bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of the state of atmospheric air in the vicinity of non-ferrous metallurgy facilities and the power line tower damage
Authors: Begunova L A , Soboleva V G , Filatova E G
Published: November 2020

In the studies of the state of land areas performed using the advanced methods, in images from space, the industrial region around the city of Norilsk can be seen as a blurred spot that occupies an area of more than 900 km2. Among diverse pollutants forming the picture, sulfur and nitrogen compounds, nitrates, sulfates, phenols, industrial dust, and heavy metals have a particular impact. The release of sour gases results in acid rains, which are among the major pollutants forming the whole picture. These substances affect humans, all objects of the environment, and sources of anthropogenic activities including engineering installations of power plant enterprises. The direct impact on the state of metal towers decreases significantly their lifetimes and increases the risk of emergencies. In this paper, the research data on the state of power line towers of different types are provided and the effect of acid precipitation on structures is shown.
Statistically distributed characteristics of wastewater discharged from Kamskiy Kabel, LTD and containing organic phenolic compounds
Authors: Bukalova N P
Published: November 2020

A method of drawing up a statistically distributed characteristics of wastewater with the specified accuracy has been considered, which allows to study the patterns of fluctuation in the concentrations of organic phenolic substances in wastewater, on the example of the water discharged from Kamskiy Kabel, LTD. Based on the performed research, a model of the expected value and of mean square deviation of the fluctuation in the concentrations of organic phenolic substances has been built. It has been found that the fluctuation in the concentration of organic solvents in wastewater is seasonal, and the statistically distributed curve of the concentrations fluctuation has three extremum points.
Phytoremediation potential of aquatic plants in Uzbekistan for the treatment of cyanide-containing wastewater
Authors: Timofeeva S S , Timofeev S S , Boboev A A
Published: November 2020

For over a century now, the mining industry has been using cyanides for gold and silver recovery. Cyanides are highly toxic for human beings, animals, and aquatic organisms. The available physical and chemical methods of wastewater treatment are cost-ineffective. Certain microorganisms are capable of use cyanides as sources of carbon and nitrogen and turn those into ammonia and carbonate. Some plants are also efficient for the processes of cyanides destruction. Phytoremediation of cyanides may be efficient, cost-effective, environmentally friendly, and be used as an attractive alternative to traditional physical and chemical processes. This article considers the capability of aquatic plants, which grow in the valley of Zerafshan River on the territory of Uzbekistan, to dispose of cyanides and recover the cyanides-contaminated tailings of Navoi Mining & Metallurgical Combinat. Such aspects as the mechanisms of enzymatic detoxification of cyanides by aquatic plants and microorganisms are discussed. The most promising plants to be bedded in the tailings dump are selected.
Study of peak temperatures in friction stir spot welding of AA2024-Al/polycarbonate and AA2024-Al/polypropylene systems
Authors: Mohammed R K , Mohammed S S , Mahmoud T S
Published: November 2020

Compared to ordinary fusion welding processes, friction stir spot welding (FSSW) have significant advantages for example: joining of conventionally non-weldable alloys, improved mechanical properties and reduced distortion of weldable alloys joints due to the pure solid-state joining of metals. This welding technique gives the online feedback control and opportunity of automation, allowing automatic adaptation to geometrical and environmental variations of the component. However, several fundamentals of the process such as the temperature inside the stirred zone of the weld and its power on mechanical properties, are not yet fully understood. In the present study, FSSW was adopted to weld AA2024 aluminium alloy sheets with both polycarbonate (PC) and polypropylene sheets using two different tools having two different pin configurations. The two tools have conical pin with 2.5 mm height, however, tool (T1) has draft angle of ≈ 16.69° and the tool (T2) has a draft angle of ≈ 6°.The effects of FSSW parameters of the process, typically, the tool rotational speeds and dwell time, on temperature variation in the tool/work piece interface was also recorded, via an infrared camera. The results revealed that, increasing the tool rotational speed and/or the dwell time increase(s) the peak temperature in FSSW of both AA2024Al/polycarbonate and AA2024Al/polypropylene welded joints. For AA2024Al/polycarbonate joints, the peak temperatures recorded for tool T1 are higher than those recorded using tool T2. The peak temperature ranges were found to vary from 54 to 150 °C and from 45 to 136 °C, for joints welded using T1 and T2 tools, respectively. While, for AA2024Al/polypropylene joints, the peak temperatures recorded for tool T2 are higher than those recorded using tool T1. The peak temperature ranges were found to vary from 40 to 115 °C and from 61 to 143 °C, for joints welded using T1 and T2 tools, respectively.
Passive vibration attenuation: a comparison study
Authors: Abdelghany A A , Hegazy M M , Badawy A
Published: November 2020

