bluuebunny/crossref_metadata_2025 huggingface dataset:
The Resting Oxidized State of Small Laccase Analyzed with Paramagnetic NMR Spectroscopy
Authors: Dasgupta Rubin , Gupta Karthick B. S. S. , de Groot Huub J. M. , Ubbink Marcellus
Published: March 2021

The enzyme laccase catalyzes the reduction of dioxygen to water at the trinuclear copper center (TNC). The TNC comprises a type‐3 (T3) and a type‐2 (T2) copper site. The paramagnetic NMR spectrum of the small laccase from Streptomyces coelicolor (SLAC) without the substrate shows a mixture of two catalytic states, the resting oxidized (RO) state and the native intermediate (NI) state. An analysis of the resonances of the RO state is reported. In this state, hydrogen resonances only of the T3 copper ligands can be found, in the region of 12–22 ppm. Signals from all six histidine ligands are found and can be attributed to Hδ1, Hβ or backbone amide HN nuclei. Two sequence‐specific assignments are proposed on the basis of a second‐coordination shell variant that also lacks the copper ion at the T1 site, SLAC−T1D/Q291E. This double mutant is found to be exclusively in the RO state, revealing a subtle balance between the RO and the NI states.
Diameter limits impede restoration of historical conditions in dry mixed‐conifer forests of eastern Oregon, USA
Authors: Johnston James D. , Greenler Skye M. , Miller Becky A. , Reilly Matthew J. , Lindsay Amanda A. , Dunn Christopher J.
Published: March 2021

The U.S. Forest Service is reconsidering policies that limit the size of trees that can be removed in the course of restoration treatments in dry forests of eastern Oregon. To evaluate the effects of diameter limits on the ability of managers to meet restoration objectives, we used an existing network of long‐term research plots to summarize historical and contemporary structure and composition of mixed‐conifer forests within a one million‐ha study area in eastern Oregon. Then, we used a novel thinning simulation procedure to quantify the degree to which thinning using different diameter limits restored stands to historical conditions. Contemporary mixed‐conifer forests within the study area are significantly denser, have more basal area, and have a greater proportion of shade‐tolerant species than historical conditions. Our simulations of thinning under current policy that prohibits cutting of trees ≥53 cm show that a quarter of mixed‐conifer stands cannot be restored to within the historical range of basal area or density. Those stands that could be restored to within historical basal area ranges still had a substantially higher component of shade‐tolerant trees than historical stands. Permitting larger shade‐tolerant trees to be removed allowed restoration of all or most of stands to within historical structural and compositional ranges. Forest conditions in the late 1800s may not necessarily provide the best template for management because climate and disturbance projections suggest that eastern Oregon forests will be less well suited to shade‐tolerant species in the future. Adapting stands to future conditions will require robust monitoring of forest structural and compositional response to restoration treatments.
A DFT Study on the Mechanism and Origin of Regioselectivity in the Rhodium/Diene‐Catalyzed Ring‐Opening Reactions of C1‐Substituted Oxabenzonorbornadienes with Arylboronic Acids
Authors: Pounder Austin , Bishop Fiona , Chen Leanne D. , Tam William
Published: March 2021

The mechanism and the origin of the regioselectivity of the rhodium/diene‐catalyzed ring‐opening reactions of C1‐substituted oxabenzonorbornadienes with arylboronic acids has been examined using hybrid density functional theory (DFT). The overall mechanism for the reaction is considered as a four‐step reaction including transmetalation, carborhodation, β‐oxygen elimination, and protonolysis. The free energy profiles show that the rate‐determining step is involved in the protonolysis step which differs from previous mechanistic studies on metal‐catalyzed ring‐opening reactions of oxabenzonorbornadienes. Additionally, it is theorized the β‐oxygen elimination step is the origin of regioselectivity. DFT calculations predict the formation of the 1,2,4‐trisubstituted naphthalene framework is selective over the 1,1,2‐trisubstituted product, in agreement with experimental observations.
Development of an Innovative Nitrite Sensing Platform Based on the Construction of an Electrochemical Composite Sensor of Polymer Coated CNTs and Decorated with Magnetite Nanoparticles
Authors: Atta Nada F. , Galal Ahmed , Ahmed Yousef M. , Abdelkader Mohamed G.
Published: March 2021

Electrochemical determination of nitrite in real water samples is achieved using simple and efficient electrochemical sensor. The sensor is fabricated by electrodeposition of a thin layer of poly(3,4‐ethylenedioxythiophene) sandwiched by drop‐casting two thin layers of CNTs and iron oxide nanoparticles (Fe3O4) over a GC electrode surface. Voltammetry determination of nitrite in tap water and wastewater samples in the concentration range (0.5–150 μM) is successfully achieved with detection limits of 22 and 24 nM, respectively. Practical application of the GC/CNT/PEDOT/Fe3O4 sensor is efficiently assessed in real water samples for nitrite determination with acceptable recoveries, excellent anti‐interference ability and long‐term stability.
Do pharmaceutical prices rise anticipating branded competition?
Authors: Ellyson Alice M. , Basu Anirban
Published: March 2021

