bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic modeling of ligand density variations on anion exchange chromatography
Authors: Sanchez‐Reyes Gabriela , Graalfs Heiner , Hafner Mathias , Frech Christian
Published: December 2020

Ion exchange chromatography is a powerful and ubiquitous unit operation in the purification of therapeutic proteins. However, the performance of an ion‐exchange process depends on a complex interrelationship between several parameters, such as protein properties, mobile phase conditions, and chromatographic resin characteristics. Consequently, batch variations of ion exchange resins play a significant role in the robustness of these downstream processing steps. Ligand density is known to be one of the main lot‐to‐lot variations, affecting protein adsorption and separation performance. The use of a model‐based approach can be an effective tool for comprehending the impact of parameter variations (e.g., ligand density) and their influence on the process.

The objective of this work was to apply mechanistic modeling to gain a deeper understanding of the influence of ligand density variations in anion exchange chromatography. To achieve this, 13 prototype resins having the same support as the strong anion exchange resin Fractogel® EMD TMAE (M), but differing in ligand density, were analyzed. Linear salt gradient elution experiments were performed to observe the elution behavior of a monoclonal antibody and bovine serum albumin. A proposed isotherm model for ion exchange chromatography, describing the dependence of ligand density variations on protein retention, was successfully applied.
Polymerizations by RAFT: Developments of the Technique and Its Application in the Synthesis of Tailored (Co)polymers
Authors: Semsarilar Mona , Abetz Volker
Published: December 2020

Reversible addition–fragmentation chain transfer (RAFT) polymerization is an increasingly popular method of controlled radical polymerization and remarkable advances is made in recent years. This polymerization technique offers great chances for more sustainable routes to obtain tailor‐made polymers with high precision. This article may be of interest not only for readers familiar with the technique, but also to newcomers to the field or colleagues, who are looking for more sustainable or safer polymerization techniques to obtain an extensive number of possible polymer structures. After an introduction to RAFT polymerization, different novel paths to carry out RAFT polymerization are discussed in terms of their potential and also advancements in the polymerization technology such as polymerization induced self‐assembly or carrying out the polymerization in continuous flow reactors are highlighted. At the end some upcoming application areas of polymers prepared by RAFT are presented.
Poisson μ‐pseudo almost automorphic stochastic processes and its applications to nonlinear Sobolev‐type SDEs with Markov switching
Authors: Zhu Ping
Published: December 2020

This paper investigates the equivalence between p‐mean Poisson μ‐pseudo almost automorphic and Poisson asymptotically almost automorphic stochastic processes outside one μ‐ergodic zero set and then obtains the completeness of the space of Poisson μ‐pseudo almost automorphic stochastic processes without the Lipschitz condition. These properties established enrich the knowledge of Poisson μ‐pseudo almost automorphic stochastic processes. Meanwhile, a more significant point is that without the Amerio semiseparation condition, we establish the Amerio‐type theorem that all the Lp‐bounded mild solutions are μ‐pseudo almost automorphic in distribution for a class of nonlinear Sobolev‐type stochastic differential equations with Markov switching and jumps. In this sense, we partly contribute to a better understanding of the stochastic analysis between Lp‐bounded mild solutions and μ‐pseudo almost automorphic mild solutions in distribution for nonlinear SDEs. Finally, we give an example to illustrate the effectiveness of our results.
Measuring pulmonary gas exchange using compartment‐selective xenon‐polarization transfer contrast (XTC) MRI
Authors: Amzajerdian Faraz , Ruppert Kai , Hamedani Hooman , Baron Ryan , Xin Yi , Loza Luis , Achekzai Tahmina , Duncan Ian F. , Qian Yiwen , Pourfathi Mehrdad , Kadlecek Stephen , Rizi Rahim R.
Published: December 2020

Purpose

To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)‐specific gas‐phase (GP) depolarization maps using xenon‐polarization transfer contrast (XTC) MR imaging.

Methods

Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single‐breath XTC data were acquired through a series of three GP images using a 2D multi‐slice GRE during a 12 s breath‐hold. A series of 8 ms Gaussian inversion pulses spaced 30 ms apart were applied in‐between the images to quantify the exchange between the GP and dissolved‐phase (DP) compartments. Inversion pulses were either centered on‐resonance to generate contrast, or off‐resonance to correct for other sources of signal loss. For an alternative scheme, inversions of both RBC and TP resonances were inserted in lieu of off‐resonance pulses. Finally, this technique was extended to a multi‐breath protocol consistent with tidal breathing, involving 30 consecutive acquisitions.

Results

Inversion pulses shifted off‐resonance by 20 ppm to mimic the distance between the RBC and TP resonances demonstrated selectivity, and initial GP depolarization maps illustrated stark magnitude and distribution differences between healthy and diseased subjects that were consistent with traditional approaches.

