bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of classification criteria for hand osteoarthritis: comparative analyses of persons with and without hand osteoarthritis
Authors: Haugen Ida K , Felson David T , Abhishek Abhishek , Berenbaum Francis , Bierma-Zeinstra Sita , Borgen Tove , Herrero Beaumont Gabriel , Ishimori Mariko , Jonsson Helgi , Kroon Féline PB , Maheu Emmanuel , Ramonda Roberta , Ritschl Valentin , Stamm Tanja A , van der Heijde Desirée , Wittoek Ruth , Greibrokk Elsie , Smeets Wilma , Kloppenburg Margreet
Published: June 2020

Objectives

Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.

Methods

In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC).

Results

Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies.

Conclusions

Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups.
Rheumatology practice amidst the COVID-19 pandemic: a pragmatic view
Authors: Romão Vasco C , Cordeiro Inês , Macieira Carla , Oliveira-Ramos Filipa , Romeu José Carlos , Rosa Carlos Miranda , Saavedra Maria João , Saraiva Fernando , Vieira-Sousa Elsa , Fonseca João Eurico
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic has come with many challenges for healthcare providers and patients alike. In addition to the direct burden it has placed on societies and health systems, it had a significant impact in the care of patients with chronic diseases, as healthcare resources were deployed to fight the crisis, and major travel and social restrictions were adopted. In the field of rheumatology, this has required notable efforts from departments and clinicians to adapt to the novelstatus quoand assure the follow-up of patients with rheumatic and musculoskeletal diseases. In the present viewpoint, we provide a practical approach to tackle this reality. Key measures include setting up preventive team management strategies, optimising communication with patients and reorganising patient care in all its dimensions. We then anticipate the nuances of rheumatology practice as restrictive measures are progressively lifted, while an effective vaccine is still pending. This includes the need to reimpose the same strategy as further waves unfold. Finally, we look ahead and address the lessons we can incorporate into post-COVID-19 rheumatology.
Mixed Mycobacterium avium subspecies avium and M avium subspecies paratuberculosis infection in a wild red deer (Cervus elaphus) in Belgium
Authors: Volpe Rosario , Fett Thomas , Cassart Dominique , Godfroid Jacques , Linden Annick
Published: June 2020

This report describes a mixed Mycobacterium avium subspecies avium and M avium subspecies paratuberculosis infection in a free‐ranging red deer (Cervus elaphus). The gross presentation was consistent with clinical paratuberculosis as previously reported in red deer and for other ruminants, with poor body condition, diarrhoea and mesenteric lymphadenitis. However, this animal presented unusual lung lesions, with necrosis and calcification similar to those reported for Mycobacterium bovis infection in wild and domestic ruminants. A mixed M avium subspecies avium and M avium subspecies paratuberculosis was shown by quantitative PCR (qPCR) performed on digestive tract samples. In addition, M avium subspecies avium was also detected in the respiratory tract (lungs and bronchial lymph nodes) by qPCR. These results were confirmed by classical bacteriology. Lesions induced by those mycobacteria cannot be differentiated from M bovis lesions. This point is particularly important with regards to increasing interactions between livestock and wild animals.
We will see future disease outbreaks if we don't speak out on the dangers of TCMs
Authors: Sturgeon Ben
Published: June 2020

Ben Sturgeon argues that the rise in unregulated wet markets and traditional Chinese medicine production will potentially lead to further disease outbreaks and loss of important animal populations.
Reactions of a pincer proligand with copper iodide: bridging instead of C–H metalation
Authors: Chahrour Taghrid , Castonguay Annie , Oguadinma Paul O. , Schaper Frank , Zargarian Davit
Published: June 2020

Various precursors of divalent copper have been treated with the meta-disubstituted phenylene-based proligand POC(H)OP (1,3-(i-Pr2PO)2C6H4) with the objective of preparing classical pincer complexes (POCOP)CuX. However, in no case was such species obtained, presumably owing to the difficult C–H metallation step. Analogous reactions of monovalent precursors were also unsuccessful, whereas reaction of POC(H)OP with CuI under different conditions gave the non-metallated adducts {(μ, κP, [Formula: see text]-POC(H)OP)Cu(μ-Ι)}2, 1, {(μ, κP, [Formula: see text]-POC(H)OP)Cu2(μ-Ι)2(DMAP)2}, 2 (DMAP = 4-dimethylaminopyridine), and {(μ, κP, [Formula: see text]-POC(H)OP)Cu2(μ3-Ι)2}2, 3. Treating 1 with DMAP gave the adduct 2, whereas 3 could be obtained by treating 1 with BuLi or by sublimation of 1. The solid state structures of these complexes revealed the tetrahedral geometry that might be anticipated for the d10 Cu(I) centers, in addition to fairly close I–H distances; on the other hand, no C–H interaction (agostic or otherwise) was observed with the Cu centers in any of these structures. The unsuccessful metallation of the C(2)–H moiety is thought to be a result of the strong preference of monovalent copper center to form bridging interactions with iodide and the POC(H)OP ligand; this appears to prevent the approach of the central carbon of the ligand to the Cu centers.
CDC Credence durum wheat
Authors: Pozniak C.J. , Clarke J.M. , Haile T.A.
Published: June 2020

