bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis between Dijkstra and Bellman-Ford Algorithms in Shortest Path Optimization
Authors: AbuSalim Samah W.G. , Ibrahim Rosziati , Zainuri Saringat Mohd , Jamel Sapiee , Abdul Wahab Jahari
Published: September 2020

Due to the tremendous development in the field of computer and software sciences, the theory of graphics has spread widely and quickly, even becoming one of the most important sciences that played a large role in solving many problems of many diverse applications. These applications include computer protocols, Google Maps, games and more. Many researches have discussed shortest path algorithms to solve the shortest path problem in these applications. In this study, a very popular algorithms called Dijkstra algorithm and Bellman-Ford algorithm are used to make a comparison between them on the basis of complexity and performance in terms of shortest path optimization. Our results show that Dijkstra is better than the Bellman-Ford interms of execution time and more efficient for solving the shortest path issue, but the algorithm of Dijkstra work with non-negative edge weights.
Comparing and Assessing the Enhancements of DYMO and OLSR in VANETs
Authors: Khalid Ahmed Waleed , Nazri bin Mohd Warip Mohd , Khalid Abduljabbar Waleed , Elshaikh Mohamed
Published: September 2020

The main aspect of this work is to study the differences and define the behaviour of two different routing protocols. The first side is Dynamic MANETs On- Demand (DYMO) while the other side is proactive, optimal link-state routing (OLSR) and both the first and second are interactive routing protocols in the Ad-hoc network (VANET). The efficiency of these protocols was analysed and studied based on the use of three performance indicators: PDR, normal load (NRO) and end-to-end de1ay (E2ED) on the ability to change the size of different nodes. Omnet ++ was used by the INET Framework. We also used the SUMO simulation tool to build random movement patterns for VANET. From full simulation, we noticed that OLSR is doing better than DYMO for VANET at a price. Late and, as a result, the development of OLSR work in VANETs compared to DYMO, packet receipt ratios (PDR), side-to-side delay, normal path load, and VANETs.
Hybrid Genetic Manta Ray Foraging Optimization and Its Application to Interval Type 2 Fuzzy Logic Control of An Inverted Pendulum System
Authors: Azwan bin Abdul Razak Ahmad , Nor Kasruddin bin Nasir Ahmad , Maniha Abdul Ghani Nor , Mohammad Shuhairie , Falfazli Mat Jusof Mohd , Amira Mhd Rizal Nurul
Published: September 2020

This paper presents an improvised version of Manta-Ray Foraging Optimization (MRFO) by using components in Genetic Algorithm (GA). MRFO is a recent proposed algorithm which based on the behaviour of manta rays. The algorithm imitates three foraging strategies of this cartilaginous fish, which are chain foraging, cyclone foraging and somersault foraging to find foods. However, this optimization algorithm can be improved in its strategy which increases its accuracy. Thus, in this proposed improvement, mutation and crossover strategy from GA were adopted into MRFO. Crossover operation is a convergence action which is purposely to pull the agents towards an optimum point. At the meanwhile, mutation operation is a divergence action which purposely to spread out the agents throughout wider feasible region. Later, the algorithms were performed on several benchmark functions and statically tested by using Wilcoxon signed-rank test to know their performances. To test the algorithm with a real application, the algorithms were applied to an interval type 2 fuzzy logic controller (IT2FLC) of an inverted pendulum system. Result of the test on benchmark functions shows that GMRFO outperformed MRFO and GA and it shows that it provides a better parameter of the control system for a better response.
MloDisDB: a manually curated database of the relations between membraneless organelles and diseases
Authors: Hou Chao , Xie Haotai , Fu Yang , Ma Yao , Li Tingting
Published: September 2020

Cells are compartmentalized by numerous membrane-bounded organelles and membraneless organelles (MLOs) to ensure temporal and spatial regulation of various biological processes. A number of MLOs, such as nucleoli, nuclear speckles and stress granules, exist as liquid droplets within the cells and arise from the condensation of proteins and RNAs via liquid–liquid phase separation (LLPS). By concentrating certain proteins and RNAs, MLOs accelerate biochemical reactions and protect cells during stress, and dysfunction of MLOs is associated with various pathological processes. With the development in this field, more and more relations between the MLOs and diseases have been described; however, these results have not been made available in a centralized resource. Herein, we build MloDisDB, a database which aims to gather the relations between MLOs and diseases from dispersed literature. In addition, the relations between LLPS and diseases were included as well. Currently, MloDisDB contains 771 curated entries from 607 publications; each entry in MloDisDB contains detailed information about the MLO, the disease and the functional factor in the relation. Furthermore, an efficient and user-friendly interface for users to search, browse and download all entries was provided. MloDisDB is the first comprehensive database of the relations between MLOs and diseases so far, and the database is freely accessible at http://mlodis.phasep.pro/.
Computational prediction and interpretation of cell-specific replication origin sites from multiple eukaryotes by exploiting stacking framework
Authors: Wei Leyi , He Wenjia , Malik Adeel , Su Ran , Cui Lizhen , Manavalan Balachandran
Published: September 2020

