bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying myocardial injuries in “normal-appearing” myocardium in pediatric patients with clinically suspected myocarditis using mapping techniques
Authors: Wang Haipeng , Zhao Bin , Yang Huan , Qian Tianyi , Han Bo , Jia Haipeng , An Jing , Zhao Junyu , Wang Ximing , Wang Cuiyan
Published: November 2020

Background

Mapping techniques using cardiac magnetic resonance imaging have significantly improved the diagnostic accuracy for myocarditis with focal myocardial injuries. The aim of our study was to determine whether T1 and T2 mapping techniques could identify diffuse myocardial injuries in “normal-appearing” myocardium in pediatric patients with clinically suspected myocarditis and to evaluate the associations between diffuse myocardial injuries and cardiac function parameters.

Methods

Forty-six subjects were included in this study: 20 acute myocarditis patients, 11 subacute/chronic myocarditis patients and 15 control children. T2 values, native T1 values and the extracellular volume (ECV) of “normal-appearing” myocardium were compared among the three groups of patients. Associations between diffuse myocardial injuries and cardiac function parameters were also evaluated.

Results

The ECV of “normal-appearing” myocardium was significantly higher in the subacute/chronic myocarditis group than in the control group (30.1 ± 0.9 vs 27.0 ± 0.6, P =0.004). No significant differences in T1 and T2 values between the acute myocarditis and control groups were found. In the subacute/chronic myocarditis group, a significant association between ECV and left ventricle ejection fraction was found (P=0.03).

Conclusions

Diffuse myocardial injuries are likely to occur in subacute/chronic myocarditis patients with prolonged inflammatory responses. Mapping techniques have great value for the diagnosis and monitoring of myocarditis.
A CONCEPTUAL STUDY ON TRIDOSHA PERSPECTIVE OF MILD COGNITIVE IMPAIRMENT: A REVIEW
Authors: D S Vinod , Patil Usha
Published: November 2020

Mild cognitive impairment is featured by its utility to identify individuals more susceptible to Dementia. In Ayurveda, this condition can be studied as a prodromal stage of diseases causing impairment in cognition; Tridoshas, by its unique nature of maintaining and vitiating both bodily and psychic factors including that of cognition, find an indispensable role in the pathology of mild cognitive impairment. Knowledge of other factors involved and associated in the cognitive process can enrich its scientific understanding in the clinical scenario.
ORAL INSULIN DELIVERY: AN OVERVIEW
Authors: P V Swamy , D D Phanisri , Rani G Prasanna
Published: November 2020

Oral insulin is an exciting space of research and development within the field of diabetology. The oral route is taken into account to be the foremost convenient and desired route of drug delivery, particularly, when repeated or routine administration is necessary. Diabetes mellitus is a serious pathologic condition that is to blame for major healthcare problems. Insulin replacement therapy has been employed in the clinical management of diabetes mellitus for over 90 years. So, the development of oral insulin remains an ultimate goal to both enhance ease of use and to produce therapeutic benefits rooted in its direct delivery to the portal vein and liver. This brief review covers the importance, novel approaches of oral insulin delivery as well as challenges, market status and future perspectives of oral insulin products.
CUBOSOMES: A NOVEL DRUG DELIVERY SYSTEM OVERVIEW
Authors: Yalavarthi Lakshmi Prasanna , Jonnadula Pavan Kumar , Manthina Mohan Varma , Addagalla Anand
Published: November 2020

Cubosomes are self-assembled, nanostructured, thermodynamically stable, square and rounded particles with cubic lattices visible. These are considered as versatile systems because of their properties and hence administrable in different ways such as orally, percutaneously, and parenterally. Cubosomes are organized in three dimensions as honey combed structures that are comprised of curved bicontinuous lipid bilayers which are divided into two internal aqueous channels that can be exploited by various bioactive ingredients, such as chemical drugs, peptides and proteins. Cubosomes can easily be incorporated into product formulations as they remain stable almost at any dilution level because of the relative insolubility of cubic phase forming lipid in water. This article gives an overview on structure, classification, properties, components, forms, preparation methods, evaluation and applications of cubosomes.
EFFICACY OF CHAKRAMARDA PATRA SWARASA (CASSIA TORA LINN) AND DADHI IN KRIMIJA ATISARAM: A PRECLINICAL APPROACH
Authors: S Sreelekshmi , S Priya , B Priyalatha
Published: November 2020

