predictions (regression and classification). The grid data object can be represented as vectors (in 1D), matrices (in 2D), or tensors (in 3D or higher dimensions) and can incorporate multiple channels (thus providing high flexibility in the input data representation). CNNs highlight features from the grid data by performing convolution operations with different types of operators. The operators highlight different types of features (e.g., patterns, gradients, geometrical features) and are learned by using optimization techniques. In other words, CNNs seek to identify optimal operators that best map the input data to the output data. A common misconception is that CNNs are only capable of processing image or video data but their application scope is much wider; specifically, datasets encountered in diverse applications can be expressed as grid data. Here, we show how to apply CNNs to new types of applications such as optimal control, flow cytometry, multivariate process monitoring, and molecular simulations.
Liquid Metal‐Based Strain Sensor with Ultralow Detection Limit for Human–Machine Interface Applications
Authors: Wu Yuanzhao , Zhou Youlin , Asghar Waqas , Liu Yiwei , Li Fali , Sun Dandan , Hu Chao , Wu Zhenguang , Shang Jie , Yu Zhe , Li Run-Wei , Yang Huali
Published: May 2021

Flexible strain sensors play vital role in human–machine interaction. Despite their vast development, a strain sensor having broad strain sensing range, ultralow detection limit, and negligible hysteresis still remains a challenge. Herein, a liquid metal (LM)‐based stretchable resistive strain sensor, prepared by selective wetting and transferring process to attain improved compatibility between LM and polydimethylsiloxane substrate, is reported. This sensor exhibits broad strain sensing range (105%), with ultralow detection limit (0.05%), minimal hysteresis, fast response time (58 ms), and excellent repeatability. When practically demonstrated, this sensor successfully monitored various human activities, such as blink motion monitoring, voice intensity differentiation, heartbeat and wrist pulse monitoring. Moreover, when the current sensor is used in the form of smart kneecap and smart glove, it efficiently detected various human gestures, which confirms its great application potential in the fields of human health and motion monitoring, human–machine interface, and virtual reality applications.
Quantum Logic Gates Based on DNAtronics, RNAtronics, and Proteintronics
Authors: Sheu Sheh-Yi , Hsu Hua-Yi , Yang Dah-Yen
Published: May 2021

Quantum computers (QCs) adopt ann‐state quantum mechanical system to manipulate the superposition state. However, molecular transistors are not used to build up the quantum logic gate. Herein, it is demonstrated that DNA, RNA, and protein are promising media for QCs, and one uses residue pairs, including nucleotide base pairs and amino acid pairs, via proton‐coupled electron transfer to fabricate a quantum logic gate. In the residue pair, the proton transfer between donor and acceptor states fulfills a qubit. Both the DNA‐CG (3‐qubit) nucleobase pair and nucleotide base pair obey the Toffoli gate. AT (2‐qubit) nucleotide base pair behaves as a SWAP gate and a CNOT gate. Furthermore, the AU and RNA‐CG nucleotide base pairs follow the CNOT gate and Toffoli gate, respectively. In addition, a pair of amino acids achieves 1‐qubit and satisfies the Pauli‐X, ‐Y, and ‐Zgates. The generators of universal quantum logic gates are obtained.
Liquid Metal Enabled Biodevices
Authors: Cole Tim , Khoshmanesh Khashayar , Tang Shi-Yang
Published: May 2021

