bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel function for Rab proteins during maturation of secretory granules
Authors: Neuman Sarah D. , Lee Annika R. , Selegue Jane E. , Cavanagh Amy T. , Bashirullah Arash
Published: March 2021

Regulated exocytosis is an essential process whereby professional secretory cells synthesize and secrete specific cargo proteins in a stimulus-dependent manner. Cargo-containing secretory granules are synthesized in thetrans-GolgiNetwork (TGN); after budding from the TGN, granules undergo many modifications, including a dramatic increase in size. These changes occur during a poorly understood process called secretory granule maturation. Here we leverage the professional secretory cells of theDrosophilalarval salivary glands as a model system to characterize a novel and unexpected role for Rab GTPases during secretory granule maturation. We find that secretory granules in the larval salivary glands increase in size ~300-fold between biogenesis and release, and loss ofRab1orRab11dramatically reduces granule size. Surprisingly, we find that Rab1 and Rab11 protein localize to secretory granule membranes. Rab11 associates with granule membranes throughout the maturation process, and Rab11 is required for recruitment of Rab1. In turn, Rab1 associates specifically with immature secretory granules and drives granule growth. In addition to their roles in granule growth, bothRab1andRab11appear to have additional roles during exocytosis;Rab11function is necessary for exocytosis, while the presence ofRab1on immature granules may prevent precocious exocytosis. Overall, these results highlight a new and unexpected role for Rab GTPases in secretory granule maturation.
Organizing municipal audit: contracting out and audit costs in Norway
Authors: Johnsen Åge
Published: March 2021

Purpose

This paper analyses the deregulation of the municipal audit market in Norway, in particular how organization of the service affected audit costs.

Design/methodology/approach

The paper uses multiple regression analysis of administrative as well as survey data of organizational structure and audit costs from 312 municipalities in Norway in 2012.

Findings

The introduction of contracting out in the municipal audit market in Norway in 2004 contributed to a reduction in audit fees eight years after the deregulation, compared to the situation four years before the deregulation. The type of audit, mixing inter-municipal co-operation and contracting private auditors, was related to lower costs.

Research limitations/implications

The data does not include audit quality and are restricted to one country.

Practical implications

The municipalities that combined inter-municipal co-operation and contracting a private auditor achieved the lowest costs. Hence, neither pure in-house production (“make”) nor outsourcing (“buy”) but mixing several governance forms (hybrid organization) was related to low costs.

Social implications

Contracting out is a core element of new public management (NPM) but has often been a contested tool in public policy. This paper provides empirical evidence on the effects of a reform of a professional service, which is relevant for many services in the public sector.

Originality/value

This paper contributes by filling some of the gaps in the public sector accounting and public management reform literature by studying the organization and costs of the municipal audit, specifically by including transaction costs, addressing plural governance forms in addition to pure in-house production, inter-organizational co-operation and market contracting and by studying long-term effects.
Team social media usage and intra-team competition and cooperation: a social information processing perspective
Authors: Zhang Shuqin , Huang Qian , Liu Hefu , Wang Youying
Published: March 2021

Purpose

This study aims to explore how team task-related social media usage (TSMU) and social-related social media usage (SSMU) affect employees' perceptions of intra-team cooperation and competition and further individual creativity.

Design/methodology/approach

This study conducted a questionnaire survey on enterprises in China that have implemented social media and obtained 348 useable questionnaires from 55 work teams.

Findings

The results revealed that employees' perceptions of intra-team cooperation and competition can promote employees' creativity. Employees' cooperation perception can be significantly positively affected by TSMU and SSMU, whereas employees' competition perception can be significantly positively affected by TSMU. Regarding congruence, the results indicated that the more balanced between TSMU and SSMU, the stronger the competition perception.

Practical implications

Managers should pay critical attention to the role of team social media usage (SMU) in shaping employees' perceptions of their team environments. They should realize the different outcomes and the joint effects of the different types of SMU.

Originality/value

This study contributes to the social media literature by explaining the impact of team SMU on employees' perceptions and evaluations of team environments based on the social information processing theory. The study presents the relationships among team SMU, employees' perceptions of cooperation and competition and employee creativity. Moreover, this study expands research on the trade-off of SMU by exploring the impact of balanced and imbalanced SMU in a work team.
Tacrolimus dose, blood concentrations and acute nephrotoxicity, but not CYP3A5/ABCB1 genetics, are associated with allograft tacrolimus concentrations in renal transplant recipients
Authors: Sallustio Benedetta C. , Noll Benjamin D. , Hu Rong , Barratt Daniel T. , Tuke Jonathan , Coller Janet K. , Russ Graeme R. , Somogyi Andrew A.
Published: March 2021

Aims

Long‐term use of the immunosuppressant tacrolimus is limited by nephrotoxicity. Following renal transplantation, the risk of nephrotoxicity may be determined more by allograft than by blood tacrolimus concentrations, and thus may be affected by donor CYP3A5 and ABCB1 genetics. Little is known regarding factors that determine tacrolimus intrarenal exposure.

