bluuebunny/crossref_metadata_2025 huggingface dataset:
CEP290 is essential for the initiation of ciliary transition zone assembly
Authors: Wu Zhimao , Pang Nan , Zhang Yingying , Chen Huicheng , Peng Ying , Fu Jingyan , Wei Qing
Published: December 2020

Cilia play critical roles during embryonic development and adult homeostasis. Dysfunction of cilia leads to various human genetic diseases, including many caused by defects in transition zones (TZs), the “gates” of cilia. The evolutionarily conserved TZ component centrosomal protein 290 (CEP290) is the most frequently mutated human ciliopathy gene, but its roles in ciliogenesis are not completely understood. Here, we report that CEP290 plays an essential role in the initiation of TZ assembly inDrosophila. Mechanistically, the N-terminus of CEP290 directly recruits DAZ interacting zinc finger protein 1 (DZIP1), which then recruits Chibby (CBY) and Rab8 to promote early ciliary membrane formation. Complete deletion of CEP290 blocks ciliogenesis at the initiation stage of TZ assembly, which can be mimicked by DZIP1 deletion mutants. Remarkably, expression of the N-terminus of CEP290 alone restores the TZ localization of DZIP1 and subsequently ameliorates the defects in TZ assembly initiation incep290mutants. Our results link CEP290 to DZIP1-CBY/Rab8 module and uncover a previously uncharacterized important function of CEP290 in the coordination of early ciliary membrane formation and TZ assembly.
Multiobjective optimization identifies cancer-selective combination therapies
Authors: Pulkkinen Otto I. , Gautam Prson , Mustonen Ville , Aittokallio Tero
Published: December 2020

Combinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the search space spanned by the therapeutic and nonselective effects of combinations. We demonstrate the performance of the method in the context of BRAF-V600E melanoma treatment, where the optimal solutions predicted a number of co-inhibition partners for vemurafenib, a selective BRAF-V600E inhibitor, approved for advanced melanoma. We experimentally validated many of the predictions in BRAF-V600E melanoma cell line, and the results suggest that one can improve selective inhibition of BRAF-V600E melanoma cells by combinatorial targeting of MAPK/ERK and other compensatory pathways using pairwise and third-order drug combinations. Our mechanism-agnostic optimization method is widely applicable to various cancer types, and it takes as input only measurements of a subset of pairwise drug combinations, without requiring target information or genomic profiles. Such data-driven approaches may become useful for functional precision oncology applications that go beyond the cancer genetic dependency paradigm to optimize cancer-selective combinatorial treatments.
The ELAV/Hu protein Found in neurons regulates cytoskeletal and ECM adhesion inputs for space-filling dendrite growth
Authors: Alizzi Rebecca A. , Xu Derek , Tenenbaum Conrad M. , Wang Wei , Gavis Elizabeth R.
Published: December 2020

Dendritic arbor morphology influences how neurons receive and integrate extracellular signals. We show that the ELAV/Hu family RNA-binding protein Found in neurons (Fne) is required for space-filling dendrite growth to generate highly branched arbors ofDrosophilalarval class IV dendritic arborization neurons. Dendrites offnemutant neurons are shorter and more dynamic than in wild-type, leading to decreased arbor coverage. These defects result from both a decrease in stable microtubules and loss of dendrite-substrate interactions within the arbor. Identification of transcripts encoding cytoskeletal regulators and cell-cell and cell-ECM interacting proteins as Fne targets using TRIBE further supports these results. Analysis of one target, encoding the cell adhesion protein Basigin, indicates that the cytoskeletal defects contributing to branch instability infnemutant neurons are due in part to decreased Basigin expression. The ability of Fne to coordinately regulate the cytoskeleton and dendrite-substrate interactions in neurons may shed light on the behavior of cancer cells ectopically expressing ELAV/Hu proteins.
MreC and MreD balance the interaction between the elongasome proteins PBP2 and RodA
Authors: Liu Xiaolong , Biboy Jacob , Consoli Elisa , Vollmer Waldemar , den Blaauwen Tanneke
Published: December 2020

