bluuebunny/crossref_metadata_2025 huggingface dataset:
MealTime-MS: A Machine Learning-Guided Real-Time Mass Spectrometry Analysis for Protein Identification and Efficient Dynamic Exclusion
Authors: Pelletier Alexander R. , Chung Yun-En , Ning Zhibin , Wong Nora , Figeys Daniel , Lavallée-Adam Mathieu
Published: May 2020

Mass spectrometry-based proteomics technologies are the prime methods for the high-throughput identification of proteins in complex biological samples. Nevertheless, there are still technical limitations that hinder the ability of mass spectrometry to identify low abundance proteins in complex samples. Characterizing such proteins is essential to provide a comprehensive understanding of the biological processes taking place in cells and tissues. Still today, most mass spectrometry-based proteomics approaches use a data-dependent acquisition strategy, which favors the collection of mass spectra from proteins of higher abundance. Since the computational identification of proteins from proteomics data is typically performed after mass spectrometry analysis, large numbers of mass spectra are typically redundantly acquired from the same abundant proteins, and little to no mass spectra are acquired for proteins of lower abundance. We therefore propose a novel supervised learning algorithm that identifies proteins in real-time as mass spectrometry data are acquired and prevents further data collection from confidently identified proteins to ultimately free mass spectrometry resources to improve the identification sensitivity of low abundance proteins. We use real-time simulations of a previously performed mass spectrometry analysis of a HEK293 cell lysate to show that our approach can identify 92.1% of the proteins detected in the experiment using 66.2% of the MS2 spectra. We also demonstrate that our approach outperforms a previously proposed method, is sufficiently fast for real-time mass spectrometry analysis, and is flexible. Finally, MealTime-MS’ efficient usage of mass spectrometry resources will provide a more comprehensive characterization of proteomes in complex samples.
An embryonic stem cell-specific heterochromatin state allows core histone exchange in the absence of DNA accessibility
Authors: Navarro Carmen , Elsässer Simon J
Published: May 2020

Nucleosome turnover concomitant with incorporation of the replication-independent histone variant H3.3 is a hallmark of regulatory regions in the animal genome. In our current understanding, nucleosome turnover is universally linked to DNA accessibility and histone acetylation. In mouse embryonic stem cells, H3.3 is also highly enriched at interstitial heterochromatin, most prominently intracisternal-A particle endogenous retroviral elements. Interstitial heterochromatin is established over confined domains by the TRIM28/SETDB1 corepressor complex and has stereotypical features of repressive chromatin, such as H3K9me3 and recruitment of all HP1 isoforms. Here, we demonstrate that fast histone turnover and H3.3 incorporation is compatible with these hallmarks of heterochromatin. Further, we find that histone H3.3 is required to maintain minimal DNA accessibility in this surprisingly dynamic heterochromatin state. Loss of H3.3 in mouse embryonic stem cells elicits a highly specific opening of interstitial heterochromatin with minimal effects on other silent or active regions of the genome.
On Using Transfer Learning For Plant Disease Detection
Authors: Sagar Abhinav , Jacob Dheeba
Published: May 2020

Deep neural networks has been highly successful in image classification problems. In this paper, we show how neural networks can be used for plant disease recognition in the context of image classification. We have used publicly available Plant Village dataset which has 38 classes of diseases. Hence, the problem that we have addressed is a multi class classification problem. We compared five different architectures including VGG16, ResNet50, InceptionV3, InceptionResNet and DenseNet169 as the backbones for our work. We found that ResNet50 achieves the best result on the test set. For evaluation, we used metrics: accuracy, precision, recall, F1 score and class wise confusion metric. Our model achieves the best of results using ResNet50 with accuracy of 0.982, precision of 0.94, recall of 0.94 and F1 score of 0.94.
Detection of a multi-disease biomarker in Saliva with Graphene Field Effect Transistors
Authors: Kumar Narendra , Gray Mason , Ortiz-Marquez Juan C. , Weber Andrew , Desmond Cameron R. , Argun Avni , van Opijnen Tim , Burch Kenneth S.
Published: May 2020

Human carbonic anhydrase 1 (CA1) has been suggested as a biomarker for identification of several diseases including cancers, pancreatitis, diabetes, and Sjogren’s syndrome. However, the lack of a rapid, cheap, accurate, and easy-to-use quantification technique has prevented widespread utilization of CA1 for practical clinical applications. To this end, we present a label-free electronic biosensor for detection of CA1 utilizing highly sensitive graphene field effect transistors (G-FETs) as a transducer and specific RNA aptamers as a probe. The binding of CA1 with aptamers resulted in a positive shift in Dirac voltageVDof the G-FETs, the magnitude of which depended on target concentration. These aptameric G-FET biosensors showed the binding affinity (KD) of ∼ 2.3 ng/ml (70 pM), which is four orders lower than that reported using a gel shift assay. This lower value ofKDenabled us to achieve a detection range (10 pg/ml - 100 ng/ml) which is well in line with the clinically relevant range. These highly sensitive devices allowed us to further prove their clinical relevance by successfully detecting the presence of CA1 in human saliva samples. Utilization of this label-free biosensor could facilitate the early stage identification of various diseases associated with changes in concentration of CAs.
Evidence for dosage compensation inCoccinia grandis, a plant with a highly heteromorphic XY system
Authors: Fruchard Cécile , Badouin Hélène , Latrasse David , Devani Ravi S. , Muyle Aline , Rhoné Bénédicte , Renner Susanne S. , Banerjee Anjan K. , Bendahmane Abdelhafid , Marais Gabriel A.B.
Published: May 2020