Growth in pharmaceutical prices is a major policy issue in the United States. Competition is encouraged to counteract such growth, yet less is known about the effect of brand competition on prices. We discover a unique feature of this market by studying the pricing strategies of incumbent drug manufacturers under tiered‐insurance anticipating branded competition. Using the insulin market as a natural experiment, we exploit exogenous variation in several potential entrants' completion of clinical trials to identify the effect of drug pipeline pressure on the prices of incumbent drugs. We find that pipeline pressure exerts cumulative and significant upward pressure on prices of incumbent drugs. In the insulin market such pressure explained 10.5% of the growth of prices. We were able to replicate these findings among incumbents with other emerging biosimilars. Insurance designs that fail to promote price competition through negotiations and value‐based principles may contribute to such price increases.
Novel thiazolidin‐4‐one clubbed thiophene derivatives via Gewald synthesis as anti‐tubercular and anti‐inflammatory agents
Authors: Nayak Soukhyarani Gopal , Poojary Boja , Kamat Vinuta , Puthran Divyaraj
Published: March 2021

In aim of obtaining novel bio‐active compounds, a new series of 5‐(3,5‐difluorophenyl)‐2‐(2‐imino‐5‐arylidene)‐4‐oxothiazolidin‐3‐yl)thiophene‐3‐carbonitrile (6a–d) and N‐(3‐cyano‐5‐(3,5‐difluorophenyl)thiophen‐2‐yl)‐2‐(substitutedamino)acetamide (7a–f) were synthesized via Gewald's method and characterized by 1H/13C nuclear magnetic resonance, Fourier‐transform infrared, mass spectrometry, and elemental analyses. All the newly prepared compounds were screened for their in vitro anti‐tubercular activity against virulent strain M. tuberculosis (H37Rv) at different concentrations ranging from 0.2 to 100 μg/ml. Most of the compounds were potent showing better inhibition at concentrations 6.25, 12.5, 25, 50, and 100 μg/ml. The anti‐inflammatory activity of the compounds was studied using inhibition of albumin denaturation technique. Tested compounds exhibited remarkable anti‐inflammatory activity. Hemolytic assay also confirmed that compounds are non‐toxic with a percentage hemolysis ranging from 1.81 to 14.94 at a concentration of 1 mg/ml. The results suggest that amino‐substituted acetamide and thiazolidin‐4‐one moiety, as well as the substitution pattern on the heterocyclic ring, have an effect on bioactivity.
High Tm Poly(l‐lactide)s by Means of Bismuth Catalysts?
Authors: Kricheldorf Hans R. , Meyer Andreas , Weidner Steffen M.
Published: March 2021

One series of BiSub‐catalyzed ring‐opening polymerizations (ROPs) is performed at 160 °C for 3 days with addition of difunctional cocatalysts to find out, if poly(l‐lactide) crystallizes directly from the reaction mixture. An analogous series is performed with monofunctional cocatalysts. High Tm crystallites (Tm > 190 °C) are obtained from all bifunctional cocatalysts, but not from all monofunctional ones. It is shown by means of SAXS measurements that the high Tm values are mainly a consequence of a transesterification–homogenization process across the lamellar surfaces resulting in thickness and smoothing of the surfaces. An unusual enthalpy‐driven modification of the molecular weight distribution is found for samples that have crystallized during the polymerization. A third series of ROPs is performed at 170 °C for 2 h followed by annealing at 120 °C (2 h) to induce crystallization. Complete transformation of the resulting low Tm crystallites (Tm < 180 °C) into the high Tm crystallites by annealing at 170 °C for 1 d is not achieved, despite variation of the cocatalyst.
Utilization of moringa oleifera and nanofiltration membrane to treat palm oil mill effluent (POME)
Authors: Naidua T. , Qadir D. , Nasir R. , Mannan H.A. , Mukhtar H. , Maqsood K. , Ali A. , Abdulrahman A.
Published: March 2021

The palm oil mill effluent imposes environmental issues because of natural and supplement substance. This waste has a significant amount of biological oxygen demand, total suspended solids, chemical oxygen demand, and turbidity. Moringa oleifera seeds′ performance analysis as natural coagulants during the pretreatment stage of palm oil mill effluent before it is filtered through commercial nanofiltration membrane is the focus of the current study. The untreated palm oil mill effluent has 2,410 mg/L biological oxygen demand, 3,900 mg/L chemical oxygen demand, 865 NTU turbidity, 41,900 mg/L total suspended solids, and 4.61 pH. The significant reduction occurred in the feed parameters viz., 91.7 % for biological oxygen demand, 83.0 % for chemical oxygen demand, 67.7 % for total dissolved solids, and 72.8 % for turbidity after the pretreatment; however, the pH increased to 4.88. Design expert® was used to design the experiments and optimize the palm oil mill effluent pretreatment process via a one‐factor experimental design. The optimized solution has a 0.994 desirability index. Finally, it was concluded that with ever‐tightening environmental standards, moringa oleifera could provide a cheap, green, and potential natural alternative to the existing coagulants employed to treat the palm oil mill effluent.
Thermal cycles and their effects during friction stir welding of AA7075 thicker plates with and without in‐process cooling
Authors: Srinivasa Rao T. , Selvaraj M. , Koteswara Rao S.R. , Ramakrishna T.
Published: March 2021