Methods

This study investigated the relationship between trough blood (C0Blood) and allograft (CGraft) tacrolimus concentrations and tacrolimus dose, haematocrit, genetics, acute nephrotoxicity, rejection status, delayed graft function, and time post‐transplant. C0Blood and CGraft were quantified in 132 renal transplant recipients together with recipient and donor CYP3A5 (rs776746) and ABCB1 3435 (rs1045642) genotypes.

Results

C0Blood ranged from 2.6 to 52.3 ng/mL and CGraft from 33 to 828 pg/mg tissue. Adjusting for dose, recipients who were CYP3A5 expressors had lower C0Blood compared to nonexpressors, whilst delayed graft function was associated with higher C0Blood. Linear regression showed that the significant predictors of CGraft were C0Blood (point‐wise P = 7 × 10−10), dose (P = .004) acute nephrotoxicity (P = .002) and an interaction between C0Blood and acute tacrolimus nephrotoxicity (P = .0002), with an adjusted r2 = 0.35 and no contribution from donor or recipient CYP3A5 or ABCB1 genotype. The association between CGraft and acute nephrotoxicity depended on one very high CGraft (828 pg/mg tissue).

Conclusions

Recipient and donor CYP3A5 and ABCB1 3435C>T genotypes are not determinants of allograft tacrolimus exposure in kidney transplant recipients. However, tacrolimus dose and C0Blood were significant predictors of CGraft, and the relationship between C0Blood and CGraft appeared to differ in the presence or absence of acute nephrotoxicity.
Spliced HLA-bound peptides: a Black Swan event in immunology
Authors: Faridi P , Dorvash M , Purcell A W
Published: March 2021

Peptides that bind to and are presented on the cell surface by human leucocyte antigen (HLA) molecules play a critical role in adaptive immunity. For a long time it was believed that all the HLA-bound peptides were generated through simple proteolysis of linear sequences of cellular proteins, and therefore are templated in the genome and proteome. However, evidence for untemplated peptide ligands of HLA molecules has accumulated during the last two decades, with a recent global analysis of HLA-bound peptides suggesting that a considerable proportion of HLA-bound peptides are potentially generated through splicing/fusion of discontinuous peptide segments from one or two distinct proteins. In this review, we will evaluate recent discoveries and debates on the contribution of spliced peptides to the HLA class I immunopeptidome, consider biochemical rules for splicing and the potential role of these spliced peptides in immune recognition.
The longitudinal relationship between cannabis use and hypertension
Authors: Haleem Ahmed , Hwang Yoseob Joseph , Elton‐Marshall Tara , Rehm Jürgen , Imtiaz Sameer
Published: March 2021

Introduction

The relationship between cannabis use and hypertension is not clear based on prior epidemiological studies. Thus, we examined this relationship over a 3‐year follow‐up period using a large population‐based sample from the USA.

Methods

Self‐reported longitudinal data were obtained from the National Epidemiologic Survey on Alcohol and Related Conditions Wave 1 (2001/2002) and Wave 2 (2004/2005). The sample was restricted to participants who did not report hypertension at baseline (n = 26 844; 51% 40 years and older, 51% female, 71% white). χ2‐tests were used to examine the distributions of confounders stratified by the incidence of hypertension. Thereafter, multiple logistic regression analyses were conducted to quantify the relationships between lifetime cannabis use, 12‐month cannabis use and 12‐month cannabis use frequency and incidence of hypertension while adjusting for confounders.

Results

Cannabis use was associated with a decreased incidence of hypertension in the unadjusted analyses. However, the relationships were confounded by age. After adjustment for all confounders, neither lifetime cannabis use (odds ratio, 95% confidence interval 0.89, 0.77 to 1.02), 12‐month cannabis use (0.78, 0.56 to 1.09) nor 12‐month cannabis use frequency [at least monthly use (0.85, 0.57 to 1.28) and less than monthly use (0.67, 0.40 to 1.11)] were associated above chance with the incidence of hypertension.

Discussion and Conclusions

Lifetime cannabis use, 12‐month cannabis use and 12‐month cannabis use frequency were not associated with the incidence of hypertension.
Hauling up a hefty meal: Long‐Jawed spider (Araneae, Tetragnathidae) uses silk lines to transport large prey vertically through the air in the absence of a web
Authors: Gould John
Published: March 2021