Diarrhoea is a major public health problem especially in developing countries. The signs and symptoms of Diarrhoea can nearly be co-related to Atisara. Diarrhoea caused by bacterial pathogens can be equated with the lakshanas seen in Krimija Atisara. Hetu vyadhi pratyanika chikitsa is explained by Acharya Sushruta for treating Krimija Atisara. In Yogamritam Atisara chikitsa Adhikara; it is explained that Chakramarda patra Swarasa, taken along with Dadhi is effective in Atisara. Hence, the study has been undertaken as a pre-clinical step- In vitro Agar well diffusion model, Microorganisms used for the study are E coli and Staphylococcus aureus. Two trial groups were included in this study; trial group 1- Chakramarda patra Swarasa alone, Trial group 2- Chakramarda patra Swarasa with Dadhi. Gentamicin was used as Standard. It was observed that the 2 trial groups showed Zone of inhibition against E coli and Staphylococcus aureus. Both the trial groups showed More Zone of inhibition against Staphylococcus aureus than E coli. Mean zone of inhibition of the 2 trial groups was found to be lower as compared to that of Mean zone of inhibition of the standard against E coli and Staphylococcus aureus. Student ’t’ test is used to analyze the data. The ‘t’ value is not statistically significant at the level of P < 0.05. Hence null hypothesis is accepted and alternate hypothesis is rejected.This article aims to give a scientific validity to usage of Chakramarda patra Swarasa with Dadhi in Krimija Atisara.
Trends in Area, Production and Productivity in Onion in Tamil Nadu
Authors: Parimalarangan R.
Published: November 2020

India ranks first in area in onion and second in production next to China, but productivity is low as compared to Netherland, USA, China. Growth rates are widely employed in the field of agriculture as these have important policy implications. To study the trends of growth in area, production and productivity of onion crop compound growth rate were worked out. The study concluded that In India, Even though there was decline in area, increasing trend in production was noticed. It was due to increase in Productivity. In Tamil Nadu, the trend in area, production and productivity of Onion was found to be stable.
Circular RNA profiling identifies circ102049 as a key regulator of colorectal liver metastasis
Authors: Zhi Qiaoming , Wan Daiwei , Ren Rui , Xu Zhihua , Guo Xiaobo , Han Ye , Liu Fei , Xu Ye , Qin Lei , Wang Yilin
Published: November 2020

Circular RNA (circRNA) plays an essential role in the development and progression of various cancers. However, the functions and mechanisms of circRNA in colorectal liver metastasis have not been fully elucidated. We performed circRNA microarray analysis to screen differentially expressed circRNA in the pathology of colorectal liver metastasis. Quantitative real‐time PCR was used to detect the expression of hsa_circ_102049 (circ102049) in colorectal cancer (CRC) samples. CRC cells were transfected with circ102049 overexpression vector or small interfering (si)RNA to assess the effects of circ102049 in vitro. Bioinformatics analysis, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull‐down and luciferase reporter assays were conducted to confirm the relationship of circ102049, miR‐761, miR‐192‐3p and FRAS1. The mechanism by which circ102049 recruits and distributes DGCR8 protein in the cytoplasm was also investigated. We found that circ102049 was highly expressed in primary CRC tumors with liver metastasis and closely correlated with the prognosis of patients with CRC. Circ102049 significantly enhanced the adhesion, migration and invasion abilities of CRC cells, and promoted CRC progression via a micro (mi)R‐761/miR‐192‐3p‐FRAS1‐dependent mechanism. Notably, due to the distribution of DGCR8 protein, circ102049 may also indirectly reduce the levels of mature miR‐761 and miR‐192‐3p in the cytoplasm. In addition, the role of circ102049 in promoting colorectal liver metastasis was confirmed in vivo. Our findings provide new evidence that circ102049 may be a potential prognostic factor in CRC, and that the circ102049‐miR‐761/miR‐192‐3p–FRAS1 axis may be an anti‐metastatic target for CRC patients.
Randomized Quasi‐Monte Carlo
Authors: L'Ecuyer Pierre
Published: November 2020

Monte Carlo (MC) methods useindependentuniform random numbers to sample realizations of random variables and sample paths of stochastic processes, often to estimate high‐dimensional integrals that can represent mathematical expectations. Randomized quasi‐Monte Carlo (RQMC) methods replace the independent random numbers bydependentuniform random numbers that cover the space more evenly. When estimating an integral, they can provide unbiased estimators whose variance converges at a faster rate than with Monte Carlo. RQMC can also be effective for the simulation of Markov chains, to approximate or optimize functions, to solve partial differential equations, for density estimation, and so on.
Forecasting with the Theta Method
Authors: Nikolopoulos Konstantinos , Thomakos Dimitrios D.
Published: November 2020