Friction stir welding of AA 7075 plates in three different thicknesses such as 10, 16 and 25 mm at natural convection condition was carried out successfully without defects. Water cooled friction stir welds were also produced on 16 mm thick plates. The thermal cycles at different locations of the plate, during the friction stir welding process, were predicted using a three‐dimensional thermal model. Mechanical properties of the welds were evaluated using tensile and hardness tests. Weld microstructures were also examined with optical and transmission electron microscopes. The weld hardness values and tensile properties were found to decrease with increase in plate thickness. The use of water cooling was found to improve the weld properties to some extent, although not to the level of base metal. The reasons for this behavior are discussed, correlating thermal cycles, mechanical properties, fracture locations and precipitate morphology.
Laser parameter optimization for surface texturing of inconel 625
Authors: Fidan S. , Canel T. , Sınmazçelik T.
Published: March 2021

The optimum laser parameters required for the inconel 625 alloy surfaces to have the desired properties have been determined. Process parameters were optimized to get maximum heat affected zone depth (HAZ) and width and maximum aspect ratio and minimum defect outside of the spot area independently of each other. Also, the effect rates of the examined process parameters on the treated surface quality were determined separately for each surface feature. As a result of optimization using Taguchi method, the most effective parameters to obtain the desired surface were obtained as gas type with 72.26 % for heat affected zone depth, gas type with 90.46 % for heat affected zone width, gas type with 81.57 % for aspect ratio, pulse energy with 30.99 % for minimum defect outside of the spot area. The best results were obtained on the surfaces obtained as a result of the confirmation experiment with the new parameters obtained with the Taguchi method. Since the results of the confirmation experiments are highly compatible with the results suggested by the Taguchi method, the Taguchi method may be concluded as reliable in the laser ablation of the inconel 625 surface.
Nerve recognition in percutaneous transforaminal endoscopic discectomy using convolutional neural network
Authors: Cui Peng , Shu Tao , Lei Jun , Chen Wenxi
Published: March 2021

Purpose

Percutaneous transforaminal endoscopic discectomy (PTED) is one of the most common minimally invasive surgery methods used in clinic in recent years. In this study, we developed a computer‐aided detection system (CADS) based on convolutional neural network (CNN) to automatically recognize nerve and dura mater images under PTED surgery.

Methods

We collected surgical videos from 65 patients with lumbar disc herniation who underwent PTED; we then converted the videos into images, and randomly divided some images into a training dataset, a validation dataset, test dataset. The training dataset and validation dataset were composed of 10 454 images containing nerve and dura mater from 50 randomly selected patients; test dataset contained 12 000 images from the remaining 15 patients.

Results

The results showed that sensitivity, specificity, and accuracy reached 90.90%, 93.68%, and 92.29%, respectively. CADS could recognize the nerve and dura mater with no significant difference (P > 0.05) between each patient in test dataset. In comparison with clinicians of different levels, the performance of CADS was lower than that of a spinal endoscopist, but significantly higher than that of general surgeons. With the assistance of CADS, the performance of the general surgeons approached that of the spinal endoscopist.

Conclusions

CNN can recognize well nerve and dura mater images in PTED surgery, and can help general surgeons to improve their ability to recognize tissues during the operation.
Preserving general physical properties in model reduction of dynamical systems via constrained‐optimization projection
Authors: Schein Alexander , Carlberg Kevin T. , Zahr Matthew J.
Published: March 2021

Model‐reduction techniques aim to reduce the computational complexity of simulating dynamical systems by applying a (Petrov–)Galerkin projection process that enforces the dynamics to evolve in a low‐dimensional subspace of the original state space. Frequently, the resulting reduced‐order model (ROM) violates intrinsic physical properties of the original full‐order model (e.g., global conservation, Lagrangian structure, state‐variable bounds) because the projection process does not generally ensure preservation of these properties. However, in many applications, ensuring the ROM preserves such intrinsic properties can enable the ROM to retain physical meaning and lead to improved accuracy and stability properties. In this work, we present a general constrained‐optimization formulation for projection‐based model reduction that can be used as a template to enforce the ROM to satisfy specific properties on the kinematics and dynamics. We introduce constrained‐optimization formulations at both the time‐continuous (i.e., ODE) level, which leads to a constrained Galerkin projection, and at the time‐discrete level, which leads to a least‐squares Petrov–Galerkin projection, in the context of linear multistep schemes. We demonstrate the ability of the proposed formulations to equip ROMs with desired properties such as global energy conservation and bounds on the total variation.
Lagrangian–Eulerian multidensity topology optimization with the material point method
Authors: Li Yue , Li Xuan , Li Minchen , Zhu Yixin , Zhu Bo , Jiang Chenfanfu
Published: March 2021

In this paper, a hybrid Lagrangian–Eulerian topology optimization (LETO) method is proposed to solve the elastic force equilibrium with the Material Point Method (MPM). LETO transfers density information from freely movable Lagrangian carrier particles to a fixed set of Eulerian quadrature points. This transfer is based on a smooth radial kernel involved in the compliance objective to avoid the artificial checkerboard pattern. The quadrature points act as MPM particles embedded in a lower‐resolution grid and enable a subcell multidensity resolution of intricate structures with a reduced computational cost. A quadrature‐level connectivity graph‐based method is adopted to avoid the artificial checkerboard issues commonly existing in multiresolution topology optimization methods. Numerical experiments are provided to demonstrate the efficacy of the proposed approach.
Free energy of conformational change in a single chain of polyvinylidene fluoride using molecular simulations
Authors: Mireja Shubham , Khakhar Devang V.
Published: March 2021

