bluuebunny/crossref_metadata_2025 huggingface dataset:
MEMBRANE PROTEIN STRUCTURES AND INTERACTIONS FROM COVALENT LABELING COUPLED WITH MASS SPECTROMETRY
Authors: Pan Xiao , Vachet Richard W.
Published: November 2020

Membrane proteins are incredibly important biomolecules because they mediate interactions between a cell's external and internal environment. Obtaining information about membrane protein structure and interactions is thus important for understanding these essential biomolecules. Compared with the analyses of water‐soluble proteins, the structural analysis of membrane proteins is more challenging owing to their unique chemical properties and the presence of lipid components that are necessary to solubilize them. The combination of covalent labeling (CL) and mass spectrometry (MS) has recently been applied with great success to study membrane protein structure and interactions. These studies have demonstrated the many advantages that CL‐MS methods have over other traditional biophysical techniques. In this review, we discuss both amino acid‐specific and non‐specific labeling approaches and the special considerations needed to address the unique challenges associated with interrogating membrane proteins. This review highlights the aspects of this approach that require special care to be applied correctly and provides a comprehensive review of the membrane protein systems that have been studied by CL‐MS. © 2020 John Wiley & Sons Ltd. Mass Spec Rev
Four‐Year Follow‐up of [18F]Fluorodeoxyglucose Positron Emission Tomography–Based Parkinson's Disease–Related Pattern Expression in 20 Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder Shows Prodromal Progression
Authors: Kogan Rosalie V. , Janzen Annette , Meles Sanne K. , Sittig Elisabeth , Renken Remco J. , Gurvits Vita , Mayer Geert , Leenders Klaus L. , Oertel Wolfgang H. ,   and the REMPET Working Group
Published: November 2020

Background

Isolated rapid eye movement sleep behavior disorder is known to be prodromal for alpha‐synucleinopathies, such as Parkinson's disease (PD) and dementia with Lewy bodies. The [18F]fluorodeoxyglucose‐positron emission tomography (PET)–based PD‐related brain pattern can be used to monitor disease progression.

Objective

We longitudinally investigated PD‐related brain pattern expression changes in 20 subjects with isolated rapid eye movement sleep behavior disorder to investigate whether this may be a suitable technique to study prodromal PD progression in these patients and to identify potential phenoconverters.

Methods

Subjects underwent two [18F]fluorodeoxyglucose‐PET brain scans ~3.7 years apart, along with baseline and repeated motor, cognitive, and olfactory testing within roughly the same time frame.

Results

At baseline, 8 of 20 (40%) subjects significantly expressed the PD‐related brain pattern (with z scores above the receiver operating characteristic–determined threshold). At follow‐up, six additional subjects exhibited significant PD‐related brain pattern expression (70% in total). PD‐related brain pattern expression increased in all subjects (P = 0.00008). Four subjects (20%), all with significant baseline PD‐related brain pattern expression, phenoconverted to clinical PD.

Conclusions

Suprathreshold PD‐related brain pattern expression and greater score rate of change may signify greater shorter‐term risk for phenoconversion. Our results support the use of serial PD‐related brain pattern expression measurements as a prodromal PD progression biomarker in patients with isolated rapid eye movement sleep behavior disorder. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Idealized force decay of orthodontic elastomeric chains follows Nutting Equation
Authors: Freeman David H. , Johnston William M. , Brantley William A. , Firestone Allen R.
Published: November 2020

The force decay of orthodontic elastomeric modules has been of considerable interest since these biomechanical force‐generating appliances were introduced five decades ago. Two mathematical approaches, a power‐law equation and a Maxwell–Weichert model, have been used by previous investigators to predict the in vitro force degradation under idealized conditions. In this study, the principal sensor approach had the test specimen being strained continuously using a digital force gauge. Test specimens of 13 products from 8 manufacturers were stretched to 25 mm and tested in an artificial saliva at 37°C in both the as‐received condition and after 24 h conditioning. Measurements for specimens strained continuously on the digital force gauge were compared with intermittent measurements for other specimens transferred to this gauge after 19.2 h ageing on a stretching rack, the approach in most past studies. Force data at equally spaced logarithmic time points, normalized to initial force and induced strain, were used to present degradation curves for individual products. Nonlinear regression analyses were used to fit both mathematical models to each product and conditioning state. Statistical analyses show that the power‐law equation (historically the Nutting equation) provides a more accurate prediction of idealized in vitro force decay for the elastomeric products.
Predicted structural differences of four fertility‐related Y‐chromosome proteins in Macaca mulatta, M. fascicularis, and their Indochinese hybrids
Authors: Ruiz Cody A. , Chaney Morgan E. , Imamura Masanori , Imai Hiroo , Tosi Anthony J.
Published: November 2020