Biodevices are crucial for monitoring vital physiological signals, managing chronic health conditions, developing artificial organs for assisting people with disabilities, and conducting various clinical and surgical procedures. However, existing biodevices are mostly composed of rigid components, which can cause discomfort to the user, whereas the high stiffness of implants is known to be the major cause of inflammation and scarring. Gallium‐based liquid metals are intrinsically soft and possess desirable properties, including low toxicity, high conductivity, and deformability, which make them ideally suited for developing soft, deformable, reconfigurable, and healable biodevices. Herein, recent advancements in the emerging field of liquid‐metal‐based biodevices are discussed. This includes a description of the properties of gallium‐based liquid metals which make them so distinct from conventional materials, a brief outline of various techniques devised for fabrication of liquid‐metal‐based devices/structures, and an overview of the diverse range of wearable or implantable liquid‐metal‐enabled biodevices. The outlook and challenges are also discussed.
Morphological analysis of new Dryas Monkey specimens from the Central Congo Basin: Taxonomic considerations and an emended diagnosis
Authors: Gilbert Christopher C. , Gilissen Emmanuel , Arenson Julia L. , Patel Biren A. , Nakatsukasa Masato , Hart Terese B. , Hart John A. , Detwiler Kate M. , Sargis Eric J.
Published: May 2021

Objectives

The little known guenon Cercopithecus dryas has a controversial taxonomic history with some recognizing two taxa (C. dryas and C. salongo) instead of one. New adult specimens from the TL2 region of the central Congo Basin allow further assessment of C. dryas morphology and, along with CT scans of the juvenile holotype, provide ontogenetically stable comparisons across all C. dryas and “C. salongo” specimens for the first time.

Materials and Methods

The skins and skulls of two newly acquired C. dryas specimens, male YPM MAM 16890 and female YPM MAM 17066, were compared to previously described C. dryas and “C. salongo” specimens, along with a broader guenon comparative sample (cranial sample n = 146, dental sample n = 102). Qualitative and quantitative assessments were made on the basis of commonly noted pelage features as well as craniodental characters in the form of shape ratios and multivariate discriminant analyses.

Results

All C. dryas specimens, including the TL2 adults, are comparatively small in overall cranial size, have relatively small I1s, and display tall molar cusps; these osteological characters, along with pelage features, are shared with known “C. salongo” specimens. Discriminant analyses of dental features separate C. dryas/salongo specimens from all other guenons.

Discussion

In addition to pelage‐based evidence, direct osteological evidence suggests “C. salongo” is a junior synonym of C. dryas. Combined with molecular analyses suggesting C. dryas is most closely related to Chlorocebus spp., we emend the species diagnosis and support its transfer to Chlorocebus or possibly a new genus to reflect its distinctiveness.
Footloose: Articular surface morphology and joint movement potential in the ankles of lorisids and cheirogaleids
Authors: Yapuncich Gabriel S. , Granatosky Michael C.
Published: May 2021

Objectives

The competing functional demands of diarthrodial joints, permitting mobility while retaining enough stability to transmit forces across the joint, have been linked with the shape and size of the joint's articular surfaces. A clear understanding of the relationship between joint morphology and joint movement potential is important for reconstructing locomotor behaviors in fossil taxa.

Methods

In a sample of matched tali and calcanei of lorisids (n = 28) and cheirogaleids (n = 38), we quantify the surface areas of the talar and calcaneal ectal (=posterior talocalcaneal) articular surfaces and model the principal curvatures of these surfaces with quadric formulas. These two taxonomic groups have similar body masses, but differ substantially in positional behavior, so that differences in joint surface morphology should reflect adaptive demands of their locomotor behavior.

Results

Compared with cheirogaleids, lorisids exhibit: (a) a significantly greater area difference between their paired joint surfaces; and (b) a more pronounced saddle shape for the talar ectal facet.

Conclusion

The increased subtalar joint mobility observed in lorisids may be achieved by increasing the amount of sliding and rolling that can occur at the subtalar joint. The subtalar joint morphology observed in two fossil euarchontans, the plesiadapiforms Purgatorius sp. and Plesiadapis cookei, compares favorably with the morphology observed among lorisids, potentially suggesting antipronograde postures within these extinct taxa.
Production of biodegradable rods of polycaprolactone/olanzapine for potential application in treatment of Schizophrenia
Authors: de Almeida Hellen Regina Oliveira , de Carvalho Patricio Beatriz Ferreira , do Anjos Garcia Yasmin , da Silva Talita Goulart , Pereira Debora Baptista , Sarcinelli Michelle Alvares , Rocha Helvécio Vinícius Antunes , Mendonça Roberta Helena
Published: May 2021