The most well‐known use of silk among spiders is the formation of webs to capture flying prey. However, spiders have evolved many different foraging strategies involving silk, including the capture and subsequent manipulate of prey prior to consumption. Herein, I report on the use of silk lines by a long‐jawed spider from the Tetragnatha genus to move a large prey item vertically through the air. Field observations revealed a long‐jawed spider attaching multiple silk lines across the body of an adult dragonfly that had recently emerged from its final moult and attaching these threads to overlying vegetation to incrementally haul the prey item from the surface of a waterbody. My observations suggest that some Tetragnatha spiders are able to move large prey items that are much heavier then themselves using a series of silk lines that allow lift to be accomplished in a gradual and controlled manner. This is an interesting finding, given that other individuals from the same population were using web structures to passively catch much smaller, flying prey. This indicates that some Tetragnatha spiders not only participate in the mobile pursuit of prey but that they possess multiple foraging strategies that may allow them to exploit a larger number of prey types.
Reservoir fertilisation and fishery response in a highly managed reservoir with uncertain flows: Ecosystem‐based management using decision analysis
Authors: Woodruff Patricia , van Poorten Brett T. , Christensen Villy , Walters Carl J.
Published: March 2021

Inland fisheries managers must account for multiple competing uses for aquatic resources; using methods such as ecosystem‐based management allows for different priorities for aquatic ecosystems to be accounted for. Declining abundance of kokanee salmon Oncorhynchus nerka (Walbaum) in Arrow Lakes Reservoir in the 1990s led to the use of large‐scale nutrient addition to improve productivity of kokanee and large piscivores. However, it is unclear what effect these measures had on the system given high discharge and highly variable annual flow regime throughout the watershed. An Ecopath with Ecosim model of the ecosystem was fitted to the available data and used to predict ecosystem structure and reservoir objectives under different nutrient addition strategies and varying annual flow regimes. Results from the model indicate that nutrient addition is an important driver in the system, with lower flows resulting in higher biomass for higher trophic levels. Decision analysis demonstrated the importance of maintaining nutrient additions to achieve management objectives despite losses in some high‐flow years.
Effect of sonication on microwave inactivation of Escherichia coli in an orange juice beverage
Authors: Kernou Ourdia‐Nouara , Belbahi Amine , Amir Akila , Bedjaoui Kenza , Kerdouche Kamelia , Dairi Sofiane , Aoun Omar , Madani Khodir
Published: March 2021

The survival of Escherichia coli ATCC 25922 in orange juice treated with microwave and/or ultrasound was evaluated; Weibull model was fitted to survival curves to describe inactivation kinetics; and the effect of combined microwave‐ultrasound treatments was assessed. Ultrasonic treatment (42 kHz) has no significant effect on the survival rate reduction (1.3 log for 60 min of sonication) of E. coli. However, sonication can increase the efficiency of microwave inactivation. The use of ultrasound as pre‐treatment was more effective than when used in post‐treatment, that is, a reduction of 8.0 log was achieved by a combination of ultrasound (20 min) followed by a microwave (900 W/30 s), while 4.0 log was obtained when these both processes were reversed. The scale parameter α estimated from microwave‐inactivation kinetics combined with an ultrasound pre‐treatment was found to be lower than those obtained with a post‐treatment, which, in turn, are lower than those estimated for microwave or ultrasound alone. These results demonstrate the effectiveness of ultrasound as a pre‐treatment to improve the inactivation of E. coli by microwave processing in orange juice beverages.

Practical applications

High‐temperature short‐time (HTST) type processes are preferred by the food industry to reduce the adverse thermal degradation in food quality while ensuring food safety for liquid food. The microwave heating is fast and can significantly reduce the come‐up time to the desired process temperature. The hydrodynamic action of ultrasound on microorganisms is a great potential to improve microbial decontamination efficiency by microwave processing. This study contributes to the design and control of an effective combination treatment of ultrasound and microwave to improve pasteurization processes for orange juice beverages.
GENDER DIVERSITY IN RESEARCH TEAMS AND CITATION IMPACT IN ECONOMICS AND MANAGEMENT
Authors: Maddi Abdelghani , Gingras Yves
Published: March 2021

The aim of this paper is twofold: (1) contribute to a better understanding of the place of women in Economics and Management disciplines by characterizing the difference in levels of scientific collaboration between men and women at the specialties’ level; and (2) investigate the relationship between gender diversity and citation impact in Economics and Management. Our data, extracted from the Web of Science database, cover global production as indexed in 302 journals in Economics and 370 journals in Management, with, respectively, 153,667 and 163,567 articles published between 2008 and 2018. Results show that collaborative practices between men and women are quite different in Economics and Management. We also find that there is a modest positive and significant effect of gender diversity on the citation impact of publications. Mixed‐gender publications (coauthored by men and women) receive more citations than nonmixed papers (written by same‐gender author teams) or single‐author publications. The regression analysis also indicates that there is, for Economics, a small negative effect on citations received if the corresponding author is a woman. Finally, the country (affiliation) of the corresponding author affects the citations received in the two disciplines.
National level adjustments to the challenges of the SARS‐CoV2 pandemic on blood banking operations
Authors: Matusovits Andrea , Nagy Sándor , Baróti‐Tóth Klára , Nacsa János , Lázár Mária , Marton Imelda , Andrikovics Hajnalka , Vokó Zoltan , Tordai Attila
Published: March 2021

Background

SARS‐CoV2 causing coronavirus disease (COVID‐19) is responsible for an unprecedented worldwide pandemic severely affecting all activities of societies including blood banking. We aimed to systematically collect key indicators in a nationally centralized blood banking system and to perform comparisons between 2020 and 2019.