Conclusion

The proposed DP‐compartment selective XTC MRI technique provides information on gas exchange between all three detectable states of xenon in the lungs and is sufficiently sensitive to indicate differences in lung function between the study subjects. Investigated extensions of this approach to imaging schemes that either minimize breath‐hold duration or the overall number of breath‐holds open avenues for future research to improve measurement accuracy and patient comfort.
Non‐fullerene all small molecule OBHJSCs with profound device characteristics
Authors: Busireddy Manohar Reddy , Appalanaidu Ejjurothu , Bharath Dyaga , Chereddy Narendra Reddy , Shanigaram Balaiah , Sharma Ganesh Datt , Vaidya Jayathirtha Rao
Published: December 2020

In this work, we have reported two donor materials ONAF and SNAF that complement the widely used non‐fullerene acceptor ITIC, with the aim to develop non‐fullerene all small molecule organic bulk heterojunction solar cells (NF‐ASM‐OBHJSCs). Two small molecule donors A‐D‐D'‐D‐A architecture, namely ONAF and SNAF are synthesized and explored their ability to act as donor material along with the ITIC acceptor. Benzodithiophene (BDT) is used as central donor unit (dialkoxy‐BDT for ONAF and Dialkylthiophene‐BDT for SNAF) along with novel naphthodithiophene (NDT) terminal donor to improve light harvesting and charge conducting ability of the donor materials. N‐Butylrhodanine is employed as terminal acceptor to enhance the intramolecular charge transfer (ICT) and to place energy level of the donor materials. Both the small molecule donor materials have good thermal stability, broad and intense absorption displayed in the UV‐vis region with energy levels suitable for ITIC acceptor. NF‐ASM‐OBHJSCs are fabricated by using all small molecules (ONAF & SNAF) as donors and ITIC as acceptor. OBHJSCs based on SNAF displayed superior photovoltaic properties with power conversion efficiency (PCE) as 9.94 % (Jsc = 15.93 mA cm‐2, Voc = 0.96 V and FF = 0.65) compared to ONAF based devices with PCE as 7.48 % (Jsc = 14.93 mA cm‐2, Voc = 0.82 V and FF = 0.61). The substantial high PCE of SANF is attributed to the broad absorption, relatively well‐matched HOMO‐LUMO energy levels between SNAF – ITIC acceptor, better film morphology for efficient charge transport and exciton dissociation at donor/acceptor (D‐A) junction. The observed PCE is one of the best reported for the NDT‐BDT‐based all small molecule non‐fullerene OBHJSCs. Moreover, simplicity in the device fabrication procedures and low energy loss associated are added advantages with the SNAF based devices. We predict that the HOMO‐LUMO levels (CV) of D/A falling in this category, as in Figure S7, with further close energy levels will have implications on the efficiency of OBHJSCs.
Body mass index and risk of obesity‐related conditions in a cohort of 2.9 million people: Evidence from a UK primary care database
Authors: Haase Christiane L. , Eriksen Kirsten T. , Lopes Sandra , Satylganova Altynai , Schnecke Volker , McEwan Phil
Published: December 2020

Objective

Obesity rates in the United Kingdom are some of the highest in Western Europe, with considerable clinical and societal impacts. Obesity is associated with type 2 diabetes (T2D), osteoarthritis, cardiovascular disease, and increased mortality; however, relatively few studies have examined the occurrence of multiple obesity‐related outcomes in the same patient population. This study was designed to examine the associations between body mass index (BMI) and a broad range of obesity‐related conditions in the same large cohort from a UK‐representative primary care database.

Methods

Demographic data and diagnosis codes were extracted from the Clinical Practice Research Datalink GOLD database in January 2019. Adults registered for ≥ 3 years were grouped by BMI, with BMI 18.5–24.9 kg/m2 as reference group. Associations between BMI and 12 obesity‐related outcomes were estimated using Cox proportional hazard models, adjusted for age, sex, and smoking.

Results

More than 2.9 million individuals were included in the analyses and were followed up for occurrence of relevant outcomes for a median of 11.4 years during the study period. Generally, there was a stepwise increase in risk of all outcomes with higher BMI. Individuals with BMI 40.0–45.0 kg/m2 were at particularly high risk of sleep apnea (hazard ratio [95% confidence interval] vs. reference group: 19.8 [18.9–20.8]), T2D (12.4 [12.1–12.7]), heart failure (3.46 [3.35–3.57]), and hypertension (3.21 [3.15–3.26]).

Conclusions

This study substantiates evidence linking higher BMI to higher risk of a range of serious health conditions, in a large, representative UK cohort. By focusing on obesity‐related conditions, this demonstrates the wider clinical impact and the healthcare burden of obesity, and highlights the vital importance of management, treatment approaches, and public health programs to mitigate the impact of this disease.
Rational approaches for optimizing chemical functionality of plasma polymers: A case study with ethyl trimethylacetate
Authors: Saboohi Solmaz , Coad Bryan R. , Short Robert D. , Michelmore Andrew , Griesser Hans J.
Published: December 2020

Improved retention of desirable chemical structures during plasma polymerization requires rational tailoring of plasma‐phase conditions. Using ethyl trimethylacetate, we studied the effects of pressure and power on the contribution of intact molecular ions to deposition and retention of ester groups. The abundance of protonated molecular ions in plasmas varies with pressure and power, but the functionality of plasma polymers, assessed by X‐ray photoelectron spectroscopy and time‐of‐flight secondary ion mass spectrometry, is not correlated. Together with high ion flux, the ion energy distribution was found to be a key parameter and needs to be tailored to enable the soft landing of ions on the surface after traversing the sheath. The compromise between the abundance of ions and their energy distribution is optimal near the transition between the α and γ plasma phases.
The use of plasma‐activated water in viticulture: Induction of resistance and agronomic performance in greenhouse and open field
Authors: Laurita Romolo , Contaldo Nicoletta , Zambon Yuri , Bisag Alina , Canel Alessandro , Gherardi Matteo , Laghi Giulia , Bertaccini Assunta , Colombo Vittorio
Published: December 2020