Rod-shape of most bacteria is maintained by the elongasome, which mediates the synthesis and insertion of peptidoglycan into the cylindrical part of the cell wall. The elongasome contains several essential proteins, such as RodA, PBP2, and the MreBCD proteins, but how its activities are regulated remains poorly understood. Using E. coli as a model system, we investigated the interactions between core elongasome proteins in vivo. Our results show that PBP2 and RodA form a complex mediated by their transmembrane and periplasmic parts and independent of their catalytic activity. MreC and MreD also interact directly with PBP2. MreC elicits a change in the interaction between PBP2 and RodA, which is suppressed by MreD. The cytoplasmic domain of PBP2 is required for this suppression. We hypothesize that the in vivo measured PBP2-RodA interaction change induced by MreC corresponds to the conformational change in PBP2 as observed in the MreC-PBP2 crystal structure, which was suggested to be the “on state” of PBP2. Our results indicate that the balance between MreC and MreD determines the activity of PBP2, which could open new strategies for antibiotic drug development.
Effect of harvest season on the nutritional value of bee pollen protein
Authors: Al-Kahtani Saad N. , Taha El-Kazafy , Khan Khalid Ali , Ansari Mohammad Javed , Farag Soha A. , Shawer Dalia M. B. , Elnabawy El-Said Mohamed
Published: December 2020

Bee pollen is a natural product that has valuable nutritional and medicinal characteristics and has recently garnered increasing attention in the food industry due to its nutritive value. Here, we harvested pollen loads from the Al-Ahsa oasis in eastern Saudi Arabia during spring, summer, autumn, and winter in 2018/2019 to compare the nutritional value of bee pollen protein with the amino acid requirements of honeybees and adult humans. Based on the nutritional value of bee pollen protein, the optimal season for harvesting bee pollen was determined. The composition of the bee pollen showed the highest contents of crude protein, total amino acids, leucine, glutamic acid, valine, isoleucine, threonine, and glycine in samples collected in spring. The highest contents of lysine, phenylalanine, threonine, tryptophan, arginine, tyrosine, and cysteine were observed in samples collected in winter. The highest contents of histidine, methionine, and serine were in samples collected in autumn. Moreover, the highest levels of aspartic acid, proline, and alanine were in samples collected in summer. Leucine, valine, lysine, histidine, threonine, and phenylalanine (except in autumn bee pollen) contents in pollen from all four seasons were above the requirements of honeybees. Leucine, valine, histidine, isoleucine (except in autumn bee pollen), lysine (except in spring and summer bee pollen), and threonine (except in winter and spring bee pollen) in all tested samples were above the requirements of adult humans. In comparison with the minimal amino acid requirements of adult humans and honeybees, the 1stlimiting amino acid in bee pollen collected during the different seasons was methionine. Bee pollen collected during spring (March–May) and winter (December–February) can be considered a nutritive food source for adult humans and honeybees.
Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma
Authors: Frias Sara , Van Hummelen Paul , Meistrich Marvin L. , Wyrobek Andrew J.
Published: December 2020

Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual’s burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.
Cooperation in the face of thresholds, risk, and uncertainty: Experimental evidence in fisher communities from Colombia
Authors: Rocha Juan C. , Schill Caroline , Saavedra-Díaz Lina M. , Moreno Rocío del Pilar , Maldonado Jorge Higinio
Published: December 2020

Cooperation is thought to be a necessary condition to solve collective action dilemmas such as climate change or the sustainable use of common pool resources. Yet, it is poorly understood how situations pervaded by thresholds shape the behaviour of people facing collective dilemmas. Here we provide empirical evidence that resource users facing thresholds maintain on average cooperative behaviours in the sense of maximising their individual earnings while ensuring future group opportunities. A framed field experiment in the form of a dynamic game with 256 Colombian fishers helped us investigate individual behavioural responses to the existence of thresholds, risk and uncertainty. Thresholds made fishers extract less fish compared to situation without thresholds, but risk had a stronger effect on reducing individual fishing effort. Contrary to previous expectations, cooperation did not break down. If cooperation can be maintained in the face of thresholds, then communicating uncertainty is more policy-relevant than estimating precisely where tipping points lay in social-ecological systems.
Ischemia and reperfusion injury to mitochondria and cardiac function in donation after circulatory death hearts- an experimental study
Authors: Akande Oluwatoyin , Chen Qun , Toldo Stefano , Lesnefsky Edward J. , Quader Mohammed
Published: December 2020

The ultimate treatment for patients with end-stage heart failure is heart transplantation. The number of donor hearts which are primarily procured from donation after brain death (DBD) donors is limited, but donation after circulatory death (DCD) donor hearts can increase the heart donor pool. However, ischemia and reperfusion injuries associated with the DCD process causes myocardial damage, limiting the use of DCD hearts in transplantation. Addressing this problem is critical in the exploration of DCD hearts as suitable donor hearts for transplantation. In this study, rat hearts were procured following the control beating-heart donor (CBD) or DCD donation process. Changes in mitochondria and cardiac function from DCD hearts subjected to 25 or 35 minutes of ischemia followed by 60 minutes of reperfusion were compared to CBD hearts. Following ischemia, rates of oxidative phosphorylation and calcium retention capacity were progressively impaired in DCD hearts compared to CBD hearts. Reperfusion caused additional mitochondrial dysfunction in DCD hearts. Developed pressure, inotropy and lusitropy, were significantly reduced in DCD hearts compared to CBD hearts. We, therefore, suggest that interventional strategies targeted before the onset of ischemia and at reperfusion could protect mitochondria, thus potentially making DCD hearts suitable for heart transplantation.
Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis
Authors: Cerdà Pau , Ribas Jesus , Iriarte Adriana , Mora-Luján José María , Torres Raquel , del Río Belén , Jofre Héctor Ignacio , Ruiz Yolanda , Huguet Marta , Fuset Mari Paz , Martínez-Yélamos Sergio , Santos Salud , Llecha Núria , Corbella Xavier , Riera-Mestre Antoni
Published: December 2020