Methods

Count data for January–December 2020 and 2019 were extracted from the integrated informatics system of Hungarian National Blood Transfusion Service and analyzed by simple graphics, tabulations, and statistics.

Results

Whole blood donation activity showed a highly significant decline due to a sharp decrease in field donations by an average fall of 24% (range:17%–28%) during March–May 2020 compared to identical period of 2019. A second, more moderate decline accompanied the second wave in late fall. The simultaneous increase in institutional donations did not counterbalance this decline. Donor exclusion rates fell significantly by an average of 1,1% (range:0.9%–1.6%) in the three spring lockdown‐affected months. First‐time and repeat donors showed decreased turn‐out in larger proportions compared to highly repeat donors. Interestingly, among repeat and highly repeat donors, females showed less‐pronounced declines compared to males while this was not observed among first‐time donors. In June–September, a remarkable swing‐back was observed among highly repeat female donors. Product utilization fell most notably for RBC (mean:26.2%) but also for PLT (mean:19.8%) and FFP (mean:24.3%) and showed a full recovery in June–September followed by a second decline.

Conclusion

Trends and reaction patterns of blood banking reported by our study may be useful in future planning and adjustments of blood banking activities.
Demonstration to Show Resonant Oscillations of a Simple Pendulum Coupled to a Mass-Spring Oscillator
Authors: Baker Blane , Park Sungjune
Published: March 2021

Resonance is a widely observed physical phenomenon, occurring when an oscillator experiences a driving force whose frequency closely matches one of its own natural frequencies. Due to its broad applicability in physics, resonance is a familiar topic in the physics teaching literature. Previous studies include resonant energy transfer between similar mechanical systems such as coupled pendulums, resonant oscillations of wine glasses driven by sound waves, and resonance in AC circuits. Moreover, special drivers have been constructed to produce resonant oscillations of a variety of mechanical systems.
Projectile Motion: The “Coming and Going” Phenomenon
Authors: Ribeiro Williams J. M. , Sousa J. Ricardo de
Published: March 2021

During elementary physics courses, many examples in mechanics are studied without considering air resistance effects. We can mention, for example, projectile motion and free fall, among many others. Only brief studies of such systems in classical mechanics courses consider linear air resistance (Fdrag ∝ v), which is the simplest model to account for the drag effect by modeling objects moving in viscous media with small velocities (more precisely, small Reynolds number). Quadratic air resistance (Fdrag ∝ v2), which applies for objects moving in resistive media with high velocities (high Reynolds number), is hardly mentioned, but it can be found in many papers. However, in nature air resistance plays a big role in the motion of bodies and so it must be included when studying any kind of phenomena related to mechanics.
Introducing the Future Circular Collider (FCC) into Secondary Classrooms
Authors: Cid-Vidal Xabier , Cid Ramon , Cliff Harry Victor
Published: March 2021

This article presents some simple calculations related to the Future Circular Collider (FCC), which is being studied at CERN as a potential future replacement for the world’s largest particle accelerator, the Large Hadron Collider (LHC). The aim of this article is to bring particle physics into secondary school classrooms using the physics of the FCC. This article presents some methods to calculate some of the accelerator’s important parameters. In this way, it is possible to explore a range of physical concepts and to introduce one of the most relevant research projects in science today.
An Arduino-Based Experiment Designed to Investigate Gas Pressure
Authors: Salar Riza
Published: March 2021

This study aims to showcase an experiment for introductory physics students that quantitatively describes the relationship between gas pressure, volume, and temperature. For this purpose, an Arduino Uno Microcontroller and BMP180 pressure sensor are used. The BMP180 can also measure temperature, so another temperature sensor is not needed. Pressure-volume and pressure-temperature graphs are plotted with the experimental setup using cheap and easily accessible materials. It can be seen that the drawn graphs correspond well to the theory. It is hoped that this experimental setup can be used by teachers in STEM activities, especially for physics courses.
Misconceptions Arising From the Infinite Solenoid Magnetic Field Formula
Authors: Wilson Marcus T.
Published: March 2021

Many high school and first-year university courses include discussion of the magnetic effect of currents. Frequently discussed textbook examples include long, straight wires, circular current loops, and solenoids, partly because these examples are tractable mathematically. The solenoid naturally leads to discussion on magnetic materials since it is readily demonstrated that a paramagnetic core significantly boosts the strength of an electromagnet. However, magnetic effects of solid and even liquid materials are subtle and confusing and the mathematics is not straightforward. This leads to confusion amongst students (and their teachers), which, when taken to more advanced study, leads to significant misconceptions about the nature of magnetic properties and fields. These misconceptions can become problematic when practical (rather than stereotyped) magnetic design and analysis is required such as for transformers, magnetic recording materials, geomagnetic sensors, or biological stimulators to name a few. In this article, I highlight examples of this confusion, in particular the failure in realistic situations of the well-quoted formula for an infinite solenoid with a paramagnetic core, and the physical interpretation of the relative permeability of a material, µr.
Determination of gravity acceleration with smartphone ambient light sensor
Authors: Silva-Alé Jhon Alfredo
Published: March 2021