Origins of replication sites (ORIs), which refers to the initiative locations of genomic DNA replication, play essential roles in DNA replication process. Detection of ORIs’ distribution in genome scale is one of key steps to in-depth understanding their regulation mechanisms. In this study, we presented a novel machine learning-based approach called Stack-ORI encompassing 10 cell-specific prediction models for identifying ORIs from four different eukaryotic species (Homo sapiens, Mus musculus, Drosophila melanogaster and Arabidopsis thaliana). For each cell-specific model, we employed 12 feature encoding schemes that cover nucleic acid composition, position-specific and physicochemical properties information. The optimal feature set was identified from each encoding individually and developed their respective baseline models using the eXtreme Gradient Boosting (XGBoost) classifier. Subsequently, the predicted scores of 12 baseline models are integrated as a novel feature vector to train XGBoost and develop the final model. Extensive experimental results show that Stack-ORI achieves significantly better performance as compared with their baseline models on both training and independent datasets. Interestingly, Stack-ORI consistently outperforms existing predictor in all cell-specific models, not only on training but also on independent test. Moreover, our novel approach provides necessary interpretations that help understanding model success by leveraging the powerful SHapley Additive exPlanation algorithm, thus underlining the most important feature encoding schemes significant for predicting cell-specific ORIs.
Serum Antibody Profile of a Patient With Coronavirus Disease 2019 Reinfection
Authors: To Kelvin Kai-Wang , Hung Ivan Fan-Ngai , Chan Kwok-Hung , Yuan Shuofeng , To Wing-Kin , Tsang Dominic Ngai-Chong , Cheng Vincent Chi-Chung , Chen Zhiwei , Kok Kin-Hang , Yuen Kwok-Yung
Published: September 2020

We recently reported a patient with coronavirus disease 2019 reinfection. Here, we show that serum neutralizing antibodies could be detected during the first episode but not at the presentation of the second episode. During reinfection, neutralizing antibodies and high avidity immunoglobulin G were found within 8 days after hospitalization, whereas immunoglobulin M response was absent.
Metabolic Response in Patients With Post-treatment Lyme Disease Symptoms/Syndrome
Authors: Fitzgerald Bryna L , Graham Barbara , Delorey Mark J , Pegalajar-Jurado Adoracion , Islam M Nurul , Wormser Gary P , Aucott John N , Rebman Alison W , Soloski Mark J , Belisle John T , Molins Claudia R
Published: September 2020

Background

Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of patients with Lyme disease following antibiotic treatment. Biomarkers or specific clinical symptoms to identify patients with PTLDS do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ≥6 months following antibiotic treatment for Lyme disease.

Methods

Untargeted liquid chromatography–mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients. Evaluation of biosignatures included (1) defining altered classes of metabolites, (2) elastic net regularization to define metabolites that most strongly defined PTLDS and non-PTLDS patients at different time points, (3) changes in the longitudinal abundance of metabolites, and (4) linear discriminant analysis to evaluate robustness in a second patient cohort.

Results

This study determined that observable metabolic differences exist between PTLDS and non-PTLDS patients at multiple time points. The metabolites with differential abundance included those from glycerophospholipid, bile acid, and acylcarnitine metabolism. Distinct longitudinal patterns of metabolite abundance indicated a greater metabolic variability in PTLDS versus non-PTLDS patients. Small numbers of metabolites (6 to 40) could be used to define PTLDS versus non-PTLDS patients at defined time points, and the findings were validated in a second cohort of PTLDS and non-PTLDS patients.

Conclusions

These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.
Durability of Response to Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence in Patients With Clostridioides difficile Infection
Authors: Saha Srishti , Mara Kristin , Pardi Darrell S , Khanna Sahil
Published: September 2020

Background

Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI.

Methods

We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure.

Results

Overall, 460 patients were included (median age, 57 years [18–94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%–84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15–.49; P < .001).

Conclusions

The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.
Early Impact of Social Distancing in Response to Coronavirus Disease 2019 on Hospitalizations for Acute Bronchiolitis in Infants in Brazil
Authors: Friedrich Frederico , Ongaratto Renata , Scotta Marcelo C , Veras Tiago N , Stein Renato T , Lumertz Magali Santos , Jones Marcus Herbert , Comaru Talitha , Pinto Leonardo Araújo
Published: September 2020

Background

Interventions to tackle the coronavirus disease 2019 (COVID-19) pandemic may affect the burden of other respiratory diseases. Considering the repercussions of these unique social experiences to infant health, this study aims to assess the early impact of social distancing due to the COVID-19 pandemic in hospital admissions for acute bronchiolitis.

Methods

Data from hospitalizations of acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2020. These data were also analyzed by macroregions of Brazil (North, Northeast, Southeast, South, and Midwest). To evaluate the effect of social distancing strategy on the incidence of acute bronchiolitis, the absolute and relative reductions were calculated by analyzing the yearly subsets of 2016 vs 2020, 2017 vs 2020, 2018 vs 2020, and 2019 vs 2020.