CDC Credence durum wheat is adapted to the durum production area of the Canadian prairies. This conventional height durum wheat cultivar combines high grain yield potential with high grain and pasta color and low grain cadmium. CDC Credence is resistant to leaf, stem, and stripe rusts and common bunt and demonstrated end-use quality suitable for the Canada Western Amber Durum class.
Courant bracket found out to be T-dual to Roytenberg bracket
Authors: Ivanišević I. , Davidović Lj. , Sazdović B.
Published: June 2020

Bosonic string moving in coordinate dependent background fields is considered. We calculate the generalized currents Poisson bracket algebra and find that it gives rise to the Courant bracket, twisted by a 2-form $$2B_{\mu \nu }$$2Bμν. Furthermore, we consider the T-dual generalized currents and obtain their Poisson bracket algebra. It gives rise to the Roytenberg bracket, equivalent to the Courant bracket twisted by a bi-vector $$\Pi ^{\mu \nu }$$Πμν, in case of $$\Pi ^{\mu \nu } = 2 {^\star B}^{\mu \nu } = \kappa \theta ^{\mu \nu }$$Πμν=2⋆Bμν=κθμν. We conclude that the twisted Courant and Roytenberg brackets are T-dual, when the quantities used for their deformations are mutually T-dual.
Constraints on Newton’s constant from cosmological observations
Authors: Wang Ke , Chen Lu
Published: June 2020

Newton’s constant has observational effects on both the CMB power spectra and the light curves of SNIa. We use Planck data, BAO data and the SNIa measurement to constrain the varying Newton’s constant G during the CMB epoch and the redshift ranges of PANTHEON samples, and find no evidence indicating that G is varying with redshift. By extending the $$\Lambda $$ΛCDM model with one free parameter G, we get $$G =(6.65635_{-0.18560}^{+0.18766} ) \times 10^{-11} \text {m}^3\,\text {kg}^{-1}\,\text {s}^{-2}$$G=(6.65635-0.18560+0.18766)×10-11m3kg-1s-2 and $$H_0=67.62^{+1.24}_{-1.25}$$H0=67.62-1.25+1.24 km s$$^{-1}$$-1 Mpc$$^{-1}$$-1 at 68$$\%$$% CL from Planck$$+$$+BAO$$+$$+uncalibrated PANTHEON. The results show the value of G is consistent with CODATA 2018, but the $$H_0$$H0 tension can’t be solved in this way.
The Influence of Entrepreneurs’ Political Connections on Enterprise Innovation Intention
Authors: Su Yi , Wang Xue
Published: June 2020

Based on the data of the Growth Enterprise Market (GEM)-listed companies in the Shenzhen Stock Exchange of China, this paper researched the influence mechanism of political connections on enterprise innovation intention. This paper is based on the theory of reciprocal exchange of social capital. The research found that the entrepreneur’s political connections are detrimental to the improvement of enterprise innovation intention, and the differentiation strategy has a mediation effect between them. Moreover, the market competition intensity of enterprise production adjusts the influence of the differentiation strategy on enterprise innovation intention, and it can alleviate the negative influence of the political connection on the innovation intention through the differentiation strategy. Although the country’s innovation-driven strategy will provide more innovative resources for enterprises, securing the survival and development of an enterprise is becoming increasingly narrower by relying solely on establishing connections with the government.
Observational constraints of emergent universe in f(R,T) gravity with bulk viscosity
Authors: Debnath Partha Sarathi , Paul Bikash Chandra
Published: June 2020

Emergent universe (EU) cosmological models with viscosity in a modified gravity which contains a general function [Formula: see text], where [Formula: see text] and [Formula: see text] denote the curvature scalar and the trace of the energy–momentum tensor, respectively, are studied in a flat Friedmann–Robertson–Walker metric. Cosmological solutions are obtained in [Formula: see text] theory of gravity, which represented as [Formula: see text] with bulk viscosity that described by Eckart theory, truncated Israel Stewart theory and full Israel Stewart Theory. The physical and geometrical features of the EU models in [Formula: see text] gravity, where [Formula: see text] and [Formula: see text] are coupling parameters, with bulk viscosity are studied in details. Constraints of the EU models parameters in [Formula: see text] gravity with bulk viscosity are estimated from observational data set. The stability analysis of the equilibrium points admitting cosmological solutions of the dynamical system associated with the evolution in the modified gravity is studied in Eckart theory, truncated Israel Stewart theory and full Israel Stewart theory.
Noncommutative wormholes solutions with conformal motion in the background of f(𝔾, 𝕋) gravity
Authors: Mustafa G. , Shamir M. Farasat , Ashraf Asifa , Xia Tie-Cheng
Published: June 2020