In this study, two different cold atmospheric‐pressure plasmas are used for the production of plasma‐activated water (PAW). To evaluate the effectiveness of PAW as a possible means to control plant diseases, grapevines in an open field and a greenhouse are treated, evaluating qualitative and quantitative yield parameters, phytoplasma presence, and gene expression. The results show the capability of PAW to enhance plant defense mechanisms and, as demonstrated in the field trials, confirm its ability to improve the health status of the treated plants.
Flower strips as a bridge habitat facilitate the movement of predatory beetles from wheat to maize crops
Authors: Yang Quanfeng , Men Xingyuan , Zhao Wenlu , Li Chao , Zhang Qingqing , Cai Zhiping , Ge Feng , Ouyang Fang
Published: December 2020

BACKGROUND

Generalist predators play a key role in the biocontrol of insect pests in agricultural systems. However, predators are subject to frequent mortality events due to periodic disturbance regimes such as crop planting and harvest, which inevitably affect the population development of predators. Conservation of predators in this critical period is important for double‐cropping systems such as winter wheat and summer maize, the most widely used cropping system in North China.

RESULTS

Planting Cnidium monnieri flower strips at field borders could not only serve as a bridge habitat to conserve the dominant predator Propylaea japonica in wheat fields during harvest but also help the predator immigrate to adjacent maize fields. The predator abundance was 7‐fold higher on flower strips than that on natural vegetation strips during the wheat postharvest period and before the maize plant emergence for about a month, and its abundance in maize fields planted with flower strips was nearly 2‐fold higher than that in maize fields planted with natural vegetation strips. Moreover, 77.56% of predators that entered maize fields were proven to originate from flower strips.

CONCLUSION

Our findings provided evidence that manipulating flower strips as a bridge habitat in wheat–maize rotation fields could conserve P. japonica during crop phenophase changes, and we quantitatively testified that the proportion of this predator in maize fields derived from flower strips. In practice, such a strategy may also be applied in other double‐cropping and triple‐cropping systems. © 2020 Society of Chemical Industry
Azadirachtin downregulates the expression of the CREB gene and protein in the brain and directly or indirectly affects the cognitive behavior of the Spodoptera litura fourth‐instar larvae
Authors: Qin Deqiang , Zhou You , Zhang Peiwen , Liu Benju , Zheng Qun , Zhang Zhixiang
Published: December 2020

BACKGROUND

Azadirachtin has the potential to be used for pest control. Nevertheless, few studies have investigated the effects of azadirachtin on the cognitive behavior of pests. In this study, expression of the cAMP response element‐binding protein (CREB) and its gene were studied via a series of experiments in Spodoptera litura larvae treated with azadirachtin.

RESULTS

RNA‐Seq analysis of S. litura larvae treated with azadirachtin was undertaken. According to Kyoto Encyclopedia of Genes and Genomes analysis, the top 20 enriched pathways included neuroactive ligand–receptor interaction pathways, with seven significantly differentially expressed genes including CREB. Quantitative real time polymerase chain reaction (qRT‐PCR) results indicated that the CREB gene was expressed during all developmental stages of S. litura, but relative expression of the CREB gene was significantly downregulated after treatment with azadirachtin. Grayscale statistical analysis also showed that expression levels of protein kinase A (PKA), extracellular signal‐regulated kinase (ERK) and CREB proteins were significantly downregulated after treatment with azadirachtin. Moreover, RNA interference results showed that the effect of azadirachtin on the cognitive behavior of S. litura was consistent with that seen after interfering with CREB. In addition, larval selectivity to addictive odor sources was reduced, and the initial reaction time was increased.

CONCLUSIONS

This study clarified that azadirachtin can affect the cognitive behavior of S. litura and treatment with azadirachtin resulted in a downregulation of gene and protein expression of CREB and its pathway proteins. © 2020 Society of Chemical Industry
Cross and multiple herbicide resistance in annual bluegrass (Poa annua) populations from eastern Texas golf courses
Authors: Singh Vijay , dos Reis Fabricia C , Reynolds Casey , Elmore Matthew , Bagavathiannan Muthukumar
Published: December 2020

BACKGROUND

Annual bluegrass is a troublesome weed in managed turf systems. A survey was conducted to evaluate the prevalence of herbicide resistance in golf course populations of annual bluegrass in eastern Texas. Screenings were conducted for two photosystem II (PS II)‐inhibitor herbicides [simazine preemergence (PRE), amicarbazone postemergence (POST)], two acetolactate synthase (ALS) inhibitors (foramsulfuron POST, trifloxysulfuron POST) and one microtubule assembly inhibitor (pronamide PRE/POST).