A comparison study between two different approaches for passive vibration attenuation of solar array had been presented. A powerful finite element software “Ansys” was used to perform this study. Finite element models of a cantilever rectangular aluminum plate are created in order to model the satellite solar array. Stiffeners and circular patches (passive masses) are used separately in order to attenuate the vibration of the plate. The output results of the mode shapes and the FRF of the plate are investigated in order to figure out the best and adequate vibration attenuation technique for satellite solar array, the results showed that using stiffeners have a better effect on vibration attenuation more than using circular patches. A further investigation for vibration attenuation using stiffener is conducted to study the effect of changing the aspect ratio of stiffener.
Fracture toughness assessment of axial partially through cracks in X65 and X70 steel pipes
Authors: Said A E , Hassan H A , Abu-El-Yazied T G , Makady A M
Published: November 2020

This paper presents analysis of fracture assessment methods of axial partially-through crack in X65 and X70 steel pipes with internal pressure. Two analytical methods Folin–Ciocalteu method (FC method) and Gauss–Seidel method (GS method)) are used to make assessment for two steel pipes (steel X65 and X70). Finite Element model of X65 and X70 steel full-scale pipes with axial part-through crack was established. In this work, a comparison is made between results obtained from FC and GS methods and finite element model with previous experimental results. The GS is more conservative assessment method as it provides smaller crack depth (a) corresponding to (Jcr). Finite Element model in case of steel X70 is more conservative than the analytical methods and its results close to the experimental values.
Transient heat transfer for GPMG’s barrel 7.62x51mm
Authors: Ghanem M , Abdelsalam O
Published: November 2020

In this paper, a modified analytical solution for time-dependent one dimension heat diffusion equation in cylindrical coordinate had been mathematically solved to calculate the temperature distribution through thick-walled weapon barrel subjected to successive shots. The analytical solution has been compared with experimental measurements for the temperature at the outer surface of the barrel at two different positions. The General Purpose Machine Gun (GPMG) 7.62X51 mm was considered as the case of study. The results show a good agreement between the analytical model and the experimental work with a difference less than 3 %. The main difference between them mainly as a result of the very short time of the heating phenomena as it takes about 6 (ms) only, although the used Data Acquisition System was able to take a high sampling rate and a high sensitive thermocouple type k with only 0.5 mm thickness had been used.
Passive vibration damping of a cantilever plate
Authors: Mohamed A , Hassan A , Omer A A
Published: November 2020

Vibration control of mechanical systems divided into two types active and passive, this case study illustrates other approach of passive control of the cantilever plate by using double layers of the viscoelastic material (Dyad 606) one in the upper face of the Al substrate (5051) and the second one in the lower face. This layers are affected by axial uniform distributed force by applying tension load, the damping level depend on the value of this axial force where the vertical component of this force consistently the other way of the vibrating element that reduce vibration amplitude in this direction by about (95%) of the original amplitude without damping layers. Computational analysis using ANSYS program are used firstly to verify that the results from the software are compatible with that obtained from analytical and experimental evaluation by comparing the values of natural frequencies. Then using ANSYS model to calculate the reduction occurs in the lateral vibration with changing of the axial loads on the viscoelastic plates. The benefits of this model are enhancing the reliability and reducing the cost.
Estimation of the relative permittivity from the molecular structure of polymers used in automotive industries
Authors: Bonfig Teresa , Körner Enrico , Jebramcik Jochen , Kroll Lothar , Rolfes Ilona , Jan Barowski
Published: November 2020

To scan a vehicle’s environment frequency modulated continuous wave (FMCW) radar sensors are essential. The implementable driver assistance systems based on these sensors increase the comfort of an automobile. When integrating them into the car, the radar sensor’s cover must be taken into account. These parts serve as protection against external chemical and mechanical influences, but they should also support the vehicle design and appearance. Usually, painted polymer components are used as a radome. Depending on their material parameters (i.e. relative permittivity and loss-tangent) polymer covers lead to reflections and absorption, which may impair the radar performance, if they are not properly designed from a microwave point of view. For an appropriate design procedure, the polymer properties, have to be known precisely beforehand or need to be analyzed in realistic experimental configurations. Within this paper it is shown by measurements around the 80 GHz automotive radar bands and calculations based on the polymers repeating unit that the relative permittivity can be estimated from knowledge of the molecule structure. This allows the calculation of the relative permittivity of polymer molecules that have not yet been measured in the W-band at 80 GHz at a very early stage of the design process. Additionally it is shown that it has to be taken into account if the polymer is semi-crystalline or amorphous. Furthermore, the density or crystallinity has to be known.
Biochar produced from tobacco stalks, eggshells, and Mg for phosphate adsorption from a wide range of pH aqueous solutions
Authors: He Qiuping , Luo Yuan , Feng Yiyang , Xie Kun , Zhang Keqiang , Shen Shizhou , Luo Yanli , Wang Feng
Published: November 2020