Species in the genus Macaca typically live in multimale‐multifemale social groups with male macaques exhibiting some of the largest testis: body weight ratios among primates. Males are believed to experience intense levels of sperm competition. Several spermatogenesis genes are located on the Y‐chromosome and, interestingly, occasional hybridization between two species has led to the introgression of the rhesus macaque (Macaca mulatta) Y‐chromosome deep into the range of the long‐tailed macaque (M. fascicularis). These observations have led to the prediction that the successful introgression of the rhesus Y‐haplotype is due to functional differences in spermatogenesis genes compared to those of the native long‐tailed Y‐haplotype. We examine here four Y‐chromosomal loci—RBMY, XKRY, and two nearly identical copies of CDY—and their corresponding protein sequences. The genes were surveyed in representative animals from north of, south of, and within the rhesus x long‐tailed introgression zone. Our results show a series of non‐synonymous amino acid substitutions present between the two Y‐haplotypes. Protein structure modeling via I‐TASSER revealed different folding patterns between the two species' Y‐proteins, and functional predictions via TreeSAAP further reveal physicochemical differences as a result of non‐synonymous substitutions. These differences inform our understanding of the evolution of primate Y‐proteins involved in spermatogenesis and, in turn, have biomedical implications for human male fertility.
Molecular dynamics simulations identify the regions of compromised thermostability in SazCA
Authors: Kumar Shashi , Seth Deepak , Deshpande Parag Arvind
Published: November 2020

The present study examined the structure and dynamics of the most active and thermostable carbonic anhydrase, SazCA, probed using molecular dynamics simulations. The molecular system was described by widely used biological force‐fields (AMBER, CHARMM22, CHARMM36, and OPLS‐AA) in conjunction with TIP3P water model. The comparison of molecular dynamics simulation results suggested AMBER to be a suitable choice to describe the structure and dynamics of SazCA. In addition to this, we also addressed the effect of temperature on the stability of SazCA. We performed molecular dynamics simulations at 313, 333, 353, 373, and 393 K to study the relationship between thermostability and flexibility in SazCA. The amino acid residues VAL98, ASN99, GLY100, LYS101, GLU145, and HIS207 were identified as the most flexible residues from root‐mean‐square fluctuations. The salt bridge analysis showed that ion‐pairs ASP113‐LYS81, ASP115‐LYS81, ASP115‐LYS114, GLU144‐LYS143, and GLU144‐LYS206, were responsible for the compromised thermal stability of SazCA.
Analysis of correlated multivariate degradation data in accelerated reliability growth
Authors: Ruiz Cesar , Liao Haitao , Pohl Edward A.
Published: November 2020

Modern engineering systems have become increasingly complex and at the same time are expected to be developed faster. To shorten the product development time, organizations commonly conduct accelerated testing on a small number of units to help identify failure modes and assess reliability. Many times design changes are made to mitigate or reduce the likelihood of such failure modes. Since failure‐time data are often scarce in reliability growth programs, existing statistical approaches used for predicting the reliability of a system about to enter the field are faced with significant challenges. In this work, a statistical model is proposed to utilize degradation data for system reliability prediction in an accelerated reliability growth program. The model allows the components in the system to have multiple failure modes, each associated with a monotone stochastic degradation process. To take into account unit‐to‐unit variation, the random effects of degradation parameters are explicitly modeled. Moreover, a mean‐degradation‐stress relationship is introduced to quantify the effects of different accelerating variables on the degradation processes, and a copula function is utilized to model the dependency among different degradation processes. Both a maximum likelihood (ML) procedure and a Bayesian alternative are developed for parameter estimation in a two‐stage process. A numerical study illustrates the use of the proposed model and identifies the cases where the Bayesian method is preferred and where it is better to use the ML alternative.
Mitochondrial replacement by genome transfer in human oocytes: Efficacy, concerns, and legality
Authors: Yamada Mitsutoshi , Sato Suguru , Ooka Reina , Akashi Kazuhiro , Nakamura Akihiro , Miyado Kenji , Akutsu Hidenori , Tanaka Mamoru
Published: November 2020

Background

Pathogenic mitochondrial (mt)DNA mutations, which often cause life‐threatening disorders, are maternally inherited via the cytoplasm of oocytes. Mitochondrial replacement therapy (MRT) is expected to prevent second‐generation transmission of mtDNA mutations. However, MRT may affect the function of respiratory chain complexes comprised of both nuclear and mitochondrial proteins.

Methods

Based on the literature and current regulatory guidelines (especially in Japan), we analyzed and reviewed the recent developments in human models of MRT.

Main findings

MRT does not compromise pre‐implantation development or stem cell isolation. Mitochondrial function in stem cells after MRT is also normal. Although mtDNA carryover is usually less than 0.5%, even low levels of heteroplasmy can affect the stability of the mtDNA genotype, and directional or stochastic mtDNA drift occurs in a subset of stem cell lines (mtDNA genetic drift). MRT could prevent serious genetic disorders from being passed on to the offspring. However, it should be noted that this technique currently poses significant risks for use in embryos designed for implantation.