Theta method is the most successful univariate time series forecasting method of the past two decades, since its origination in 1999. The method's success has been demonstrated in applications in demand forecasting, marketing, and supply chain forecasting contexts; nevertheless, the success in extensive
blind
empirical forecasting competitions also involved thousands of series from finance, economics, and a wide range of applications and thus attested for generalizability. The superior performance of Theta method originally was proved in the M3 completion in 2000, where the Theta method was the only method that outperformed Forecast Pro and dominated a pool of 18 academic methods and 5 software packages. The performance in M4 competition was also very commendable where the method outperformed – in both accuracy and computational time – all standard forecasting benchmarks, most notably the well‐celebrated ETS method and the ARIMA models in all their variants. Theta method has also been an essential part of most of the well‐performing combinations that participated in M4. In essence, Theta method and Dampen Trend Exponential Smoothing are the two benchmarks that any new forecasting method should outperform, in order to pass the test of time.
Statistical Process Monitoring for Manifold Data
Authors: del Castillo Enrique , Zhao Xueqi
Published: November 2020

Manifold data is a fundamental type of complex data that are common in modern industry. It occurs when data lie on a lower dimensional, curved subspace or manifold. This article reviews the recent approaches for statistical process monitoring of a discrete‐part manufacturing system based on the manifold data obtained from part metrology. The approaches reviewed are based on estimating the spectrum of the Laplace–Beltrami (LB) operator of the scanned parts and using it in a multivariate nonparametric control chart for online process control. This intrinsic method has the computational advantage of avoiding the difficult part registration problem.
Statistical Software
Authors: Schissler Alfred G. , Knudson Alexander D.
Published: November 2020

This article presents a fairly comprehensive view of contemporary statistical software. Our goal is to guide users transitioning from basic statistical applications (problems of small‐to‐medium complexity) to large‐scale and computationally intense applications. Such computationally intense tasks include elaborate statistical modeling and machine learning, large‐scale simulations, and big data situations (such as streaming data). Throughout, we emphasize the growing diversity of tools required for the modern data scientist. To that end we cover a broad number of statistical software packages and related programs. To aid in the discussion, we categorize software into three classes: popular statistical software, related and noteworthy statistical software, and promising/emerging statistical software. We also discuss user environments and workflow considerations to provide practical guidance, aiming to increase user efficiency. We conclude with some prognostications about the future of statistical software.
Functional Data Visualization
Authors: Genton Marc G. , Sun Ying
Published: November 2020

This article reviews tools to visualize functional data, that is, curves, surfaces/images, and trajectories. These tools are based on ranking functional data by means of notions of depth/outlyingness and make use of methods for functional outlier detections. For univariate functional data, the functional boxplot and surface boxplot are emphasized. For multivariate functional data, the magnitude–shape plot, the two‐stage functional boxplot, and the trajectory functional boxplot are described. A bivariate functional dataset of the angles formed by the hip and knee of 39 children over their gait cycles is used throughout for illustration of the various visualization tools.
Monetizing Industry 4.0 and IoT Data for Marketing and Sales – Collected from Connected Cars
Authors: Coleman Shirley Y. , Ahlemeyer‐Stubbe Andrea
Published: November 2020

Connected cars use sensors to collect diverse and massive amounts of data. Wise companies are well aware of the importance of data arising from such
Industry 4.0
sensors. They are able to develop new business models, initiate disruptive innovations, and open up new sources of revenue. At the same time, society is becoming more and more familiar with data from the so‐called IoT, the
Internet of Things
. The less‐technical areas of
marketing and sales
can also benefit from this mass of data, and it is this vital part of the business chain upon which this article focuses. This article discusses concrete examples from the area of connected cars. It describes the data which is generated and shows value creation opportunities for marketing and sales both in large companies and small or medium enterprises (SMEs).
The association of frailty with olfactory and gustatory dysfunction in older adults: a nationally representative sample
Authors: Bernstein Isaac A. , Roxbury Christopher R. , Lin Sandra Y. , Rowan Nicholas R.
Published: November 2020

Background

Olfaction and gustation are associated with age‐related decline. Deficits in these chemosenses have been associated with significant comorbidities. Meanwhile, frailty, defined as a reduced physiological reserve, is well correlated with mortality and worse health outcomes. We sought to analyze a nationally representative patient population to determine the association between chemosensory dysfunction and frailty.

Methods

Cross‐sectional analysis of U.S. National Health and Nutrition Examination Survey (NHANES) 2013‐2014 was performed, using multivariate logistic regression to examine the association between chemosensory dysfunction and frailty in adults aged ≥40 years (n = 3547). Self‐reported olfactory dysfunction (sOD) and gustatory dysfunction (sGD), and measured olfactory dysfunction (mOD) and gustatory dysfunction (mGD) were assessed for all participants. Frailty was operationalized using a 39‐item frailty index (FI) and stratified into 4 groups using validated cutoffs.