Results

There was a significant reduction in all comparisons, ranging from −78% (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI}, .20–.24]) in 2016 vs 2020 to −85% (IRR, 0.15 [95% CI, .13–.16]) in 2019 vs 2020, for the data from Brazil. For analyses by macroregions, the reduction varied from −58% (IRR, 0.41 [95% CI, .37–.45]) in the Midwest in 2016 vs 2020 to −93% (IRR, 0.07 [95% CI, .06–.08]) in the South in 2019 vs 2020.

Conclusions

There was a significant reduction in hospitalization for acute bronchiolitis in children <1 year old in Brazil, on the order of >70% for most analysis. Our data suggest an important impact of social distancing on reducing the transmission of viruses related to acute bronchiolitis. Such knowledge may guide strategies for prevention of viral spread.
Predictors at Admission of Mechanical Ventilation and Death in an Observational Cohort of Adults Hospitalized With Coronavirus Disease 2019
Authors: Jackson Brendan R , Gold Jeremy A W , Natarajan Pavithra , Rossow John , Neblett Fanfair Robyn , da Silva Juliana , Wong Karen K , Browning Sean D , Bamrah Morris Sapna , Rogers-Brown Jessica , Hernandez-Romieu Alfonso C , Szablewski Christine M , Oosmanally Nadine , Tobin-D’Angelo Melissa , Drenzek Cherie , Murphy David J , Hollberg Julie , Blum James M , Jansen Robert , Wright David W , Sewell William M , Owens Jack D , Lefkove Benjamin , Brown Frank W , Burton Deron C , Uyeki Timothy M , Bialek Stephanie R , Patel Priti R , Bruce Beau B
Published: September 2020

Background

Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions.

Methods

We conducted a retrospective observational cohort investigation of 297 adults admitted to 8 academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for predictors of invasive mechanical ventilation (IMV) and death.

Results

Compared with age <45 years, ages 65–74 years and ≥75 years were predictors of IMV (aORs, 3.12 [95% CI, 1.47–6.60] and 2.79 [95% CI, 1.23–6.33], respectively) and the strongest predictors for death (aORs, 12.92 [95% CI, 3.26–51.25] and 18.06 [95% CI, 4.43–73.63], respectively). Comorbidities associated with death (aORs, 2.4–3.8; P < .05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Prehospital use vs nonuse of angiotensin receptor blockers (aOR, 2.02 [95% CI, 1.03–3.96]) and dihydropyridine calcium channel blockers (aOR, 1.91 [95% CI, 1.03–3.55]) were associated with death.

Conclusions

After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.
Causal Relationship between Plasma Adiponectin and Body Mass Index: One- and Two-Sample Bidirectional Mendelian Randomization Analyses in 460 397 Individuals
Authors: Nielsen Maria Booth , Çolak Yunus , Benn Marianne , Nordestgaard Børge Grønne
Published: September 2020

Background

Adiponectin is a protein hormone produced by adipocytes that may play an important role in obesity. However, the causal interrelation between plasma adiponectin and body mass index (BMI) is still uncertain. We tested the hypotheses that (a) plasma adiponectin and BMI are inversely associated observationally, (b) genetically high BMI is associated with lower plasma adiponectin, and (c) genetically high plasma adiponectin is associated with lower BMI.

Methods

Information on 108 896 individuals from the Copenhagen General Population Study was used in observational and bidirectional one-sample Mendelian randomization analyses, using 5 genetic variants for BMI and 3 for adiponectin. For independent confirmation, information on 322 154 individuals from the GIANT consortium, and 29 347 individuals from the ADIPOGen consortium was used in bidirectional two-sample Mendelian randomization analysis, using 68 genetic variants for BMI and 14 for adiponectin.

Results

In observational analyses, a 1 kg/m2 increase in BMI was associated with −0.44 µg/mL (95% confidence interval: −0.46, −0.42) in plasma adiponectin, whereas a 1 µg/mL increase in plasma adiponectin was associated with −0.11 kg/m2 (−0.12, −0.11) in BMI. In causal genetic analyses, no associations were observed between BMI and plasma adiponectin and vice versa. In one-sample Mendelian randomization analyses, a 1 kg/m2 genetically determined increase in BMI was associated with −0.13 µg/mL (−0.53, 0.28) in plasma adiponectin, whereas a 1 µg/mL genetically determined increase in plasma adiponectin was associated with 0.01 kg/m2 (−0.05, 0.07) in BMI. Corresponding estimates in the two-sample Mendelian randomization analyses were 0.03 µg/mL (−0.02, 0.07) and 0.03 kg/m2(−0.02, 0.07), respectively.