Some ~15.000 angiosperms are dioecious, but mechanisms of sex determination in plants remain poorly understood. In particular, how Y chromosomes evolve and degenerate, and whether dosage compensation evolves as a response, are matters of debate. Here we focus onCoccinia grandis, a dioecious cucurbit with the highest level of X/Y heteromorphy recorded so far. We identified sex-linked genes using RNA sequences from a cross and a model-based method termed SEX-DETector. Parents and F1 individuals were genotyped and the transmission patterns of SNPs then analysed. In the >1300 sex-linked genes studied, X-Y divergence was 0.13 - 0.17, and substantial Y degeneration is implied by an average Y/X expression ratio of 0.63 and an inferred gene loss on the Y of ~40%. We also found reduced Y gene expression being compensated by elevated expression of corresponding genes on the X and an excess of sex-biased genes on the sex chromosomes. Molecular evolution of sex-linked genes inC. grandisis thus comparable to that inSilene latifolia, another dioecious plant with a strongly heteromorphic XY system, and cucurbits are the fourth plant family in which dosage compensation is described, suggesting it might be common in plants.
Innovating business processes in public administrations: towards a systemic approach
Authors: Forliano Canio , De Bernardi Paola , Bertello Alberto , Temperini Valerio
Published: May 2020

Purpose

The purpose of this paper is to study the credit collection process in public administrations in order to develop a conceptual model which goes beyond the traditional logic of linearity, adopting system thinking approaches.

Design/methodology/approach

This study analyses the case of an Italian local government-owned enterprise. Data collection through semi-structured interviews and document analysis has enabled the development of propositions, the identification of systemic variables, and the development of an explanatory modeling process based on the system dynamics approach.

Findings

This paper shows that public administrations can effectively involve external actors, especially citizens, as knowledge and public value co-creators only when considering systemic, unintended, and delayed implications of decision-making activities related to the provision of sensitive public services such as credit collection.

Originality/value

Business process modelling should address some key fragilities of traditional modeling processes, especially in the public sector. This paper develops a novel systemic conceptual model which lays the groundwork for empirically testing business process innovation in public administrations.
Predation risk, market power and cash policy
Authors: Mitani Hidetaka
Published: May 2020

Purpose

The purpose of the present study is to discuss the combined effect of predation risk and firms' market power on cash holdings.

Design/methodology/approach

The authors tested hypotheses by using consolidated financial data in Japanese firms.

Findings

The authors find that firms' cash holdings increase with a rise in predation risk faced by firms. However, the higher the firm's market power, the weaker the above interplay becomes. Moreover, the authors find that even when firms' investments are decreased at the industry level, firms with larger cash holdings seek to mitigate predation risk by funding strategic investments with the potential to steal rivals' market share.

Originality/value

The authors recognize the importance of a firm's market power. Take a firm's market power into consideration to analyze the mechanism of a firm's cash holdings, there is a possibility that the mechanism of a firm's cash holdings as presented by the previous studies will be changed.
Does social thermal regulation constrain individual thermal tolerance in an ant species?
Authors: Villalta Irene , Oms Cristela Sánchez , Angulo Elena , Molinas‐González Carlos R. , Devers Séverine , Cerdá Xim , Boulay Raphaël
Published: May 2020

In ants, social thermal regulation is the collective maintenance of a nest temperature that is optimal for individual colony members. In the thermophilic ant Aphaenogaster iberica, two key behaviours regulate nest temperature: seasonal nest relocation and variable nest depth. Outside the nest, foragers must adapt their activity to avoid temperatures that exceed their thermal limits.

It has been suggested that social thermal regulation constrains physiological and morphological thermal adaptations at the individual level. We tested this hypothesis by examining the foraging rhythms of six populations of A. iberica, which were found at different elevations (from 100 to 2,000 m) in the Sierra Nevada mountain range of southern Spain. We tested the thermal resistance of individuals from these populations under controlled conditions.

Janzen's climatic variability hypothesis (CVH) states that greater climatic variability should select for organisms with broader temperature tolerances. We found that the A. iberica population at 1,300 m experienced the most extreme temperatures and that ants from this population had the highest heat tolerance (LT50 = 57.55°C). These results support CVH's validity at microclimatic scales, such as the one represented by the elevational gradient in this study.

Aphaenogaster iberica maintains colony food intake levels across different elevations and mean daily temperatures by shifting its rhythm of activity.