Preparing biochar from tobacco stalks modified with Mg is a feasible way to utilize tobacco stalks as a resource. However, the capacity of phosphate removal of Mg-biochar is affected greatly with increasing pH. In the present work, biochar produced from the tobacco stalks was modified via Mg addition and eggshells during the preparation for improving the phosphate adsorption performance at higher pH. The results revealed that the theoretical maximum adsorption capacity of phosphate for the biochar increased from 110.62 to 272.37 mg P/g when the mass ratio of Mg to tobacco stalk increased from 0.12:1 to 0.48:1 (M-C). The adsorption capacity of the biochar with a mass ratio of 0.3:1 (M-C2) was more than 200 mg P/g in the pH range of 3 to 7 but with further increase of pH from 7 to 12 the capacity decreased from 205 to 135.2 mg P g−1. Addition of eggshells with the magnesium solution during the dipping process can effectively improve the capacity of the modified biochar for phosphate in the alkaline condition. When the mass ratio of eggshell to tobacco stalk was ≥0.25:1, the phosphate adsorption capacities of the biochar can reach above 200 mg P/g within a wide pH range of 3 to 12, and the maximum adsorption capacity can reach more than 270 mg P g−1 for the mass ratio of 1:1 (EM-C24). The characterization results demonstrated that Ca and Mg were loaded on the biochar. The high adsorption performance provides reference values for the utilization of tobacco stalks and eggshells.
An investigation on microstructure and mechanical behaviour of copper-nickel coated carbon fibre reinforced aluminium composites
Authors: Gajalakshmi K , Senthilkumar N , Mohan B , Anbuchezhiyan G
Published: November 2020

In the present investigation, mechanical, corrosion and fatigue characterization is performed on the fabricated aluminium metal matrix composite (AMMC), by reinforcing nickel (Ni) and copper (Cu) coated 4% carbon fibre (CF) in aluminium alloy (AA6026) matrix. With a view of enhancing the strength of the aluminium alloy, an optimal percentage (4 wt%) of CFs is reinforced; as CFs cannot be directly reinforced in the aluminium matrix due to poor wettability, CFs are coated with Ni and Cu using electroless plating technique for better wettability and bonding between reinforcement and matrix. Properties of the cast alloy and coated CF reinforced composite are compared and the composite with better properties is identified as 4% Cu coated CFs reinforced AMMC. When compared with as-cast alloy and Ni coated CF reinforced composite, the tensile strength of Cu coated CFs composite was higher by 15.36% and 2.55%. Similarly, micro-Vickers hardness was improved by 7.61% and 3.09%, impact strength by 19.61% and 3.39%, flexural strength by 87.50% and 15.38%. The corrosion rate (mils/year) was reduced with incorporation of 4% Cu coated CFs in AA6026 by 59.72% and 23.23% as compared with as-cast and Ni coated CF reinforced composition.
Effect of ultra-trace rare earth elements on continuous cooling transformation curve of low carbon steel
*
Authors: Dong Ruifeng , Li Hua , Deng Xiangtao , Liu Zhiliang
Published: November 2020

Two groups of low carbon steel with ultra-micro amount (less than 20 ppm) rare earth lanthanum and without rare earth element were taken as experimental objects. Continuous cooling transformation curves of two kinds of low carbon steels were drawn by Formaster-F II automatic phase transformation instrument, alloy phase method and hardness method. According to the measured CCT curve, the microstructure and hardness of low carbon steel under different cooling rates were studied and analysed. The results show that the addition of ultra-trace rare earth elements can increase the Ac1 and Ac3 points of low carbon steel by about 20 °C; the starting temperature of martensite transformation MS point decreased by 19 °C, and the end temperature Mf point decreased by 6 °C; at low cooling rate, the transformation range of ferrite is increased and that of pearlite is decreased; the starting temperature of bainite Bs point increased by 20 °C, and the end temperature of bainite Bf increased by 13 °C; at low cooling rate, the ferrite transformation range becomes larger, while at high cooling rate, the ferrite transformation range becomes smaller.
Solar synthesis of nanostructured zirconia: microstructural and thermal characterization
Authors: Ceballos-Mendivil Laura G , Carvajal-Campos Yannely , Tánori-Córdova Judith , Luque-Ceballos Jonathan C , Villafán-Vidales Heidi , Estrada Claudio A
Published: November 2020

The use of concentrated solar energy in processing ceramic materials is an attractive route to obtain these materials with low CO2 emissions. In this work, nanostructures of monoclinic zirconia (m-ZrO2) were obtained using concentrated solar energy provided by the IER-UNAM solar furnace as a heat source. In the first stage of the process, a Zr/O/C complex was obtained by sol-gel method at a temperature of 120 °C using zirconium n-propoxide and sorbitol as precursors reagents. This complex was used in a second stage to obtain m-ZrO2 by heating it at a temperature of 1200 °C for one hour in air atmosphere. This last stage was performed in a solar furnace. Samples were analyzed by characterization techniques: FT-IR, TGA/DSC, XRD, TEM, and SEM confirming the formation of nanostructures of zirconia in monoclinic phase.
Modification of exposure conditions by the magnetic field configuration in helicon antenna-excited helium plasma
Authors: HUANG Tianyuan , JI Peiyu , HUANG Jianjun , YU Bin , WU Xuemei
Published: November 2020