Conclusions

Observationally, plasma adiponectin and BMI are inversely associated. In contrast, genetically high plasma adiponectin is unlikely to influence BMI, and genetically high BMI is unlikely to influence plasma adiponectin.
Evaluation of postoperative outcomes of valve reoperation: a retrospective study
Authors: Tatsuishi Wataru , Kumamaru Hiraku , Nakano Kiyoharu , Miyata Hiroaki , Motomura Noboru
Published: September 2020

OBJECTIVES

The aim of this study was to compare the incidence of operative death and postoperative complications between primary and reoperation valve surgeries and to identify independent risk factors for these events among valve-reoperation patients.

METHODS

Between 2013 and 2015, 54 269 patients who underwent valve surgery were retrospectively analyzed using the Japan Cardiovascular Surgery Database. They were divided into the primary (group P; n = 49 833) and reoperation (group R; n = 4436) surgery groups. Among the reoperation patients, we conducted multivariable logistic regression analyses to identify risk factors for the incidences of operative mortality and postoperative complications. Then, we also conducted propensity score matched analyses to compare the incidences of these 2 outcomes for primary versus reoperation procedures separately for patients with and without infective endocarditis (IE).

RESULTS

Incidences of postoperative mortality (4.6% vs 9.1%; P < 0.001) and any complications (36.6% vs 41.4%; P < 0.001) were higher in the reoperation group. For patients undergoing reoperation, strong risk factors for operative mortality included urgency status, ejection fraction <30%, IE, dialysis, chronic kidney disease, New York Heart Association class 3/4, concomitant coronary artery bypass grafting and aorta procedure, tricuspid valve surgery only, multivalve surgery and age. In the propensity score matched cohort, the relative odds of operative mortality were 1.53 (95% confidence interval: 1.26–1.86, P < 0.001) among patients with IE and were 1.58 (95% confidence interval: 1.18–2.13, P < 0.002) among those without.

CONCLUSIONS

Outcomes for reoperation were significantly worse than those for primary surgery. At the primary operation, the risk of reoperation should be considered and when considering the indications for reoperation, the preoperative state, surgical timing and intervention method should be considered.
Factors related to maxillary expander loss due to anchoring deciduous molars exfoliation during treatment in the mixed dentition phase
Authors: Quinzi Vincenzo , Federici Canova Fabio , Rizzo Fiorella Alessandra , Marzo Giuseppe , Rosa Marco , Primozic Jasmina
Published: September 2020

Objectives

The aim was to identify factors associated with maxillary expander loss due to anchoring deciduous molars exfoliation and assess the diagnostic accuracy of the upper second premolar cusp position as a prognostic factor for the exfoliation of its corresponding deciduous molar.

Materials/methods

Ninety-two subjects aged 8.4 ± 1.1 years, treated with a Haas or hyrax expander, and using the same expansion protocol and deciduous teeth as anchorage were included. The position of the upper second premolar cusp, according to the half pulp chamber (HPC) line of the ipsilateral upper first permanent molar, was assessed on pre-treatment panoramic radiographs.

Results

A significant association between anchoring deciduous molar exfoliation and the position of the upper second premolar cusp according to the HPC line (P = 0.002; odds ratio = 5.7) was seen, while there was no association with gender, age, treatment duration, and type of expander. The median survival time for an anchoring deciduous molar, when the underlying premolar cusp was touching/crossing the HPC line, was 13.0 (11.7; 14.2) months. The upper second premolar cusp position to the HPC line showed high accuracy (at least 76.11 per cent) and substantial repeatability (at least 0.7) as a prognostic factor for the corresponding second deciduous molar exfoliation.

Limitations

Applicability in the mixed dentition phase with fully erupted upper first permanent molars.

Conclusions

The probability of a second deciduous molar to be successfully used as maxillary expander anchorage for at least 16 months is above 94 per cent; when at baseline, the corresponding premolar cusp is apical to the HPC line.
Newly introducedCardiniumendosymbiont reduces microbial diversity in the rice brown planthopperNilaparvata lugens
Authors: Li Tong-Pu , Zha Si-Si , Zhou Chun-Ying , Gong Jun-Tao , Zhu Yu-Xi , Zhang Xu , Xi Zhiyong , Hong Xiao-Yue
Published: September 2020

Symbiotic microorganisms in invertebrates play vital roles in host ecology and evolution. Cardinium, a common intracellular symbiont, is transinfected into the important agricultural pest Nilaparvata lugens (rice brown planthopper) to regulate its reproduction, but how this impacts its microbial community is unknown. Here, we characterized the bacterial microbiota from N. lugens, with or without Cardinium, at different developmental stages and in various adult tissues using 16S ribosomal ribonucleic acid (16S rRNA) gene sequencing. Upon infection with Cardinium, we found that microbial diversity in the different developmental stages of N. lugens (especially females), and in female midguts and male testes, was lower than that in the uninfected control. There was a negative correlation between Cardinium and most related genera and between Bacteroidetes and Proteobacteria. Although the microbial structure varied during Cardinium infection, Acinetobacter spp. were a core microbiome genus. The Cardinium infection enhanced the relative density of midgut-associated Acinetobacter spp., with both bacteria exhibiting tissue-specific tropism. In addition, this infection caused the changes of main microbial functions in N. lugens. These results offer insights into the effects of alien (i.e. newly introduced from other organism) Cardinium infection on N. lugens-associated microbiotas, aiding in the development of transinfected endosymbionts for pest control.
Conceptualizing Food Insecurity Among Older Adults: Development of a Summary Indicator in the National Health and Aging Trends Study
Authors: Tucher Emma L , Keeney Tamra , Cohen Alicia J , Thomas Kali S
Published: September 2020

Objectives

Measurement of food insecurity in older adults is focused on financial barriers to food access. Given that older adults are particularly susceptible to additional access-related barriers including functional limitations and lack of social support, the objective of this study was to construct a summary indicator of food insecurity incorporating these domains.