This study explores the wormhole solutions in [Formula: see text] Gravity. For this purpose we assume two sorts of matter density profiles, which satisfy the Gaussian and Lorentzian noncommutative distributions. Further, we employ the conformal motions in the back ground of nonzero conformal killing vectors to find the shape-function from the modified field equations of [Formula: see text] gravity. By defining the connection between Gaussian and Lorentzian noncommutative distributions with conformal Killing vectors, it has been investigated that wormhole solutions would exist under the particular values of involved parameters in [Formula: see text] gravity.
Coupled dispersionless and generalized Heisenberg ferromagnet equations with self-consistent sources: Geometry and equivalence
Authors: Yesmakhanova Kuralay , Nugmanova Gulgassyl , Shaikhova Gaukhar , Bekova Guldana , Myrzakulov Ratbay
Published: June 2020

We propose a new integrable coupled dispersionless equation with self-consistent sources (CDESCS). We obtain the Lax pair and the equivalent generalized Heisenberg ferromagnet equation (GHFE), demonstrating its integrability. Specifically, we explore the geometry of these equations. Last, we consider the relation between the motion of curves/surfaces and the CDESCS and the GHFE.
MANAGEMENT INNOVATION, DRIVERS AND OUTCOMES: THE MODERATING ROLE OF ORGANISATIONAL SIZE
Authors: KAFETZOPOULOS DIMITRIOS , GOTZAMANI KATERINA , VOUZAS FOTIS
Published: June 2020

This article proposes a conceptual model to analyse the role of quality orientation and collaborations in firms’ management innovation, and also the impact of management innovation to product, process and marketing innovation. Moreover, the analysis considers organisational size as a key moderating factor in order to investigate whether the relationships among the model factors vary between small and medium size firms. To achieve these objectives an empirical survey was conducted among 429 firms. The structural relationships among the latent factors were determined through SEM. The findings show that the probability of success increases when firms use quality orientation and collaboration to support management innovation efforts. In addition, the findings suggest that management innovation positively affects product, process and marketing innovation while the organisational size acts as a moderator in the relationships among quality orientation, collaborations, management innovation, — product, process and marketing innovation, respectively.
A Strategy for Microwave-Controlled Release of Anticancer Drugs: (Fe3O4/nGO)@mSiO2/GQDs Nanocomposite Carrier Jointly Enhanced by nGO and GQDs
Authors: Wang Lian Huan , Bu Yu Mei , Liu Ye , Yao Ya Ping , Yang Zhen Feng , Chen Ping , Tang De Jian , Meng Li , Cui Bin
Published: June 2020

We constructed a multifunctional (Fe3O4/nGO)@mSiO2/GQDs drug carrier for loading and microwave-controlled release of an etoposide (VP16) as the anticancer drug. This nanocomposite consisted of magnetic core Fe3O4, microwave-absorbing nanographene oxide (nGO), fluorescent graphene quantum dots (GQDs) and intermediate barrier layer (mesoporous silica). It has a large surface area of 359.8[Formula: see text]m2/g, excellent fluorescence emission and ample magnetic performance of 36.00[Formula: see text]emu/g. After microwave irradiation for 140 s, the temperature of (Fe3O4/nGO)@mSiO2/GQDs nanoparticles rapidly went up to 90∘C. The loading rate of VP16 was as high as 68%, the release rate reached 87% within 280[Formula: see text]min under microwave irradiation. Therefore, the functionalized (Fe3O4/nGO)@mSiO2/GQDs nanoparticles will have potential application for clinical treatment as drug delivery system.
One-Step Self-Assembly of ZnPc/KMnF3: Yb, Er upconversion Photodynamic Therapy System for Antibacterial Applications
Authors: Zhu Xingqi , Zhen Deshuai , Li Chenyi , Jiang Ning , Geng Hongchao , Qiao Yan , Cai Qingyun
Published: June 2020

Photodynamic therapy (PDT) holds great promise as an effective approach to kill multidrug resistant (MDR) bacteria. In this study, KMnF3:Yb,Er upconversion nanoparticles (UCNPs) were prepared and modified with zinc phthalocyanine (ZnPc), a photosensitizer with a major absorption band at 670[Formula: see text]nm. ZnPc absorbs the emission at 660[Formula: see text]nm of the UCNPs producing reactive oxygen species (ROS) which kill the surrounding bacteria. The UCNPs were also modified with Tween to make them water-soluble and biocompatible, and oleylamine to provide positive charges to shorten the distance from bacteria. Detection of singlet oxygen production, bacteria viability test and confocal imaging were performed, respectively. The as-prepared system (UCNPs@ZnPc@Tween) shows enhanced efficiency of PDT against both Gram-negative and Gram-positive bacteria.
Aspects of the palaeontology of Salthill Quarry, Clitheroe, Lancashire (Mississippian), NW England
Authors: Donovan Stephen K. , Tenny Andrew
Published: June 2020