Olanzapine (OLZ) is a commonly antipsychotic used to treat schizophrenia, a mental illness, with fewer side effects when compared with other drugs of the same class. It is commercialized mainly as oral tablets and orally disintegrating tablets. However, this drug oral bioavailability is affected by the first pass effect and low solubility in water. This requires high daily doses that can cause more side effects and poor treatment compliance. Also, the frequency of frequency of tablet intake is commonly related to patients' abandonment of schizophrenia treatment. So, the development of implantable biomaterials for OLZ delivery can be an alternative to solve both problems, since this material can, potentially, be used subcutaneously in less frequent administrations, thus the treatment has a greater chance of success. Therefore, the objective of this work was to produce polycaprolactone (PCL) rods incorporated with OLZ by hot‐melt extrusion technique. The rods were characterized by different techniques, which showed an amount of 6.78 ± 0.56 mg of OLZ per rod. The in vitro release studies were performed and they showed a controlled release of the drug that followed the Higuchi's model. These results indicated that the PCL/OLZ rods have potential application in the schizophrenia treatment.
Rapid response of fish and aquatic habitat to removal of a tidal barrier
Authors: Sun Jingrui , Galib Shams M. , Lucas Martyn C.
Published: May 2021

River barrier removal is used increasingly as a conservation tool to restore lotic habitat and river connectivity, but evidence of its efficacy is incomplete. This study used a before–after methodology to determine the effects of removing a tidal‐limit barrier on the fishes, macroinvertebrates, and habitats of an English coastal stream.

Following barrier removal, habitat diversity increased immediately upstream and remained similar downstream. Mobilized silt altered the substrate composition immediately downstream, but this was temporary as silt was flushed out the following winter. Changes to macroinvertebrate communities occurred upstream and downstream of the former barrier but these were transient.

A dramatic and sustained increase in fish density occurred immediately upstream of the barrier after its removal, but effects downstream were minor. The fish community upstream changed, largely due to rapid recruitment and dispersal of endangered European eel (Anguilla anguilla). Eel density in the formerly impounded zone increased from 0.5 per 100 m2 before barrier removal to 32.5 per 100 m2 5 months after removal. By 17 months after barrier removal there was no difference in eel density across the six sections sampled.

Although resident stream fishes such as bullhead (Cottus gobio species complex, protected under the European Habitats Directive) were abundant in middle and upper‐stream sections, brown trout (Salmo trutta, a listed species for biodiversity conservation in England and Wales) density remained low during the study and recruitment was poor. This suggests that although colonization access for anadromous trout was available, habitat upstream may have been unsuitable for reproduction, indicating that wider catchment management is required to complement the restoration of connectivity.

These findings suggest that tidal barrier removal is an effective method of restoring lotic habitats and connectivity, and can be beneficial for resident and migratory fishes including those of conservation importance (e.g. European eel) in coastal streams.
Highly Diastereoselective Hydrosilane‐Assisted Rhodium‐Catalyzed Spiro‐Type Cycloisomerization of Succinimide and Pyrazolone‐Based Functional 1,6‐Dienes
Authors: Li Hui‐Lin , Huang Wei‐Sheng , Ling Fang‐Ying , Li Li , Yan Jun‐Hao , Xu Hao , Xu Li‐Wen
Published: May 2021

Organosilicon compounds are important reagents and synthetic intermediates that play a key role in the construction of new materials and complex products. Here we show a highly diastereoselective rhodium‐catalyzed cycloisomerization of 1,6‐dienes, in which the use of (EtO)3SiH accelerates the intramolecular cyclization reaction to afford a novel spiro‐fused succinimide and pyrazolone derivatives in moderate to excellent yields as a single diastereoisomer. The proposed mechanism involves an active Rh−H species from the hydrosilane that is the H‐donor in this spiro‐type cycloisomerization reaction.
A segmented energy‐based nonlinear tracking control method for quadrotor transport system
Authors: Qi Juntong , Ping Yuan , Wang Mingming , Wu Chong
Published: May 2021