Methods

We used nationally representative survey data from Round 5 of the National Health and Aging Trends Study (NHATS; n = 7,070). We constructed a summary indicator of food insecurity using factors within the following three domains: functional, social support, and financial limitations. First, we identified the prevalence of food insecurity among the sample as defined by the new summary indicator. Then, we estimated unadjusted and adjusted logistic regression models to assess the association between the expanded measure of food insecurity and biopsychosocial factors.

Results

In 2015, 4.3% (95% confidence interval [CI] 3.75–4.94) of community-dwelling older adults, approximately 1,673,775 million people, were characterized as having food insecurity. Multivariable-adjusted regression models identified that being homebound (odds ratio [OR] 3.49, 95% CI 2.03, 6.00), frail (OR 9.50, 95% CI 4.92–18.37), and experiencing community disability (OR 5.19, 95% CI 3.90–6.90) was associated with food insecurity.

Discussion

Food insecurity among older adults is broader than lacking adequate financial resources to obtain food; it is also associated with social and functional limitations. A more comprehensive conceptualization will aid future study on the impact of food insecurity on health status, utilization, and outcomes to inform senior nutrition program targeting and services.
Amplitude and phase changes for reflected and transmitted waves from a curved interface in anisotropic media
Authors: Ursin Bjørn , Favretto-Cristini Nathalie , Cristini Paul
Published: September 2020

It is well known that seismic data that have been recorded in complex geological environments must be compensated for geometrical spreading before AVO/AVA (amplitude-versus-offset/amplitude-versus-angle) analysis, in order to avoid erroneous imaging interpretation. By investigating analytically both the effect of the geometrical spreading and the effect of the reflector curvature on amplitude and phase changes for reflected and transmitted waves between anisotropic media, using ray theory, we show that these data should be compensated for interface effects as well. In order to gain insight more specifically in the focusing effect of the interface, the special case of homogeneous isotropic media separated by a curved interface of syncline type is discussed and compared to the case of a plane interface. 3-D numerical simulations of wave reflection from curved interfaces using a spectral element method validate our analytical derivations. In particular, numerical seismograms obtained at a vertical receiver array highlight that the effect of interface curvature on the reflected events is much more pronounced in a restricted area associated with the existence of caustics, which is consistent with our analytical predictions. Moreover, comparisons between the numerical and the analytical results confirm the fact that using plane-wave reflection coefficients without correction for the interface effect may lead to wrong interpretation of AVA/AVO analysis.
Career advice for those who cannot walk on water—build bridges!
Authors: Moore Marianne V
Published: September 2020

From landlocked Iowa to the outback of Australia and the interior of Siberia, I found water and opportunities to build bridges between disciplines and among scientists from different countries and cultures. What I have learned is that preparation, persistence when challenged, daring to follow the path of opportunity, and generously sustaining collaborations can lead to a successful, adventure-filled, and satisfying career.
Epigenetic Regulation of GABAergic Neurotransmission and Neurosteroid Biosynthesis in Alcohol Use Disorder
Authors: Gatta Eleonora , Guidotti Alessandro , Saudagar Vikram , Grayson Dennis R , Aspesi Dario , Pandey Subhash C , Pinna Graziano
Published: September 2020

Background

Alcohol use disorder (AUD) is a chronic relapsing brain disorder. GABAA receptor (GABAAR) subunits are a target for the pharmacological effects of alcohol. Neurosteroids play an important role in the fine-tuning of GABAAR function in the brain. Recently, we have shown that AUD is associated with changes in DNA methylation mechanisms. However, the role of DNA methylation in the regulation of neurosteroid biosynthesis and GABAergic neurotransmission in AUD patients remains under-investigated.

Methods

In a cohort of postmortem brains from 20 male controls and AUD patients, we investigated the expression of GABAAR subunits and neurosteroid biosynthetic enzymes and their regulation by DNA methylation mechanisms. Neurosteroid levels were quantified by gas chromatography-mass spectrometry.

Results

The α 2 subunit expression was reduced due to increased DNA methylation at the gene promoter region in the cerebellum of AUD patients, a brain area particularly sensitive to the effects of alcohol. Alcohol-induced alteration in GABAAR subunits was also observed in the prefrontal cortex. Neurosteroid biosynthesis was also affected with reduced cerebellar expression of the 18kDa translocator protein and 3α-hydroxysteroid dehydrogenase mRNAs. Notably, increased DNA methylation levels were observed at the promoter region of 3α-hydroxysteroid dehydrogenase. These changes were associated with markedly reduced levels of allopregnanolone and pregnanolone in the cerebellum.