This efficient colony‐level thermal regulation and the significant differences in individual heat tolerance that we observed among the populations suggest that behaviourally controlled thermal regulation does not constrain individual physiological adaptations for coping with extreme temperatures.
Drought legacies are short, prevail in dry conifer forests and depend on growth variability
Authors: Gazol Antonio , Camarero Jesús Julio , Sánchez‐Salguero Raul , Vicente‐Serrano Sergio M. , Serra‐Maluquer Xavier , Gutiérrez Emilia , de Luis Martín , Sangüesa‐Barreda Gabriel , Novak Klemen , Rozas Vicente , Tíscar Pedro A. , Linares Juan C. , Martínez del Castillo Edurne , Ribas Montse , García‐González Ignacio , Silla Fernando , Camisón Álvaro , Génova Mar , Olano José M. , Hereş Ana‐Maria , Curiel Yuste Jorge , Longares Luis A. , Hevia Andrea , Tomas‐Burguera Miquel , Galván Juan Diego
Published: May 2020

The negative impacts of drought on forest growth and productivity last for several years generating legacies, although the factors that determine why such legacies vary across sites and tree species remain unclear.

We used an extensive network of tree‐ring width (RWI, ring‐width index) records of 16 tree species from 567 forests, and high‐resolution climate and normalized difference vegetation index (NDVI) datasets across Spain during the common period 1982‒2008 to test the hypothesis that climate conditions and growth features modulate legacy effects of drought on forests. Legacy effects of drought were calculated as the differences between detrended‐only RWI and NDVI series (i.e. after removing long‐term growth trends) and pre‐whitened RWI and NDVI series predicted by a model including drought intensity. Superposed Epoch Analysis (SEA) was used to estimate whether legacy effects differed from random. Finally, legacy effects were related to water balance, growth persistence and variability, and tree species identity.

We found a widespread occurrence of drought legacy effects on both RWI and NDVI, but they were seldom significant. According to SEA, first‐year drought legacies were negative and different from random in 9% and 5% of the RWI and NDVI series respectively. The number of significant second‐ and third‐year legacies was substantially lower. Differences between RWI and NDVI legacies indicate that canopy greenness and radial growth responses to drought are decoupled. We found variations in legacies between tree species with gymnosperms presenting larger first‐year drought legacies than angiosperms, which were exposed to less severe droughts. Greater growth variability can explain the presence of first‐year RWI legacies in gymnosperms from dry sites despite that the relationship between growth variability and legacies was complex.

Synthesis. Accounting for species and site responses to drought provides a better understanding of the magnitude and duration of drought legacies on forest growth and productivity. Despite the widespread occurrence of growth reductions in the years during and after drought occurrence, significant legacies were not very common, mostly lasted one year, and were more widespread in gymnosperms. These are relevant factors to be considered in the future when studying the consequences of drought on forest productivity and tree growth.
Dynamic interplay between contractual and relational governance: An empirical study in Australian healthcare outsourcing
Authors: Young Suzanne , Nguyen Phuc , Macinati Manuela S.
Published: May 2020

The introduction of New Public Management (NPM)‐inspired reforms in the public sector in the 1990s saw a big leap in public–private outsourcing partnerships in public service delivery; however, many of these have failed, resulting in backsourcing. Although effective governance of the ongoing relationship between outsourcing partners is arguably key to a successful partnership, the findings as to the optimal type of relationship between two main governance mechanisms – contractual and relational – remain inconclusive. Adopting Huber et al.’s dynamic perspective of governance mechanism interplay as a research framework, this paper empirically investigates the interplay in two problematic outsourcing public–private partnerships, that is the delivery of services has been backsourced or considered to be backsourced. Our data confirm the existence of a dynamic interplay between contractual and relational governance. The findings, however, do not represent a perfect fit with Huber et al.’s conceptualizations, signalling the significance of our research as to a more diverse and complicated group of interactions. Our analysis also reveals the potential interference of additional contextual factors in the interplay. Further research that explores and tests these contextual factors is warranted.
Advances in exogenous docosahexaenoic acid‐containing phospholipids: Sources, positional isomerism, biological activities, and advantages
Authors: Zhang Yao , Wu Gangcheng , Zhang Yanjie , Wang Xingguo , Jin Qingzhe , Zhang Hui
Published: May 2020

In recent years, docosahexaenoic acid‐containing phospholipids (DHA‐PLs) have attracted much attention because of theirs unique health benefits. Compared with other forms of docosahexaenoic acid (DHA), DHA‐PLs possess superior biological effects (e.g., anticancer, lipid metabolism regulation, visual development, and brain and nervous system biochemical reactions), more intricate metabolism mechanisms, and a stronger attraction to consumer. The production of DHA‐PLs is hampered by several challenges associated with the limited content of DHA‐PLs in natural sources, incomplete utilization of by‐products, few microorganisms for DHA‐PLs production, high cost, and complex process of artificial preparation of DHA‐PLs. In this article, the sources, biological activities, and commercial applications of DHA‐PLs were summarized, with intensive discussions on advantages of DHA‐PLs over DHA, isomerism of DHA in phospholipids (PLs), and brain health. The excellent biological characteristics of DHA‐PLs are primarily concerned with DHA and PLs. The metabolic fate of different DHA‐PLs varies from the position of DHA in PLs to polar groups in DHA‐PLs. Overall, well understanding of DHA‐PLs about their sources and characteristics is critical to accelerate the production of DHA‐PLs, economically enhance the value of DHA‐PLs, and improve the applicability of DHA‐PLs and the acceptance of consumers.
Modulation of the human gut microbiota by phenolics and phenolic fiber‐rich foods
Authors: Loo Yit Tao , Howell Kate , Chan Miin , Zhang Pangzhen , Ng Ken
Published: May 2020