Modification of exposure conditions downstream in the diffusion chamber has been performed in helicon antenna-excited helium plasma by adjusting the magnetic field (intensity and geometry). In the inductively coupled mode (H mode), a reduction in ion and heat fluxes is found with increasing magnetic field intensity, which is further explained by the more highly magnetized ions off-axis around the last magnetic field lines (LMFL). However, in helicon wave mode (W mode), the increase in magnetic field intensity can dramatically increase the ion and heat fluxes. Moreover, the effect of LMFL geometry on exposure conditions is investigated. In H mode with contracting LMFL, off-axis peaks of both plasma density and electron temperature profiles shift radially inwards, bringing about a beam with better radial uniformity and higher ion and heat fluxes. In W mode, although higher ion and heat fluxes can be achieved with suppressed plasma cross-field diffusion under converging LMFL, the poor radial uniformity and a small beam diameter will limit the size of samples suitable for plasma irradiation experiments.
Implicit ligand theory for relative binding free energies: II. An estimator based on control variates
Authors: Nguyen Trung Hai , Minh David D L
Published: November 2020

Implicit ligand theory describes the relationship between the noncovalent binding free energy and the binding free energy between a ligand and multiple rigid receptor conformations. We have previously shown that if the receptor conformations are sampled from or reweighed to a holo ensemble, the binding free energy relative to the ligand that defines the ensemble can be calculated. Here, we apply a variance reduction technique known as control variates to derive a new statistical estimator for the relative binding free energy. In applications to a data set of 6 reference ligands and 18 test ligands, statistically significant differences between the estimators are not observed for most systems. However, in cases where such differences are observed, the new estimator is more accurate, precise, and converges more quickly. Performance improvements are most consistent where there is a clear correlation, with a correlation coefficient greater than 0.3, between the control variate and the statistic being averaged.
Novel cost-effective and electrocatalytically active intermetallic nickel aluminide counter electrode for dye sensitized solar cells
Authors: Sahare Sanjay , A Santhosh Kumar , Bhave Tejashree , Abhyankar Ashutosh
Published: November 2020

The very high cost, scarcity and dissolubility of platinum (Pt) is the center of debates as a counter electrode (CE) in dye sensitized solar cells (DSSCs) research domain. To deal with such core issues, herein, novel low-cost and electro-catalytically active inter-metallic nickel aluminide (Ni3Al) thin films have been fabricated successfully on fluorine-doped tin oxide substrates by DC magnetron sputtering at room temperature. For the first time, Ni3Al has been utilized as a CE for DSSCs application. Further, the solar cell performance of Ni3Al based DSSC has compared with the sputtered coated Pt thin film based DSSC performance. Under open atmospheric experimental preparation conditions (in air), a maximum power conversion efficiency of 3% has been achieved with Ni3Al CE. The obtained efficiency is quite analogous to a DSSC fabricated with a Pt CE. Further, as-fabricated Ni3Al CEs have exhibited better electrochemical catalytic activity and anti-corrosion effect than that of sputtered Pt CEs. The low-cost and excellent electrocatalytic properties of intermetallic Ni3Al thin films may pave the way towards development of Pt-free CE for DSSCs.
A proof of Sørensen’s conjecture on Hermitian surfaces
Authors: Beelen Peter , Datta Mrinmoy , Homma Masaaki
Published: November 2020

In this article we prove a conjecture formulated by A. B. Sørensen in 1991 on the maximal number of

F

q
2

\mathbb {F}_{q^2}

-rational points on the intersection of a non-degenerate Hermitian surface and a surface of degree

d
≤
q
.

d \le q.
A Comparative Evaluation of Capillary Electrophoresis, Cation-Exchange High-Performance Liquid Chromatography, and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Screening of Hemoglobin Variants
Authors: Xu Miao , Wang Yajun , Xu Anping
Published: November 2020

Objectives

The present study was conducted to evaluate the usefulness of capillary electrophoresis (CE), cation-exchange high-performance liquid chromatography (HPLC), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) for the screening of hemoglobin (Hb) variants prevalent in southern China.

Methods

A total of 102 types of Hb variants in 1,083 variant carriers were identified over a 5-year period. These variants were analyzed by a CE method (Capillarys 3 TERA), a cation-exchange HPLC analyzer (Variant II Turbo 2.0), and a MALDI-TOF MS system (QuanTOF).