RESULTS

Ninety percent of the populations were found to be resistant to at least one of the tested herbicides. The TX15‐14 population was >490‐, 178‐, 10‐, 26‐, 4.3‐ and 3.8‐fold, and the TX15‐27 population was >490‐, 16‐, 28‐, 84‐, 5.2‐ and 4.1‐fold less sensitive to simazine, amicarbazone, foramsulfuron, trifloxysulfuron, pronamide POST and pronamide PRE, respectively, compared to the susceptible standard TX15‐SUS. Populations resistant to pronamide POST were completely controlled by pronamide PRE at the label recommended rate. The ALS and psbA gene sequence analysis indicated the presence of target site mutations (Ser‐264‐Gly in the psbA gene of TX15‐14 and Trp‐574‐Leu in the ALS gene of TX15‐27). However, given the absence of any target‐site mutation in the ALS gene of TX15‐14, the psbA gene of TX15‐27 and α‐tubulin of both populations, nontarget site mechanisms of resistance are suspected.

CONCLUSION

This is the first case of multiple herbicide resistance in annual bluegrass populations to three herbicide modes of action. Results show the widespread occurrence of multiple herbicide resistance in golf course annual bluegrass populations in eastern Texas and emphasize the need for the development and implementation of effective resistance management practices. © 2020 Society of Chemical Industry
Multiple action mechanism and in vivo antimicrobial efficacy of antimicrobial peptide Jelleine‐I
Authors: Jia Fengjing , Wang Jiayi , Zhang Lishi , Zhou Jingjing , He Yuhang , Lu Yaqi , Liu Kexin , Yan Wenjin , Wang Kairong
Published: December 2020

With the extensive use of antibiotics in medicine, agriculture and food chemistry, the emergence of multi‐drug resistant bacteria become more and more frequent and posed great threats to human health and life. So novel antimicrobial agents were urgently needed to defend the resistant bacteria. Jelleine‐I was a small antimicrobial peptide (AMP) with eight amino acids in its sequence. It was believed to be an ideal template for developing antimicrobial agents. In the present study, the possible action mode against both gram‐negative bacteria and gram‐positive bacteria and in vivo antimicrobial activity was explored. Our results showed that Jelleine‐I exhibits its antimicrobial activity mainly by disrupting the integrity of the cell membrane, which would not be affected by the conventional resistant mechanism. It also aims at some intracellular targets such as genomic DNA to inhibit the growth of microbes. In addition, the result of in vivo antimicrobial activity experiment showed that Jelleine‐I performed a good therapeutic effect toward the mice with Escherichia coli infected peritonitis. Notably, Jelleine‐I has negligible cytotoxicity toward the tested mammalian cells, indicating excellent cell selectivity between prokaryotic cells and eurkayotic cells. In summary, our results showed that Jelleine‐I would be a potential candidate to be developed as a novel antimicrobial agent.
Unmanned aircraft flight control aided by phased‐array radio navigation
Authors: Gryte Kristoffer , Bryne Torleiv H. , Johansen Tor A.
Published: December 2020

Navigation systems of safety‐critical unmanned aircraft need an alternative position aiding source to global navigation satellite system. One promising alternative, is position measurements from phased‐array radio systems. The presented navigation system consist of a multiplicative extended Kalman filter that utilize these measurements, along with an exogenous altitude measurement, to aid an inertial navigation system. The reliability and accuracy of the navigation system is demonstrated through beyond‐visual‐line‐of‐sight flights with a fixed‐wing unmanned aerial vehicle, without the use of global navigation satellite systems. This uses a conventional guidance controller module, which also monitor the navigation quality.
New One‐Pot Synthesis of Catechol Thioethers Based on H2S and Unsaturated Hydrocarbons
Authors: Burmistrova Daria , Smolyaninov Ivan , Berberova Nadezhda , Eremenko Igor
Published: December 2020

New one‐pot synthesis of catechol thioethers based on the reaction between H2S, 3,5‐di‐tert‐butyl‐o‐benzoquinone and unsaturated hydrocarbons was developed. This synthetic approach allows to produce target compounds in the media of alkenes or alkynes via an activation of H2S by 3,5‐di‐tert‐butyl‐o‐benzoquinone at room temperature. The method consists in sequential thiolation of an unsaturated hydrocarbon and a sterically hindered o‐benzoquinone. The reaction makes it possible to use hydrogen sulfide as a source of the sulfur atom in the synthesis of biologically active organosulfur compounds. Antioxidant activity of synthesized thioethers in CUPRAC‐test, induced oxidation of DNA or glutathione was determined. The proposed synthetic way is more effective than the synthesis of catechol thioethers via Michael addition of thiols because the formation of disulfide by‐products is reduced. In this study the application of available and cheap reagents such as hydrogen sulfide, alkenes, or alkynes to prepare sterically hindered catechols with thioether group was established.
Near‐Infrared Regulated Nanozymatic/Photothermal/Photodynamic Triple‐Therapy for Combating Multidrug‐Resistant Bacterial Infections via Oxygen‐Vacancy Molybdenum Trioxide Nanodots
Authors: Zhang Yan , Li Danxia , Tan Jinshan , Chang Zhishang , Liu Xiangyong , Ma Weishuai , Xu Yuanhong
Published: December 2020