Salthill Quarry, Clitheroe, Lancashire (Mississippian, early Visean, Chadian) is a Site of Special Scientific Interest on the basis of its diverse fauna of invertebrates preserved in a Waulsortian mud mound setting. Important new specimens are described from the limestones and thin mudstones of the Hodder Mudstone Formation, on the southern margin of the quarry. A rare echinoid, archaeocidarid? gen. et sp. indet., is incomplete, but unusually retains the original curvature of the test. A columnal of
Bystrowicrinus
(col.)
westheadi
Donovan was derived from a radicular runner and has a dense cluster of radice scars on one side only. The columnal had a wedge-like section, thus suggesting a curvature of the stem. A cluster of solitary rugose corals on the base of a limestone bed includes at least two geniculated specimens in life position, the calice raised above the base of the bed. This is more likely to be due to burial
in situ
than a current accumulation.
Ostiocavichnus
Bohatý
et al.
is not an ichnotaxon, but a palaeopathology identified as a swollen crinoid pluricolumnal; broadly analogous structures are identified in fossil decapod crustaceans.
Female medal and fund recipients of the Geological Society of London: a historical perspective
Authors: Burek Cynthia V.
Published: June 2020

The Geological Society of London has historically awarded medals and funds to early career geologists and for career achievement recognition. Mid-career and outreach awards were later added as categories. This paper will concentrate on early recipients of funds and medal winners mainly during the nineteenth and twentieth centuries.

In the nineteenth century, only two women received recognition by the Geological Society for their work through early career funds (not medals): Catherine Raisin in 1893 and Jane Donald in 1898.

From 1900 to 1919, no woman received a medal but funds were collected by men on behalf of Gertrude Elles, Elizabeth Gray, Ethel Wood, Helen Drew, Ida Slater and Ethel Skeat. The first woman to collect her own Fund was Ethel Skeat in 1908.

Pre-World War II, only four women received career recognition in the form of a medal. Gertrude Elles in 1919 and Ethel Shakespear in 1920 received the Murchison Medal. No further medals were awarded to women until Maria Ogilvie Gordon in 1932 and Eleanor Mary Reid in 1936. It was not until the end of the 1990s and into the twenty-first century that a significant number of women received medals. It is noted that the William Smith Medal was only received by a woman in 2019 and the Dewey Medal has yet to be received by a woman. An analysis of the different medals and funds awarded to females through the Geological Society is discussed in detail with snapshots of the women who were so recognized. As we move into the twenty-first century we see an increase in these awards to women.
Personalism and the Trajectories of Populist Constitutions
Authors: Landau David
Published: June 2020

This article reassesses the relationship between populism, democracy, and constitutionalism in light of the strong tendency toward personalism that populism often carries. Populists who have taken power in recent years have often sought to carry out formal or informal constitutional changes. Whereas some of these changes have been celebrated as constitutional innovations, many have been viewed as threats to democracy. Focusing on examples from Latin America, this article shows that despite the stress populists put on constitutional change, the phenomenon remains tied to the charisma of individual leaders. Populist leaders go to great lengths to remain in office, and succession poses an acute regime crisis. A core task for constitutional design is incentivizing populist leaders to leave power, which is more likely to be achieved by channeling politics than by judicial fiat. If this can be accomplished, the ultimate legacy of populist constitutions may be more beneficial, and less harmful, than commonly thought.
Image-Computable Ideal Observers for Tasks with Natural Stimuli
Authors: Burge Johannes
Published: June 2020

An ideal observer is a theoretical model observer that performs a specific sensory-perceptual task optimally, making the best possible use of the available information given physical and biological constraints. An image-computable ideal observer (pixels in, estimates out) is a particularly powerful type of ideal observer that explicitly models the flow of visual information from the stimulus-encoding process to the eventual decoding of a sensory-perceptual estimate. Image-computable ideal observer analyses underlie some of the most important results in vision science. However, most of what we know from ideal observers about visual processing and performance derives from relatively simple tasks and relatively simple stimuli. This review describes recent efforts to develop image-computable ideal observers for a range of tasks with natural stimuli and shows how these observers can be used to predict and understand perceptual and neurophysiological performance. The reviewed results establish principled links among models of neural coding, computational methods for dimensionality reduction, and sensory-perceptual performance in tasks with natural stimuli.
Preferential Stripping of a Lithium Protrusion Resulting in Recovery of a Planar Electrode
Authors: Maslyn Jacqueline A. , McEntush Kyle D. , Harry Katherine J. , Frenck Louise , Loo Whitney S. , Parkinson Dilworth Y. , Balsara Nitash P.
Published: June 2020

Lithium metal is a high-energy-density battery electrode material, but the largely irreversible growth of lithium protrusions on an initially planar electrode during cycling makes it unsuitable for incorporation into a commercial battery. In this study, a lithium electrode with globular protrusions was stripped electrochemically, and the local morphology of the electrode as a function of time was determined by hard X-ray tomography. We demonstrate that globules are preferentially stripped compared to a planar electrode in our system, which incorporates a nanostructured block copolymer electrolyte. We report current density at the electrode as a function of micron-scale position and time. The local current density during the electrode healing process calculated from a reference frame at the electrode/electrolyte interface provides insight into the driving forces responsible for selective stripping of the globule. These results imply the possibility of discharging protocols that may return a lithium electrode to its initial planar state.
Printed Resistive Sensor Array Combined with a Flexible Substrate for Ethanol and Methane Detection
Authors: Wei Hua-Lin , Kumar Parkarsh , Yao Da-Jeng
Published: June 2020