The gut microbiota plays a prominent role in human health. Alterations in the gut microbiota are linked to the development of chronic diseases such as obesity, inflammatory bowel disease, metabolic syndrome, and certain cancers. We know that diet plays an important role to initiate, shape, and modulate the gut microbiota. Long‐term dietary patterns are shown to be closely related with the gut microbiota enterotypes, specifically long‐term consumption of carbohydrates (related to Prevotella abundance) or a diet rich in protein and animal fats (correlated to Bacteroides). Short‐term consumption of solely animal‐ or plant‐based diets have rapid and reproducible modulatory effects on the human gut microbiota. These alterations in microbiota profile by dietary alterations can be due to impact of different dietary macronutrients, carbohydrates, protein, and fat, which have diverse modulatory effects on gut microbial composition. Food‐derived phenolics, which encompass structural variants of flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, coumarins, stilbenes, ellagitannins, and lignans can modify the gut microbiota. Gut microbes have been shown to act on dietary fibers and phenolics to produce functional metabolites that contribute to gut health. Here, we discuss recent studies on the impacts of phenolics and phenolic fiber‐rich foods on the human gut microbiota and provide an insight into potential synergistic roles between their bacterial metabolic products in the regulation of the intestinal microbiota.
Microbial quality and safety of milk and milk products in the 21st century
Authors: Fusco Vincenzina , Chieffi Daniele , Fanelli Francesca , Logrieco Antonio F. , Cho Gyu‐Sung , Kabisch Jan , Böhnlein Christina , Franz Charles M. A. P.
Published: May 2020

Milk and milk products have been utilized by humans for many thousands of years. With the advent of metagenomic studies, our knowledge on the microbiota of milk and milk products, especially as affected by the environment, production, and storage parameters, has increased. Milk quality depends on chemical parameters (fat and protein content and absence of inhibitory substances), as well as microbial and somatic cells counts, and affects the price of milk. The effects of hygiene and effective cooling on the spoilage microbiota have shown that proteolytic and lipolytic bacteria such as Pseudomonas or Acinetobacter spp. predominate the spoilage bacterial populations. These bacteria can produce heat‐stable proteases and lipases, which remain active after pasteurization and thus can spoil the milk during prolonged storage. Additionally, milk can become contaminated after pasteurization and therefore there is still a high demand on developing better cleaning and sanitation regimes and equipment, as well as test systems to (quantitatively) detect relevant pathogenic or spoilage microorganisms. Raw milk and raw milk cheese consumption is also increasing worldwide with the growing demand of minimally processed, sustainable, healthy, and local foods. In this context, emerging and re‐emerging pathogens once again represent a major food safety challenge. As a result of global warming, it is conceivable that not only microbiological risks but also chemical risks relating to presence of mycotoxins or plant toxins in milk will increase. Herein, we provide an overview of the major microbial hazards occurring in the 21st century.
Fearful futures and haunting histories in women's desistance from crime: A longitudinal study of desistance as an uncanny process*
Authors: Fredriksson Tea , Gålnander Robin
Published: May 2020

Although desistance is increasingly recognized as a series of complex processes by which individuals transform from offenders into nonoffenders, few desistance scholars have studied this process in depth. In recent years, however, some have begun to explore how desistance is a process rife with setbacks and struggles. Through an analysis of repeated in‐depth interviews with ten desisting women, in this study, we have found such struggles to be unsettling and outright frightening. Examples of this were prevalent throughout the women's narratives. The results of our analysis show how frightening aspects of desistance processes stem from making an unfamiliar, normative lifestyle familiar, while unfamiliarizing oneself with a familiar, deviant lifestyle. As such, desistance processes can be conceptualized as uncanny, that is, as pertaining to the frightening and uncertain. Although uncanniness is not a theoretical framework one tends to find in desistance research, it has the potential to develop the understanding of the struggles, fears, and anxieties of desistance processes. Through our analysis, we engage with how uncanniness can nuance established concepts in desistance research. Implications for theory as well as for criminal justice practice are discussed.
Effect of mating period and time‐of‐day for bloodmeal on rearing of Asian tiger mosquito (Aedes albopictus) in laboratory conditions
Authors: Kim Domin , Kim Donghun
Published: May 2020

Colonization and maintenance of mosquitoes in the laboratory is required to study physiology, ecology, and behavior of mosquitoes and interactions between mosquito and pathogens. Artificial blood feeding systems have been widely used to maintain the laboratory colony of Aedes albopictus. In this study, we investigated the effects of mating period (1, 3, 6, and 10 days) and time‐of‐day for bloodmeal (08:00, 13:00, and 18:00) in the use of an artificial feeding system on blood‐feeding rate, female fecundity, egg hatching rate, and developmental time of the Asian tiger mosquito, A. albopictus. Younger females mated for three or fewer days reproduced more eggs compared to those of oldest females mated for ten days. Similar to the result for eggs laid, the mean egg‐hatching rate was significantly higher from the offspring of younger females than from those of older females. However, mating period and time‐of‐day for bloodmeal had no effect on the blood feeding rate and developmental time. Taken together, we suggest that three‐day mating with bloodmeal at 18:00 is optimal for maintaining colonies of A. albopictus in laboratory conditions.
Circ‐RNF111 contributes to paclitaxel resistance in breast cancer by elevating E2F3 expression via miR‐140‐5p
Authors: Zang Hongliang , Li Yuhui , Zhang Xue , Huang Guomin
Published: May 2020