Bacterial infections have become a major danger to public health because of the appearance of the antibiotic resistance. The synergistic combination of multiple therapies should be more effective compared with the respective one alone, but has been rarely demonstrated in combating bacterial infections till now. Herein, oxygen‐vacancy molybdenum trioxide nanodots (MoO3−x NDs) are proposed as an efficient and safe bacteriostatic. The MoO3−x NDs alone possess triple‐therapy synergistic efficiency based on the single near‐infrared irradiation (808 nm) regulated combination of photodynamic, photothermal, and peroxidase‐like enzymatic activities. Therein, photodynamic and photothermal therapies can be both achieved under the excitation of a single wavelength light source (808 nm). Both the photodynamic and nanozyme activity can result in the generation of reactive oxygen species (ROS) to reach the broad‐spectrum sterilization. Interestingly, the photothermal effect can regulate the MoO3−x NDs to their optimum enzymatic temperature (50 °C) to give sufficient ROS generation in low concentration of H2O2 (100 µm). The MoO3−x NDs show excellent antibacterial efficiency against drug‐resistance extended spectrum β‐lactamases producing Escherichia coli and methicillin‐resistant Staphylococcus aureus (MRSA). Animal experiments further indicate that the MoO3−x NDs can effectively treat wounds infected with MRSA in living systems.
Mixed effects envelope models
Authors: Shi Yuyang , Ma Linquan , Liu Lan
Published: December 2020

When multiple measures are collected repeatedly over time, redundancy typically exists among responses. The envelope method was recently proposed to reduce the dimension of responses without loss of information in regression with multivariate responses. It can gain substantial efficiency over the standard least squares estimator. In this paper, we generalize the envelope method to mixed effects models for longitudinal data with possibly unbalanced design and time‐varying predictors. We show that our model provides more efficient estimators than the standard estimators in mixed effects models. Improved accuracy and efficiency of the proposed method over the standard mixed effects model estimator are observed in both the simulations and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.
Sustainability and Chaos in the Abiotic Polymerization of 3’,5’ Cyclic Guanosine Monophosphate: The Role of Aggregation
Authors: Costanzo Giovanna , Šponer Judit E. , Šponer Jiří , Cirigliano Angela , Benedetti Piero , Giliberti Valeria , Polito Raffaella , Di Mauro Ernesto
Published: December 2020

The front cover artwork is provided by Judit Šponer (Institute of Biophysics, Czech Academy of Sciences). The image shows that polymerization of H‐form 3’,5’ cyclic guanosine monophosphate (GMP) exhibits an oscillatory behavior when studying the reaction on longer time scales (of several days). Domains of the material, differing in the level of hydration, interlock like pieces of a puzzle, resulting in a complex chemical system working far from equilibrium. Read the full text of the Article at 10.1002/syst.202000011.
Prediction of Chip Solder Fatigue in IGBTs
Authors: Wang Xiping , Li Zhigang , Yao Fang , Tang Shengxue
Published: December 2020

Chip solder degradation is one of the main factors affecting the reliable operation of insulated gate bipolar transistor (IGBT) modules. However, there are still many challenges to get the real lifetime of chip solder. This paper proposes a lifetime consumption prediction method based on chip solder failure. First, the constant high junction temperature fluctuations are applied to IGBT modules for the power cycling tests. The transient thermal resistance is measured to monitor the degradation process of IGBT modules for every 1000 times of aging tests. And the failure degree of chip solder is analyzed by the integral structure function. With the help of scanning acoustic microscope, the failure analysis of aging modules is carried out. The finite element simulation model is established to analyze the transient thermomechanical characteristics of chip solder. Then, the influences of different power cycling conditions on the viscoplastic strain of chip solder are analyzed quantitatively. The average value of the viscoplastic strain increment is obtained by the integral method under large thermal loading. Meanwhile, the method is also applicable to the low thermal loading. Finally, a study case of IGBT modules in a 1.5 MW grid‐side wind power converter is given to demonstrate the validity of the proposed method. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Fetal Wound Healing
Authors: Ulrich Magda M. W.
Published: December 2020

First- and second-trimester fetal skin wounds are known to heal without scarring.

Research has excluded factors like the sterile uterine environment as the cause of scarless repair, and it is believed that scarless healing is an intrinsic property of early fetal skin. However, increasing wound size and induction of the inflammatory reaction can evoke a scar response in the fetus.

For decades, research is performed to elucidate the mechanisms responsible for scarless healing in fetuses. Much research has been performed in animal studies, and several mechanisms have been proposed to be involved such as the microenvironment and the extracellular matrix, a reduced inflammatory response, differences in growth factor profile, and differences in fibroblast phenotype.

It is clear that the wound healing process leading to scarless healing cannot be attributed to just one factor or mechanism but will be the result of a complex of interconnected processes.