Polyvinylidene fluoride (PVDF) has several crystal forms of which theα‐form is nonpolar, while theβ‐form is polar and has the highest piezoelectric constant.αPVDF, when stretched, transforms into theβform, which has wide applications in sensors and actuators. Steered molecular dynamics simulations are used to study the transformation of a single chain of PVDF from a trans–gauche conformation to an all trans one. The Helmholtz free energy change (∆F) is estimated using Jarzynski's equality. The transformation starts at the chain ends followed by the transformation of the remaining chain. The free energy change for the transformation is found to be always positive, indicating that theTGTG' form has higher thermodynamic stability than the all trans form throughout the studied temperature range. With increasing temperature, free energy change for the transformation increases monotonically.
Targeted and Specific Modification with 4‐Carboxybenzeneboronic Acid and TPGS of Fluorescent Gold Nanoparticles and the Enhanced Antitumor Activity Research
Authors: Zhou Qiaoqiao , Wang Shaochen , Hu Peng , Yu Shuling , Shi Jiahua , Yuan Jintao
Published: March 2021

A targeting and specific fluorescent gold nanoparticle is prepared for tracing of drug and effective treatment of cancers. First, 4‐carboxybenzeneboronic acid (CBPA) and D‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS) are used to modify cyclodextrins (CDs), then modified cyclodextrins and polyethylene glycol (PEG) are used to stabilize gold nanoclusters to prepare fluorescent gold nanoparticles (AuNCs@CD‐TPGS‐CBPA/PEG). CBPA has targeting and TPGS can induce apoptosis, therefore, AuNCs@CD‐TPGS‐CBPA/PEG has targeting and certain anti‐tumor activity. The structure and morphology of the nanomaterial are characterized by using nuclear magnetic resonance (NMR) spectroscopy and transmission electron microscope (TEM). Paclitaxel (PTX) is loaded into the hydrophobic cavity of CDs to form targeting specific drug‐loaded fluorescent gold nanoparticles (AuNCs@CD‐TPGS‐CBPA/PEG/PTX). Biological performances of AuNCs@CD‐TPGS‐CBPA/PEG are studied by in vitro and in vivo experiments. In vitro test results confirm that AuNCs@CD‐TPGS‐CBPA/PEG could be internalized by tumor cells, and effectively against tumor cells, but it is biocompatible to normal cells. In vivo experiments prove that AuNCs@CD‐TPGS‐CBPA/PEG has excellent targeting, biocompatibility, and enhanced antitumor capability, could enrich and stay for a long time in the tumor regions, effectively prolong the lifetime of tumor‐bearing mice. Therefore, this work provides an insight into the development of fluorescent gold nanomaterials for practical biomedical application.
Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease
Authors: McKetney Justin , Panyard Daniel J. , Johnson Sterling C. , Carlsson Cynthia M. , Engelman Corinne D. , Coon Joshua J.
Published: March 2021

Proteomic analysis of cerebrospinal fluid (CSF) holds great promise in understanding the progression of neurodegenerative diseases, including Alzheimer's disease (AD). As one of the primary reservoirs of neuronal biomolecules, CSF provides a window into the biochemical and cellular aspects of the neurological environment. CSF can be drawn from living participants allowing the potential alignment of clinical changes with these biochemical markers. Using cutting‐edge mass spectrometry technologies, we perform a streamlined proteomic analysis of CSF. We quantify greater than 700 proteins across 10 pairs of age‐ and sex‐matched participants in approximately one hour of analysis time each. Using the paired participant study structure, we identify a small group of biologically relevant proteins that show substantial changes in abundance between cognitive normal and AD participants, which were then analyzed at the peptide level using parallel reaction monitoring experiments. Our findings suggest the utility of fractionating a single sample and using matching to increase proteomic depth in cerebrospinal fluid, as well as the potential power of an expanded study.
Wettability Control on YW2 Cemented Carbide Surface by Femtosecond Laser Irradiation
Authors: Yang Qibiao , Zhou Wei , Wang Li , Ren Xiaoping , Wang Yutao , Lou Deyuan , Chen Lie , Cheng Jian , Zheng Zhong , Liu Dun
Published: March 2021

The surface wettability control of cemented carbide tools is beneficial to the improvement of tool life and surface quality of workpieces in wet cutting. To clarify the correlation between the surface topography and wettability, squared microdimples are fabricated on the cemented carbide surface using a femtosecond laser. The dependencies of the side length, the depth, and the distribution density of squared microdimples on the surface topography and contact angle are studied. As the average laser power, and the number of scanning passes, increase, both the side length and depth of the squared microdimples increase. The contact angle decreases from hydrophilic to superhydrophilic. Moreover, the roughness height parameters have a great influence on the surface wettability, the larger the surface arithmetic average height, the smaller the kurtosis, the larger the skewness, and the better the hydrophilicity. The results of the scanning electron microscope (SEM) and energy‐dispersive spectrometer (EDS) reflect that the changes in the micro–nano protrusions, carbon, and oxygen elements cause deviation between the calculated contact angle and the actual contact angle. The friction coefficient of textured tools is lower than that of untextured tools at high sliding speed. Reasonable design of surface texture accurately controls surface wettability.
Complete response in a patient with lung cancer suffering from three pembrolizumab‐induced immune‐related adverse events including retinal vasculitis
Authors: Mimura Chihiro , Tachihara Motoko , Kusuhara Sentaro , Fukuoka Hidenori , Nishimura Yoshihiro
Published: March 2021