Among the serious experimental uses given to smartphones in physics, the use of integrated sensors, video analysis, and mixed uses as simultaneous material and instruments stand out for their frequency. Regarding the use of integrated sensors, there are many proposals that use the accelerometer, the magnetometer, or other sensors (e.g, camera or microphone) to find experimental values of physical constants, such as acceleration of gravity (g), thereby trying to contribute to the studies of statics, kinematics, and dynamics. However, there are few studies that use the ambient light sensor for this kind of purpose.
Targeting a neoantigen derived from a common
TP53
mutation
Authors: Hsiue Emily Han-Chung , Wright Katharine M. , Douglass Jacqueline , Hwang Michael S. , Mog Brian J. , Pearlman Alexander H. , Paul Suman , DiNapoli Sarah R. , Konig Maximilian F. , Wang Qing , Schaefer Annika , Miller Michelle S. , Skora Andrew D. , Azurmendi P. Aitana , Murphy Michael B. , Liu Qiang , Watson Evangeline , Li Yana , Pardoll Drew M. , Bettegowda Chetan , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Gabelli Sandra B. , Zhou Shibin
Published: March 2021

Turning a tumor suppressor into a target

Tumor-suppressor genes such as
TP53
(tumor protein P53) play key roles in the pathogenesis of cancer but, unfortunately, they are difficult to target because they do not create an overactive protein that can be inhibited with a drug. Hsiue
et al.
discovered a way to target a cancer-associated mutant form of the p53 protein using the body's own immune system (see the Perspective by Weidanz). The authors identified a distinct fragment of this mutant protein, characterized the structural basis for its presentation to T cells, and designed a bispecific antibody to stimulate T cell killing of p53-mutant cancer cells.

Science
, this issue p.
eabc8697
; see also p.
996
Targeting cancer with bispecific antibodies
Authors: Weidanz Jon
Published: March 2021

Bispecific antibodies might provide off-the-shelf immunotherapeutics for treating cancer
Changes in Cell Size and Shape during 50,000 Generations of Experimental Evolution with Escherichia coli
Authors: Grant Nkrumah A. , Abdel Magid Ali , Franklin Joshua , Dufour Yann , Lenski Richard E.
Published: March 2021

Bacteria exhibit great morphological diversity, yet we have only a limited understanding of how their cell sizes and shapes evolve and of how these features affect organismal fitness. This knowledge gap reflects, in part, the paucity of the fossil record for bacteria.
Introduction of Two Prolines and Removal of the Polybasic Cleavage Site Lead to Higher Efficacy of a Recombinant Spike-Based SARS-CoV-2 Vaccine in the Mouse Model
Authors: Amanat Fatima , Strohmeier Shirin , Rathnasinghe Raveen , Schotsaert Michael , Coughlan Lynda , García-Sastre Adolfo , Krammer Florian
Published: March 2021

A vaccine for SARS-CoV-2 is urgently needed. A better understanding of antigen design and attributes that vaccine candidates need to have to induce protective immunity is of high importance. The data presented here validate the choice of antigens that contain the PP mutations and suggest that deletion of the polybasic cleavage site may lead to a further-optimized design.
Evaluating the health effect of a Social Housing programme, Minha Casa Minha Vida, using the 100 million Brazilian Cohort: a natural experiment study protocol
Authors: Ferreira Andrêa J F , Pescarini Julia , Sanchez Mauro , Flores-Ortiz Renzo Joel , Teixeira Camila Silveira , Fiaccone Rosemeire , Ichihara Maria Yury , Oliveira Rodrigo , Aquino Estela M L , Smeeth Liam , Craig Peter , Ali Sanni , Leyland Alastair H , Barreto Mauricio L , Ribeiro Rita de Cássia , Katikireddi Srinivasa Vittal
Published: March 2021

Introduction

Social housing programmes have been shown to influence health, but their effects on cardiovascular mortality and incidence of infectious diseases, such as leprosy and tuberculosis, are unknown. We will use individual administrative data to evaluate the effect of the Brazilian housing programme Minha Casa Minha Vida (MCMV) on cardiovascular disease (CVD) mortality and incidence of leprosy and tuberculosis.

Methods and analysis

We will link the baseline of the 100 Million Brazilian Cohort (2001–2015), which includes information on socioeconomic and demographic variables, to the MCMV (2009–2015), CVD mortality (2007–2015), leprosy (2007–2015) and tuberculosis (2007–2015) registries. We will define our exposed population as individuals who signed the contract to receive a house from MCMV, and our non-exposed group will be comparable individuals within the cohort who have not signed a contract for a house at that time. We will estimate the effect of MCMV on health outcomes using different propensity score approaches to control for observed confounders. Follow-up time of individuals will begin at the date of exposure ascertainment and will end at the time a specific outcome occurs, date of death or end of follow-up (31 December 2015). In addition, we will conduct stratified analyses by the follow-up time, age group, race/ethnicity, gender and socioeconomic position.