Results

Participants with sOD and mOD had significantly higher mean FI scores (sOD: 0.18 vs 0.13, p < 0.001; mOD: 0.20 vs 0.14, p < 0.001), whereas subjects with sGD, but not mGD, had higher mean FI scores (sGD: 0.21 vs 0.13, p < 0.001; mGD: 0.14 vs 0.14, p = 0.953). Multivariate logistic regression demonstrated frail participants had significantly greater odds of sGD (odds ratio [OR] 4.11; 95% confidence interval [CI], 3.46 to 4.88), sOD (OR 2.35; 95% CI, 1.98 to 2.78), and mOD (OR 1.58; 95% CI, 1.22 to 2.05), but not mGD (OR 1.21; 95% CI, 0.91 to 1.61). This association was strongest in the frailest group.

Conclusion

Self‐reported chemosensory dysfunction and mOD are independently associated with measures of frailty, suggesting a novel method to assess or predict frailty.
Wood flour‐high density polyethylene composites: Influence of silanization and esterification on mechanical properties
Authors: Bijaisoradat Orachitr , Yue Liang , Manas‐Zloczower Ica , Manuspiya Hathaikarn
Published: November 2020

Silanization and esterification are strategies used to treat wood flour (WF) to produce surface functionalized hydrophobic WF leading to an improvement in dispersion and compatibility between wood phase and polymer phase. Silanization involves functionalization of alkyl groups by coupling trimethoxy (propyl) silane (MPS), and esterification functionalizes WF with ester groups, using acetic anhydride (Ac). Modified WF was incorporated into recycled high‐density polyethylene (HDPE) to form reHDPE/mod‐WF composite system. Both modifications produced highly hydrophobic WF surfaces which improved the dispersion in the reHDPE matrix; resulting in a significant difference in impact strength, specifically at 20 wt% filler, from 74.5 Jm−1 to 146.3 Jm−1 and 113.5 Jm−1, that is, up to 96% and 52% for MPS‐WF and Ac‐WF, respectively. However, filler agglomeration higher than 20 wt% reduces the composite impact strength. The results herein demonstrate that alkyl‐functionalized WF show excellent dispersion in the reHDPE system and is the preferred technique to improve system mechanical resilience as compared to esterification.
The male external urethral sphincter is autonomically innervated
Authors: Nyangoh Timoh Krystel , Moszkowicz David , Creze Maud , Zaitouna Mazen , Felber Margaux , Lebacle Cédric , Diallo Djibril , Martinovic Jelena , Tewari Ashutosh , Lavoué Vincent , Ghukasyan Gevorg , Benoit Gerard , Bessede Thomas
Published: November 2020

Introduction

The aim of the present study was to describe autonomic urethral sphincter (US) innervation using specific muscular and neuronal antibody markers and 3D reconstruction.

Material and methods

We performed en‐bloc removal of the entire pelvis of three male human fetuses between 18 and 40 weeks. Serial whole mount sections (5 μm intervals) were stained and investigated. The sections were stained with Masson's trichrome and Eosin Hematoxylin, and immunostained with: anti‐SMA antibody for smooth muscle; anti‐S100 antibody for all nerves; and anti‐PMP22 antibody, anti‐TH antibody, anti‐CGRP antibody, anti‐NOS antibody for somatic, adrenergic, sensory and nitrergic nerve fibers, respectively. The slides were digitized for 3D reconstruction to improve topographical understanding. An animated reconstruction of the autonomic innervation of the US was generated.

Results

The external and internal US are innervated by autonomic nerves of the inferior hypogastric plexus (IHP). These nerves are sympathetic (positive anti‐TH antibody), sensory (positive anti‐CGRP antibody), and nitrergic (positive anti‐NOS antibody). Some autonomic fibers run within the neurovascular bundles, posterolaterally. Others run from the IHP to the posteromedial aspect of the prostate apex, above an through the rectourethral muscle. The external US is also innervated by somatic nerves (positive anti‐PMP22 antibody) arising from the pudendal nerve, joining the midline but remaining below the rectourethral.

Conclusions

This study provides anatomical evidence of an autonomic component in the innervation of the external US that travels in the neurovascular bundle. During radical prostatectomy, the rectourethral muscle and the neurovascular bundles are to be preserved, particularly during apical dissection.
An atypical presentation of Kikuchi‐Fujimoto disease: A case report & literature review
Authors: Halawa Abdul Rahman R. , Ahmad Muayad K. , Nashwan Abdulqadir J.
Published: November 2020

The authors urge clinicians to consider the possibility of Kikuchi‐Fujimoto Disease associated with autoimmune hemolytic anemia with possible correlation with systemic lupus erythematosus in patients presented with lymphadenopathy and fever.
Diabetes association with self‐reported health, resource utilization, and prognosis post‐myocardial infarction
Authors: Nicolau José C. , Brieger David , Owen Ruth , Furtado Remo H.M. , Goodman Shaun G. , Cohen Mauricio G. , Simon Tabassome , Westermann Dirk , Granger Christopher B. , Grieve Richard , Yasuda Satoshi , Chen Jiyan , Hedman Katarina , Mellström Carl , Brandrup‐Wognsen Gunnar , Pocock Stuart J.
Published: November 2020

Background

Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health‐related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post‐myocardial infarction (MI) patients with and without DM.