Results

The presence of 85 (83.3%, 85/102), 84 (82.4%, 84/102), and 62 (60.8%, 62/102) Hb variants was detected by Capillarys 3 TERA, Variant II Turbo 2.0, and QuanTOF, respectively. Of the three methods, only Capillarys 3 TERA recognized all 10 of the most frequent Hb variants in southern China. There were six, two, and three Hb variants that can only be detected by Capillarys 3 TERA, Variant II Turbo 2.0, and QuanTOF, respectively. The detection limit of mass difference for QuanTOF was approximately 11 to 20 Da.

Conclusions

MALDI-TOF MS is suitable for use as an auxiliary method rather than a stand-alone method for the screening of Hb variants prevalent in southern China.
An Analysis of Patient-Reported Recovery Outcomes of Topical Tripeptide/Hexapeptide Formulations Utilized in a Prospective Randomized Double-Blind Split Neck and Body Study
Authors: Casas Laurie A , Bell Michaela , Claytor Brannon , Ziegler Mary E , Widgerow Alan D
Published: November 2020

Background

Physicians strive to improve the postsurgical experience and optimize patient-reported recovery outcome measures (PROMs) following elective cosmetic surgical procedures. Our previous pilot feasibility study demonstrated that twice daily postoperative topical body treatment with tripeptide and hexapeptide (TransFORM Body Treatment with TriHex Technology [TFB, Alastin Skincare, Inc., Carlsbad, CA]) reduced PROMs of swelling, induration, soft tissue fibrosis, and pain as well as improved visible and palpable skin quality.

Objectives

Evaluate whether adding a tripeptide/hexapeptide anhydrous gel (Regenerating Skin Nectar with TriHex Technology [RSN, Alastin Skincare, Inc., Carlsbad, CA]) pre- and post-procedure to the existing postsurgical regimen of TFB significantly improves 6 PROMs in patients undergoing neck and body contouring cosmetic surgical procedures.

Methods

Ten female patients underwent 15 neck and body contouring procedures and were blindly randomized to 1 of 2 topical treatment protocols (1 [TFB] and 2 [RSN/TFB]) pre- and post-procedure. Patient-reported scores of 5 skin parameters (skin discoloration, ecchymosis, edema, induration, and subcutaneous fibrous banding) and pain scores using the Visual Analog Scale were collected at 8 intervals for 12 weeks post-procedure.

Results

The treatment side that used both topicals showed significantly reduced scores of edema, induration, and subcutaneous fibrous banding compared with the side that only used 1 topical, on days 5–7 and 10–14 (P < 0.05). All patients observed slower soft tissue recovery on the side that was treated with TFB alone and opted to break the code and use both topical treatments.

Conclusions

Patients had statistically significant improved patient-reported measures of skin edema, skin induration, and subcutaneous banding on the operated side that used both topicals.

Level of Evidence: 2
The SARS-CoV-2 receptor, angiotensin-converting enzyme 2, is required for human endometrial stromal cell decidualization†
Authors: Chadchan Sangappa B , Popli Pooja , Maurya Vineet K , Kommagani Ramakrishna
Published: November 2020

The coronavirus disease 2019 (COVID-19) first appeared in December 2019 and rapidly spread throughout the world. The SARS-CoV-2 virus enters the host cells by binding to the angiotensin-converting enzyme 2 (ACE2). Although much of the focus is on respiratory symptoms, recent reports suggest that SARS-CoV-2 can cause pregnancy complications such as pre-term birth and miscarriages; and women with COVID-19 have had maternal vascular malperfusion and decidual arteriopathy in their placentas. Here, we report that the ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and the expression increases in stromal cells in the secretory phase. It was observed that the ACE2 mRNA and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. Furthermore, HESCs transfected with ACE2-targeting siRNA impaired the full decidualization response, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1. Additionally, in mice during pregnancy, the ACE2 protein was expressed in the uterine epithelial cells, and stromal cells increased through day 6 of pregnancy. Finally, progesterone induced Ace2 mRNA expression in mouse uteri more than vehicle or estrogen. These data establish a role for ACE2 in endometrial physiology, suggesting that SARS-CoV-2 may be able to enter endometrial stromal cells and elicit pathological manifestations in women with COVID-19, including an increased risk of early pregnancy loss.
Hearing and dementia: from ears to brain
Authors: Johnson Jeremy C S , Marshall Charles R , Weil Rimona S , Bamiou Doris-Eva , Hardy Chris J D , Warren Jason D
Published: November 2020

The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between ‘peripheral’ and ‘central’ hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer’s disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory ‘cognitive stress tests’ and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticity.
When can maximal efficacy occur with repeat botulinum toxin injection in upper limb spastic paresis?
Authors: Gracies Jean-Michel , Jech Robert , Valkovic Peter , Marque Philippe , Vecchio Michele , Denes Zoltan , Vilain Claire , Delafont Bruno , Picaut Philippe
Published: November 2020