This chapter describes some of the possible mechanisms which may play a role in scarless healing.
Scar Symptom: Erythema and Thickness
Authors: Yang Yating , Wu Xiaoli , Liu Wei
Published: December 2020

Erythema is a word derived from the Greek erythros, which describes red color of the skin or mucous membrane. In particular, erythema and redness in scar are important as they are closely related to scar symptoms and tissue maturation, and thus can serve as an indicator for scar prognosis. There is rich information in the literature regarding its clinical manifestation, pathological mechanism, and its relation to inflammation and symptoms of pain and itching as well as the clinical treatment. Scar thickness reflects the accumulation of collagen content and there is no necessary association between scar redness and thickness. This chapter mainly focuses on the overview of scar erythema/redness in the aspects of definition, possible mechanism related to clinical manifestation and symptoms, and finally the therapeutic options.
Scar Symptoms: Pigmentation Disorders
Authors: Pijpe A. , Gardien K. L. M. , van Meijeren-Hoogendoorn R. E. , Middelkoop E. , van Zuijlen Paul P. M.
Published: December 2020

This chapter provides an overview of the epidemiology, pathophysiology, course, measurement, and potential therapies for pigmentation disorders in scars. Pigmentation problems are a common consequence of deep partial- and full-thickness burns, other skin trauma or disease, and surgical procedures. Both hypopigmentation and hyperpigmentation can cause esthetic and psychological issues, which may influence quality of life. The role of melanocytes and the maturation of pigmentation problems are discussed. To determine the severity of pigmentation problems and for therapeutic evaluation, different subjective and objective methods have been validated. Simple and easy-to-use measurement instruments are available based on spectrophotometric techniques. Also scar assessment scales with subscales for color and pigmentation are convenient and validated methods for quantitative evaluation of skin pigment disorders. Treatment options are discussed and include camouflage therapy, topical treatments, chemical peels, laser therapy, dermatography, dermabrasion, microneedling, skin grafting, cell therapy, and excision. It is advised to first try the conservative options and to dose and monitor the treatment to prevent overshoot and complications.
Scar Contractures
Authors: Masanovic Marguerite Guillot , Téot Luc
Published: December 2020

Scar retractions occurring on mobile areas on the body surface, like the neck, the joints, the hand, and the face may induce functional limitations in skin availability during movements. Extensive burns, trauma, and infected wounds may be found as risk factors. The activation of populations of myofibroblasts may explain the occurrence of skin contracture, as they mechanically act on the matrix and induce skin retraction (Kwan and Tredget, Hand Clin 33(2):277–292, 2017). Pathological consequences of the contractures may vary from a moderate limitation of movement over a digital joint to a permanent neck contracture impairing eye vision in the horizontal plane. The shortage of skin capacity may vary from 2 to 10 cm. Most of the contractures respond to an active early treatment when there is an early diagnosis at 1 month after wound healing, but if diagnosed later specific surgical procedures are needed, like skin grafting, local or regional flaps, but also complex microsurgical flaps. Specific indications depend on the necessity to restore the function.
Scar Assessment Scales
Authors: Carrière Michelle E. , van de Kar Annekatrien L. , van Zuijlen Paul P. M.
Published: December 2020

Over the last decades, many scar assessment scales have been developed, not only to evaluate the effectiveness of new and existing treatments in the research setting but also to monitor scars in individual patients. Clinician-reported scar scales allow for the evaluation of observable aspects of the scar, while patient-reported scar scales enable the evaluation of additional health domains that cannot be observed by clinicians, such as scar symptoms or sensations and quality of life. The quality of scar assessment scales is determined by several measurement properties (i.e., validity, reliability, and responsiveness). This chapter provides an overview of the content and development of the most frequently used scar assessment scales.
Japan Scar Workshop (JSW) Scar Scale (JSS) for Assessing Keloids and Hypertrophic Scars
Authors: Ogawa Rei
Published: December 2020

The Vancouver scar scale, the Manchester scar scale, and the Patient and Observer Scar Assessment Scale (POSAS) are all very well-known scar evaluation methods. These tools are based on a number of scar variables, including color, height, and pliability. However, since all were mainly developed to evaluate burn scars, they are difficult to use in clinical practice for keloids and hypertrophic scars. This is because these pathological scars require both differential diagnosis and a way to evaluate their response to therapy. The Japan Scar Workshop (JSW) has sought to develop a scar assessment scale that meets these clinical needs. The first version of this scar assessment tool was named the JSW scar scale (JSS), and it was reported in 2011. In 2015, the revised second version was reported. The JSS consists of two tables. One is a scar classification table that is used to determine whether the scar is a normal mature scar, a hypertrophic scar, or a keloid. This grading system helps the user to select the most appropriate treatment method for the scar. The other table in the JSS is an evaluation table that is used to judge the response to treatment and for follow-up. Both tables contain sample images of each subjective keloid/hypertrophic scar item that allow the user to evaluate each item without hesitation.
Objective Assessment Technologies: General Guidelines for Scar Assessment
Authors: Poetschke Julian , Gauglitz Gerd G.
Published: December 2020

Scar assessment has long relied on a variety of instruments, most of them questionnaires or scales that are susceptible to bias and limit the level of evidence in research. Throughout recent years, a variety of objective assessment tools have been developed. They allow for the exact quantification of different scar parameters such as texture, pliability, color, and size, thus facilitating detailed progress analysis throughout treatment.

The advent of new technology, however, has its pitfalls, too. The number of different technologies available is hard to review, and oftentimes, clinical validation is lacking, making it hard for researchers to gauge whether a certain instrument is adequate for their individual projects.