Conclusion

Given the key role of neurosteroids in modulating the strength of GABAAR-mediated inhibition, our data suggest that alcohol-induced impairments in GABAergic neurotransmission might be profoundly impacted by reduced neurosteroid biosynthesis most likely via DNA hypermethylation.
On Faces of Quasi-arithmetic Coxeter Polytopes
Authors: Bogachev Nikolay , Kolpakov Alexander
Published: September 2020

We prove that each lower-dimensional face of a quasi-arithmetic Coxeter polytope, which happens to be itself a Coxeter polytope, is also quasi-arithmetic. We also provide a sufficient condition for a codimension $1$ face to be actually arithmetic, as well as a few computed examples.

In memoriam È. B. Vinberg 1937–2020
Wuhan's experience in curbing the spread of coronavirus disease (COVID-19)
Authors: Li Wei-Ying , Dai Yong , Chau Pui-Hing , Yip Paul S F
Published: September 2020

Background

Since December 2019, coronavirus disease (COVID-19) has affected over 50 000 people in Wuhan, China. However, the number of daily infection cases, hospitalization rate, lag time from onset to diagnosis date and their associations with measures introduced to slow down the spread of COVID-19 have not been fully explored.

Methods

This study recruited 6872 COVID-19 patients in the Wuchang district, Wuhan. All of the patients had an onset date from 21 December 2019 to 23 February 2020. The overall and weekly hospitalization rate and lag time from onset to diagnosis date were calculated. The number of daily infections was estimated by the back-projection method based on the number of daily onset cases. Their association with major government reactions and measures was analyzed narratively.

Results

The overall hospitalization rate was 45.9% (95% CI 44.7 to 47.1%) and the mean lag time from onset to diagnosis was 11.1±7.4 d. The estimated infection curve was constructed for the period from 14 December 2019 to 23 February 2020. Raising public awareness regarding self-protecting and social distancing, as well as the provision of timely testing and inpatient services, were coincident with the decline in the daily number of infections.

Conclusion

Early public awareness, early identification and early quarantine, supported by appropriate infrastructure, are important elements for containing the spread of COVID-19 in the community.
Mystery and history: when did Catherine the Great purchase the Lyde Browne collection?
Authors: Kruglov Alexander V
Published: September 2020

Documents preserved in the Russian State Historical Archives shed light on the acquisition by Empress Catherine II of the renowned collection of classical sculpture assembled by the antiquary Lyde Browne (d. 1787) – its purchase, arrival and first display in the pavilions of the imperial summer residence in Tsarskoe Selo near St Petersburg. The date for the sale, once assumed to have been 1787, is most widely accepted as 1785, or, as recently suggested, 1784. In fact, there are two dates – 1783 and 1784 – as established by Catherine’s payments (a total sum equivalent to £22,630) for the sculptures as delivered. The archival lists show considerably more items than does the catalogue of Browne’s collection from 1779, while the dispersal of Catherine’s collection of antiquities by her son, Paul I, a partial export to Poland, the formation of the Imperial Hermitage Museum, and later events all contribute to the complex history of the Lyde Browne sculptures in Russia.
Recent advances and future perspectives in adjuvant and neoadjuvant immunotherapies for lung cancer
Authors: Yotsukura Masaya , Nakagawa Kazuo , Suzuki Kenji , Takamochi Kazuya , Ito Hiroyuki , Okami Jiro , Aokage Keiju , Shiono Satoshi , Yoshioka Hiroshige , Aoki Tadashi , Tsutani Yasuhiro , Okada Morihito , Watanabe Shun-ichi ,   the Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG)
Published: September 2020

The superior efficacy of immune checkpoint inhibitors for the treatment of advanced non-small cell lung cancer has inspired many clinical trials to use immune checkpoint inhibitors in earlier stages of lung cancer worldwide. Based on the theoretical feasibility that neoantigens derived from a tumor tissue are present in vivo, some clinical trials have recently evaluated the neoadjuvant, rather than the adjuvant, use of immune checkpoint inhibitors. Some of these trials have already produced evidence on the safety and efficacy of immune checkpoint inhibitors in a neoadjuvant setting, with a favorable major pathologic response and few adverse events. In the most impactful report from Johns Hopkins University and the Memorial Sloan Kettering Cancer Center, the programed death-1 inhibitor nivolumab was administered to 21 patients in a neoadjuvant setting. The authors reported a major pathologic response rate of 45%, with no unexpected delay of surgery related to the adverse effects of nivolumab. The adjuvant as well as the neoadjuvant administration of immune checkpoint inhibitors has also been considered in various clinical trials, with or without the combined use of chemotherapy or radiotherapy. The development of appropriate biomarkers to predict the efficacy of immune checkpoint inhibitors is also underway. The expression of programed death ligand-1 and the tumor mutation burden are promising biomarkers that have been evaluated in many settings. To establish an appropriate method for using immune checkpoint inhibitors in combination with surgery, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group will manage clinical trials using a multimodality treatment, including immune checkpoint inhibitors and surgery.
Effect of the unfolded protein response and oxidative stress on mutagenesis in CSF3R: a model for evolution of severe congenital neutropenia to myelodysplastic syndrome/acute myeloid leukemia
Authors: Sapra Adya , Jaksik Roman , Mehta Hrishikesh , Biesiadny Sara , Kimmel Marek , Corey Seth J
Published: September 2020