Repeated injection cycles with abobotulinumtoxinA, a botulinum toxin type A, are recommended in current clinical guidelines as a treatment option for adults with upper limb spastic paresis. However, the magnitude of the maximal therapeutic effect of repeated abobotulinumtoxinA treatment across different efficacy parameters and the number of injection cycles required to reach maximal effect remain to be elucidated. Here, we present a post hoc exploratory analysis of a randomized, double-blind, placebo-controlled trial (12–24 weeks; NCT01313299) and open-label extension study (up to 12 months; NCT0131331), in patients aged 18–80 years with hemiparesis for ≥6 months after stroke/traumatic brain injury. Two inferential methods were used to assess the changes in efficacy parameters after repeat abobotulinumtoxinA treatment cycles: Mixed Model Repeated Measures analysis and Non-Linear Random Coefficients analysis. Using the latter model, the expected maximal effect size (not placebo-controlled) and the number of treatment cycles to reach 90% of this maximal effect were estimated. Treatment responses in terms of passive and perceived parameters (i.e. modified Ashworth scale in primary target muscle group, disability assessment scale for principal target for treatment or limb position, and angle of catch at fast speed) were estimated to reach near-maximal effect in two to three cycles. Near-maximal treatment effect for active parameters (i.e. active range of motion against the resistance of extrinsic finger flexors and active function, assessed by the Modified Frenchay Scale) was estimated to be reached one to two cycles later. In contrast to most parameters, active function showed greater improvements at Week 12 (estimated maximal change from baseline-modified Frenchay Scale overall score: +0.8 (95% confidence interval, 0.6; 1.0) than at Week 4 (+0.6 [95% confidence interval, 0.4; 0.8]). Overall, the analyses suggest that repeated treatment cycles with abobotulinumtoxinA in patients chronically affected with upper limb spastic paresis allow them to relearn how to use the affected arm with now looser antagonists. Future studies should assess active parameters as primary outcome measures over repeated treatment cycles, and assess efficacy at the 12-week time-point of each cycle, as the benefits of abobotulinumtoxinA may be underestimated in the studies of insufficient duration.

Abbreviated summary

In this post hoc analysis of repeated abobotulinumtoxinA injection cycles in upper limb spastic paresis, Gracies et al. used statistical modelling to elucidate the maximal therapeutic effect of abobotulinumtoxinA. Notably, the number of injections required to reach this maximal effect was higher for active (e.g. active function) compared with passive (e.g. tone) parameters.
Immunomodulation as Treatment for Severe Coronavirus Disease 2019: A Systematic Review of Current Modalities and Future Directions
Authors: Meyerowitz Eric A , Sen Pritha , Schoenfeld Sara R , Neilan Tomas G , Frigault Matthew J , Stone John H , Kim Arthur Y , Mansour Michael K
Published: November 2020

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral load peaks early and declines quickly after symptom onset. Severe coronavirus disease 2019 (COVID-19) is marked by aberrant innate and adaptive immune responses with an abnormal cytokine profile and multiorgan system dysfunction that persists well after viral clearance. A purely antiviral treatment strategy may therefore be insufficient, and antiviral agents have not shown a benefit later in the illness course. A number of immunomodulatory strategies are being tested, including corticosteroids, cytokine and anticytokine therapies, small molecule inhibitors, and cellular therapeutics. To date, the only drug to show a mortality benefit for COVID-19 in a randomized, controlled trial is dexamethasone. However, there remains uncertainty about which patients may benefit most and about longer-term complications, including secondary infections. Here, we review the immune dysregulation of severe COVID-19 and the existing data behind various immunomodulatory strategies, and we consider future directions of study.
RegulomePA: a database of transcriptional regulatory interactions in Pseudomonas aeruginosa PAO1
Authors: Galán-Vásquez Edgardo , Luna-Olivera Beatriz Carely , Ramírez-Ibáñez Marcelino , Martínez-Antonio Agustino
Published: November 2020

We present RegulomePA, a database that contains biological information on regulatory interactions between transcription factors (TFs), sigma factor (SFs) and target genes in Pseudomonas aeruginosa PAO1. RegulomePA consists of 4827 regulatory interactions between 2831 nodes, which represent the interactions of TFs and SFs with their target genes, from the total of predicted RegulomePA including 27.27% of the TFs, 54.16% of SFs and 50.8% of the total genes. Each entry in the database corresponds to one node in the network and provides comprehensive details about the gene and its regulatory interactions such as gene description, nucleotide sequence, genome-strand position and links to other databases as well as the type of regulation it exerts or to which it is being subject (repression or activation), the associated experimental evidence and references, and topological information. Additionally, RegulomePA provides a way to recover information on the regulatory circuits of the network to which a gene pertains and also makes available the source codes to analyze the topology of any other regulatory network. The database will be updated yearly, by our team, with the contributions from ourselves and users, since the users are provided with an interactive platform where they can add interactions to the regulatory network feeding it with their respective references.