Background

A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.

Methods

This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients.

Results

Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1–11208.9] vs 626.0 [374.0–2382.2]; p = 0.004); week 3 (3893.1 [1388.2–6694.0] vs 1184.4 [461.8–2447.8]; p = 0.003); and week 4 (2736.3 [1202.1–8514.1] vs 1129.1 [542.5–2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02–23.05] vs 1.57 [0.64–2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.

Conclusions

Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.
Occupational exposures and exacerbations of asthma and COPD—A general population study
Authors: Skaaby Stinna , Flachs Esben Meulengracht , Lange Peter , Schlünssen Vivi , Marott Jacob Louis , Brauer Charlotte , Nordestgaard Børge G. , Sadhra Steven , Kurmi Om , Bonde Jens Peter Ellekilde
Published: December 2020

Purpose

Recent studies suggest that occupational inhalant exposures trigger exacerbations of asthma and chronic obstructive pulmonary disease, but findings are conflicting.

Methods

We included 7,768 individuals with self-reported asthma (n = 3,215) and/or spirometric airflow limitation (forced expiratory volume in 1 second (FEV1)/ forced expiratory volume (FVC) <0.70) (n = 5,275) who participated in The Copenhagen City Heart Study or The Copenhagen General Population Study from 2001–2016. Occupational exposure was assigned by linking job codes with job exposure matrices, and exacerbations were defined by register data on oral corticosteroid treatment, emergency care unit assessment or hospital admission. Associations between occupational inhalant exposure each year of follow-up and exacerbation were assessed by Cox regression with time varying exposure and age as the underlying time scale.

Results

Participants were followed for a median of 4.6 years (interquartile range, IQR 5.4), during which 870 exacerbations occurred. Exacerbations were not associated with any of the selected exposures (high molecular weight sensitizers, low molecular weight sensitizers, irritants or low and high levels of mineral dust, biological dust, gases & fumes or the composite variable vapours, gases, dusts or fumes). Hazards ratios ranged from 0.8 (95% confidence interval: 0.7;1.0) to 1.2 (95% confidence interval: 0.9;1.7).

Conclusion

Exacerbations of obstructive airway disease were not associated with occupational inhalant exposures assigned by a job exposure matrix. Further studies with alternative exposure assessment are warranted.
Using enriched semantic event chains to model human action prediction based on (minimal) spatial information
Authors: Ziaeetabar Fatemeh , Pomp Jennifer , Pfeiffer Stefan , El-Sourani Nadiya , Schubotz Ricarda I. , Tamosiunaite Minija , Wörgötter Florentin
Published: December 2020

Predicting other people’s upcoming action is key to successful social interactions. Previous studies have started to disentangle the various sources of information that action observers exploit, including objects, movements, contextual cues and features regarding the acting person’s identity. We here focus on the role of static and dynamic inter-object spatial relations that change during an action. We designed a virtual reality setup and tested recognition speed for ten different manipulation actions. Importantly, all objects had been abstracted by emulating them with cubes such that participants could not infer an action using object information. Instead, participants had to rely only on the limited information that comes from the changes in the spatial relations between the cubes. In spite of these constraints, participants were able to predict actions in, on average, less than 64% of the action’s duration. Furthermore, we employed a computational model, the so-called enriched Semantic Event Chain (eSEC), which incorporates the information of different types of spatial relations: (a) objects’ touching/untouching, (b) static spatial relations between objects and (c) dynamic spatial relations between objects during an action. Assuming the eSEC as an underlying model, we show, using information theoretical analysis, that humans mostly rely on a mixed-cue strategy when predicting actions. Machine-based action prediction is able to produce faster decisions based on individual cues. We argue that human strategy, though slower, may be particularly beneficial for prediction of natural and more complex actions with more variable or partial sources of information. Our findings contribute to the understanding of how individuals afford inferring observed actions’ goals even before full goal accomplishment, and may open new avenues for building robots for conflict-free human-robot cooperation.
ACE2 polymorphisms as potential players in COVID-19 outcome
Authors: Khayat André Salim , de Assumpção Paulo Pimentel , Meireles Khayat Bruna Claudia , Thomaz Araújo Taíssa Maíra , Batista-Gomes Jéssica Almeida , Imbiriba Luciana Carvalho , Ishak Geraldo , de Assumpção Paula Baraúna , Moreira Fabiano Cordeiro , Burbano Rommel Rodriguez , Ribeiro-dos-Santos André , Ribeiro-dos-Santos Ândrea Kelly , dos Santos Ney Pereira Carneiro , dos Santos Sidney Emmanuel Batista
Published: December 2020