Severe congenital neutropenia (SCN) is a rare blood disorder characterised by abnormally low levels of circulating neutrophils. The most common recurrent mutations that cause SCN involve neutrophil elastase (ELANE). The treatment of choice for SCN is the administration of granulocyte-colony stimulating factor (G-CSF), which increases the neutrophil number and improves the survival and quality of life. Long-term survival is however linked to the development of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). About 70% of MDS/AML patients acquire nonsense mutations affecting the cytoplasmic domain of CSF3R (the G-CSF receptor). About 70% of SCN patients with AML harbour additional mutations in RUNX1. We hypothesised that this coding region of CSF3R constitutes a hotspot vulnerable to mutations resulting from excessive oxidative stress or endoplasmic reticulum (ER) stress. We used the murine Ba/F3 cell line to measure the effect of induced oxidative or ER stress on the mutation rate in our hypothesised hotspot of the exogenous human CSF3R, the corresponding region in the endogenous Csf3r, and Runx1. Ba/F3 cells transduced with the cDNA for partial C-terminal of CSF3R fused in-frame with a green fluorescent protein (GFP) tag were subjected to stress-inducing treatment for 30 days (~51 doubling times). The amplicon-based targeted deep sequencing data for days 15 and 30 samples show that although there was increased mutagenesis observed in all the three genes of interest (partial CSF3R, Csf3r and Runx1), there were more mutations in the GFP region compared with the partial CSF3R region. Our findings also indicate that there is no correlation between the stress-inducing chemical treatments and mutagenesis in Ba/F3 cells. Our data suggest that oxidative or ER stress induction does not promote genomic instability, affecting partial C-terminal of the transduced CSF3R, the endogenous Csf3R and the endogenous Runx1 in Ba/F3 cells that could account for these targets to being mutational hotspots. We conclude that other mechanisms to acquire mutations of CSF3R that help drive the evolution of SCN to MDS/AML.
Reducing salt intake by urine chloride self-measurement in non-compliant patients with chronic kidney disease followed in nephrology clinics: a randomized trial
Authors: Panuccio Vincenzo , Mallamaci Francesca , Pizzini Patrizia , Tripepi Rocco , Garofalo Carlo , Parlongo Giovanna , Caridi Graziella , Provenzano Michele , Mafrica Angela , Simone Giuseppina , Cutrupi Sebastiano , D’Arrigo Graziella , Porto Gaetana , Tripepi Giovanni , Nardellotto Antonella , Meneghel Gina , Dattolo Piero , Pizzarelli Francesco , Rapisarda Francesco , Ricchiuto Anna , Fatuzzo Pasquale , Verdesca Simone , Gallieni Maurizio , Gesualdo Loreto , Conte Giuseppe , Plebani Mario , Zoccali Carmine
Published: September 2020

Background

Adherence to low salt diets and control of hypertension remain unmet clinical needs in chronic kidney disease (CKD) patients.

Methods

We performed a 6-month multicentre randomized trial in non-compliant patients with CKD followed in nephrology clinics testing the effect of self-measurement of urinary chloride (69 patients) as compared with standard care (69 patients) on two primary outcome measures, adherence to a low sodium (Na) diet (<100 mmol/day) as measured by 24-h urine Na (UNa) excretion and 24-h ambulatory blood pressure (ABPM) monitoring.

Results

In the whole sample (N = 138), baseline UNa and 24-h ABPM were143 ± 64 mmol/24 h and 131 ± 18/72 ± 10 mmHg, respectively, and did not differ between the two study arms. Patients in the active arm of the trial used >80% of the chloride strips provided to them at the baseline visit and at follow-up visits. At the third month, UNa was 35 mmol/24 h (95% CI 10.8–58.8 mmol/24 h; P = 0.005) lower in the active arm than the control arm, whereas at 6 months the between-arms difference in UNa decreased and was no longer significant [23 mmol/24 h (95% CI −5.6–50.7); P = 0.11]. The 24-h ABPM changes as well as daytime and night-time BP changes at 3 and 6 months were similar in the two study arms (Month 3, P = 0.69–0.99; Month 6, P = 0.73–0.91). Office BP, the use of antihypertensive drugs, estimated Glomerular Filtration Rate (eGFR) and proteinuria remained unchanged across the trial.