Conclusion

The maternal genome is fundamentally compatible with different mitochondrial genotypes, and vertical inheritance is not required for normal mitochondrial function. Unresolved questions regarding mtDNA genetic drift can be addressed by basic research using MRT.
Evolving the validity of a mental toughness measure: Refined versions of the Mental Toughness Questionnaire‐48
Authors: Kawabata Masato , Pavey Toby G. , Coulter Tristan J.
Published: November 2020

The Mental Toughness Questionnaire‐48 (MTQ48) is a 48‐item self‐report instrument to measure one's level of mental toughness. Despite its wide popularity in psychological studies, the questionnaire has been criticized due to its factorial validity. The present study aimed to re‐assess the factorial validity of the instrument and propose alternative models to provide researchers with theoretically and practically useful instruments to measure mental toughness. Two studies were conducted using large samples of university students (Study 1: n = 2186; Study 2: n = 3209). In Study 1, none of one‐, four‐ and six‐factor models with 48 items satisfactorily fit the data set. Instead, two refined 18‐ and 6‐item versions of the questionnaire, covering six aspects of mental toughness, were proposed: the Short MTQ and Very Short MTQ. Both measures demonstrated excellent fit to the data. These results were replicated with a larger independent sample in Study 2. With the Short MTQ, it is possible to represent mental toughness as a multidimensional construct consisting of a global mental toughness factor and six specific factors. The Very Short MTQ is a practical tool for occasions where constraints prevent use of the Short MTQ. The refined questionnaires are promising options to measure and understand individuals' mental toughness with the MTQ.
Grain Boundaries Boost Oxygen Evolution Reaction in NiFe Electrocatalysts
Authors: Park Hoon Kee , Ahn Hehsang , Lee Tae Hyung , Lee Jae Yoon , Lee Mi Gyoung , Lee Sol A. , Yang Jin Wook , Kim Sang Jun , Ahn Sang Hyun , Kim Soo Young , Lee Chul‐Ho , Park Eun Soo , Jang Ho Won
Published: November 2020

In a polycrystalline material, the grain boundaries (GBs) can be effective active sites for catalytic reactions by providing an electrodynamically favorable surface. Previous studies have shown that grain boundary density is related to the catalytic activity of the carbon dioxide reduction reaction, but there is still no convincing evidence that the GBs provide surfaces with enhanced activity for oxygen evolution reaction (OER). Combination of various electrochemical measurements and chemical analysis reveals the GB density at surface of NiFe electrocatalysts directly affects the overall OER. In situ electrochemical microscopy vividly shows that the OER occurs mainly at the GB during overall reaction. It is observed that the reaction determining steps are altered by grain boundary densities and the meaningful work function difference between the inside of grain and GBs exists. High‐resolution transmission electron microscopy shows that extremely high index planes are exposed at the GBs, enhancing the oxygen evolution activity. The specific nature of GBs and its effects on the OER demonstrated in this study can be applied to the various polycrystalline electrocatalysts.
Fast Diagnosis of Failure Mechanisms and Lifetime Prediction of Li Metal Batteries
Authors: Gao Ningshengjie , Abboud Alexander W. , Mattei Gerard S. , Li Zhuo , Corrao Adam A. , Fang Chengcheng , Liaw Boryann , Meng Ying Shirley , Khalifah Peter G. , Dufek Eric J. , Li Bin
Published: November 2020

Lithium (Li) metal serving as an anode has the potential to double or triple stored energies in rechargeable Li batteries. However, they typically have short cycling lifetimes due to parasitic reactions between the Li metal and electrolyte. It is critically required to develop early fault‐detection methods for different failure mechanisms and quick lifetime‐prediction methods to ensure rapid development. Prior efforts to determine the dominant failure mechanisms have typically required destructive cell disassembly. In this study, non‐destructive diagnostic method based on rest voltages and coulombic efficiency are used to easily distinguish the different failure mechanisms—from loss of Li inventory, electrolyte depletion, and increased cell impedance—which are deeply understood and well validated by experiments and modeling. Using this new diagnostic method, the maximum lifetime of a Li metal cell can be quickly predicted from tests of corresponding anode‐free cells, which is important for the screenings of electrolytes, anode stabilization, optimization of operating conditions, and rational battery design.
Pragmatism in professional practice
Authors: Ormerod Richard John
Published: November 2020