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.
Ethnic variation and the relevance of homozygous RNF 213 p.R4810.K variant in the phenotype of Indian Moya moya disease
Authors: K. Arun , Shafeeque C. M. , Sudhir Jayanand B. , Banerjee Moinak , P. N. Sylaja
Published: December 2020

Background and purpose

Polymorphisms in Ring Finger Protein 213 (RNF 213) gene have been detected to confer genetic susceptibility to Moya moya disease (MMD) in the East Asian population. We investigated the frequency of RNF 213 gene polymorphism and its association with MMD phenotypes in the Indian population.

Materials and methods

A case-control study for RNF 213 polymorphism involving 65 MMD patients, 75 parents, and 120 controls were performed. A total of 21 SNPs were screened, of which 17 SNPs were monomorphic. Allelic and genotypic frequency of all polymorphic SNPs were assessed and its association with MMD phenotypes was evaluated.

Results

The median age of symptom onset was 9 (range 2–17) and 37 years (range 20–58) in paediatric and adult patients respectively. A strong association was observed with RNF 213 rs112735431(p.R4810K) and MMD. Out of 65 patients with MMD, five patients carried the homozygous risk AA genotype. None of the healthy controls carried this homozygous mutation. The mutant allele was detected in MMD patients from Tamil Nadu and North eastern states of India (p = <0.0001). All the patients carrying the mutant allele had an early age of onset (p = <0.0001), higher incidence of bilateral disease (p = <0.002), positive family history (p = 0.03), higher Suzuki angiographic stage (≥3) (p<0.0006) and recurrent neurological events (ischemic strokes and TIAs) (p = <0.009).

Conclusion

The homozygous rs112735431(p.R4810K) variant in RNF 213 variant not only predicts the risk for MMD but can also predict the phenotypic variants.
Prevalence, vulnerability and epidemiological characteristics of snakebite in agricultural settings in rural Sri Lanka: A population-based study from South Asia
Authors: Jayawardana Subashini , Arambepola Carukshi , Chang Thashi , Gnanathasan Ariaranee
Published: December 2020

Background

The burden of snakebite remains poorly characterised because of the paucity of population-based data. Further, factors determining the vulnerability of individuals within rural communities to snakebite have been rarely investigated. We undertook a population-based study to determine the prevalence, vulnerability and epidemiological characteristics of snakebite in rural Sri Lanka.

Methods and findings

A population-based cross-sectional study was conducted among 8707 current residents in the district of Ampara, representing typical rural Sri Lanka. The sample was recruited using multi-stage cluster sampling with probability proportionate-to-size. Snakebite victims were identified using the WHO criteria. Data were collected using a pre-tested interviewer-administered questionnaire.

Each household had on average 3.8 persons; mean age 28.3 years (SD = 18.2); 51.3% males. The one-year point prevalence of snakebites was 17.6 per 1000 residents (95% CI: 15–20.6) and 6.12 per 100 households (95% CI: 5.25–7.13), while the lifetime prevalence was 9.4 per 100 residents (95% CI: 8.8–10.0) and 30.5 per 100 households (95% CI: 28.6–32.2) with a case fatality ratio of 0.033. Venomous snakebites accounted for 28.1%; snakes were unidentified among 30.1%. Compared to the non-snakebite victims, being single, males, of Sinhala ethnicity, aged >19 years, low education and socioeconomic status, engaging in farming or unskilled outdoor occupations denoted vulnerability to snakebites. Outdoor bites (77.8%) were more common among males; during daytime; mostly while walking; within the rural terrains and home gardens; on lower limbs; mostly by hump-nosed and Russell viper. Indoor bites were more common among females; during night-time; while sleeping and barefooted; on lower limbs; mostly by hump-nosed vipers, kraits and non-venomous snakes.