Background

Circular RNAs (circRNAs) have been demonstrated to act as key regulators in the chemoresistance of human cancers, including breast cancer (BC). Here, we aimed to explore the role of circ‐RNF111 in paclitaxel (PTX) resistance of BC.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) was employed to determine the expression of circ‐RNF111, microRNA‐140‐5p (miR‐140‐5p) and E2F transcription factor 3 (E2F3) mRNA. The half maximal inhibitory concentration (IC50) of PTX, cell viability, colony formation and cell invasion were assessed by cell counting kit‐8 (CCK‐8) assay, colony formation assay and transwell assay, respectively. Glucose consumption and lactate production were determined by specific kits. A murine xenograft model was established to investigate the role of circ‐RNF111 in PTX resistance of BC in vivo. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationship between miR‐140‐5p and circ‐RNF111 or E2F3. Western blot assay was conducted to examine the protein level of E2F3.

Results

Circ‐RNF111 was upregulated in PTX‐resistant BC tissues and cells. Circ‐RNF111 knockdown restrained IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis in PTX‐resistant BC cells in vitro and enhanced PTX sensitivity in vivo. MiR‐140‐5p was a target of circ‐RNF111 and miR‐140‐5p expression was negatively correlated with circ‐RNF111 expression in BC tissues. The effect of circ‐RNF111 knockdown on PTX resistance was rescued by miR‐140‐5p deletion. Additionally, miR‐140‐5p could interact with E2F3 and negatively regulate E2F3 expression. Moreover, miR‐140‐5p suppressed IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis by targeting E2F3.

Conclusions

Circ‐RNF111 improved PTX resistance of BC by upregulating E2F3 via sponging miR‐140‐5p.
Mobile Smartphone Technology Is Associated With Out‐of‐hospital Cardiac Arrest Survival Improvement: The First Year “Greater Paris Fire Brigade” Experience
Authors: Derkenne Clément , Jost Daniel , Roquet Florian , Dardel Paul , Kedzierewicz Romain , Mignon Alexandre , Travers Stéphane , Frattini Benoit , Prieux Laurent , Rozenberg Emmanuel , Demaison Xavier , Gaudet John , de Charry Félicité , Stibbe Olivier , Briche Frédérique , Lemoine Frédéric , Lesaffre Xavier , Maurin Olga , Gauyat Eric , Faraon Eric , Lemoine Sabine , Prunet Bertrand
Published: May 2020

Background

Out‐of‐hospital cardiac arrest (OHCA) remains associated with very high mortality. Accelerating the initiation of efficient cardiopulmonary resuscitation (CPR) is widely perceived as key to improving outcomes. The main goal was to determine whether identification and activation of nearby first responders through a smartphone application named Staying Alive (SA) can improve survival following OHCA in a large urban area (Paris).

Methods

We conducted a nonrandomized cohort study of all adults with OHCA managed by the Greater Paris Fire Brigade during 2018, irrespective of mobile application usage. We compared survival data in cases where SA did or did not lead to the activation of nearby first responders. During dispatch, calls for OHCA were managed with or without SA. The intervention group included all cases where nearby first responders were successfully identified by SA and actively contributed to CPR. The control group included all other cases. We compared survival at hospital discharge between the intervention and control groups. We analyzed patient data, CPR metrics, and first responders' characteristics.

Results

Approximately 4,107 OHCA cases were recorded in 2018. Among those, 320 patients were in the control group, whereas 46 patients, in the intervention group, received first responder–initiated CPR. After adjustment for confounders, survival at hospital discharge was significantly improved for patients in the intervention group (35% vs. 16%, adjusted odds ratio = 5.9, 95% confidence interval = 2.1 to 16.5, p < 0.001). All CPR metrics were improved in the intervention group.

Conclusions

We report that mobile smartphone technology was associated with OHCA survival through accelerated initiation of efficient CPR by first responders in a large urban area.
IgM and IgA in addition to IgG autoantibodies against FcɛRIα are frequent and associated with disease markers of chronic spontaneous urticaria
Authors: Altrichter Sabine , Zampeli Vasiliki , Ellrich André , Zhang Ke , Church Martin K , Maurer Marcus
Published: May 2020

Background

IgG autoantibodies against the high‐affinity IgE receptor, FcɛRIα, contribute the pathogenesis of autoimmune chronic spontaneous urticaria (CSU). However, it is not known whether such patients also exhibit IgM or IgA autoantibodies against FcɛRIα. To address this question we developed an ELISA to assess serum levels of IgG, IgM, and IgA autoantibodies against FcɛRIα and investigated whether their presence is linked to clinical features of CSU including the response to autologous serum skin testing (ASST).