In recent years, there has been a resurgence of interest in the American philosophy of pragmatism. The paper reviews the application of pragmatisms in five selected areas of professional practice: technology, law, politics, medical and social work, and education. Each area is examined for evidence that the ideas of pragmatism have been taken up academically in the research literature. The literature is then examined for evidence that the academic work has permeated the actions of professionals. Each of the chosen practice areas is clearly dominated by pragmatic, instrumental activities. Despite this and a good deal of discussion in the academic literature, there is only limited evidence that professionals, in so far as they exhibit pragmatist behaviour, make any explicit connection with the philosophy of pragmatism. The early pragmatists argued that pragmatic behaviour arises from man's need to solve problems quickly, using his limited understanding of the situation, in order to survive and flourish: no philosophy had been required to guide such behaviour. Today, philosophy is often consulted on questions of ethical and moral dilemmas in most practice areas, but the philosophy of pragmatism may well not feature in such discussions. Experience in operational research (OR) practice is reviewed and compared with that in the five other practice areas. From the reviews, a list of the habits and orientations is synthesized, habits and orientations that could be taken to characterize pragmatism in professional practice.
Predictive value of presence of amniotic sac without visible embryonic heartbeat in diagnosis of early embryonic demise
Authors: Dooley W. M. , De Braud L. , Thanatsis N. , Memtsa M. , Jauniaux E. , Jurkovic D.
Published: November 2020

Objectives

To assess the diagnostic value and impact on management of visualizing on ultrasound an amniotic sac without a live embryo (amniotic sac sign). We also examined the potential effect on the number of follow‐up visits in early pregnancy units of incorporating this sign into current diagnostic algorithms.

Methods

This was a prospective cohort study of all pregnant women who attended a single specialist early pregnancy unit from July 2017 to November 2018 with symptoms of pain and/or bleeding, or with a history of ectopic pregnancy or miscarriage, at < 14 weeks' gestation. Detailed initial ultrasound findings were documented, including whether an amniotic sac was present in a normally sited intrauterine pregnancy with absence of a live embryo. Women were followed up until a conclusive diagnosis was made.

Results

The study included 6012 women who attended our unit with early pregnancy complications during the study period. A conclusive diagnosis was reached on the initial scan in 4221 (70.2%), whilst 1135 (18.9%) women had a pregnancy of uncertain viability and 656 (10.9%) had a pregnancy of unknown location (PUL). All women with a pregnancy of uncertain viability required follow‐up ultrasound scans to differentiate between a live pregnancy and early embryonic demise. An amniotic sac in the absence of a live embryo was found in 174/1135 (15.3%) women with a pregnancy of uncertain viability at the initial ultrasound scan. The diagnosis of early embryonic demise was confirmed in all 134 of these women who attended their follow‐up scans. The presence of an amniotic sac without a live embryo at the initial visit had a specificity of 100% (95% CI, 98.53–100.00%) and positive predictive value of 100% (95% CI, 97.2–100.0%) for the diagnosis of early pregnancy failure.

A total of 1403/6012 (23.3%) women were asked to attend for a follow‐up ultrasound scan to resolve diagnostic uncertainties, including 268/656 (40.9%) women with a PUL. The majority of follow‐up scans needed to reach a conclusive diagnosis were in women with a pregnancy of uncertain viability (1135/1403 (80.9%)). By using the presence of the amniotic sac sign to diagnose early pregnancy failure at the first visit, the number of follow‐up scans for pregnancies of uncertain viability would be reduced by 14.4%, which accounted for 11% of all follow‐up scans during the study period.

Conclusions

The finding on ultrasound of an amniotic sac without a live embryo (amniotic sac sign) is a reliable marker of early pregnancy failure and could reduce the number of follow‐up scans by 11% in cases of diagnostic uncertainty. © 2020 International Society of Ultrasound in Obstetrics and Gynecology
Schwann cell development: From neural crest to myelin sheath
Authors: Muppirala Anoohya N. , Limbach Lauren E. , Bradford Elisabeth F. , Petersen Sarah C.
Published: November 2020

Vertebrate nervous system function requires glial cells, including myelinating glia that insulate axons and provide trophic support that allows for efficient signal propagation by neurons. In vertebrate peripheral nervous systems, neural crest‐derived glial cells known as Schwann cells (SCs) generate myelin by encompassing and iteratively wrapping membrane around single axon segments. SC gliogenesis and neurogenesis are intimately linked and governed by a complex molecular environment that shapes their developmental trajectory. Changes in this external milieu drive developing SCs through a series of distinct morphological and transcriptional stages from the neural crest to a variety of glial derivatives, including the myelinating sublineage. Cues originate from the extracellular matrix, adjacent axons, and the developing SC basal lamina to trigger intracellular signaling cascades and gene expression changes that specify stages and transitions in SC development. Here, we integrate the findings from in vitro neuron–glia co‐culture experiments with in vivo studies investigating SC development, particularly in zebrafish and mouse, to highlight critical factors that specify SC fate. Ultimately, we connect classic biochemical and mutant studies with modern genetic and visualization tools that have elucidated the dynamics of SC development.