Conclusions

The burden of snakebite is considerably high among rural populations. The concept of vulnerability can be useful in healthcare decision-making and resource allocation.
Transplantation of chicken egg white extract-induced rabbit PBMCs as a treatment for renal ischemia-reperfusion injury in rabbits
Authors: Ruan Guang-ping , Yao Xiang , Lin Qing-keng , Li Zi-an , Cai Xue-min , Pang Rong-qing , Pan Xing-hua
Published: December 2020

Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into four groups of 10 rabbits each. Thirty rabbits were used to establish the renal ischemia-reperfusion injury model, and ten rabbits served as the model group and were not treated. Among the 30 rabbits with renal ischemia-reperfusion injury, 10 rabbits were treated with induced peripheral blood mononuclear cells (PBMCs), and 10 other rabbits were treated with noninduced PBMCs. After three weekly treatments, the serum creatinine levels, urea nitrogen levels and urine protein concentrations were quantified. The kidneys were stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome and then sent for commercial metabolomic testing. The kidneys of the rabbits in the model group showed different degrees of pathological changes, and the recovery of renal function was observed in the group treated with induced cells. The results indicate that PBMCs differentiate into multipotent stem cells after induction and exert a therapeutic effect on renal ischemia-reperfusion injury.
Fragmentation of production amplifies systemic risks from extreme events in supply-chain networks
Authors: Colon Célian , Brännström Åke , Rovenskaya Elena , Dieckmann Ulf
Published: December 2020

Climatic and other extreme events threaten the globalized economy, which relies on increasingly complex and specialized supply-chain networks. Disasters generate (i) direct economic losses due to reduced production in the locations where they occur, and (ii) to indirect losses from the supply shortages and demand changes that cascade along the supply chains. Firms can use inventories to reduce their risk of shortages. Since firms are interconnected through the supply chain, the level of inventory hold by one firm influences the risk of shortages of the others. Such interdependencies lead to systemic risks in supply chain networks. We introduce a stylized model of complex supply-chain networks in which firms adjust their inventory to maximize profit. We analyze the resulting risks and inventory patterns using evolutionary game theory. We report the following findings. Inventories significantly reduce disruption cascades and indirect losses at the expense of a moderate increase in direct losses. The more fragmented a supply chain is, the less beneficial it is for individual firms to maintain inventories, resulting in higher systemic risks. One way to mitigate such systemic risks is to prescribe inventory sizes to individual firms—a measure that could, for instance, be fostered by insurers. We found that prescribing firm-specific inventory sizes based on their position in the supply chain mitigates systemic risk more effectively than setting the same inventory requirements for all firms.
A qualitative study of e-cigarette use among young people in Ireland: Incentives, disincentives, and putative cessation
Authors: Hanafin Joan , Clancy Luke
Published: December 2020

Background

Smoking prevalence in Ireland is falling in all age groups, but e-cigarette use is rising among young people. This qualitative study explores young people’s accounts of e-cigarette use in Ireland.

Methods

Semi-structured individual (22) and focus group (8) interviews were conducted with 62 young people aged 18–22 years, recruited from a higher-education institution and youth organisations working with early school-leavers across Dublin. All were smokers or ex-smokers; 41 had tried e-cigarettes, 11 continued as dual users. We identified themes using thematic data analysis.

Results

Three broad themes were identified: incentivising features, disincentivising features, and ambivalent and unsuccessful cessation, named putative smoking cessation. Incentivising features included price, pleasing taste/ flavours, and the possibility of indoor use. Disincentivising features related to adverse health effects (pain, discomfort, sore throat, coughing, headache) and unpleasant physical effects (bad taste, problems resulting from device faults). Other disincentives were over-consumption arising from inability to control intake, "greater addictiveness", product taste, and device faults. Putative cessation refers to the conflict between participants' expected use of e-cigarettes as a smoking cessation/reduction aid and their observed reality of e-cigarettes’ failure in this regard, with reported outcomes including: failure to quit or reduce; continued or resumed cigarette and/or roll-your-own smoking; dual use of e-cigarettes and other tobacco products; and inability to quit e-cigarettes.

Conclusions

Participants were sceptical about e-cigarettes’ "purported relative healthiness", concerned about addictiveness and potential long-term health consequences, and critically aware of advertising and industry strategies. E-cigarettes were viewed as being less denormalised, in part because they could be used in indoor spaces where smoking is banned in Ireland. Although price, taste, and perceived renormalisation were important motivators for young people's use of e-cigarettes, they wanted to quit smoking. The regulation of e-cigarettes through age restriction of access, licensing of outlets, pricing, point of sale and advertising restrictions as well as through the banning of indoor use should be considered by legislators and tobacco control policymakers.
Deterministic modelling of seed dispersal based on observed behaviours of an endemic primate in Brazil
Authors: Raghunathan Nima , François Louis , Cazetta Eliana , Pitance Jean-Luc , De Vleeschouwer Kristel , Hambuckers Alain
Published: December 2020