A 71‐year‐old man was diagnosed with squamous cell lung carcinoma with high expression of programmed cell death ligand 1 (PDL1) (cT4N1M1b stage IVA). He was treated with pembrolizumab, but 14 days later, he suffered from pembrolizumab‐related retinal vasculitis as an immune‐related adverse event (irAE). The symptoms were ameliorated by oral corticosteroids. We succeeded in switching to topical treatment as early as possible with the help of an ophthalmologist. Six months after discontinuing treatment with oral prednisolone, hypophysitis and thyroiditis occurred in six cycles of pembrolizumab. Finally, he suffered from three irAEs, but the antitumour effect resulted in a remarkable response.
Model‐based clustering of time‐dependent categorical sequences with application to the analysis of major life event patterns
Authors: Zhang Yingying , Melnykov Volodymyr , Zhu Xuwen
Published: March 2021

Clustering categorical sequences is a problem that arises in many fields. There is a few techniques available in this framework but none of them take into account the possible temporal character of transitions from one state to another. A mixture of Markov models is proposed, where transition probabilities are represented as functions of time. The corresponding expectation–maximization algorithm is discussed along with related computational challenges. The effectiveness of the proposed procedure is illustrated on the set of simulation studies, in which it outperforms four alternative approaches. The method is applied to major life event sequences from the British Household Panel Survey. As reflected by Bayesian Information Criterion, the proposed model demonstrates substantially better performance than its competitors. The analysis of obtained results and related transition probability plots reveals two groups of individuals: people with a conventional development of life course and those encountering some challenges.
Synthesis of Benzoxazole‐2‐carboxylate Derivatives: Electronic‐ and Position‐effect of Functional Groups and Computational Modeling of the Selectivity for Oxazole Ring
Authors: Kuzu Burak , Sari Ozlem , Erdem Safiye Sag , Algul Oztekin , Menges Nurettin
Published: March 2021

In this study, Mitsunobu reagent, DEAD (diethyl azodicarboxylate) and PPh3, and ethyl‐oxalamide derivatives of 2‐aminophenol were reacted under mild reaction conditions. As a result of the cyclization reaction, benzoxazole derivatives bearing an ester group in the C‐2 position were obtained in a one‐pot protocol. It was observed that the electron‐donating groups at the C‐5 position and the electron‐withdrawing groups at the C‐6 position of the benzene ring increased the yield of the cyclic product. It was found that the cyclization does not occur when the carboxylic acid group is substituted in the benzene ring. The cyclization reaction we performed preferred the 5‐endo‐trig reaction instead of the 6‐exo‐trig. This experimental result was examined in detail with density functional theory (DFT) calculations as well. A computational exploration is presented herein that elucidates the detailed mechanism for Huisgen zwitterion‘s reaction with ethyl‐oxalamide derivatives of 2‐aminophenol. Potential alternative mechanisms were modeled with DFT calculations via CPCM/M06‐2X/6‐311++G(d,p)//B3LYP/6‐31+G(d,p) level method in tetrahydrofuran to understand shed light on the mechanism. Our computational results are in good agreement with experimental findings that benzoxazole derivatives are the sole products in this reaction.
Multiparametric Profiling of Single Nanoscale Extracellular Vesicles by Combined Atomic Force and Fluorescence Microscopy: Correlation and Heterogeneity in Their Molecular and Biophysical Features
Authors: Cavallaro Sara , Pevere Federico , Stridfeldt Fredrik , Görgens André , Paba Carolina , Sahu Siddharth S. , Mamand Doste R. , Gupta Dhanu , El Andaloussi Samir , Linnros Jan , Dev Apurba
Published: March 2021

Being a key player in intercellular communications, nanoscale extracellular vesicles (EVs) offer unique opportunities for both diagnostics and therapeutics. However, their cellular origin and functional identity remain elusive due to the high heterogeneity in their molecular and physical features. Here, for the first time, multiple EV parameters involving membrane protein composition, size and mechanical properties on single small EVs (sEVs) are simultaneously studied by combined fluorescence and atomic force microscopy. Furthermore, their correlation and heterogeneity in different cellular sources are investigated. The study, performed on sEVs derived from human embryonic kidney 293, cord blood mesenchymal stromal and human acute monocytic leukemia cell lines, identifies both common and cell line‐specific sEV subpopulations bearing distinct distributions of the common tetraspanins (CD9, CD63, and CD81) and biophysical properties. Although the tetraspanin abundances of individual sEVs are independent of their sizes, the expression levels of CD9 and CD63 are strongly correlated. A sEV population co‐expressing all the three tetraspanins in relatively high abundance, however, having average diameters of <100 nm and relatively low Young moduli, is also found in all cell lines. Such a multiparametric approach is expected to provide new insights regarding EV biology and functions, potentially deciphering unsolved questions in this field.
Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes: a nationwide observational study in Scotland
Authors:   On behalf of the Scottish Diabetes Research Network (SDRN) Epidemiology Group, Jeyam Anita , Gibb Fraser W. , McKnight John A. , Kennon Brian , O’Reilly Joseph E. , Caparrotta Thomas M. , Höhn Andreas , McGurnaghan Stuart J. , Blackbourn Luke A. K. , Hatam Sara , McCrimmon Rory J. , Leese Graham , Lindsay Robert S. , Petrie John , Chalmers John , Philip Sam , Wild Sarah H. , Sattar Naveed , McKeigue Paul M. , Colhoun Helen M.
Published: March 2021

Aims/hypothesis

Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA1c levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA1c.