Database URL: www.regulome.pcyt.unam.mx.
Ileal Transcriptomic Analysis in Paediatric Crohn’s Disease RevealsIL17-andNOD-signalling Expression Signatures in Treatment-naïve Patients and Identifies Epithelial Cells Driving Differentially Expressed Genes
Authors: Ashton James J , Boukas Konstantinos , Davies James , Stafford Imogen S , Vallejo Andres F , Haggarty Rachel , Coelho Tracy A F , Batra Akshay , Afzal Nadeem A , Vadgama Bhumita , Williams Anthony P , Beattie R Mark , Polak Marta E , Ennis Sarah
Published: November 2020

Background and Aims

Crohn’s disease [CD] arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD.

Methods

We employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted gene co-expression network analysis [WGCNA] was performed and differentially expressed genes [DEGs] were determined. We integrated clinical data to determine co-expression modules associated with outcomes.

Results

In all, 27 treatment-naive CD [TN-CD], 26 established CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established CD, nor controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes, including S100A12 and the calprotectin subunit S100A9, were significantly upregulated in TN CD compared with controls [p = 2.61 x 10-15 and p = 9.13 x 10-14, respectively] and established CD [both p = 0.0055]. Gene-enrichment analysis confirmed upregulation of the IL17-, NOD- and Oncostatin-M-signalling pathways in TN-CD patients, identified in both WGCNA and DEG analyses. An upregulated gene signature was enriched for transcripts promoting Th17-cell differentiation and correlated with prolonged time to relapse [correlation-coefficient-0.36, p = 0.07]. Single-cell sequencing of TN-CD patients identified specialised epithelial cells driving differential expression of S100A9. Cell groups, determined by single-cell gene expression, demonstrated enrichment of IL17-signalling in monocytes and epithelial cells.

Conclusions

Ileal tissue from treatment-naïve paediatric patients is significantly upregulated for genes driving IL17-, NOD- and Oncostatin-M-signalling. This signal is driven by a distinct subset of epithelial cells expressing antimicrobial gene transcripts.
Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab Concentrations
Authors: Van den Berghe Nathalie , Verstockt Bram , Gils Ann , Sabino João , Ferrante Marc , Vermeire Séverine , Declerck Paul , Thomas Debby
Published: November 2020

Background and Aims

Some patients with ulcerative colitis [UC] do not respond to vedolizumab treatment despite adequate drug exposure in serum. This study aimed to investigate vedolizumab in tissue and questioned whether insufficient tissue exposure could explain non-response in UC patients with adequate serum vedolizumab concentrations.

Methods

A paired serum sample and colonic mucosal biopsy was collected from 40 UC patients [20 endoscopic responders, 20 non-responders] at week 14 of vedolizumab treatment. Vedolizumab, soluble [s]-mucosal addressin cell adhesion molecule-1 [MAdCAM-1], s-vascular cell adhesion molecule-1 [VCAM-1] and s-intercellular adhesion molecule-1 [ICAM-1] were measured in serum and/or tissue. Endoscopic response was defined as Mayo endoscopic sub-score ≤1.

Results

A significant positive correlation was observed between vedolizumab serum and colonic tissue concentrations [ρ = 0.84, p < 0.0001], regardless of the macroscopic inflammatory state of the tissue. Vedolizumab tissue concentrations were lower in non-responders than in responders [0.07 vs 0.11 µg/mg, p = 0.04]. In the subgroup of patients with adequate vedolizumab serum concentrations [>14.6 µg/mL], tissue vedolizumab was not significantly different between responders and non-responders [0.15 vs 0.13 µg/mg; p = 0.92]. Serum sMAdCAM-1 concentrations, but not serum sICAM-1 or sVCAM-1 concentrations, were significantly higher in responders than in non-responders with adequate vedolizumab serum concentrations [1.04 vs 0.83 ng/mL, p = 0.03].

Conclusions

Vedolizumab concentrations in colonic mucosal tissue of UC patients reflect the concentration in serum regardless of the macroscopic inflammatory state of the tissue. Our data show that insufficient tissue exposure does not explain non-response in UC patients with adequate serum vedolizumab concentrations.
Watch out for ST-elevation myocardial infarction: a case report of ST-elevation in single-lead electrocardiogram tracing of a smartwatch
Authors: Stark Konstantin , Czermak Thomas , Massberg Steffen , Orban Martin
Published: November 2020

Background

It was recently demonstrated that the detection of atrial fibrillation based on heart rate tracking by optical sensors is feasible and reliable using the Apple Watch and the corresponding application. There are already a number of smartwatches and other wearable devices alongside the Apple Watch that can additionally record a single-lead electrocardiogram (ECG) and it is reasonable to expect this technology to become a standard feature, as is already the case with automated heart rate tracking. This could potentially have enormous impact regarding the early diagnosis of several cardiac diseases.