The use of each individual instruments has different requirements regarding patient preparation and calibration, and the measurements themselves can often be adjusted through a variety of parameters. This requires intensive familiarization with the respective instruments. Additionally, interpretation of the data can be complicated, and distinguishing statistically significant differences from clinically important differences remains difficult.

Modern technology, however, allows researchers to measure treatment effects that otherwise would have eluded them through the use of subjective evaluation only.

Through objective scar assessment technology and its detailed abilities to document changes throughout treatment, the evidence in scar-related research can be greatly improved, and current as well as new treatment options can finally be adequately gauged for their efficacy.
Objective Assessment Tools: Physical Parameters in Scar Assessment
Authors: Jaspers M. E. H. , Moortgat P.
Published: December 2020

Objective assessment tools can be used to evaluate whether (new) scar treatment is effective and to monitor the scar’s response to interventions in clinical practice. It is important to take the clinimetric properties of each tool into account, especially when used for the follow-up of an individual patient. An overview is provided for three important physical scar parameters that can be assessed by noninvasive objective tools: color, elasticity, and perfusion. To assess the color of a scar, an array of tools is available, all using reflectance spectroscopy and determining color by measuring the intensity of reflected light of specific wavelengths. The handheld DSM III ColorMeter offers read-out of erythema and melanin index values as well as CIEL∗a∗b values. The interrater reliability is best for the parameter a∗ of the DSM III ColorMeter. To assess scar elasticity, the Cutometer is the most widely used tool. Scar deformation is measured using negative pressure and reflected in relative and absolute elasticity parameters. On the contrary, firmness or hardness of scar tissue can be quantified by tonometry, a technique that works by exerting pressure on the skin. Lastly, it is of interest to measure scar blood flow (i.e., perfusion) as several treatment regimens work by destructing the microvasculature and/or reducing the blood flow to enhance shrinkage of hypertrophic scar tissue. Laser Doppler imaging and laser speckle imaging can be used to quantify and visualize scar blood flow, but a thorough clinimetric evaluation of these tools in scars is not performed yet.
Objective Assessment Techniques: Physiological Parameters in Scar Assessment
Authors: Moortgat Peter , Anthonissen Mieke , Van Daele Ulrike , Meirte Jill , Vanhullebusch Tine , Maertens Koen
Published: December 2020

In order to assess new and often costly treatments, the need for objective scar measurement tools has become increasingly important. A combination of subjective and objective measures should be the aim of every researcher. Quantitative assessment of scars requires devices to measure their physical and physiological properties. Physiological scar parameters are scar characteristics relevant to pathological scarring which cannot be seen with the bare eye. This also means that they can only be assessed with objective assessment tools.

Skin hydration is defined as the water content of the epidermis and the dermis, and the ability of the skin to retain water is important to avoid dry appearance of the skin and prolonged inflammation in scarring. Many approaches exist to measure skin water content. One single method is often not enough to capture all the relevant information. Trans-epidermal water loss, stratum corneum water content, and dermal water content are equally important and related to each other.

Scar maturation has been related to transcutaneous oxygen tension, and it is hypothesized that low levels of transcutaneous oxygen pressure in evolving scars result from low oxygen diffusibility through scar tissue.

Tactile sensitivity of the skin can be measured by esthesiometers. The Semmes-Weinstein monofilament test is found to be a feasible and reliable outcome measure to evaluate touch perception threshold in older upper extremities burn scars.
Structural Assessment of Scars Using Optical Techniques
Authors: van Haasterecht L. , van Zuijlen Paul P. M. , Groot ML.
Published: December 2020

The evaluation of scar treatment benefits from exact structural measurements. Accurate assessment of thickness, surface area, and relief is crucial in routine clinical follow-up. From an experimental perspective, precise visualization of the microstructural organization is necessary for a better understanding of the mechanisms underlying pathological scarring. Structural proteins in scars differ from healthy skin in terms of amount, type, and importantly, organization. The precise quantification of this extracellular matrix (ECM) organization was, until recently, limited to two-dimensional images from fixated and stained tissue. Advances in optical techniques now allow high-resolution imaging of these structures, in some cases in vivo. The enormous potential of these techniques as objective assessment tools is illustrated by a substantial increase in available devices. This chapter describes currently used devices and techniques used in the clinical follow-up of scar progression from a volumetric standpoint. Furthermore, some of the most powerful techniques for microstructural research are described including optical coherence tomography, nonlinear optical techniques such as second harmonic generation microscopy, and confocal microscopy.
Mechanobiology of Cutaneous Scarring
Authors: Ogawa Rei
Published: December 2020

The last phase of cutaneous wound healing produces the scar. Under normal circumstances, the immature scar then undergoes the scar maturation process over several months. This process involves tissue remodeling, which associates with a natural decrease in the inflammation and the numbers of blood vessels, collagen fibers, and fibroblasts. However, sometimes the scar maturation process is not properly engaged because inflammation continues in the scar. Consequently, the immature scar stage is prolonged. This results in the pathological scars called hypertrophic scars and keloids. Many factors that prolong the inflammatory stage have been identified. However, multiple lines of evidence acquired in recent years suggest that mechanical force can be an important cause of pathological scar development.
Ethical Considerations: Scar Management
Authors: Ganier Clarisse , Gaucher Sonia
Published: December 2020