Methods

Serum samples of 35 CSU patients (25 ASST‐positive) and 52 healthy control individuals were analyzed using a newly developed competitive ELISA for IgG, IgM, and IgA autoantibodies to FcɛRIα.

Results

One in four CSU patients (8/35, 24%) had elevated serum levels of IgG‐anti‐FcɛRIα compared with (3/52, 6%) healthy controls. More than half of patients had IgM (21/35, 60%) and IgA (20/35, 57%) vs (3/52, 5%) each in healthy controls. Elevated IgM, but not IgG or IgA, autoantibodies were significantly more frequent in ASST‐positive CSU patients (18/25, 72%) compared with ASSTnegative patients (3/10, 33%, P = .022). Also, elevated levels of IgM‐anti‐FcɛRIα, but not of IgG or IgA against FcɛRIα, were linked to low blood basophil (r = .414, P = .021) and eosinophil (r = .623, P < .001) counts.

Conclusions

Increased serum levels of IgM‐anti‐FcɛRIα are common in patients with CSU and linked to features of autoimmune CSU. The role and relevance of autoantibodies to FcɛRIα in CSU can and should be further characterized in future studies, and our novel assay can help with this.
Mast cells and complement system: Ancient interactions between components of innate immunity
Authors: Elieh Ali Komi Daniel , Shafaghat Farzaneh , Kovanen Petri T. , Meri Seppo
Published: May 2020

The emergence and evolution of the complement system and mast cells (MCs) can be traced back to sea urchins and the ascidian Styela plicata, respectively. Acting as a cascade of enzymatic reactions, complement is activated through the classical (CP), the alternative (AP), and the lectin pathway (LP) based on the recognized molecules. The system's main biological functions include lysis, opsonization, and recruitment of phagocytes. MCs, beyond their classic role as master cells of allergic reactions, play a role in other settings, as well. Thus, MCs are considered as extrahepatic producers of complement proteins. They express various complement receptors, including those for C3a and C5a. C3a and C5a not only activate the C3aR and C5aR expressing MCs but also act as chemoattractants for MCs derived from different anatomic sites, such as from the bone marrow, human umbilical cord blood, or skin in vitro. Cross talk between MCs and complement is facilitated by the production of complement proteins by MCs and their activation by the MC tryptase. The coordinated activity between MCs and the complement system plays a key role, for example, in a number of allergic, cutaneous, and vascular diseases. At a molecular level, MCs and complement system interactions are based on the production of several complement zymogens by MCs and their activation by MC‐released proteases. Additionally, at a cellular level, MCs act as potent effector cells of complement activation by expressing receptors for C3a and C5a through which their chemoattraction and activation are mediated by anaphylatoxins in a paracrine and autocrine fashion.
COVID‐19: legal implications for critical care
Authors: Coghlan N. , Archard D. , Sipanoun P. , Hayes T. , Baharlo B.
Published: May 2020

The COVID‐19 pandemic has caused an unprecedented challenge for the provision of critical care. Anticipating an unsustainable burden on the health service, the UK Government introduced numerous legislative measures culminating in the Coronavirus Act, which interfere with existing legislation and rights. However, the existing standards and legal frameworks relevant to critical care clinicians are not extinguished, but anticipated to adapt to a new context. This new context influences the standard of care that can be reasonably provided and yields many human rights considerations, for example, in the use of restraints, or the restrictions placed on patients and visitors under the Infection Prevention and Control guidance. The changing landscape has also highlighted previously unrecognised legal dilemmas. The perceived difficulties in the provision of personal protective equipment for employees pose a legal risk for Trusts and a regulatory risk for clinicians. The spectre of rationing critical care poses a number of legal issues. Notably, the flux between clinical decisions based on best interests towards decisions explicitly based on resource considerations should be underpinned by an authoritative public policy decision to preserve legitimacy and lawfulness. Such a policy should be medically coherent, legally robust and ethically justified. The current crisis poses numerous challenges for clinicians aspiring to remain faithful to medicolegal and human rights principles developed over many decades, especially when such principles could easily be dismissed. However, it is exactly at such times that these principles are needed the most and clinicians play a disproportionate role in safeguarding them for the most vulnerable.
Testicular ultrasound score: A new proposal for a scoring system to predict testicular function
Authors: Pozza Carlotta , Kanakis George , Carlomagno Francesco , Lemma Andrea , Pofi Riccardo , Tenuta Marta , Minnetti Marianna , Tarsitano Maria G. , Sesti Franz , Paoli Donatella , Anzuini Antonella , Lenzi Andrea , Isidori Andrea M. , Gianfrilli Daniele
Published: May 2020

Background

Testicular ultrasound (US) is routinely employed in the evaluation of reproductive and sexual function. However, its use for characteristics other than testicular volume is hampered by a lack of information on the prognostic value of its findings, which to date have only been incorporated in a score proposed by Lenz et al in 1993.

Objectives

We sought to explore whether testicular US examination can predict the quality of spermatogenesis and provide information on testicular endocrine function.