Case summary

A 61-year-old male patient without previously known coronary artery disease was admitted with subacute ST-elevation myocardial infarction (STEMI) caused by occlusion of left anterior descending artery. Due to mildness of symptoms, the patient did only seek medical attention due to morphological changes in the single-lead ECG tracing acquired on his Apple Watch 5. The ECG recording of his smartwatch clearly showed ST-elevation, QRS widening, R-wave loss, and T-wave inversion. Coronary angiography revealed occlusion of the left anterior descending and recanalization was performed. The patient recovered without any complications and was discharged from the hospital 4 days after admission.

Discussion

While the potential of ECG recordings by smartwatches to detect atrial fibrillation is currently under scientific investigation, this case highlights the possible potential of these devices to detect STEMI.
Reporting of the methodological quality of search strategies in orthodontic quantitative systematic reviews
Authors: AlMubarak Danah , Pandis Nikolaos , Cobourne Martyn T , Seehra Jadbinder
Published: November 2020

Background

This study aimed to assess the reporting of the methodological quality of search strategies undertaken in orthodontic quantitative systematic reviews (SRs) and hence their reproducibility.

Materials and methods

A search of a single electronic database (Medline via PubMed) was undertaken to identify interventional orthodontic SRs with meta-analysis published within a 10-year period. The Cochrane Library of Systematic Reviews was also sourced. Full articles were reviewed by two assessors against the eligibility criteria. The reporting quality of each search strategy was assessed using a previously validated checklist with a score of 1 or 2 given for each of the eight items. Cumulative totals were calculated. Guided by previous research, the authors agreed the following cut-offs to categorize the overall level of quality: 8–10 (poor), 10–12 (fair), and greater than 13 (good).

Results

A total of 127 SRs were analysed. The overall median quality score for the reporting of the search strategy was 14 [interquartile range (IQR): 13–15]. Cochrane SRs and those originating in Europe received higher aggregate scores, whereas no difference was evident based on Prospero registration. The continent of the corresponding author predicated the overall score. Non-Cochrane reviews achieved lower overall scores compared to Cochrane reviews (−1.0, 95% confidence interval: −1.65, −0.34, P = 0.003). The most frequently searched database was EMBASE (N = 93) and the median number of authors was 5 (IQR 4–6). Authors of 26.8% of SRs searched the grey literature. Language restrictions were applied to the search strategies of 88 (69.3%) SRs.

Conclusions

The reporting quality of search strategies undertaken in orthodontic SRs is at a good level but differences between Cochrane and non-Cochrane reviews currently exist. The reporting of searching of the grey literature and application of no language restrictions can be improved.
The natural history of hypertrophic cardiomyopathy
Authors: Autore Camillo , Musumeci Maria Beatrice
Published: November 2020

In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life.
The new type 2 diabetes mellitus therapy: comparison between the two classes of drugs GLPR (glucagon-like peptide receptor) agonists and SGLT2 (sodium–glucose cotransporter 2) inhibitors
Authors: Borghi Claudio , Bragagni Alessio
Published: November 2020

Type 2 diabetes mellitus represents one of the most common chronic-degenerative diseases in modern society and is the cause of innumerable micro- and macrovascular complications that weigh on the national health system. Until a few years ago, there was no anti-diabetic drug that, in addition to lowering blood sugar, had an impact on cardiovascular risk in these patients. In this report, we will analyse the characteristics, contraindications, and evidence in favour of the use of two innovative categories of molecules that aim, for the first time in history, at controlling blood sugar levels and simultaneously lower cardiovascular risk in diabetics individuals: the glucagon-like peptide receptor agonists and the sodium–glucose cotransporter 2 inhibitors.
The PARAGON-HF trial: the sacubitril/valsartan in heart failure with preserved ejection fraction
Authors: Gronda Edoardo , Vanoli Emilio , Iacoviello Massimo
Published: November 2020

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril–valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous post hoc analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence.
Procedures for chronic total occlusion: when are they recommended and when not
Authors: Menozzi Mila , Piovaccari Giancarlo
Published: November 2020

Coronary chronic total occlusion (CTO) produces an important clinical problem, often treated with medical therapy or coronary artery bypass grafting. Recent clinical studies, both registries and randomized trials, demonstrated that percutaneous coronary interventions (PCI), could provide a valid therapeutic option. Nonetheless, significant reduction in all-cause mortality, cardiac mortality, myocardial infarction, MACE, and MACCE has not been demonstrated in the subgroups analysis of randomized trials. These analyses suggest that PCI for CTO should be reserved for patients with angina or with large areas of the myocardium with reversible ischaemia. Large randomized studies should search for a personalized approach, considering the risks and complexity of PCI in CTO, which should mainly consider the extension of the ischaemia and the viability of the myocardium.