The safety of the quadrotor transport system (QTS) is always threatened by the suspension load swing under the fuselage during flight. At the same time, the QTS is affected by uncertainties such as changes in desired position and cable length. Trajectory planning is often neglected during the development of the controller. Moreover, there are some shortcomings in the most control methods such as the maximum speed, acceleration, payload swing, and transportation efficiency of the system that cannot be theoretically guaranteed. Therefore, a nonlinear tracking control method is proposed using the segmented energy, which can make the quadrotor move to the target position quickly and smoothly, meanwhile, suppress the heavy swing of the payload. Furthermore, it is proved that the method proposed in this paper can achieve the asymptotic stability of the system equilibrium point and converge to the expected value by Lyapunov theorem and LaSalle's invariance principle. Simulation results show that the control method achieves good control performance and strong robustness against system parameter uncertainty.
Twenty‐two testable hypotheses about phronesis: Outlining an educational research programme
Authors: Kristjánsson Kristján
Published: May 2021

The concept of phronesis enters educational discourse at various levels of engagement, and it continues to fascinate and frustrate educational theorists in equal measure. This article begins by charting the vagaries of three educational discourses on phronesis, and by eliciting insights from the recently burgeoning wisdom research within psychology. Mindful of the fact that making progress in the educational study of phronesis is not only a conceptual or philosophical endeavour but also an empirical one, the article elicits and illustrates 22 testable (but as yet mostly untested) hypotheses about phronesis from the Aristotelian and neo‐Aristotelian literatures and hence lays the foundation of an educational research programme on phronesis. A serviceable conceptualisation will need to offer ways to evaluate the educational credibility of each hypothesis in real life, rather than just serving as a new philosophical plaything.
Simple and eco‐friendly synthesis of crude orange‐peel‐derived carbon nanoparticles for detection of Fe3+ and ascorbic acid
Authors: Hu Yuanyuan , Ji Wenxuan , Sun Junxuan , Liu Xingyue , Zhou Run , Yan Jiaying , Zhang Nuonuo
Published: May 2021

Although fluorescence sensors based on carbon dots (CDs) have been developed widely, multicomponent detection using CDs without extra and tedious surface modification remains a challenge. Here, the crude carbon nanoparticles (CPs) as a fluorescence sensor were prepared through one‐pot hydrothermal process using orange peel as the precursor. The method was simple, rapid, economical, and eco‐friendly given that such extra steps as dialysis and lyophilization were not required. By adding ethanol into the reaction solvent, the fluorescence properties of orange‐peel‐derived CPs as well as their sensitivity of detecting Fe3+ with a limit of detection of 0.25 μM were improved. Additionally, orange‐peel‐derived CPs could be used as a fluorescence sensor for detection of ascorbic acid (AA) with a LOD of 5 μM. More importantly, the proposed fluorescence methods were successfully used to qualitatively and quantitatively analyze Fe3+ and AA in real samples. Recovery of Fe3+ from tap water was within the range 97.2–105.4%. Conversely, recovery of AA from vitamin C tablets and orange juices laid within the ranges 97.7–99.3% and 93.2–97.6%, respectively.
Multiple component‐pharmacokinetic studies on 10 bioactive constituents of Peiyuan Tongnao capsule using parallel reaction monitoring mode
Authors: Wang Chenxi , Xing Yanchao , Ding Hui , Wang Ping , Zhang Lihua , Fu Zhifei , Han Lifeng , Pang Xu
Published: May 2021