Ethics and dissemination

The study was approved by the ethic committees from Instituto Gonçalo Muniz-Oswaldo Cruz Foundation and University of Glasgow Medical, Veterinary and Life Sciences College. Data analysis will be carried out using an anonymised dataset, accessed by researchers in a secure computational environment according to the Centre for Integration of Data and Health Knowledge procedures. Study findings will be published in high quality peer-reviewed research journals and will also be disseminated to policy makers through stakeholder events and policy briefs.
Development of a genomic predictive model for cholangiocarcinoma using copy number alteration data
Authors: Tavares Inês , Martins Ricardo , Ribeiro Ilda Patrícia , Esteves Luísa , Caramelo Francisco , Abrantes Ana Margarida , Neves Rita , Caetano-Oliveira Rui , Botelho Maria Filomena , Barbosa de Melo Joana , Diogo Dulce , Tralhão José Guilherme , Carreira Isabel Marques
Published: March 2021

Aims

Cholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma.

Methods

DNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed.

Results

With these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3–22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC.

Conclusions

This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.
Clinicopathological differences in attached versus loose infarcted epiploic appendages: an analysis of 52 cases
Authors: Dignan Caroline , Senior Adya , Gonzalez Raul S
Published: March 2021

Background

Epiploic appendages are fatty peritoneal structures on the external surface of the colon that can infarct and become necrotic in situ or autoamputate.

Aims

To describe clinicopathological features of infarcted epiploic appendages (IEAs).

Methods

We reviewed 52 IEAs from 49 patients, recording numerous clinical and pathological characteristics, which were compared across attached and loose IEAs.

Results

Twenty-seven IEAs were attached, and 23 were loose; location was unclear in 2. Most were incidental; 3 attached cases caused ‘appendagitis’. Most (31, 60%) had a classic ‘egg-like’ appearance. Common findings included fat necrosis (84%), calcification (67%) and fibrosis (58%). Attached cases had a larger mean size (1.8 cm vs 1.3 cm, p=0.030) and were more often haemorrhagic (37% vs 4%, p=0.0064) and inflamed (67% vs 13%, p=0.0002). Loose cases were more often necrotic (100% vs 74%, p=0.011).

Conclusions

IEAs have different morphology whether they remain attached to peritoneum or become necrotic and detached. Attached cases may cause symptoms.
Performance evaluation of a fully closed real-time PCR platform for the detection of KRAS p.G12C mutations in liquid biopsy of patients with non-small cell lung cancer
Authors: Gragnano Gianluca , Nacchio Mariantonia , Sgariglia Roberta , Conticelli Floriana , Iaccarino Antonino , De Luca Caterina , Troncone Giancarlo , Malapelle Umberto
Published: March 2021

Whenever tissue sample is not available, non-small cell lung cancer (NSCLC) biomarker testing is performed with liquid biopsy. The Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is a novel target in patients with NSCLC. In this study, 33 NSCLC frozen plasma samples, previously characterised forKRASmutational status by next generation sequencing (NGS), were processed by the fully automated IdyllaKRASassay. In 30/33 cases, archival matched cell-free DNA (cfDNA) was also directly pipetted in the cartridge. Overall, 30/33 plasma and 28/30 cfDNA samples yielded valid results. In 29/30 ofKRASp.G12C mutant plasma samples and 26/28 of cfDNA, Idylla confirmed the NGS results. In conclusion, the Idylla NSCLCKRASliquid biopsy assay may represent a reliable tool to assessKRASp.G12C mutation.
Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management
Authors: Abboud Hesham , Probasco John C , Irani Sarosh , Ances Beau , Benavides David R , Bradshaw Michael , Christo Paulo Pereira , Dale Russell C , Fernandez-Fournier Mireya , Flanagan Eoin P , Gadoth Avi , George Pravin , Grebenciucova Elena , Jammoul Adham , Lee Soon-Tae , Li Yuebing , Matiello Marcelo , Morse Anne Marie , Rae-Grant Alexander , Rojas Galeno , Rossman Ian , Schmitt Sarah , Venkatesan Arun , Vernino Steven , Pittock Sean J , Titulaer Maarten J
Published: March 2021

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management
Authors: Abboud Hesham , Probasco John , Irani Sarosh R , Ances Beau , Benavides David R , Bradshaw Michael , Christo Paulo Pereira , Dale Russell C , Fernandez-Fournier Mireya , Flanagan Eoin P , Gadoth Avi , George Pravin , Grebenciucova Elena , Jammoul Adham , Lee Soon-Tae , Li Yuebing , Matiello Marcelo , Morse Anne Marie , Rae-Grant Alexander , Rojas Galeno , Rossman Ian , Schmitt Sarah , Venkatesan Arun , Vernino Steven , Pittock Sean J , Titulaer Maarten
Published: March 2021