The purpose of this chapter was to provide an overview and potential answers to the ethical considerations of the clinical scar management. Here, we focused on two main aspects. The first aspect was to discuss the need to invoke ethics when the clinician is faced to a patient’s scar. The second aspect was to discuss the clinicians dilemmas in their daily practice when they are managing a patient’s scar.
Ideal Wound Closure Methods for Minimizing Scarring After Surgery
Authors: Ogawa Rei
Published: December 2020

Wound-healing phenomena are the result of a cascade of complex biochemical events that can be categorized into four general overlapping phases: coagulation, inflammation, proliferation, and remodeling. Significantly, all four phases of wound healing are influenced by both intrinsic and extrinsic mechanical forces. These mechanical forces provoke chronic inflammation of the dermis, namely, the unceasing influx and activation of inflammatory cells, the persistent generation of blood vessels and nerve fibers, and the constant production of collagen by the activated fibroblasts. This chronic inflammation blocks the conversion of the granulation tissue into dermis-like tissue by the remodeling process and results in an immature hypertrophic scar that is red, elevated, hard, and painful. These observations suggest that, to prevent pathological scarring after surgery, it is necessary to ensure that the sutures cause the wound edges to adhere to each other without any tension, even when strong extrinsic forces are placed on the wound. This will allow the granulation tissue to convert smoothly into dermis-like tissue, thereby yielding minimal scarring. Another way to prevent pathological scar formation in high-tension areas is to use zigzag suturing techniques such as the Z-plasty.
Treatment of Immature Scars: Evidence-Based Techniques and Treatments
Authors: Poetschke Julian , Gauglitz Gerd G.
Published: December 2020

Severe scarring is known for causing severe functional, aesthetic, and psychosocial impairments. During the last years, treatment of mature scars has evolved significantly; however, researchers and clinicians are more and more focused on preventing excessive scarring altogether, thus avoiding long and strenuous treatment. While some forms of scar prevention have been known and used for decades, others are relatively new and have yet to prove themselves. Pressure garments have long been successfully used in widespread burn scar prevention. However, reduced compliance, large treatment costs, and little hard evidence are points that should be taken into consideration regarding this well-established form of treatment. Silicone gel sheeting has also been used for a long time, and it is well regarded for its efficacy in reducing scar height and improving pliability while boasting little side effects. Its mode of action, however, remains unclear. Recently, lasers have become a new focus in the effort to prevent pathological scarring. Here, the older pulsed dye laser, as well as newer, fractional ablative and nonablative lasers, is increasingly employed for the treatment of fresh scars, where initial research is showing significant promise.

This chapter explores the currently available methods for scar prevention and examines their application and the evidence regarding their efficacy.
Silicone Gel for Scar Prevention
Authors: Mustoe Thomas A.
Published: December 2020

Silicone gel sheets and cream are nowadays used extensively in scar management. This chapter highlights the original findings, evidence, and working mechanism of silicone gel for scar prevention and management.
Onion Extract
Authors: Poetschke Julian , Gauglitz Gerd G.
Published: December 2020

Multiple studies on hypertrophic scar and keloid formation have led to a plethora of therapeutic strategies in order to prevent or attenuate keloid and hypertrophic scar formation. To date, preventing pathologic scarring remains undoubtedly more effective than treating it. Next to specific surgical techniques and an appropriate general aftercare of fresh wounds, a multitude of scar gels, creams, patches, and ointments are available and are being promoted for scarless wound healing. Next to silicone-based products, onion extract or cepalin has been highlighted as one potential anti-scarring agent over recent years. Based on several studies, onion extract alone or in combination with allantoin and heparin seems to alleviate the wound-healing process and appears beneficial for preventional application in fresh scars. The study data available, however, remains overall relatively poor and clearly objective data regarding this approach is widely missing.
Treatment of Immature Scars with Botulinum Toxin
Authors: Chambers Alexandra
Published: December 2020

Using Botulinum neurotoxin type A (BoNTA) has yielded promising results in the treatment of immature scars. The biological effects of the toxin on tissue healing appear to be complex and multidimensional and still require additional research. Nevertheless, it is clear that not only does BoNTA reduce muscle tension at the edges of wounds, but it also provides anti-inflammatory effects, promotes angiogenesis and healing, and exerts mediatory or inhibitory effects on a variety of cells. In clinical practice, this pluripotency of BoNTA has been recognized as a therapeutic choice for both prophylaxis and treatment of excessive scarring.
Compression Therapy and Conservative Strategies in Scar Management After Burn Injury
Authors: Van den Kerckhove Eric , Anthonissen Mieke
Published: December 2020

This chapter gives an overview of the different conservative therapeutic strategies that are mostly used in the rehabilitation of patients with severe scars after burn injury. These strategies include pressure therapy, the use of silicones, massage, the use of moisturizers, splinting and positioning, exercise, and mobilizations. Pressure and silicone therapy are the two most evidence-supported conservative treatments of (burn) scars, with compression therapy considered an evidence-based conservative intervention to treat the thickness of the scars. The other noninvasive treatment modalities have less supporting evidence. The relevance of these conservative therapeutic strategies will be situated within the field of the available scientific literature or guidelines.