In this research, we combined printed electrodes and a flexible substrate to develop a low-cost, resistive, gas sensor with small energy consumption. The ability to measure a gas is derived from an analysis of the resistance change resulting from gas molecules adsorbed by a polymer. With the sensor array coated with various polymers, we can identify the gas type and its concentration. Eight combinations of electrode with different width and gap were designed. The electrodes were printed on PET substrates with silver ink. Sensing material developed with mixture of Polyvinylpyrrolidone (PNVP), Carbon Black (CB) and solvent ethylene glycol (EG) was then coated on the sensors and tested with ethanol and methane. The layout design of the width and gap with the greatest sensitivity towards gases is 20 μm/20 μm. The limit of detection (LOD) is 40 ppm for ethanol and 36 ppm for methane; the resistance changes of the two gases are apparently opposite. Besides this, sensors coated with other sensing materials developed with combination of CB,polymers, poly(4-vinylpyridine)(P4VP) and polystyrene (PS) with solvent, EG and Tetrahydofuran (THF) respectively were measured with gases at varied concentration to derive the sensitivity of each. According to these experiments, a flexible gas sensor shows a great potential to achieve the purpose of establishing a wearable sensing platform.
Silicon Surface Smoothening Dynamics: Diffusion and Desorption
Authors: Kim Y-P. , Figuet C. , Kononchuk O.
Published: June 2020

Silicon surface evolution during annealing was investigated by atomic force microscopy (AFM) in a mixture of hydrogen (H2) and hydrogen chloride (HCl). The power spectrum density (PSD) calculated by experimental data was fitted to the analytical results of a continuum surface dynamics equation to determine the surface relaxation mechanism. The coexistence of two mechanisms was revealed, i.e., silicon surface diffusion and silicon desorption by chlorine adatoms, whose relative contribution depended on the HCl concentration. Thus, we proposed a unified model of silicon surface dynamics under pure H2 and HCl atmosphere, which sufficiently clarified the PSD evolution and allowed the determination of the diffusion and desorption reaction constants. Specifically, the evolution of the desorption reaction constant with increasing HCl concentration suggested a complex desorption path.
Review—Hybrid Materials Based on Phthalocyanines and Metal Nanoparticles for Chemiresistive and Electrochemical Sensors: A Mini-Review
Authors: Basova Tamara V. , Ray Asim K.
Published: June 2020

Synergetic combination of the properties of phthalocyanines and metal nanoparticles is known to result in the improvement of various properties of their hybrid materials. This review provides an overview of the application of hybrid materials based on phthalocyanines and metal nanoparticles for the development of chemiresistive and electrochemical sensors, with a focus on methods and approaches for their preparation.
Challenges in Moving to Multiscale Battery Models - Where Electrochemistry meets and demands more from Math
Authors: Shah Krishna , Subramaniam Akshay , Mishra Lubhani , Jang Taejin , Bazant Martin Z. , Braatz Richard D. , Subramanian Venkat R.
Published: June 2020

There has been significant recent interest in studying multiscale characteristics of current and next-generation batteries, including lithium-metal and lithium-sulfur batteries. Multiple studies have conveyed the importance of microscale effects, pressure effects, and morphology changes. Advances in computing power make researchers believe that the detailed multiscale models can be efficiently simulated to arrive at the insights for the degradation and performance loss; however, this is not true and special attention needs to be paid to local singularities, boundary layers, moving boundaries, etc. This article presents motivating 2D examples suggesting the importance of grid convergence studies and discusses the challenges in simulating detailed models by providing well-defined models to test the efficiency of numerical schemes. This article also provides perspectives on important numerical aspects for robustness and efficiency, and provides recommendations on the possible best practices for studies involving multiscale modeling.
Foot sole cutaneous stimulation mitigates neuromuscular fatigue during a sustained plantar flexor isometric task
Authors: Smith Simone G. V. S. , Power Geoffrey A. , Bent Leah R.
Published: June 2020

Cutaneous coupling with lower limb motor neurons has long been known. We set out to establish whether this pathway could serve a purpose other than muscular modulation during standing and walking. We found that during a submaximal contraction of the plantar flexor muscles, the addition of intermittent cutaneous stimulation to the skin of the foot sole resulted in an increase in time to task failure by 15%, which was over a minute longer in duration. We conclude that skin stimulation may serve as a mechanism to mitigate fatigue.
Fatigue-induced changes in short-interval intracortical inhibition and the silent period with stimulus intensities evoking maximal versus submaximal responses
Authors: Brownstein Callum G. , Espeit Loïc , Royer Nicolas , Lapole Thomas , Millet Guillaume Y.
Published: June 2020

This study compared the change in silent period (SP) and short-interval intracortical inhibition (SICI) with conditioning stimulus and single-pulse transcranial magnetic stimulation (TMS) intensities (for SICI and SP, respectively) eliciting maximal and submaximal SICI and SP during fatiguing exercise. The results showed that changes in SICI were only detectable with intensities evoking maximal responses, with no difference between intensities for SP. These findings highlight the importance of maximizing SICI with appropriate intensities before measuring SICI during fatiguing exercise.
Neuropathic Pain: From Mechanisms to Treatment
Authors: Finnerup Nanna Brix , Kuner Rohini , Jensen Troels Staehelin
Published: June 2020

Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia, and central poststroke pain. Most patients complain of an ongoing or intermittent spontaneous pain of, for example, burning, pricking, squeezing quality, which may be accompanied by evoked pain, particular to light touch and cold. Ectopic activity in, for example, nerve-end neuroma, compressed nerves or nerve roots, dorsal root ganglia, and the thalamus may in different conditions underlie the spontaneous pain. Evoked pain may spread to neighboring areas, and the underlying pathophysiology involves peripheral and central sensitization. Maladaptive structural changes and a number of cell-cell interactions and molecular signaling underlie the sensitization of nociceptive pathways. These include alteration in ion channels, activation of immune cells, glial-derived mediators, and epigenetic regulation. The major classes of therapeutics include drugs acting on α2δ subunits of calcium channels, sodium channels, and descending modulatory inhibitory pathways.
Moderate-Intensity Exercise and Musical Co-Treatment Decreased the Circulating Level of Betatrophin
Authors: Susanto Hendra , Taufiq Ahmad , Sugiharto  , Merawati Desiana , Marsyidah Badu Khumaira , Trijoyo Purnomo Jerry Dwi , Yuda Handaya Adeodatus
Published: June 2020

Introduction. In general, the significant contribution of lack of physical activity is strongly correlated with lipid metabolism and metabolic disorder. Hitherto, betatrophin is a potential hormone that regulates the lipid profile in the body circulation-associated triglyceride level. This study was designed to evaluate the alteration of betatrophin levels in subject-onset hypertriglyceridemia with exercise intervention co-treated with music. Materials and Methods. A total of 60 nonprofessional athletes were enrolled in this study and given moderate-intensity exercise (MIE) combined with middle rhythm musical co-treatment. The ELISA method was applied to quantify the serum level of betatrophin in all samples. The statistical analysis was performed by applying the Kolmogorov–Smirnov normality test, one-way ANOVA, and parametric linear correlation and regression. Results. Interestingly, our data show that MIE decreased the circulating level of betatrophin combined with music (12.47 ± 0.40 ng/mL) compared with that without musical co-treatment (20.81 ± 1.16 ng/mL) and high-intensity exercise (26.91 ± 2.23 ng/mL). The plasma level of betatrophin was positively correlated with triglycerides (r = 0.316, p≤0.05), systolic blood pressure (r = 0.428, p≤0.01), HDL (r = 0.366, p≤0.05), energy expenditure (r = 0.586, p≤0.001), PGC-1α (r = 0.573, p≤0.001), and irisin (r = 0.863, p≤0.001). By contrast, the plasma level of betatrophin was negatively associated with age (r = −0.298, p≤0.05) and LDL cholesterol (r = −0.372, p≤0.05). Importantly, betatrophin is a significant predictor for energy expenditure (p≤0.001) and plasma triglyceride levels (p≤0.05). Conclusions. Our data demonstrate that betatrophin levels decreased the post-MIE and musical therapeutical combination. Therefore, betatrophin may provide a benefit as the potential biomarker of physiological performance-associated physical training.
Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro
Authors: Chen Qingmin , Tan Ludong , Jin Zhe , Liu Yahui , Zhang Ze
Published: June 2020

Cellular retinoic acid‐binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA‐knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK‐8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis‐related protein expression and decreased ERK/VEGF pathway‐related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.
Self-Medication among Medical and Nonmedical Students at the University of Gondar, Northwest Ethiopia: A Cross-Sectional Study
Authors: Tesfaye Zelalem T. , Ergena Asrat E. , Yimer Bilal T.
Published: June 2020

Despite having some benefits, self-medication increases risks such as unnecessary use of medication, extended duration of consumption, incorrect diagnosis, drug-drug interactions, and polypharmacy. Thus, the purpose of this study is to compare self-medication practice between medical and nonmedical students of the University of Gondar, Northwest Ethiopia. An institutional-based cross-sectional comparative study was conducted on medical and nonmedical students of the University of Gondar from March 25 to May 15, 2018. A comparative sample of 213 medical and 212 nonmedical students were enrolled in the study. Data were collected by physically visiting the students in their campuses, using a semistructured questionnaire. Of the participants with a history of medication use in the past 12 months, 64.5% practiced self-medication. The prevalence of self-medication was 59.7% among medical students and 69.0% among nonmedical students. “Knowing the treatment of the disease” was the most frequent reason behind self-medication. Analgesics/antipyretics were the most common categories of medications used, whereas headache was the predominant ailment for which the medications were used. Self-medication practice was found to be higher in the fifth year students and nonmedical students (p<0.05). In conclusion, self-medication is common among students of the University of Gondar. Nonmedical students were more likely to have practiced self-medication as compared to medical students.
ILC2 Proliferated by IL-33 Stimulation Alleviates Acute Colitis in Rag1-/- Mouse through Promoting M2 Macrophage Polarization
Authors: You Yong , Zhang Xiaoqing , Wang Xiao , Yue Dan , Meng Fanxiang , Zhu Junfeng , Wang Yuanyuan , Sun Xun
Published: June 2020