Conclusions

The application of self-measurement of urinary chloride to guide adherence to a low salt diet had a modest effect on 24-h UNa and no significant effect on 24-h ABPM.
Occipital-Cervical Fusion and Ventral Decompression in the Surgical Management of Chiari-1 Malformation and Syringomyelia: Analysis of Data From the Park-Reeves Syringomyelia Research Consortium
Authors: CreveCoeur Travis S , Yahanda Alexander T , Maher Cormac O , Johnson Gabrielle W , Ackerman Laurie L , Adelson P David , Ahmed Raheel , Albert Gregory W , Aldana Phillipp R , Alden Tord D , Anderson Richard C E , Baird Lissa , Bauer David F , Bierbrauer Karin S , Brockmeyer Douglas L , Chern Joshua J , Couture Daniel E , Daniels David J , Dauser Robert C , Durham Susan R , Ellenbogen Richard G , Eskandari Ramin , Fuchs Herbert E , George Timothy M , Grant Gerald A , Graupman Patrick C , Greene Stephanie , Greenfield Jeffrey P , Gross Naina L , Guillaume Daniel J , Haller Gabe , Hankinson Todd C , Heuer Gregory G , Iantosca Mark , Iskandar Bermans J , Jackson Eric M , Jea Andrew H , Johnston James M , Keating Robert F , Kelly Michael P , Khan Nickalus , Krieger Mark D , Leonard Jeffrey R , Mangano Francesco T , Mapstone Timothy B , McComb J Gordon , Menezes Arnold H , Muhlbauer Michael , Oakes W Jerry , Olavarria Greg , O’Neill Brent R , Park Tae Sung , Ragheb John , Selden Nathan R , Shah Manish N , Shannon Chevis , Shimony Joshua S , Smith Jodi , Smyth Matthew D , Stone Scellig S D , Strahle Jennifer M , Tamber Mandeep S , Torner James C , Tuite Gerald F , Wait Scott D , Wellons John C , Whitehead William E , Limbrick David D
Published: September 2020

BACKGROUND

Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology.

OBJECTIVE

To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD.

METHODS

The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD.

RESULTS

All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P < .001) were increased within the OCF group, whereas only basilar invagination (1/4, P < .001) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 ± 15.3°, P = .008) and OCF/VD (115.0 ± 11.6°, P = .025) groups when compared to PFD-only group (145.3 ± 12.7°). pB-C2 did not differ among groups.

CONCLUSION

Although PFD alone is adequate for treating the vast majority of CM-1/SM patients, OCF or OCF/VD may be occasionally utilized. Cranial base and spine pathologies and CXA may provide insight into the need for OCF and/or OCF/VD.
Assessing Different Approaches to Leveraging Historical Smoking Exposure Data to Better Select Lung Cancer Screening Candidates: A Retrospective Validation Study
Authors: Kats Daniel J , Adie Yosra , Tlimat Abdulhakim , Greco Peter J , Kaelber David C , Tarabichi Yasir
Published: September 2020

Introduction

There is mounting interest in the use of risk prediction models to guide lung cancer screening. Electronic health records (EHRs) could facilitate such an approach, but smoking exposure documentation is notoriously inaccurate. While the negative impact of inaccurate EHR data on screening practices reliant on dichotomized age and smoking exposure-based criteria has been demonstrated, less is known regarding its impact on the performance of model–based screening.

Aims and Methods

Data were collected from a cohort of 37 422 ever-smokers between the ages of 55 and 74, seen at an academic safety-net healthcare system between 1999 and 2018. The National Lung Cancer Screening Trial (NLST) criteria, PLCOM2012 and LCRAT lung cancer risk prediction models were validated against time to lung cancer diagnosis. Discrimination (area under the receiver operator curve [AUC]) and calibration were assessed. The effect of substituting the last documented smoking variables with differentially retrieved “history conscious” measures was also determined.

Results

The PLCOM2012 and LCRAT models had AUCs of 0.71 (95% CI, 0.69 to 0.73) and 0.72 (95% CI, 0.70 to 0.74), respectively. Compared with the NLST criteria, PLCOM2012 had a significantly greater time–dependent sensitivity (69.9% vs. 64.5%, p < .01) and specificity (58.3% vs. 56.4%, p < .001). Unlike the NLST criteria, the performances of the PLCOM2012 and LCRAT models were not prone to historical variability in smoking exposure documentation.

Conclusions

Despite the inaccuracies of EHR–documented smoking histories, leveraging model–based lung cancer risk estimation may be a reasonable strategy for screening, and is of greater value compared with using NLST criteria in the same setting.

Implications

EHRs are potentially well suited to aid in the risk–based selection of lung cancer screening candidates, but healthcare providers and systems may elect not to leverage EHR data due to prior work that has shown limitations in structured smoking exposure data quality. Our findings suggest that despite potential inaccuracies in the underlying EHR data, screening approaches that use multivariable models may perform significantly better than approaches that rely on simpler age and exposure–based criteria. These results should encourage providers to consider using pre-existing smoking exposure data with a model–based approach to guide lung cancer screening practices.