Methods

We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA1c over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure. We then used mixed models to assess the significance of CSII exposure, taking into account: (1) the diffuse nature of the intervention (i.e. structured education often precedes initiation); (2) repeated within-person measurements; and (3) background time-trends occurring pre-intervention.

Results

HbA1c decreased after CSII initiation, with a median within-person change of −5.5 mmol/mol (IQR −12.0, 0.0) (−0.5% [IQR −1.1, 0.0]). Within-person changes were most substantial in those with the highest baseline HbA1c, with median −21.0 mmol/mol (−30.0, −11.0) (−1.9% [−2.7, −1.0]) change in those with a baseline >84 mmol/mol (9.8%) within a year of exposure, that was sustained: −19.0 mmol/mol (−27.6, −6.5) (−1.7% [−2.5, −0.6]) at ≥5 years. Statistical significance and magnitude of change were supported by the mixed models results. The crude DKA event-rate was significantly lower in post-CSII person-time compared with pre-CSII person-time: 49.6 events (95% CI 46.3, 53.1) per 1000 person-years vs 67.9 (64.1, 71.9); rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.61 (95% credible interval [CrI] 0.47, 0.77; posterior probability of reduction pp = 1.00). The crude overall SHH event-rate in post-CSII vs pre-CSII person-time was also lower: 17.8 events (95% CI 15.8, 19.9) per 1000 person-years post-exposure vs 25.8 (23.5, 28.3) pre-exposure; rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.67 (95% CrI 0.45, 1.01; pp = 0.97).

Conclusions/interpretation

CSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control.

Graphical abstract
On nonlinear dilatational strain gradient elasticity
Authors: Eremeyev Victor A. , Cazzani Antonio , dell’Isola Francesco
Published: March 2021

We call nonlinear dilatational strain gradient elasticity the theory in which the specific class of dilatational second gradient continua is considered: those whose deformation energy depends, in an objective way, on the gradient of placement and on the gradient of the determinant of the gradient of placement. It is an interesting particular case of complete Toupin–Mindlin nonlinear strain gradient elasticity: indeed, in it, the only second gradient effects are due to the inhomogeneous dilatation state of the considered deformable body. The dilatational second gradient continua are strictly related to other generalized models with scalar (one-dimensional) microstructure as those considered in poroelasticity. They could be also regarded to be the result of a kind of “solidification” of the strain gradient fluids known as Korteweg or Cahn–Hilliard fluids. Using the variational approach we derive, for dilatational second gradient continua the Euler–Lagrange equilibrium conditions in both Lagrangian and Eulerian descriptions. In particular, we show that the considered continua can support contact forces concentrated on edges but also on surface curves in the faces of piecewise orientable contact surfaces. The conditions characterizing the possible externally applicable double forces and curve forces are found and examined in detail. As a result of linearization the case of small deformations is also presented. The peculiarities of the model is illustrated through axial deformations of a thick-walled elastic tube and the propagation of dilatational waves.
Retrospektive Mortalitätsstudie natürlicher Todesfälle der Generation 65+ im Obduktionsgut der Rechtsmedizin Frankfurt am Main anhand zweier Zeitintervalle
Authors: Wach A. , Faßbender C. , Ackermann H. , Parzeller M.
Published: March 2021

Hintergrund und Ziel der Arbeit

In Deutschland vollzieht sich ein stetiger demografischer Wandel, welcher zu einer zunehmenden Alterung der Gesellschaft führt. Ziel der Arbeit war die Analyse der natürlichen Todesfälle mit einem Sterbealter ≥ 65 Jahre, da die gesundheitliche Vulnerabilität dieser Altersgruppe an Bedeutung gewinnt.

Material und Methoden

Retrospektiv wurden die Obduktionsgutachten aller natürlichen Todesfälle der ≥ 65-Jährigen im Institut der Rechtsmedizin des Universitätsklinikums der Goethe-Universität Frankfurt am Main in einem Zeitvergleich (Zeitraum I: 2000–2002; Zeitraum II: 2013–2015) ausgewertet.