Hypothesis

In post‐MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes.

Methods

The prospective, observational long‐term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post‐MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self‐reported health status was assessed at baseline, 1 and 2 years and converted to EQ‐5D scores. The main outcome measures were baseline HRQoL and HRU during follow‐up.

Results

DM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ‐5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All‐cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2‐year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively.

Conclusions

Stable post‐MI patients with DM (especially insulin treated) had poorer EQ‐5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high‐risk population should be developed to improve outcomes.

Trial registration

ClinicalTrials.gov: NCT01866904 (https://clinicaltrials.gov).
Analysis of experiments to determine individual colour preference
Authors: Yu Luwen , Westland Stephen , Li Zhenhong
Published: November 2020

Finding an efficient way to understand individual colour preference is important to researchers and designers. This article compares three research strategies to test individual colour preference including two research experimental environments (online and laboratory) and two research methods (multiple choice for N‐alternative‐forced‐choice and multiple choice for rank‐order). Three psychophysical experiments have been carried out. Participants were presented with six colour patches (red, orange, yellow, green, blue, and purple) arranged in a random order on a computer display. In the first two experiments (Online experiment and Laboratory experiment I), participants were asked to indicate which colour square they prefer most; in the third experiment (Laboratory experiment II), participants were asked to rank their colour preferences of the six colour patches. The similarity between the results obtained from two experimental environments provides some validation for the online protocol and suggests that online experiments could be used more often. Pairwise comparisons for individual colour preference between genders and nationalities were carried out, and it was found that male and female responses were significantly different; but there was no statistical significance between Chinese and UK participants. The results from Monte Carlo simulations suggested that the rank‐order method should be preferred for individual colour preference studies involving small numbers of participants (especially less than 15 participants).
Validation of the Questionnaire for Symptom Assessment in Pain disorders for Back pain patients (Q‐SAP)
Authors: Otto Jan Carl , Gierthmühlen Janne , Kirchhofer Viktoria , Borzikowsky Christoph , Baron Ralf
Published: November 2020

Background

Previous studies have shown that not only pain intensity but also impairment of quality of life and functionality are important parameters for the evaluation of treatment of chronic low back pain patients. The aim of the study was to validate a specific self‐questionnaire for symptom assessment and their influence on quality of life and functionality of chronic low back pain patients (Questionnaire for Symptom Assessment in Pain disorders for back pain patients, Q‐SAP).

Methods

The self‐questionnaire consists of two parts (for back and if applicable leg symptoms) and was tested in 152 chronic low back pain patients with and without radiculopathy. Test–retest reliability, exploratory factor analysis, convergent validity, criterion‐related validity and the sensitivity to detect patient reported changes were investigated.

Results

The questionnaire showed a good to excellent test–retest reliability. In the factor analysis nociceptive and neuropathic pain components could be separated and the highest convergent validities were shown for the painDETECT, EQ‐5D‐3L and the FFbH‐R. The criterion‐related validity showed concordance of QST and the Q‐SAP Back for warmth induced pain and numbness. Regarding the sensitivity to patient‐reported changes, a moderate correlation was found for both parts of the questionnaire.

Conclusions

The Q‐SAP was tested as a useful, valid and reliable tool. This new questionnaire records classical nociceptive and neuropathic pain symptoms of chronic low back pain patients depending on their local distribution. Furthermore, the questionnaire records the intensity of these symptoms and their influence on quality of life and functionality and can be used for the evaluation of treatment.

Significance

The Q‐SAP Back/Leg is a new self‐questionnaire for CLBP patients with or without radiating leg pain that precisely assesses neuropathic and nociceptive symptoms. In contrast to other questionnaires, the Q‐SAP Back/Leg evaluates not only symptom intensities but also their impact on the patient's quality of life and functionality. Furthermore, this questionnaire requests the symptoms depending on their anatomical distribution.
Words Matter
Authors: Kaebnick Gregory E.
Published: November 2020

The lead article in this, the September‐October 2020, issue of the Hastings Center Report considers the use of metaphors in communications with clinicians and patients.
Perceptual learning of tone patterns changes the effective connectivity between Heschl's gyrus and planum temporale
Authors: Lumaca Massimo , Dietz Martin J. , Hansen Niels Chr. , Quiroga‐Martinez David R. , Vuust Peter
Published: November 2020