Materials and methods

We retrospectively reviewed 6210 testicular US examinations, finally selecting examinations from 2230 unique men. The following variables were considered: bitesticular volume and testicular asymmetry, parenchymal echotexture, echogenicity and presence of microlithiasis, solid lesions and varicocoele. Concurrent fasting hormonal data were available for 1160 men, while 979 had a semen sample available from the same day as the US examination.

Results

We derived a new US score, termed TU score, that can predict both impaired spermatogenesis (AUC 0.73, sensitivity 72%, specificity 61%, P < .001) and hypogonadism (AUC 0.71, sensitivity 71%, specificity 53%, P < .001) more accurately than the Lenz's score. In a multivariate analysis, a reduced sperm composite index (defined as total spermatozoa × total motility × normal forms) was independently predicted by bitesticular volume and by inhomogeneous echotexture, while hypogonadism was independently predicted also by reduced echogenicity and presence of microlithiasis.

Discussion and conclusions

We describe the testicular US characteristics that are independently associated with impaired spermatogenesis and hypogonadism and propose the TU score as a simple screening method for use in subjects referred for testicular US.
Prevention of nosocomial Acinetobacter baumannii infections with a conserved immunogenic fimbrial protein
Authors: Mahmoudi Zeinab , Rasooli Iraj , Jahangiri Abolfazl , Darvish Alipour Astaneh Shakiba
Published: May 2020

Acinetobacter baumannii, one of the most life‐threatening nosocomial drug‐resistant pathogens, imposes high morbidity and mortality rates, thus highlighting immunization‐based treatments or prevention measures. The selection of appropriate antigens can elicit protective immunity. The gene encoding a fimbrial protein introduced via reverse vaccinology was cloned, expressed and evaluated for immunogenicity in a murine model. Mice immunized with the recombinant protein were challenged with A. baumannii ATCC 19606. Adherence to A549 cell line of specific anti‐sera treated A. baumannii was also assessed. Passive immunity was evaluated in a murine pneumonia model. Indirect ELISA showed a high specific antibody titre. Adherence of A. baumannii to A549 cell line decreased by 40% after incubation with 1:250 dilution of specific anti‐sera. All the actively immunized mice survived. Bacterial load in the spleen and liver of the immunized mice was 3‐fold lower than those of the control. The number of bacteria in the lungs of passively immunized mice was about 6‐fold lower than the control mice. The fimbrial protein could be considered as a promising protective immunogen against A. baumannii.
Clonal relationship in multisited mucosa‐associated lymphoid tissue lymphomas: a single‐centre experience
Authors: Condom Maria , Climent Fina , Fernández Davinia , Colomer Dolors , Lopez‐Guerra Mónica , Varela Mar , Carro Itziar , Maluquer Clara , Mercadal Santiago , Oliveira Ana Carla , Pané Maria , Matias‐Guiu Xavier , González‐Barca Eva , Sureda Anna , Domingo‐Domenech Eva
Published: May 2020

Clonal heterogeneity in multisited or recurrent lymphoid neoplasms is a phenomenon that has been increasingly studied in recent years. However, in mucosa‐associated lymphoid tissue (MALT) lymphomas it remains largely unexplored. Patients diagnosed at our institution with multisited MALT lymphoma, from January 2009 to October 2018, were studied. Molecular studies were performed for the detection of clonally rearranged immunoglobulin by polymerase chain reaction.In all, 91 patients were included. Of those, 28 had a multisited disease and in 16 clonality studies were done. In eight cases, multifocal involvement was synchronous and in eight metachronous. Patients with non‐gastric gastrointestinal tract involvement tended to disseminate within the same tract, without observing other specific dissemination patterns. Four cases (25%) had clonal heterogeneity at the different organs involved. All patients with late relapses (two patients) had different clones. The majority of patients with multisited MALT lymphomas presented with the same clone in the different involved organs, identifying a different clone in those with late relapses. These patients could represent de novo neoplasms, rather than a relapse. This could mean that some individuals might have a genetic predisposition to develop this type of lymphoma and it could also have clinical implications regarding therapeutic decisions.
AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs
Authors: Tong Xishuai , Ganta Roman R. , Liu Zongping
Published: May 2020

Osteoclasts are multinucleated giant cells, responsible for bone resorption. Osteoclast differentiation and function requires a series of cytokines to remove the old bone, which coordinates with the induction of bone remodelling by osteoblast‐mediated bone formation. Studies have demonstrated that AMP‐activated protein kinase (AMPK) play a negative regulatory role in osteoclast differentiation and function. Research involving AMPK, a nutrient and energy sensor, has primarily focused on osteoclast differentiation and function; thus, its role in autophagy, inflammation and immunity remains poorly understood. Autophagy is a conservative homoeostatic mechanism of eukaryotic cells, and response to osteoclast differentiation and function; however, how it interacts with inflammation remains unclear. Additionally, based on the regulatory function of different AMPK subunits for osteoclast differentiation and function, its activation is regulated by upstream factors to perform bone metabolism. This review summarises the critical role of AMPK‐mediated autophagy, inflammation and immunity by upstream and downstream signalling during receptor activator of nuclear factor kappa‐B ligand‐induced osteoclast differentiation and function. This pathway may provide therapeutic targets for bone‐related diseases, as well as function as a biomarker for bone homoeostasis.
Workplace mobility in Canadian urban agglomerations, 1996 to 2016: Have workers really flown the coop?
Authors: Putri Danisa , Shearmur Richard
Published: May 2020