Plant species models are among the available tools to predict the future of ecosystems threatened by climate change, habitat loss, and degradation. However, they suffer from low to no inclusion of plant dispersal, which is necessary to predict ecosystem evolution. A variety of seed dispersal models have been conceived for anemochorous and zoochorous plant species, but the coupling between vegetation models and seed dispersal processes remains rare. The main challenge in modelling zoochoric dispersal is simulating animal movements in their complex habitat. Recent developments allow straightforward applications of hidden Markov modelling (HMM) to animal movements, which could ease generalizations when modelling zoochoric seed dispersal. We tested the use of HMM to model seed dispersal by an endangered primate in the Brazilian Atlantic forest, to demonstrate its potential simplicity to simulate seed dispersal processes. We also discuss how to adapt it to other species. We collected information on movement, fruit consumption, deposition, and habitat use of Leontopithecus chrysomelas. We analysed daily trajectories using HMM and built a deterministic Model Of Seed Transfer (MOST), which replicated, with good approximation, the primate’s movement and seed deposition patterns as observed in the field. Our results suggest that the dispersal behaviour and short daily-trajectories of L. chrysomelas restrict the species’ role in large-scale forest regeneration, but contribute to the prevalence of resource tree species locally, and potentially maintaining tree diversity by preventing local extinction. However, it may be possible to accurately simulate dispersal in an area, without necessarily quantifying variables that influence movement, if the movement can be broken down to step-length and turning angles, and parametrised along with the distribution of gut-transit times. For future objectives, coupling MOST with a DVM could be used to test hypotheses on tree species survival in various scenarios, simulating regeneration and growth at regional scales by including data on main dispersal agents over the area of interest, distribution of tree species, and land use data. The principal advantage of the MOST model is its functionality with data available from the literature as the variables are easy to parametrise. We suggest using the coupled model to perform experiments using only available information, but varying the numbers and species of seed dispersers, or modifying land cover or configuration to test for possible thresholds preventing the extinction of selected tree species.
Divergence of photosynthetic strategies amongst marine diatoms
Authors: Fisher Nerissa L. , Campbell Douglas A. , Hughes David J. , Kuzhiumparambil Unnikrishnan , Halsey Kimberly H. , Ralph Peter J. , Suggett David J.
Published: December 2020

Marine phytoplankton, and in particular diatoms, are responsible for almost half of all primary production on Earth. Diatom species thrive from polar to tropical waters and across light environments that are highly complex to relatively benign, and so have evolved highly divergent strategies for regulating light capture and utilization. It is increasingly well established that diatoms have achieved such successful ecosystem dominance by regulating excitation energy available for generating photosynthetic energy via highly flexible light harvesting strategies. However, how different light harvesting strategies and downstream pathways for oxygen production and consumption interact to balance excitation pressure remains unknown. We therefore examined the responses of three diatom taxa adapted to inherently different light climates (estuarine Thalassioisira weissflogii, coastal Thalassiosira pseudonana and oceanic Thalassiosira oceanica) during transient shifts from a moderate to high growth irradiance (85 to 1200 μmol photons m-2 s-1). Transient high light exposure caused T. weissflogii to rapidly downregulate PSII with substantial nonphotochemical quenching, protecting PSII from inactivation or damage, and obviating the need for induction of O2 consuming (light-dependent respiration, LDR) pathways. In contrast, T. oceanica retained high excitation pressure on PSII, but with little change in RCII photochemical turnover, thereby requiring moderate repair activity and greater reliance on LDR. T. pseudonana exhibited an intermediate response compared to the other two diatom species, exhibiting some downregulation and inactivation of PSII, but high repair of PSII and induction of reversible PSII nonphotochemical quenching, with some LDR. Together, these data demonstrate a range of strategies for balancing light harvesting and utilization across diatom species, which reflect their adaptation to sustain photosynthesis under environments with inherently different light regimes.
Survey of doctors’ perception of professional values
Authors: Minicuci Nadia , Giorato Cinzia , Rocco Ilaria , Lloyd-Sherlock Peter , Avruscio Giampiero , Cardin Fabrizio
Published: December 2020

Background

New challenges in the medical field of the third millennium emphasise the "humanization of medicine" leading to a redefinition of doctors’ values, limits and roles. The study aims to assess whether there are different personality dimensions of physicians in relation to their perception of professional values and public expectations.

Methods

A questionnaire on the perception of professional values and the opinion on work in the medical field, work relationships and public expectations was administered to 374 doctors attending Continuing Medical Education courses.