Peiyuan Tongnao capsule (PTC) plays an important role in clinical application due to its excellent curative efficacy in the treatment of ischemic stroke and chronic cerebral circulation insufficiency. To standardize and rationalize the clinical application of PTC, a rapid and sensitive method based on ultra‐high performance liquid chromatography/quadrupole‐Orbitrap mass spectrometry with parallel reaction monitoring (PRM) mode was developed and validated for the pharmacokinetic (PK) study. Ten bioactive compounds (aucubin, salidroside, echinacoside, paeoniflorin, verbascoside, liquiritin, 2,3,5,4′‐tetrahydroxy stilbene‐2‐O‐β‐d‐glucoside, coumarin, glycyrrhizic acid, and emodin) were simultaneously determined in rat plasma. All calibration curves exhibited good linearity (r2 > 0.99). The lower limits of quantification were 0.082–13.291 ng mL−1. The intra‐ and inter‐day precision was 0.54–12.36%, whereas the intra‐ and inter‐day accuracy ranged from 100.45 to 114.00%. The mean extraction recoveries were 81.77–117.66%, and the average matrix effects (MEs) were 86.23–109.96%. The high extraction recoveries and acceptable MEs indicated that the pretreatment method was feasible. And the stability was acceptable under various storage conditions and processing procedures. The validated method was successfully applied to the multiple components‐PK studies, which lay the foundation for further pharmacological and clinical research of PTC and may provide a reference for other traditional Chinese medicines.
LncRNA GAS8‐AS1 downregulates lncRNA NEAT1 to inhibit glioblastoma cell proliferation
Authors: Wu Xiaoming , Jiang Tingting , Huang Rui , Xiao Xue
Published: May 2021

Background

LncRNA GAS8‐AS1 has been reported to participate in several types of cancer, while its role in glioblastoma (GBM) is unknown. In the present study, we aimed to investigate the function of GAS8‐AS1 in GBM and the underlying mechanisms.

Methods

The expression levels of GAS8‐AS1 and NEAT1 in GBM patients and the healthy controls were measured by performing RT‐qPCR. Diagnostic values of plasma GAS8‐AS1 and NEAT1 for GBM were analyzed by performing ROC curve analysis with GBM patients as true positive cases and the healthy controls as true negative cases. Linear regression analysis was performed to study the correlation between the expression levels of GAS8‐AS1 and NEAT1. The expression levels of GAS8‐AS1 and NEAT1 in GBM cells were also determined by RT‐qPCR. CCK‐8 and transwell invasion assays were performed to detect the proliferation and invasion of GBM cells. Western blot assay was performed to detect the expression levels of β‐catenin, Axin2, c‐myc, cyclin D1, and GAPDH in GBM cells.

Results

GAS8‐AS1 was downregulated, while lncRNA NEAT1 was upregulated in the plasma of GBM patients. Altered expression levels of GAS8‐AS1 and NEAT1 distinguished GBM patients from the healthy controls. The expression of GAS8‐AS1 and NEAT1 was inversely correlated only in GBM patients. Overexpression of GAS8‐AS1 reduced the expression levels of NEAT1 in GBM cells, while knock‐down of GAS8‐AS1 increased the expression levels of NEAT1. However, overexpression of NEAT1 showed no significant effects on the expression of GAS8‐AS1. Knock‐down of GAS8‐AS1 promoted GBM cell proliferation and invasion and enhanced the activation of the Wnt/β‐catenin pathway. However, the effects of knock‐down of GAS8‐AS1 were alleviated by the knock‐down of NEAT1.

Conclusion

Overexpression of GAS8‐AS1 inhibits GBM cell proliferation and invasion by downregulating NEAT1.
Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort
Authors: Ito Katsuhiro , Kobayashi Takashi , Kojima Takahiro , Hikami Kensuke , Yamada Takeshi , Ogawa Kosuke , Nakamura Kenji , Sassa Naoto , Yokomizo Akira , Abe Takashige , Tsuchihashi Kazunari , Tatarano Shuichi , Inokuchi Junichi , Tomida Ryotaro , Fujiwara Maki , Takahashi Atsushi , Matsumoto Kazumasa , Shimizu Kosuke , Araki Hiromasa , Kurahashi Ryoma , Osaki Yu , Tashiro Yu , Uegaki Masayuki , Ogawa Osamu , Kitamura Hiroshi , Nishiyama Hiroyuki
Published: May 2021

Background

The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum‐refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug.