Ergebnisse

In den Zeiträumen I und II wurden insgesamt 1206 Obduktionen in dieser Altersgruppe ermittelt. Davon wiesen 404 (33,5 %) eine nichtnatürliche Todesart auf, in 39 Fällen (3,2 %) lag eine Kombination aus natürlichem und nichtnatürlichem Tod vor, und in 94 Fällen (7,8 %) war die Todesart unklar. Die Mehrheit (n = 669; 55,5 %) verstarb an einer natürlichen Todesart. Die größte Gruppe davon (n = 350; 52,3 %) betraf kardiale Todesursachen, gefolgt von 132 (19,7 %) respiratorischen und 47 (7,0 %) abdominellen Todesursachen. Zudem lagen 37 (5,5 %) maligne Neoplasien, 37 (5,5 %) sonstige natürliche Todesursachen, 33 (4,9 %) Rupturen großer Gefäße und 33 (4,9 %) zerebrale Todesursachen vor. Im Vergleich der Zeiträume I und II fiel eine signifikante Abnahme der kardialen Todesursachen auf. Es kam insbesondere zu einer signifikanten Abnahme der hochgradigen bis verschließenden Koronarsklerosen. Zwischen beiden Geschlechtern zeigten sich signifikante Unterschiede. So wiesen Männer signifikant mehr Bypässe, Stents und Herznarben auf und erlitten ca. 10 Jahre vor den Frauen einen Myokardinfarkt.

Diskussion/Schlussfolgerung

Die Ergebnisse decken sich größtenteils mit der Literatur. Die Abnahme kardialer Todesursachen könnte auf eine zunehmend bessere medizinische Versorgung und eine signifikant zunehmende Implantationsrate von Stents zurückzuführen sein. Die Rolle der forensischen Gerontologie wird –gerade in Pandemiezeiten– zunehmend an Bedeutung gewinnen.
A comparison of positivity in complex and tropical toric geometry
Authors: Burgos Gil José Ignacio , Gubler Walter , Jell Philipp , Künnemann Klaus
Published: March 2021

Given a smooth complex toric variety we will compare real Lagerberg forms and currents on its tropicalization with invariant complex forms and currents on the toric variety. Our main result is a correspondence theorem which identifies the cone of invariant closed positive currents on the complex toric variety with closed positive currents on the tropicalization. In a subsequent paper, this correspondence will be used to develop a Bedford–Taylor theory of plurisubharmonic functions on the tropicalization.
Global prevalence and types of complementary and alternative medicines use amongst adults with diabetes: systematic review and meta-analysis
Authors: Alzahrani Abdulaziz S. , Price Malcolm J. , Greenfield Sheila M. , Paudyal Vibhu
Published: March 2021

Aim

This study aimed to undertake a systematic review and meta-analysis of global prevalence and types of complementary and alternative medicine (CAM) use amongst adults with diabetes.

Methods

Nine databases, including MEDLINE and EMBASE, were searched for studies published between 2009 and 2019 which included extractable data for CAM use in adult patients with diabetes. Study characteristics, types of CAM, and overall and subgroup prevalence data in relation to CAM use were extracted. Meta-analysis of aggregate level data on prevalence and prevalence ratios (PRs) was performed using a random effects model.

Results

From the 38 studies included in the review, a total of 37 types of CAM and 223 types of herbs were identified. Pooled prevalence of CAM use was 51%. A wide variation in prevalence rates (predictive interval 8–93%) was observed. In the context of high heterogeneity, we found no evidence that CAM use was associated with gender, chronicity or type of diabetes. Approximately one third of patients did not disclose their use of CAM to healthcare professionals (95% PrI 25%, 97%). Herbal medicines, acupuncture, homoeopathy and spiritual healing were the common CAM types reported.

Conclusions

A wide variation in prevalence of CAM use by patients with diabetes was identified. Healthcare professionals should be aware of their patients’ use of CAM to ensure treatment optimization, avoid herb–drug interactions and promote medication adherence in diabetes. Diabetic reviews and clinical guidelines should incorporate exploration of patient use of CAM as many patients do not proactively disclose the use of CAM to their healthcare professionals.

Registration

The protocol for this study was registered with the Centre for Review and Dissemination (CRD). Protocol registration number CRD42019125036.
Pain Interference and Decreased Physical Function After Emergency General Surgery: Measuring Patient‐Reported Outcomes
Authors: Hatchimonji Justin S. , Bader Amanda L. , Ma Lucy W. , Chreiman Kristen , Byrne James P. , Reilly Patrick M. , Braslow Benjamin M. , Seamon Mark J. , Holena Daniel N.
Published: March 2021

Introduction

There is increasing emphasis on patient‐reported outcomes (PROs) measures in healthcare, but this area remains largely unexplored in emergency general surgery (EGS) conditions. We hypothesized that postoperative patients in our EGS clinic would report detrimental changes in several domains of health‐related quality of life (HRQoL).

Methods

We administered the PROMIS‐29, a HRQoL measurement tool, to postoperative patients in our EGS clinic (11/2019–4/2020). Patients responded to measures of 7 domains. Domain scores were converted to t‐scores, allowing comparison to average values within the general US population (set to 50 by definition). We report the mean scores within each domain. Higher scores in negatively worded domains (e.g., “Depression”) are worse; vice versa for positively worded domains (e.g., “Physical Function”). Changes in scores at subsequent clinic visits were analyzed using the paired t‐test.

Results

There were 97 patients who completed the PROMIS‐29 at the first postoperative visit. Mean (SD) age was 54.1 (16.2) years; 51% were male. There was no difference in our patients from the average US population in the domains of Ability to Participate in Social Roles and Activities, Anxiety, Fatigue, and Sleep Disturbance. However, EGS patients experienced significantly greater Pain Interference (56.1 [54.1, 58.1]) and worse Physical Function (40.6 [38.4, 42.7]) than average. For patients seen in follow‐up twice (13 patients, median interval between clinic visits 21 days), there were improvements in the domains of Physical Function (42.9 vs 37.3; p = 0.04) and Fatigue.