Results

Two personality dimensions were identified: the first dimension (which we termed "Performance Attainment") is associated preeminently with values of competence, advocacy, confidentiality, spirit of enquiry, integrity, responsibility and commitment; the second dimension (which we called “Personal Involvement”) focuses on concern and compassion. The doctors that have more difficulty accepting judgements on their activity are those who think that “Performance attainment” is less important (β = 6.01; p-value = 0.007). Instead, the doctors who believe “public expectation of the health system” is not high enough, tend to think that “Performance Attainment” is more important (β = -6.08; p-value = 0.024). The less importance is given to the values of "Personal Involvement", the less is the doctor’s perception of having a leading role in respect to other health professionals (β = -2.37; p-value = 0.018).

Conclusions

Our results demonstrate that there are two different attitudes in terms of recognition and selection of the essential values to better practice the medical profession. Whether the doctors attach more importance to one dimension or the other, they do not differ in our analysis for how they answered the questions about relationships with patients, colleagues or family commitments in the questionnaire, even if they work in different areas. This suggests that in our research there is no single personal attitude that characterizes “a good doctor”.
Prediction of preeclampsia risk in first time pregnant women: Metabolite biomarkers for a clinical test
Authors: Kenny Louise C. , Thomas Grégoire , Poston Lucilla , Myers Jenny E. , Simpson Nigel A. B. , McCarthy Fergus P. , Brown Leslie W. , Bond Alison E. , Tuytten Robin , Baker Philip N. ,   on behalf of the Screening for Pregnancy Endpoints Consortium
Published: December 2020

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. Accurate prediction of preeclampsia risk would enable more effective, risk-based prenatal care pathways. Current risk assessment algorithms depend on clinical risk factors largely unavailable for first-time pregnant women. Delivering accurate preeclampsia risk assessment to this cohort of women, therefore requires for novel biomarkers. Here, we evaluated the relevance of metabolite biomarker candidates for their selection into a prototype rapid, quantitative Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) based clinical screening assay. First, a library of targeted LC-MS/MS assays for metabolite biomarker candidates was developed, using a medium-throughput translational metabolomics workflow, to verify biomarker potential in the Screening-for-Pregnancy-Endpoints (SCOPE, European branch) study. A variable pre-selection step was followed by the development of multivariable prediction models for pre-defined clinical use cases, i.e., prediction of preterm preeclampsia risk and of any preeclampsia risk. Within a large set of metabolite biomarker candidates, we confirmed the potential of dilinoleoyl-glycerol and heptadecanoyl-2-hydroxy-sn-glycero-3-phosphocholine to effectively complement Placental Growth Factor, an established preeclampsia biomarker, for the prediction of preeclampsia risk in first-time pregnancies without overt risk factors. These metabolites will be considered for integration in a prototype rapid, quantitative LC-MS/MS assay, and subsequent validation in an independent cohort.
Communicating risk in human-wildlife interactions: How stories and images move minds
Authors: Guenther Sara K. , Shanahan Elizabeth A.
Published: December 2020

Effectively communicating risk is critical to reducing conflict in human-wildlife interactions. Using a survey experiment fielded in the midst of contentious public debate over flying fox management in urban and suburban areas of Australia, we find that stories with characters (i.e., narratives) are more effective than descriptive information at mobilizing support for different forms of bat management, including legal protection, relocation, and habitat restoration. We use conditional process analysis to show that narratives, particularly with accompanying images, are effective because they cause emotional reactions that influence risk perception, which in turn drives public opinion about strategies for risk mitigation. We find that prior attitudes towards bats matter in how narrative messages are received, in particular in how strongly they generate shifts in affective response, risk perception, and public opinion. Our results suggest that those with warm prior attitudes towards bats report greater support for bat dispersal when they perceive impacts from bats to be more likely, while those with cool priors report greater support for bat protection when they perceive impacts from bats to be more positive, revealing 1) potential opportunities for targeted messaging to boost public buy-in of proposals to manage risks associated with human-wildlife interactions, and 2) potential vulnerabilities to disinformation regarding risk.
Connectivity assessment and prioritization of urban grasslands as a helpful tool for effective management of urban ecosystem services
Authors: Mollashahi Hassanali , Szymura Magdalena , Szymura Tomasz H.
Published: December 2020