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
Hospital admissions for stroke and bleeding in Hounslow following a quality improvement initiative
Authors: Wong Kam Ying , Davies Bethan , Adeleke Yewande , Woodcock Thomas , Matthew Dionne , Sekelj Sara , Orlowski Andi , Porter Bradley , Hashmy Sophia , Mathew Ammu , Grant Ron , Kaba Agnes , Unger-Graeber Brigitte , Petrungaro Bruno , Wallace Jordan , Bell Derek , Cowie Martin R , Khan Sadia
Published: March 2021

Objective

Atrial fibrillation (AF) is the most common arrhythmia. Undiagnosed and poorly managed AF increases risk of stroke. The Hounslow AF quality improvement (QI) initiative was associated with improved quality of care for patients with AF through increased detection of AF and appropriate anticoagulation. This study aimed to evaluate whether there has been a change in stroke and bleeding rates in the Hounslow population following the QI initiative.

Methods

Using hospital admissions data from January 2011 to August 2018, interrupted time series analysis was performed to investigate the changes in standardised rates of admission with stroke and bleeding, following the start of the QI initiative in October 2014.

Results

There was a 17% decrease in the rate of admission with stroke as primary diagnosis (incidence rate ratio (IRR) 0.83; 95% CI 0.712 to 0.963; p<0.014). There was an even larger yet not statistically significant decrease in admission with stroke as primary diagnosis and AF as secondary diagnosis (IRR 0.75; 95% CI 0.550 to 1.025; p<0.071). No significant changes were observed in bleeding admissions. For each outcome, an additional regression model including both the level change and an interaction term for slope change was created. In all cases, the slope change was small and not statistically significant.

Conclusion

Reduction in stroke admissions may be associated with the AF QI initiative. However, the immediate level change and non-significant slope change suggests a lack of effect of the intervention over time and that the decrease observed may be attributable to other events.
Surface terms in effective action of O-plane at order $$\alpha '^2$$
Authors: Akou Yasser , Garousi Mohammad R.
Published: March 2021

The effective action of string theory has both bulk and boundary terms if the spacetime is an open manifold. Recently, the known classical effective action of string theory at the leading order of $$\alpha '$$

α
′

and its corresponding boundary action have been reproduced by constraining the effective actions to be invariant under gauge transformations and under string duality transformations. In this paper, we use this idea to find the classical effective action of the O-plane and its corresponding boundary terms in type II superstring theories at order $$\alpha '^2$$

α

′
2

and for NS–NS couplings. We find that these constraints fix the bulk action and its corresponding boundary terms up to one overall factor. They also produce three multiplets in the boundary action that their coefficients are independent of the bulk couplings under the string dualities.
LOW FREQUENCY PROPERTY OF A FRACTAL VIBRATION MODEL FOR A CONCRETE BEAM
Authors: HE CHUN-HUI , LIU CHAO , HE JI-HUAN , GEPREEL KHALED A.
Published: March 2021

A concrete beam is a basic element for many applications in architectural engineering, and its vibration property plays an important role in safety and life-span. Previous vibration models were based on continuum beam theories, which could not take into account the porous property of the concrete beam. This paper adopts a two-scale fractal vibration model, and its low frequency property is revealed. This new finding can explain the vibration attenuation and vibration absorption of the porous concrete, and the present theory sheds a new light on the concrete design.
GENERALIZED KOCH CURVES AND THUE–MORSE SEQUENCES
Authors: LI YAO-QIANG
Published: March 2021

Let [Formula: see text] be the well-known [Formula: see text] Thue–Morse sequence [Formula: see text] Since the 1982–1983 work of Coquet and Dekking, it is known that [Formula: see text] is strongly related to the famous Koch curve. As a natural generalization, for [Formula: see text], we use [Formula: see text] to define the generalized Koch curve, where [Formula: see text] is the generalized Thue–Morse sequence defined to be the unique fixed point of the morphism [Formula: see text] [Formula: see text] beginning with [Formula: see text] and [Formula: see text], and we prove that generalized Koch curves are the attractors of the corresponding iterated function systems. For the case that [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], the open set condition holds, and then the corresponding generalized Koch curve has Hausdorff, packing and box dimension [Formula: see text], where taking [Formula: see text] and then [Formula: see text] will recover the result on the classical Koch curve.
ASSESSMENT OF FRACTAL DIMENSION AND PANORAMIC RADIOMORPHOMETRIC INDICES IN CRACK–COCAINE-ADDICTED MEN: A CROSS-SECTIONAL STUDY
Authors: ARAUJO NARA SANTOS , OLIVEIRA MARIA DAS GRAÇAS ALONSO , SANTOS JEAN NUNES DOS , NEVES FREDERICO SAMPAIO , CRUSOÉ-REBELLO IEDA M. , CURY PATRICIA RAMOS
Published: March 2021