Learning of complex auditory sequences such as music can be thought of as optimizing an internal model of regularities through unpredicted events (or “prediction errors”). We used dynamic causal modeling (DCM) and parametric empirical Bayes on functional magnetic resonance imaging (fMRI) data to identify modulation of effective brain connectivity that takes place during perceptual learning of complex tone patterns. Our approach differs from previous studies in two aspects. First, we used a complex oddball paradigm based on tone patterns as opposed to simple deviant tones. Second, the use of fMRI allowed us to identify cortical regions with high spatial accuracy. These regions served as empirical regions‐of‐interest for the analysis of effective connectivity. Deviant patterns induced an increased blood oxygenation level‐dependent response, compared to standards, in early auditory (Heschl's gyrus [HG]) and association auditory areas (planum temporale [PT]) bilaterally. Within this network, we found a left‐lateralized increase in feedforward connectivity from HG to PT during deviant responses and an increase in excitation within left HG. In contrast to previous findings, we did not find frontal activity, nor did we find modulations of backward connections in response to oddball sounds. Our results suggest that complex auditory prediction errors are encoded by changes in feedforward and intrinsic connections, confined to superior temporal gyrus.
Trimethoprim‐sulfamethoxazole as Pneumocystis jiroveci pneumonia prevention in patients undergoing methotrexate therapy for hematological malignancies: A review of the literature
Authors: King Liam D. , Sia Hanlon , Anoopkumar‐Dukie Shailendra
Published: November 2020

Methotrexate is a cytotoxic agent that is commonly used to treat autoimmune diseases, and both solid and hematological malignancies. Drug interactions are of particular concern during methotrexate therapy, as they have the potential to alter the pharmacokinetics of methotrexate and lead to significant toxicity. One agent that has the potential to interact with methotrexate is the antimicrobial agent trimethoprim with sulfamethoxazole. Consideration of this interaction is of importance in patients that are undergoing high‐dose methotrexate therapy for hematological malignancies as trimethoprim/sulfamethoxazole is the preferred agent for Pneumocystis jiroveci pneumonia prophylaxis. Current Australian guidelines recommend avoiding concurrent administration of high‐dose methotrexate and trimethoprim/sulfamethoxazole, yet evidence to support this recommendation is unclear. This review investigates the current available evidence that focuses on the interaction between high‐dose methotrexate and trimethoprim/sulfamethoxazole and aims provide guidance for the use of this combination in clinical practice.
Light in‐network caching enabled IP network: A large‐scale content delivery in MAN
Authors: Zhang Songzhu , Wang Xingwei , Huang Min
Published: November 2020

Although the future Internet paradigm especially Information‐Centric Networking (ICN) has been recognized and accepted in recent years, the end‐to‐end IP network structure always shows the overwhelming development tendency due to the deployment difficulty of ICN on the real and large‐scale network environment. However, each coin has two sides, that is to say, ICN also has its own unique value, that is, in‐network caching feature which is not included in the current IP network. In this letter, we propose an In‐network caching enabled IP network paradigm, which is a novel concept different from both ICN and the traditional IP network. Based on such paradigm, we present a light content delivery scheme depending on identity, with the chain‐based fine‐grained caching support. Given the NP‐hardness of delivery scheme in mesh topology, we make a case study in Metropolitan Area Network (MAN) to address the large‐scale content delivery scenario. The experimental results show that the proposal in this letter can effectively relieve the load pressure of origin server, and can also greatly improve the delivery efficiency.
Genotoxicity and subchronic toxicity studies of Lipocet®, a novel mixture of cetylated fatty acids
Authors: Brilli Elisa , Tarantino Germano
Published: November 2020

Cetylated fatty acids (CFAs) are a group of fats that contain a single ester group within a hydrocarbon chain, which are reported to have beneficial biological effects. A novel mixture of CFAs produced by combining fatty acids derived from refined olive oil with cetyl esters (Lipocet®) is proposed for use as a food ingredient and was therefore subjected to a nonclinical safety assessment. The safety of Lipocet® was evaluated in a bacterial reverse mutation test and an in vitro mammalian cell micronucleus test, followed by a 90‐day oral (gavage) toxicity study. In the 90‐day study, Sprague–Dawley rats were administered with the vehicle (corn oil) or Lipocet® at 1,500, 3,000, or 4,500 mg/kg body weight/day for 90 days. A comparator reference control group received noncetylated fatty acids derived from olive oil at 4,500 mg/kg body weight/day to identify any effects that may be expected following consumption of high doses of fat. Lipocet® was nongenotoxic in vitro. In the 90‐day study, changes observed in hematological and clinical biochemistry parameters were minor in nature and/or showed poor dose dependency. Histopathology findings in the gastrointestinal tract and lungs were noted but were not associated with a clear dose response and were likely incidental. Moreover, Lipocet® was just as well tolerated as the reference control. Therefore, 4,500 mg/kg body weight/day (the highest dose tested) was considered the no‐observed‐adverse‐effect‐level. These results support the safety of Lipocet® for use as a food ingredient.
Raman spectroscopy of human skin for kidney failure detection
Authors: Bratchenko Lyudmila A. , Bratchenko Ivan A. , Khristoforova Yulia A. , Artemyev Dmitry N. , Konovalova Daria Y. , Lebedev Peter A. , Zakharov Valery P.
Published: November 2020