Methods

This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0–1, 2, and 3–4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2.

Results

The numbers of patients with PS 0–1, 2, and 3–4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil–lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors.

Conclusions

PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.
Competing risk nomogram predicting cancer‐specific mortality for endometrial cancer patients treated with hysterectomy
Authors: Xie Guilan , Qi Cuifang , Yang Wenfang , Wang Ruiqi , Yang Liren , Shang Li , Huang Liyan , Chung Mei Chun
Published: May 2021

Background

The incidence of endometrial cancer has tended to increase in recent years. However, competing risk nomogram combining comprehensive factors for endometrial cancer patients treated with hysterectomy is still scarce. Therefore, we aimed to build a competing risk nomogram predicting cancer‐specific mortality for endometrial cancer patients treated with hysterectomy.

Methods

Patients diagnosed with endometrial cancer between 2010 and 2012 were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database. Competing risk model was performed to select prognostic variables to build the competing risk nomogram to predict the cumulative 3‐ and 5‐year incidences of endometrial cancer‐specific mortality. Harrell's C‐index, receiver operating characteristic (ROC) curve, and calibration plot were used in the internal validation. And decision curve analysis was applied to evaluate clinical utility.

Results

A total of 10,447 patients were selected for analysis. The competing risk nomogram identified eight prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, and number of regional nodes positive. The C‐index of the competing risk nomogram was 0.857 (95% confidence interval [CI]: 0.854–0.859), and the calibration plots were adequately fitted. When the threshold probabilities were between 1% and 57% for 3‐year prediction and between 2% and 67% for 5‐year prediction, the competing risk nomogram was of good clinical utility.

Conclusions

A competing risk nomogram for endometrial cancer patients treated with hysterectomy was successfully built and internally validated. It was an accurately predicted and clinical useful tool, which could play an important role in consulting and health care management of endometrial cancer patients.
Variation of Essential Oil Content and Composition, Phenolics, and Yield Related Traits Using Different Pollination Systems in Populations of Thymus Species
Authors: Khanahmadi Faranak , Rahimmalek Mehdi , Sabzalian Mohammad R. , Tohidi Behnaz
Published: May 2021

The production of self‐pollinated plants could be important for improving medicinal plants secondary metabolites. In this study, 11 Thymus populations from eight species were evaluated to determine the effect of self and open pollination on agro‐morphological characteristics, total phenolic content (TPC), essential oil (EO) content, and EO components. Inbreeding led to some positive effects of above mentioned traits in most of the studied populations. Total phenolic content ranged from 7.07 to 52.69 mg tannic acid equivalents (TAE) g−1 dry weight (DW) in open pollinated derived populations, while it varied from 1.2 to 55.03 mg TAE g−1 DW in self‐pollinated ones. Under open and self‐pollination condition, the highest EO content was obtained in T. trautvetteri (3.37 %) and T. pubescens (1.96 %), respectively. Gas chromatography‐mass spectrometry (GC/MS) identified 42 compounds including thymol, carvacrol, linalool, p‐cymene, γ‐terpinene, terpinen‐4‐ol, and α‐terpineol as the main compounds. In most cases, selfed plants compared to open pollinated ones, revealed higher thymol content. T. daenensis‐1 showed a significant increase in thymol content (from 25.22 % to 74.3 %) due to self‐pollination. Moreover, self‐pollination led to emergence of some new compounds. Carvacrol methyl ether was the constituents of Thymus EO that are being reported in self‐pollinated populations. Finally, inbreeding in Thymus might be suggested as a useful tool to increase genetic homogeneity for the selection of superior plants for improving secondary metabolite.