This article is categorized under:

Signaling Pathways > Cell Fate Signaling

Nervous System Development > Vertebrates: Regional Development
The Punjab Schools Reform Roadmap: A Medium-Term Evaluation
Authors: Chaudhry Rastee , Tajwar Abdullah Waqar
Published: November 2020

In 2010, a whole-system reform was designed and launched in the Punjab province of Pakistan called the Punjab Schools Reform Roadmap (PSRR). This reform was a direct response to the challenges of education in the province at the time, which included scale, capacity to deliver, and political will. Further, 2010 was a time at which the political and administrative landscape of Pakistan was changing: the right to education act had just been formalized and education was simultaneously devolved from a federal matter to a provincial one.

This chapter studies the outcomes of the PSRR a decade after its implementation with an emphasis on three dimensions of the reform: management capacity, teacher capacity and monitoring & information systems. Specifically, we discuss the above with reference to increasing access to and quality of education in the province while also analyzing the outcomes and sustainability of the reform 10 years from its inception.
From Content Knowledge to Competencies and Exams to Exit Profiles: Education Reform in Zimbabwe
Authors: Gory Djénéba , Bhatia Jayanti , Reddy Venkatesh Reddy Mallapu
Published: November 2020

For over two decades, Zimbabwe has been embroiled within a complex web of economic, political, and financial challenges. In 2013, the country embarked on an ambitious journey of overhauling its education system by moving from content knowledge to a competency-based curriculum. The theory of change, in particular, was that, if the curriculum is entirely overhauled from outdated knowledge-based to twenty-first-century skills and competencies, then in the long-term, students would ultimately be able to meet the economy and labor market demands. The reform was phased from 2015 to 2022 and at the time of writing is in its last leg of implementation; there is much to appreciate and learn from the progress thus far. The chapter begins with an overview of the country’s education system and conditions that shaped the reform, followed by a more detailed description of the reform. It then analyzes the reform stages through Reimers’ five perspectives of educational change (Reimers, Educating students to improve the world. Springer, Singapore, 2020), and concludes by presenting the results and challenges at the time of writing. The success of such reform requires a systemic collaboration and stable conditions, and at this stage, it remains to be seen, which direction the reform takes.
Prognosemodelle für Beckenbodenschäden im Vergleich von Vaginalgeburt und Sectio
Authors: Betschart Cornelia , Zimmermann Roland
Published: November 2020

Mehr als die Hälfte der Primiparae berichten ein Jahr nach der Geburt über Veränderungen am Beckenboden. Symptome sind Harn- oder Stuhlinkontinenz, Missempfindungen, Laxität oder Senkungsgefühl am Beckenboden. Zugrunde liegende Schädigungen können muskulärer Art (M. levator ani oder M. sphincter ani) oder ligamentärer Art sein. Risikofaktoren für Beckenbodentraumata sind höheres mütterliches Alter, eine protrahierte Austreibungsphase, Forzepsgeburt, okzipitoposteriore Einstellung und ein Dammriss III und IV°. Abgesehen vom mütterlichen Alter sind die Risikofaktoren jedoch präpartal nicht bekannt, und diese Lücke wollen Prädiktionsmodelle schließen. Das erste Prädiktionsmodell trägt den Namen UR-CHOICE. Basierend auf epidemiologischen Langzeitdaten aus den Datenbanken ProLong (UK und Neuseeland) und SWEPOP (Schweden) werden für verschiedene Parameter wie dem mütterlichen Alter, dem Body-Mass-Index (BMI), der Anzahl gewünschter Kinder und der Familienanamnese für Inkontinenz Risikogewichte etabliert, welche in der Kombination eine Prozentzahl für Urin‑, Stuhlinkontinenz und Genitaldeszensus liefern. Das zweite Modell, das „Capacity-Demand-Modell“, integriert objektive Daten aus der Bildgebung, nämlich den kindlichen Kopfumfang und den Umfang des M. levator ani, um mit einer Zuverlässigkeit von 0,8 in der Receiver-Operating-Characteristic(ROC)-Kurve ein schweres Levator-ani-Muskeltrauma vorauszusagen.
Cross-species analysis of hepatic cytochrome P450 and transport protein expression
Authors: Hammer Helen , Schmidt Felix , Marx-Stoelting Philip , Pötz Oliver , Braeuning Albert
Published: November 2020