This study was to identify functions of ILC2, a newly found innate lymphoid cell which mainly locates in mucosa organs like lungs and intestines, in IBD. We injected rIL-33 protein to C57/BL6 mouse to explore how IL-33 induces ILC2 proliferation. The results showed that ILC2 reached a proliferation peak at day 5 and expressed multiple surface markers like CD127, C-kit, CD69, CD44, ST2, CD27, DR3, MHCII, and CD90.2. ILC2 also expressed high quantity of IL-13 and IL-5 and few IL-17A which indicates a potentially immunological function in IBD development. Afterwards, we transferred sort purified ILC2 to Rag1-/- mouse given DSS to induce acute colitis in order to explore the innate function of ILC2. Data showed that ILC2 alleviates DSS-induced acute innate colitis by repairing epithelial barrier and restore body weight. Furthermore, we found that ILC2 can cause macrophages polarizing to M2 macrophages in the gut. Therefore, we concluded that ILC2 played a therapeutic role in mouse acute colitis.
Enhancing and Complementary Mechanisms of Synergistic Action of Acori Tatarinowii Rhizoma and Codonopsis Radix for Alzheimer’s Disease Based on Systems Pharmacology
Authors: Liu Shengwei , He Cui , Liao Yuan , Liu Hailin , Mao Wanli , Shen Zhengze
Published: June 2020

Background and Aim. Alzheimer’s disease (AD) is a common neurological disorder worldwide. In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) and Codonopsis Radix (CR) are common herbs used to treat AD. However, due to the many active ingredients and targets in these herbs, it is difficult to clarify the synergistic mechanism of ATR and CR. To reveal the multicomponent synergistic mechanism of ATR and CR in Alzheimer’s disease, we analyzed important components, drug targets, and crucial pathways using a systems pharmacology strategy. Materials and Methods. In this study, a systems pharmacology‐based strategy was used to elucidate the synergistic mechanism of Acori Tatarinowii Rhizoma and Codonopsis Radix for the treatment of AD. This novel systems pharmacology model consisted of component information, pharmacokinetic analysis, and pharmacological data. Additionally, the related pathways were compressed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the organ distributions were determined in the BioGPS bank. Results. Sixty‐eight active ingredients with suitable pharmacokinetic profiles and biological activities were selected through ADME screening in silico. Based on 62 AD‐related targets, such as APP, CHRM1, and PTGS1, systematic analysis showed that these two herbs were mainly involved in the PI3K‐Akt signaling pathway, MAPK signaling pathway, neuroactive ligand‐receptor interaction, and fluid shear stress and atherosclerosis, indicating that they had a synergistic effect on AD. However, ATR acted on the KDR gene, while CR acted on IGF1R, MET, IL1B, and CHUK, showing that they also had complementary effects on AD. The ingredient contribution score involved 29 ingredients contributing 90.14% of the total contribution score of this formula for AD treatment, which emphasized that the effective therapeutic effects of these herbs for AD were derived from both ATR and CR, not a single herb. Organ distribution showed that the targets of the active ingredients were mainly located in the whole blood, the brain, and the muscle, which are associated with AD. Conclusions. In sum, our findings suggest that the systems pharmacology methods successfully revealed the synergistic and complementary mechanisms of ATR and CR for the treatment of AD.
Research on Surface Failure Law of Working Faces in Large Mining Height and Shallow Buried Coal Seam
Authors: Li Zhenhua , Pang Yingkun , Bao Yongsheng , Ma Zhanyuan
Published: June 2020

In the process of high‐intensity and large‐space mining in Shendong mining area, various surface cracks are generated on the surface, resulting in serious damage to the surface buildings and the local ecological environment. To study the influence of overlying rock movement on surface failure of near‐field single key strata of near‐shallow buried and large mining height working face, the relationship between overburden movement, strata pressure appearance, and surface failure at working face 52307 in Daliuta mining area was analyzed by field measurement and numerical simulation. The results show the following: (1) there is only one thick and hard key stratum in the overburden of large mining height and near‐shallow buried working face. Under the condition of presplitting roof blasting, the first weighting step is still as high as 95 m, and the periodic breaking step of roof is 20–30 m. During the weighting, the working resistance of support is still close to the rated resistance. (2) The single key stratum plays an obvious role in controlling overburden movement. After the first weighting of the working face, a stepped subsidence crack appears on the surface within a short time, and the crack lags behind the working face for about 5 m. (3) During each periodic weighting process, the breaking and subsidence of key blocks are accompanied by surface cracks.
The Investigation of MHD Williamson Nanofluid over Stretching Cylinder with the Effect of Activation Energy
Authors: Ibrahim Wubshet , Negera Mekonnen
Published: June 2020

In this paper, we discussed the effect of activation energy on mixed convective heat and mass transfer of Williamson nanofluid with heat generation or absorption over a stretching cylinder. Dimensionless ordinary differential equations are obtained from the modeled PDEs by using appropriate transformations. Numerical results of the skin friction coefficient, Nusselt number, and Sherwood number for different parameters are computed. The effects of the physical parameter on temperature, velocity, and concentration have been discussed in detail. From the result, it is found that the dimensionless velocity decreases whereas temperature and concentration increase when the porous parameter is enhanced. The present result has been compared with published paper and found good agreement.
Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Zamarin Dmitriy , Hamid Omid , Nayak-Kapoor Asha , Sahebjam Solmaz , Sznol Mario , Collaku Agron , Fox Floyd E. , Marshall Margaret A. , Hong David S.
Published: June 2020

Purpose:

The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti–C-C chemokine receptor 4 (anti-CCR4) mAb targeting effector regulatory T cells (eTreg), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab.