The object of this paper is in vivo study of skin spectral‐characteristics in patients with kidney failure by conventional Raman spectroscopy in near infrared region. The experimental dataset was subjected to discriminant analysis with the projection on latent structures (PLS‐DA). Application of Raman spectroscopy to investigate the forearm skin in 85 adult patients with kidney failure (90 spectra) and 40 healthy adult volunteers (80 spectra) has yielded the accuracy of 0.96, sensitivity of 0.94 and specificity of 0.99 in terms of identifying the target subjects with kidney failure. The autofluorescence analysis in the near infrared region identified the patients with kidney failure among healthy volunteers of the same age group with specificity, sensitivity, and accuracy of 0.91, 0.84, and 0.88, respectively. When classifying subjects by the presence of kidney failure using the PLS‐DA method, the most informative Raman spectral bands are 1315 to 1330, 1450 to 1460, 1700 to 1800 cm−1. In general, the performed study demonstrates that for in vivo skin analysis, the conventional Raman spectroscopy can provide the basis for cost‐effective and accurate detection of kidney failure and associated metabolic changes in the skin.
A systematic review and meta‐analysis of telephone vs in‐person genetic counseling in BRCA1/BRCA2 genetic testing
Authors: Bracke Xavier , Roberts Jonathan , McVeigh Terri P.
Published: November 2020

Pathogenic variants in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer. Individuals with identified pathogenic variants in the BRCA1 or BRCA2 gene can benefit from cancer risk‐reducing strategies. In the recent years, there has been an increase in the demand of genetic services. In light of the ongoing COVID19 pandemic, alternatives to face‐to‐face consultations have had to be considered and adopted, including telemedicine. Informed consent is necessary for genetic testing. Studies have suggested that increased levels of cancer‐specific distress may impair the patient's ability to retain information, therefore, providing informed consent. This systematic review and meta‐analysis aimed to answer if telephone genetic counseling for BRCA1 and BRCA2 genetic testing is non‐inferior to in‐person genetic counseling for the outcomes of cancer‐specific distress and genetic knowledge. Databases of Medline, Embase, PsycINFO, CINAHL, SciELO, Web of Science, CENTRAL, ProQuest Dissertation & Theses Database, Clinicaltrials.gov, EU clinical trials register were accessed to identify any published or unpublished relevant literature. Random‐effects models were used for the meta‐analysis. Four studies were included in the qualitative synthesis of the results. Three studies were included in the quantitative synthesis of the results. Telephone genetic counseling was non‐inferior compared to in‐person genetic counseling for the outcomes of cancer‐specific distress and genetic knowledge. Sensitivity analysis corroborated the main results. Telephone genetic counseling for BRCA1/BRCA2 genetic testing may be an alternative model of delivering genetic services in front of the increased demand/or when required by social context. However, the paucity of the evidence prevents from drawing strong conclusions regarding the generalizability of these results. Further research is needed to strengthen the conclusions.
Tropical cyclone movement features in the western North Pacific region based on multi‐dimensional statistical analyses
Authors: Meng Wenjian , Liu Haijiang , Yang Mingzhe
Published: November 2020

In order to protect and mitigate the disaster caused by tropical cyclone (TC) in the western North Pacific (WNP) region, further understandings of the characteristics of historical TCs are important. In this study, multi‐dimensional statistical analyses are carried out to reveal the TC movement features in the WNP. Two representative TC datasets provided by China Meteorological Administration (CMA) and Japan Meteorological Agency (JMA) are used to investigate the historical TC properties in the WNP covering a time duration from 1951 to 2018. TC movement features generally show the great consistency with respect to these two datasets. Based on the regional (zero‐dimensional analysis) and zonally averaged (one‐dimensional analysis) results, it is found that TCs move northwest with a small velocity at low latitudes, whereas they tend to drift northeast with a large velocity at high latitudes. The recurvature occurs near 25°N where the direction of zonal drift velocity reverses. Applying the bivariate normal distribution method (quasi‐two‐dimensional analysis), the randomness of the zonal component is found to be generally greater than that of the meridional component. Accordingly, relevant attentions, rather than universal ones, should be paid to forecast the TC movement in different regions. Regarding the complete two‐dimensional analysis, it is found that compared with other areas, TCs have a smaller magnitude of drift velocity but stronger intensity with higher passage frequencies in the area enclosed by 10–25°N and 110–140°E, where significant TC‐induced disasters are prone to occur, resulting in a serious threat to the safety of human beings and local societies.
Meta‐analyzing count events over varying durations using the piecewise Poisson model: The case for poststroke seizures
Authors: Wang Wei‐Jhih , Devine Beth , Bansal Aasthaa , White H. Steve , Basu Anirban
Published: November 2020