Most drugs and xenobiotics are metabolized in the liver. Amongst others, different cytochrome P450 (CYP) enzymes catalyze the metabolic conversion of foreign compounds, and various transport proteins are engaged in the excretion of metabolites from the hepatocytes. Inter-species and inter-individual differences in the hepatic levels and activities of drug-metabolizing enzymes and transporters result from genetic as well as from environmental factors, and play a decisive role in determining the pharmacokinetic properties of a compound in a given test system. To allow for a meaningful comparison of results from metabolism studies, it is, therefore, of utmost importance to know about the specific metabolic properties of the test systems, especially about the levels of metabolic enzymes such as the CYPs. Using a targeted proteomics approach, we, therefore, compared the hepatic levels of important CYP enzymes and transporters in different experimental systems in vivo and in vitro, namely Wistar rats, C57/Bl6 mice, mice humanized for the two xeno-sensing receptors PXR (pregnane-X-receptor) and CAR (constitutive androstane receptor), mice with human hepatocyte-repopulated livers, human HepaRG hepatocarcinoma cells, primary human hepatocytes, and human liver biopsies. In addition, the effects of xenobiotic inducers of drug metabolism on CYP enzymes and transporters were analyzed in selected systems. This study for the first time presents a comprehensive overview of similarities and differences in important drug metabolism-related proteins among the different experimental models.
Complex patterns of secondary spread without loss of genetic diversity in invasive populations of the Asian shore crab Hemigrapsus takanoi (Decapoda) along European coasts
Authors: Geburzi Jonas C. , Ewers-Saucedo Christine , Brandis Dirk , Hartl Günther B.
Published: November 2020

Genetic studies of introduced non-native species are a valuable tool to investigate invasion history and pathways, source populations and multiple introductions of alien species, as well as evolutionary genetic changes following establishment in a new environment. We used a set of nine polymorphic microsatellites to analyse the population genetic structure of the introduced Asian shore crabHemigrapsus takanoialong European coasts. Our dataset covered the complete known European range of the species, including the most recent records from Great Britain and the southwestern Baltic Sea. The results showed a similarly high genetic diversity ofH. takanoithroughout Europe, and no indication of genetic bottlenecks during secondary spread, even in the most recently established populations. Analyses for population structure along geographic regions gave support for a separation between the Bay of Seine populations (northern France) and all other populations. Genetic differentiation within the North and Baltic Seas was more subtle and patchy, hinting to potential unrecognised introduction events, dispersal barriers and anthropogenic vector activity. The populations from the Baltic Sea and Great Britain clustered with the Wadden Sea populations, suggesting secondary introductions from the southeastern North Sea as likely invasion pathways. In summary, we suggest that a combination of anthropogenic secondary spread and the species’ reproductive biology have prevented a loss of genetic diversity during its ongoing expansion. We argue that genetic data depicting population status shortly after an introduction event—like the British and Baltic Sea populations ofH. takanoi—may provide important baseline data for investigations of genetic changes during establishment and adaptation processes.
Do species display characteristic intraspecific levels of patchiness in a given habitat type? The case of intertidal seagrass macrobenthos
Authors: Barnes R. S. K.
Published: November 2020

Intertidal macrobenthic assemblages associated with monospecific stands of Zostera muelleri, Cymodocea serratula, Halodule uninervis and Halophila ovalis seagrasses are known to display uniform spatial patchiness on the Moreton Bay coast of North Stradbroke Island, Queensland, as do those in Z. capensis in the Knysna estuarine bay, South Africa. Thirty-seven historical datasets of these macrobenthic assemblages were re-analysed to assess variation of local patchiness in each of the 18 most common individual assemblage components at each of these localities in terms of three metrics: overall patchiness (Lloyd's index of patchiness), levels of unoccupancy, and variation in abundance across occupied samples (Lloyd's index of mean crowding). Within-site patchiness was not caused by a restriction of individual species to specific subareas but by variation in their local density, particularly by the extent of unoccupied ‘interstitial’ spaces within patches. Especially in the more uniform Queensland conditions, the more common species occurred relatively widely across the whole locality; individual samples from which a given species was absent never themselves formed patches, the number of such samples conforming to points on truncated normal curves of the frequency of occurrence. Of the 36 species investigated, the two most abundant and widespread both in Queensland and in South Africa displayed significant or near-significant uniformity of levels of local patchiness, whilst five showed significantly uniform mean crowding and ten significantly uniform unoccupancy. This is the first demonstration that some species may display a characteristic level of patchiness in a given habitat type.
IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas
Authors: Di Napoli Arianna , Greco Daniele , Scafetta Giorgia , Ascenzi Francesca , Gulino Alessandro , Aurisicchio Luigi , Santanelli Di Pompeo Fabio , Bonifacino Adriana , Giarnieri Enrico , Morgan John , Mancini Rita , Kadin Marshall E.
Published: November 2020

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL.
Lysine-urethane-based tissue adhesion for mastectomy—an approach to reducing the seroma rate?
Authors: Boeer B. , Schneider J. , Schoenfisch B. , Röhm C. , Paepke S. , Oberlechner E. , Ohlinger R. , Hartkopf A. , Brucker S. Y. , Hahn M. , Marx M.
Published: November 2020

Purpose

Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu® without drainage is equal/ non-inferior to standard mastecomy with drainage.

Methods

The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups.

Results

Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu® compared to standard drainage couldn’t be reached.