The impact of crack–cocaine dependence on the quality and microarchitecture of the mandibular bone tissue requires further investigation. This cross-sectional study evaluated the fractal dimension and panoramic radiomorphometric indices in crack–cocaine-addicted men. Panoramic radiographs were obtained from 24 addicted and 24 nonaddicted men (control individuals) between the ages of 18 years and 60 years. The fractal dimensions of four different regions, along with the cortical mandibular, mental, and panoramic mandibular indices, were evaluated bilaterally. Significance level of 5% ([Formula: see text]) was adopted in the statistical analysis. Mean fractal dimension value of all the four different regions of the jaw in the addict group ([Formula: see text]) was lower than that of the nonaddict group ([Formula: see text]; [Formula: see text]). Furthermore, the inter-group panoramic radiomorphometric indices were not significantly different ([Formula: see text]). Mean fractal dimension value was associated with the duration of addiction ([Formula: see text]; [Formula: see text]), contrary to the indices ([Formula: see text]). Crack–cocaine addiction and longer duration of addiction were associated with lower fractal dimension values in the mandibular bone. Therefore, patients and dentists should be aware of this condition while planning periodontal, implant, and orthodontic therapies. Furthermore, crack–cocaine patients should be referred to a specialist for the evaluation of osteoporosis and osteopenia.
One-Step Memory Random Walk on Complex Networks: An Efficient Local Navigation Strategy
Authors: Cao Xinxin , Wang Yan , Li Cheng , Weng Tongfeng , Yang Huijie , Gu Changgui
Published: March 2021

We propose one-step memory random walk on complex networks for which at each time step, the walker will not be allowed to revisit the last position. Mean first passage time is adopted to quantify its search efficiency and a procedure is provided for calculating it analytically. Interestingly, we find that in the same circumstance, one-step memory random walk usually takes less time than random walk for finding a target given in advance. Furthermore, this navigation strategy presents a better performance even in comparison with corresponding optimal biased random walk when moving on networks without small-world effect. Our findings are confirmed on two canonical network models and a number of real networks. Our work reveals that one-step memory random walk is an efficient local search strategy, which can be applied to transportation and information spreading.
Corrosion of Ni-Fe-Cr-Mo-W-X Multi-Principal Element Alloys
Authors: Panindre A. M. , Khalifa Y. , Taylor C. D. , Frankel G. S.
Published: March 2021

An extraordinarily corrosion-resistant non-equimolar high entropy alloy with the composition Ni38Fe20Cr21Mo6W2Ru13 (referred to here as MPEA1) has been reported. Ruthenium is one important reason why the alloy exhibits excellent passivity and resistance to localized corrosion in a variety of environments. The goal of this study was to replace Ru in MPEA1 with commodity elements such as Mn, Al and Cu while minimizing the penalty on corrosion performance. Thermodynamic calculations were performed to survey the phase diagram for a stable disordered face centered cubic (fcc) phase at elevated temperatures. Five test compositions analogous to MPEA1 were conceptualized based on this design strategy. In two of these candidate alloys, the Ru content was substituted wholly by additional Fe or Ni. The other three contain Mn, Al, or Cu, respectively. Corrosion performance and passive behavior of these alloys in 0.6 M NaCl and 6 M HCl were evaluated using cyclic potentiodynamic polarization and single-frequency impedance experiments. Solutionized forms of all five alloys were found to resist localized corrosion in 0.6 M NaCl. Despite forming oxide films of similar thickness in 0.6 M NaCl solutions, X-ray photoelectron spectroscopy revealed non-congruent dissolution of constituent elements. The role of alloying elements in influencing the oxide formation process was indicated.
In Situ X-ray Tomography Observations of Initiation and Propagation of Pits During Atmospheric Corrosion of Aluminium Alloy AA2024
Authors: Glanvill Sarah J. M. , du Plessis Andrew , Street Steven R. , Rayment Trevor , Davenport Alison J.
Published: March 2021

In-situ synchrotron X-ray tomography has been used to observe the initiation and propagation of pits during atmospheric corrosion of aluminium alloy AA2024 under droplets of NaCl and simulated seawater at 21 ± 2 °C and a relative humidity of 85% over a period of 120 min. Each complete tomogram took 300 s to collect (pixel size 0.74 μm). Two metastable pits initiated at intermetallic particles, forming a crevice around the edge of the particles. Three other metastable pits formed at sites with no obvious micron-sized features. Only one pit, which had initiated under a fragment of debris, continued to stable growth. Metastable pits initiated sequentially, and all initiation events were accompanied by the formation of one or more bubbles, presumed to be hydrogen. Pit propagation was spatially non-uniform, with rapid growth in local regions while the remainder of the pit remained passive. The growth rate was highest parallel to the rolling direction of the plate. The highest local current density was estimated from the loss of metal between successive measurements to be ∼0.5 A cm−2. This is the first time that the transition from initiation to propagation of individual localised pits in an aluminium alloy has been characterised in situ.