Patients and Methods:

This was a multicenter, phase I, dose escalation study, followed by disease-specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation of durvalumab or tremelimumab in patients with advanced solid tumors. Cohort expansion occurred with mogamulizumab 1 mg/kg plus durvalumab 10 mg/kg or tremelimumab 10 mg/kg in patients with advanced pancreatic cancer.

Results:

Forty patients were enrolled during dose escalation, followed by 24 patients during dose expansion. No dose-limiting toxicities occurred during dose escalation. No new or unexpected toxicities were seen. Tolerability, the primary endpoint, was acceptable utilizing mogamulizumab 1 mg/kg plus durvalumab or tremelimumab 10 mg/kg in the combined dose escalation and dose expansion cohorts (each n = 19). At these doses, the objective response rate was 5.3% (95% confidence interval, 0.1%–26.0%; one partial response) with each combination treatment. At all doses, mogamulizumab treatment led to almost complete depletion of peripheral eTregs, as well as reduction of intratumoral Tregs in the majority of patients. There was no clear correlation of clinical response with peripheral or intratumoral reduction in CCR4+ eTregs or with baseline degree of CCR4+ expression.

Conclusions:

Mogamulizumab in combination with durvalumab or tremelimumab did not result in potent antitumor efficacy in patients with advanced solid tumors. Tolerability of mogamulizumab 1 mg/kg combined with durvalumab or tremelimumab 10 mg/kg was acceptable.
Tumor Mutational Burden, Toxicity, and Response of Immune Checkpoint Inhibitors Targeting PD(L)1, CTLA-4, and Combination: A Meta-regression Analysis
Authors: Osipov Arsen , Lim Su Jin , Popovic Aleksandra , Azad Nilofer S. , Laheru Daniel A. , Zheng Lei , Jaffee Elizabeth M. , Wang Hao , Yarchoan Mark
Published: June 2020

Purpose:

Tumor mutational burden (TMB) has emerged as a potential predictive biomarker for clinical response to ICI therapy, but whether TMB also predicts toxicity remains unknown. We investigated the relationship between TMB, objective response rate (ORR), overall survival (OS), and toxicity for ICI therapy across multiple cancer types.

Experimental Design:

We searched MEDLINE, PubMed, and ASCO/ESMO/AACR meetings for clinical trials of anti-PD(L)1, CTLA-4, or combination in 29 cancer types. We assessed ICI administered, responses (complete or partial response), median OS, OS HR, and grade 3/4 toxicity. We conducted a systematic review, meta-analysis and meta-regression using tumor level TMB data from Foundation Medicine.

Results:

One hundred seventeen clinical trials, which included 12,450 patients treated with ICI therapy were analyzed. Meta-regression analysis revealed that TMB was significantly associated with ORR for anti-PD(L)1, anti–CTLA-4, and combination (P < 0.0001 for all), but not associated with toxicity in all treatment groups. OS data were unavailable for most studies included in our meta-analysis, and the relationship between TMB and OS in this subset was not significant (P = 0.26). In high TMB tumor types (≥10 mut/megabase) the improvement of ORR and increase in grade 3/4 toxicity with combination ICI therapy as compared with PD(L)1 monotherapy were 21.13% and 25.41%, respectively, as compared with 3.73% and 18.78% in low TMB tumor types (<10 mut/megabase).

Conclusions:

There is a positive association between TMB and clinical response with anti-PD(L)1, anti–CTLA-4, and combination ICIs, but no association between TMB and toxicity. These results imply a favorable risk/benefit ratio for ICIs in tumors with a higher TMB.
Development of an Infrared Monitor-Guided Bleb Revision Procedure
Authors: Matsushita Kenji , Kawashima Rumi , Nishida Kohji
Published: June 2020

The needle revision procedure to address failing filtering blebs is a blind technique that might easily damage the scleral flap, conjunctiva, and choroid. We propose a new surgical procedure, infrared monitor-guided bleb revision, to perform bleb revision minimally invasively and effectively, and demonstrate the procedure in a patient. We developed the guided procedure with the infrared monitor to observe the bleb interior with greater contrast. Under the monitor, we dissect the hard fibrotic tissue with a bleb knife and, if necessary, remove adhesions using a needle and vitreous forceps. Finally, 5-fluorouracil is injected into the subconjunctiva. We have performed bleb revisions safely with clear visualization of the scleral flap using an infrared light. In the current case, the patient had good intraocular pressure control for about 1 year. The new infrared monitor-guided bleb revision procedure facilitates successful bleb revisions without damage to the underlying structures.