Discussion

The present evaluation shows no advantage of the tissue adhesive TissuGlu® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.
Feasibility and safety of breast-conserving surgery via a periareolar incision for cancers located far from the nipple–areolar complex: a retrospective study
Authors: Woo Joohyun , Lee Jihae , Paek Se Hyun , Lim Woosung
Published: November 2020

Purpose

We performed breast-conserving surgery (BCS) using periareolar incisions for cancers located far from the nipple–areolar complex (NAC) and examined if BCS via a periareolar incision maximized cosmesis and maintained oncologic safety. One of the most important goals of BCS is to improve cosmesis after surgery and quality of life, but the skin incision can affect cosmesis based on the tumor location.

Methods

Fifty-five patients with breast cancers located far from the NAC underwent BCS via periareolar incisions between January 2017 and April 2018. If a sentinel lymph node biopsy was required, another skin incision was created in the axilla using the conventional technique. Medical records of patients were reviewed retrospectively.

Results

The mean patient age was 48.1 ± 10.6 years. The mean tumor size was 1.8 ± 1.0 cm (range 0.2–4.5 cm) on preoperative magnetic resonance imaging (MRI); the mean distance from the NAC to the tumor was 5.9 ± 1.9 cm (range 4.0–12.3 cm). Patients with cancers in the subareolar area were excluded even though the distance from the nipple was > 4 cm on MRI. Negative microscopic margins were obtained in all patients. There was no surgical complication such as seroma, bleeding, or infection. Re-operation was not needed. All patients received whole breast radiation therapy. After surgery and radiation therapy, periareolar incision scars were nearly invisible.

Conclusion

For cancers located far from the NAC, BCS via periareolar incisions is feasible and leads to superior cosmesis in selective patients. Moreover, BCS seems oncologically safe, although long-term outcomes need to be evaluated.
Towards a Polynomial Kernel for Directed Feedback Vertex Set
Authors: Bergougnoux Benjamin , Eiben Eduard , Ganian Robert , Ordyniak Sebastian , Ramanujan M. S.
Published: November 2020

In theDirected Feedback Vertex Set (DFVS)problem, the input is a directed graphDand an integerk. The objective is to determine whether there exists a set of at mostkvertices intersecting every directed cycle ofD. DFVS was shown to be fixed-parameter tractable when parameterized by solution size by Chen et al. (J ACM 55(5):177–186, 2008); since then, the existence of a polynomial kernel for this problem has become one of the largest open problems in the area of parameterized algorithmics. Since this problem has remained open in spite of the best efforts of a number of prominent researchers and pioneers in the field, a natural step forward is to study the kernelization complexity ofDFVSparameterized by a naturallargerparameter. In this paper, we study DFVS parameterized by the feedback vertex set number of the underlyingundirected graph. We provide two main contributions: a polynomial kernel for this problem on general instances, and a linear kernel for the case where the input digraph is embeddable on a surface of bounded genus.
Prospective practice survey of management of cetuximab-related skin reactions
Authors: Lugtenberg R. T. , Boers-Doets C. B. , Witteveen P. O. , van Herpen C. M. L. , Wymenga A. N. M. , de Groot J. W. B. , Hoeben A. , del Grande C. , van Doorn B. , Koldenhof J. J. , Driessen C. M. L. , Gelderblom H.
Published: November 2020

Purpose

Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab.

Methods

An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab.

Results

A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years, n = 44 LA SCCHN, n = 16 R/M SCCHN, n = 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6–10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications.

Conclusion

A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy.
Emotional well-being and pain could be a greater determinant of quality of life compared to motor severity in cervical dystonia
Authors: Klingelhoefer Lisa , Kaiser Maximilian , Sauerbier Anna , Untucht Robert , Wienecke Miriam , Mammadova Könül , Falkenburger Björn , Gregor Olaf , Chaudhuri K. Ray , Reichmann Heinz
Published: November 2020

Non-motor symptoms (NMS) occur in patients with cervical dystonia (CD) but with variable frequencies and impact on health-related quality of life (HRQoL). To define non-motor and motor profiles and their respective impact on HRQoL in CD patients using the newly validated Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest). In an observational prospective multicentre case–control study, we enrolled 61 patients with CD and 61 age- and sex-matched healthy controls (HC) comparing demographic data, motor and non-motor symptoms and HRQoL measurements. 95% CD patients reported at least one NMS. Mean total NMS score was significantly higher in CD patients (5.62 ± 3.33) than in HC (1.74 ± 1.52; p < 0.001). Pain, insomnia and stigma were the most prevalent NMS and HRQoL was significantly impaired in CD patients compared to HC. There was strong correlation of NMS burden with HRQoL (CDQ-24: r = 0.72, EQ-5D: r = − 0.59; p < 0.001) in CD patients. Regression analysis between HRQoL and NMS suggested that emotional well-being (standardized beta = − 0.352) and pain (standardized beta = − 0.291) had a major impact on HRQoL while, in contrast motor severity had no significant impact in this model. Most NMS with the exception of pain, stigma and ADL did not correlate with motor severity. NMS are highly prevalent in CD patients and occur independent of age, sex, disease duration, duration of botulinum neurotoxin therapy and socio-economic status. Specific NMS such as emotional well-being and pain have a major impact on HRQoL and are more relevant than motor severity.
Humean supervenience and tripartite entanglement relations
Authors: Lorenzetti Lorenzo
Published: November 2020