Urban grasslands are usually managed as short-cut lawns and have limited biodiversity. Urban grasslands with low-intensity management are species rich and can perform numerous ecosystem services, but they are not accepted by citizens everywhere. Further, increasing and/or maintaining a relatively high level of plant species richness in an urban environment is limited by restricted plant dispersal. In this study, we examined the connectivity of urban grasslands and prioritized the grassland patches with regard to their role in connectivity in an urban landscape. We used high-resolution data from a land use system to map grassland patches in Wrocław city, Silesia, southwest Poland, Central Europe, and applied a graph theory approach to assess their connectivity and prioritization. We next constructed a model for several dispersal distance thresholds (2, 20, 44, 100, and 1000 m), reflecting plants with differing dispersal potential. Our results revealed low connectivity of urban grassland patches, especially for plants with low dispersal ability (2–20 m). The priority of patches was correlated with their area for all dispersal distance thresholds. Most of the large patches important to overall connectivity were located in urban peripheries, while in the city center, connectivity was more restricted and grassland area per capita was the lowest. The presence of a river created a corridor, allowing plants to migrate along watercourse, but it also created a barrier dividing the system. The results suggest that increasing the plant species richness in urban grasslands in the city center requires seed addition.
Observational study on time on treatment with abiraterone and enzalutamide
Authors: Fallara Giuseppe , Lissbrant Ingela Franck , Styrke Johan , Montorsi Francesco , Garmo Hans , Stattin Pär
Published: December 2020

Introduction

The aim of this study was to assess time on treatment with abiraterone and enzalutamide, two androgen receptor targeted (ART) drugs, the impact on time on treatment of time interval without drug supply between prescription fillings, and adherence to treatment.

Material and methods

By use of data from The National Prostate Cancer Register, The Prescribed Drug Registry and the Patient Registry, time on treatment with the abiraterone and enzalutamide was analyzed in all men with castration resistant prostate cancer (CRPC) in Sweden 2015–2019. Three time intervals between consecutive fillings, i.e. time without drug supply, were assessed. Adherence to the treatment was evaluated by use of the Medication Possession Ratio. Kaplan Meier analysis and multivariable Cox regression model were used to assess factors affecting time on treatment.

Results

Between January 2015 and October 2019, 1803 men filled a prescription for abiraterone and 4 534 men filled a prescription for enzalutamide. With a time interval of 30 days or less between two fillings, median time on treatment was 4.9 months (IQR 2.6–11.7) for abiraterone and 8.0 months (IQR 3.6–16.4) for enzalutamide. In sensitivity analyses, allowing for no more than 14 days without drug supply between fillings, median time on treatment was 3.9 months (IQR 2.1–9.0) for abiraterone and 5.9 months (IQR 2.8–12.1) for enzalutamide. Allowing for any time period without drug between fillings, median time on treatment was 5.7 months (IQR 2.7–14.0) for abiraterone and 9.8 months (IQR 4.4–21.0) for enzalutamide. Adherence to treatment was above 90% for both drugs.

Conclusion

Time on treatment with abiraterone and enzalutamide was shorter in clinical practice than in randomized controlled trials and varied almost two-fold with time interval without drug. Adherence to treatment was high. The main limitation of our study was the lack of data on use of chemotherapy.
Incorporating radiomic feature of pretreatment 18F-FDG PET improves survival stratification in patients with EGFR-mutated lung adenocarcinoma
Authors: Chen Yu-Hung , Wang Tso-Fu , Chu Sung-Chao , Lin Chih-Bin , Wang Ling-Yi , Lue Kun-Han , Liu Shu-Hsin , Chan Sheng-Chieh
Published: December 2020

Background

To investigate the survival prognostic value of the radiomic features of 18F-FDG PET in patients who had EGFR (epidermal growth factor receptor) mutated lung adenocarcinoma and received targeted TKI (tyrosine kinase inhibitor) treatment.

Methods

Fifty-one patients with stage III-IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI were retrospectively analyzed. All patients underwent pretreatment 18F-FDG PET/CT, and we calculated the PET-derived radiomic features. Cox proportional hazard model was used to examine the association between the radiomic features and the survival outcomes, including progression-free survival (PFS) and overall survival (OS). A score model was established according to the independent prognostic predictors and we compared this model to the TNM staging system using Harrell's concordance index (c-index).

Results

Forty-eight patients (94.1%) experienced disease progression and 41 patients (80.4%) died. Primary tumor SUV entropy > 5.36, and presence of pleural effusion were independently associated with worse OS (both p < 0.001) and PFS (p = 0.001, and 0.003, respectively). We used these two survival predictors to devise a scoring system (score 0–2). Patients with a score of 1 or 2 had a worse survival than those with a score of 0 (HR for OS: 3.6, p = 0.006 for score 1, and HR: 21.8, p < 0.001 for score 2; HR for PFS: 2.2, p = 0.027 for score 1 and HR: 8.8, p < 0.001 for score 2). Our scoring system surpassed the TNM staging system (c-index = 0.691 versus 0.574, p = 0.013 for OS, and c-index = 0.649 versus 0.517, p = 0.004 for PFS).

Conclusions

In this preliminary study, combining PET radiomics with clinical risk factors may improve survival stratification in stage III-IV lung adenocarcinoma with actionable EFGR mutation. Our proposed scoring system may assist with optimization of individualized treatment strategies in these patients.