Whilst workplace mobility (i.e., working from a variety of locations) has become an area of study in its own right, and has increasingly gained media attention, little is known about how prevalent or novel it is. In this paper we use Census place of work data to obtain insights into the prevalence and growth of this phenomenon in Canada's ten largest Census Metropolitan Areas (CMAs). These data do not capture all dimensions of workplace mobility, but are the best currently available to assess it population‐wide. We show that workplace mobility has increased modestly since 1996, and that it is particularly prevalent in sectors such as construction, and amongst less qualified workers. Knowledge workers, to the extent they are mobile, tend to work from home. These results do not capture fine‐grained mobility within the working day (which may indeed be increasing), but demonstrate that these finer grained mobilities have not fundamentally impacted the types of workplace that jobs are attached to.
Could FiLaC™ be effective in the treatment of anal fistulas? A systematic review of observational studies and proportional meta‐analysis
Authors: Frountzas M. , Stergios K. , Nikolaou C. , Bellos I. , Schizas D. , Linardoutsos D. , Kontzoglou K. , Vaos G. , Williams A. B. , Toutouzas K.
Published: May 2020

Aim

Fistula Laser Closure (FiLaC™) is a novel sphincter‐preserving technique that is based on new technologies and shows promising results in repairing anal fistulas whilst maintaining external sphincter function. The aim of the present meta‐analysis is to present the efficacy and the safety of FiLaC™ in the management of anal fistula disease.

Method

The present proportional meta‐analysis was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, clinicaltrials.gov, Embase, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until November 2019.

Results

Overall, eight studies were included that recruited 476 patients. The pooled success rate of the technique was 63% (95% CI 50%–75%). The pooled complication rate was 8% (95% CI 1%–18%). Sixty‐six per cent of patients had a transsphincteric fistula and 60% had undergone a previous surgical intervention, mainly the insertion of a seton (54%). The majority had a cryptoglandular fistula. Operation time and follow‐up period were described for each study.

Conclusion

FiLaC™ seems to be an efficient therapeutic option for perianal fistula disease with an adequate level of safety that preserves quality of life. Nevertheless, randomized trials need to be designed to compare FiLaC™ with other procedures for the management of anal fistulas such as ligation of intersphincteric fistula tract, anal advancement flaps, fibrin glue, collagen paste, autologous adipose tissue, fistula plug and video‐assisted anal fistula treatment.
Comparative clinical study on microwave ablation combined with gemcitabine and cisplatin or combined with pemetrexed and cisplatin in treatment of advanced NSCLC
Authors: Zhang YingQing , Feng Yan , Wu YongLei , Zhou YingXin , Wang LinLan
Published: May 2020

Objective

Solving the limitations of single chemotherapy in the treatment of non‐small cell lung cancer (NSCLC).

Methods

About 100 patients with NSCLC treated in First Hospital of Jiaxing, Zhejiang from June 2016 to June 2018 were selected and randomly divided into MPC group and MGC group, with 50 cases in each group. The patients in MPC group were treated with microwave ablation (MWA) combined with PC while patients in MGC group were given MWA combined with gemcitabine plus cisplatin (GC). The therapeutic effects of the two groups as well as the complications and adverse reactions (ADRs) were observed and recorded.

Results

There was no significant difference in disease response rate (MPC group 33.3% vs MGC group 32.0%), disease control rate (MPC group 86.4% vs MGC group 78.0%) and overall survival (1‐, 2‐ and 3‐year survival, MPC group 65%, 59%, 32.7% vs MGC group 58%, 46%, 30%) between the two groups. In addition, the ADR myelosuppression was slighter in MPC group. There were 12 cases (23%) developed myelosuppression in the MPC group and 20 cases (42%) in MGC group, with a significant difference between the two groups (P < 0.05). The treatment was interrupted for 0 case (0%) in MPC group because of myelosuppression while 4 cases (8.3%) in MGC group.

Conclusion

The two therapeutic regimens have similar efficacy in treatment of advanced NSCLC, but MPC causes slighter myelosuppression and can be the first‐line therapy for advanced NSCLC.
The Protected Area Paradox and refugee species: The giant panda and baselines shifted towards conserving species in marginal habitats
Authors: Kerley Graham I. H. , te Beest Mariska , Cromsigt Joris P. G. M. , Pauly Daniel , Shultz Susanne
Published: May 2020

Paradoxically, despite the growth in protected areas globally, many species remain threatened and continue to decline. Attempts to conserve species in suboptimal habitats (i.e., as refugee species) may in part explain this Protected Area Paradox. Refugee species yield poor conservation outcomes as they suffer lower densities and fitness. We suggest that the giant panda may serve as an iconic example, reflecting the contraction and shift in the giant panda's range, diet and habitat use over the past 3,500 years, coinciding with increasing human pressure, and now maintained by conservation efforts, this due to shifted baselines. The global bias of protected area location to less productive habitats indicates that this problem may be widespread. We urgently need efforts to identify victims of refugee species status to allow improved conservation management globally, reducing the paradoxical outcomes of our conservation efforts.