It has been argued that Humean Supervenience (HS) is threatened by the existence of quantum entanglement relations. The most conservative strategy for defending HS is to add the problematic entanglement relations to the supervenience basis, alongside spatiotemporal relations. In this paper, I’m going to argue against this strategy by showing how certain particular cases of tripartite entanglement states – i.e. GHZ states – posit some crucial problems for this amended version of HS. Moreover, I will show that the principle of free recombination – which is strictly linked to HS – is severely undermined if we add entanglement relations to the supervenience basis. I conclude that the conservative move is very unappealing, and therefore the defender of HS should pursue other, more controversial, strategies (e.g. committing to the nomological interpretation of the wave function).
Attention Deficits Influence the Development of Motor Abnormalities in High Functioning Autism
Authors: Pitzianti Mariabernarda , Fagioli Sabrina , Pontis Marco , Pasini Augusto
Published: November 2020

Early attentional dysfunction is one of the most consistent findings in autism spectrum disorder (ASD), including the high functioning autism (HFA). There are no studies that assess how the atypical attentional processes affect the motor functioning in HFA. In this study, we evaluated attentional and motor functioning in a sample of 15 drug-naive patients with HFA and 15 healthy children (HC), and possible link between attentional dysfunction and motor impairment in HFA. Compared to HC, HFA group was seriously impaired in a considerable number of attentional processes and showed a greater number of motor abnormalities. Significant correlations between attention deficits and motor abnormalities were observed in HFA group. These preliminary findings suggest that deficit of attentional processes can be implied in motor abnormalities in HFA.
Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure
Authors: Dutka Mieczysław , Bobiński Rafał , Ulman-Włodarz Izabela , Hajduga Maciej , Bujok Jan , Pająk Celina , Ćwiertnia Michał
Published: November 2020

Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly improve the prognosis. Recent clinical studies assessing a new class of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed some unexpected beneficial results. Patients treated with SGLT2is had a significant decrease in both cardiovascular (CV) and all-cause mortality and less hospitalisations due to HF compared to those given a placebo. These significant clinical benefits occurred quickly after the drugs were administered and were not solely due to improved glycaemic control. These groundbreaking clinical trials’ results have already changed clinical practice in the management of patients with diabetes at high CV risk. These trials have triggered numerous experimental studies aimed at explaining the mechanisms of action of this unique group of drugs. This article presents the current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF.
Top-k overlapping densest subgraphs: approximation algorithms and computational complexity
Authors: Dondi Riccardo , Hosseinzadeh Mohammad Mehdi , Mauri Giancarlo , Zoppis Italo
Published: November 2020

A central problem in graph mining is finding dense subgraphs, with several applications in different fields, a notable example being identifying communities. While a lot of effort has been put in the problem of finding a single dense subgraph, only recently the focus has been shifted to the problem of finding a set of densest subgraphs. An approach introduced to find possible overlapping subgraphs is the problem. Given an integer $$k \ge 1$$

k
≥
1

and a parameter $$\lambda > 0$$

λ
>
0

, the goal of this problem is to find a set of k dense subgraphs that may share some vertices. The objective function to be maximized takes into account the density of the subgraphs, the parameter $$\lambda $$
λ
and the distance between each pair of subgraphs in the solution. The problem has been shown to admit a $$\frac{1}{10}$$

1
10

-factor approximation algorithm. Furthermore, the computational complexity of the problem has been left open. In this paper, we present contributions concerning the approximability and the computational complexity of the problem. For the approximability, we present approximation algorithms that improve the approximation factor to $$\frac{1}{2}$$

1
2

, when k is smaller than the number of vertices in the graph, and to $$\frac{2}{3}$$

2
3

, when k is a constant. For the computational complexity, we show that the problem is NP-hard even when $$k=3$$

k
=
3

.
Sup-Sums Principles for F-Divergence and a New Definition for t-Entropy
Authors: Bakhtin V. I. , Lebedev A. V.
Published: November 2020

The article presents new$${\sup }$$sup-sums principles for integralF-divergence for arbitrary convex functionsFon the whole real axis and arbitrary (not necessarily positive and normalized) measures. Among applications of these results, we work out a new ‘integral’ definition fort-entropy explicitly establishing its relation to Kullback–Leibler divergence.