Conclusion

We demonstrate room for improvement in the domains of pain interference and physical function. While positive changes over a relatively short period of time are encouraging, consideration should be given to patient perceptions of illness and lifestyle impact when managing EGS patients.
Environmental impact on the mechanical properties of Porites spp. corals
Authors: Moynihan Molly A. , Amini Shahrouz , Goodkin Nathalie F. , Tanzil Jani T. I. , Chua J. Q. Isaiah , Fabbro Gareth N. , Fan Tung-Yung , Schmidt Daniela N. , Miserez Ali
Published: March 2021

Despite the economic and ecological importance of corals’ skeletal structure, as well as their predicted vulnerability to future climate change, few studies have examined the skeletal mechanical properties at the nanoscale. As climate change is predicted to alter coral growth and physiology, as well as increase mechanical stress events (e.g., bioerosion, storm frequency), it is crucial to understand how skeletal mechanical properties change with environmental conditions. Moreover, while material properties are intimately linked to the chemical composition of the skeleton, no previous study has examined mechanical properties alongside carbonate geochemical composition. Using Porites coral cores from a wide range of reef environments (Thailand, Singapore, Taiwan), we correlated coral’s micro-mechanical properties with chemical composition. In contrast to previous mechanical measurements of reef-building corals, we document unprecedented variability in the hardness, stiffness, and micro-cracking stress of Porites corals across reef environments, which may significantly decrease the structural integrity of reef substrate. Corals from environments with low salinity and high sedimentation had higher organic content and fractured at lower loads, suggesting that skeletal organic content caused enhanced embrittlement. Within individual coral cores, we observed seasonal variability in skeletal stiffness, and a relationship between high sea surface temperature, increased stiffness, and high-density. Regionally, lower Sr/Ca and higher Mg/Ca coincided with decreased stiffness and hardness, which is likely driven by increased amorphous calcium carbonate and skeletal organic content. If the coral is significantly embrittled, as measured here in samples from Singapore, faster erosion is expected. A decrease in skeletal stiffness will decrease the quality of reef substrate, enhance the rate of bioerosion by predators and borers, and increase colony dislodgement, resulting in widespread loss of structural complexity.
The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3)
Authors: Seidel Christoph , Daugaard Gedske , Nestler Tim , Tryakin Alexey , Fedyanin Mikhail , Fankhauser Christian Daniel , Hermanns Thomas , Aparicio Jorge , Heinzelbecker Julia , Paffenholz Pia , Heidenreich Axel , De Giorgi Ugo , Cathomas Richard , Lorch Anja , Fingerhut Anna , Gayer Fabian , Bremmer Felix , Giannatempo Patrizia , Necchi Andrea , Raggi Daniele , Aurilio Gaetano , Casadei Chiara , Hentrich Marcus , Tran Ben , Dieckmann Klaus-Peter , Brito Margarido , Ruf Christian , Mazzocca Alessandro , Vincenzi Bruno , Stahl Olof , Bokemeyer Carsten , Oing Christoph
Published: March 2021

Purpose

The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients.

Methods

Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR).

Results

The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p  ≤  0.001), respectively.

Conclusions

LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.
Global illumination in sparse voxel octrees
Authors: Max Nelson
Published: March 2021

This paper enhances the voxel-to-voxel radiance shooting, propagation, and scattering algorithm of Max [20]. It reduces the memory requirements by storing the radiance only on the occupied cells of a sparse voxel octree and by sampling only 24 propagation direction bins instead of 96 or more. It gives a modification of the propagation algorithm to compensate for the larger solid angle of the direction bins and allows for position-dependent fully anisotropic scattering. For a volume of $$n^3$$

n
3

voxels, the computation time is $$O(n^3(\mathrm {log}\,n)^{3/2})$$

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Similar dietary regulation of IGF-1- and IGF-binding proteins by animal and plant protein in subjects with type 2 diabetes
Authors: Schüler Rita , Markova Mariya , Osterhoff Martin A. , Arafat Ayman , Pivovarova Olga , Machann Jürgen , Hierholzer Johannes , Hornemann Silke , Rohn Sascha , Pfeiffer Andreas F. H.
Published: March 2021

Increased animal but not plant protein intake has been associated with increased mortality in epidemiological studies in humans and with reduced lifespan in animal species. Protein intake increases the activity of the IGF-1 system which may provide a link to reduced lifespan. We, therefore, compared the effects of animal versus plant protein intake on circulating levels of IGF-1 and the IGF-binding proteins (IGFBP)-1 and IGFBP-2 over a 6-week period. Thirty seven participants with type 2 diabetes consumed isocaloric diets composed of either 30% energy (EN) animal or plant protein, 30% EN fat and 40% EN carbohydrates for 6 weeks. The participants were clinically phenotyped before and at the end of the study. Both diets induced similar and significant increases of IGF-1 which was unaffected by the different amino acid compositions of plant and animal protein. Despite improvements of insulin sensitivity and major reductions of liver fat, IGFBP2 decreased with both diets while IGFBP-1 was not altered. We conclude that animal and plant protein similarly increase IGF-1 bioavailability while improving metabolic parameters and may be regarded as equivalent in this regard.