Meta‐analyzing count data can be challenging when follow‐up time varies across studies. Simply pooling aggregate data over time‐periods would result in biased estimates, which may erroneously inform clinical decision‐making. In this study, we exploit the convolution property of the Poisson distribution to develop a likelihood for observed cumulative counts over varying follow‐up periods, where different Poisson distributions are used to represent the data generating processes for the latent counts in pre‐defined successive intervals of follow‐up. We illustrate this approach using an example of poststroke seizures, a case in which risk may change over time, and mimic its survival duration with time‐varying hazard. Data were extracted from observational studies (1997‐2016) reporting poststroke seizures over a maximum of 10 years of follow‐up. Three clinically meaningful follow‐up time intervals were considered: 0 to 7 days, 8 to 365 days, and 1 to 10 years poststroke. External validation was performed using claims data. Results suggest the incidence rate of seizures was 0.0452 (95% confidence interval: 0.0429, 0.0475), 0.0001 (0, 0.016), and 0.0647 (0.0441, 0.0941) for the three time intervals, respectively, indicating that the risk of seizures changes over time poststroke. We found that the model performed well against the incidence rate of seizures among actual retrospective cohort from claims data. The piecewise Poisson model presents a flexible way to meta‐analyze count data over time and mimic survival curves. The results of the piecewise Poisson model are readily interpretable and may spur meaningful clinical action. The method may also be applied to other diseases.

Highlights

It is challenging to perform a meta‐analysis when follow‐up time varies across studies. Ideally, outcomes over different time‐periods should be pooled with individual patient‐level data (IPD).

A new model was developed to meta‐analyze count data over time using aggregate‐level data from previous published studies.

The piecewise Poisson model could be a useful tool to estimate time‐vary hazards given available data, and mimic survival curves over time which would be readily interpretable.
Alternative weighting schemes when performing matching‐adjusted indirect comparisons
Authors: Jackson Dan , Rhodes Kirsty , Ouwens Mario
Published: November 2020

Methods for indirect comparisons and network meta‐analysis use aggregate level data from multiple studies. A very common, and closely related, scenario is where a company has individual patient data (IPD) from its own trial, but only has published aggregate data from a competitor's trial, and an indirect comparison of the treatments evaluated in these two trials is required. Matching‐Adjusted Indirect Comparison (MAIC) has been developed for this situation, where we use the available IPD to adjust for between‐trial imbalances in the distributions of observed baseline covariates between the two trials. We extend the current MAIC methodology, where we compute the weights that satisfy the conventional method of moments and result in the largest possible effective sample size (ESS). We show that the approach proposed by Zubizarreta in a previous study can be used for this purpose. We derive a new analytical result that shows why this alternative approach provides a larger ESS than a conventional MAIC. We also derive a new formula for the maximum ESS that can be achieved, even when permitting negative weights, when adjusting for one covariate. This can be used as an easily computed new metric that quantifies the difficulty in adjusting for covariates.

What is already known: MAIC is an established way to perform population adjustment in the situation where IPD is available from one trial but only aggregate level data is available from another trial, and an indirect comparison is required. However the effective sample size (ESS) can be small after making the adjustment.

What is new: We show that an alternative method can result in a larger ESS. We provide new analytical results showing why this is the case. We derive a new descriptive statistic that is based on maximising the ESS that quantifies the difficulties in adjusting for particular covariates.

Potential impact for RSM readers outside the authors' field: Reweighting methods for population adjustment are becoming more commonly used and their implications for research synthesis methodology is now considerable. This paper provides important new links between the theoretical literature, and the more applied research synthesis methodology literature, relating to this topic.
Das periodische System und die Evolution des chemischen Raums
Authors: Restrepo Guillermo
Published: November 2020

Meyer und Mendelejew ordneten und klassifizierten im 19. Jahrhundert die Elemente nach chemischen Verbindungen. Wenn Chemiker jetzt immer mehr Verbindungen synthetisieren und charakterisieren, sollte ein Periodensystem dann nicht irgendwann ganz anders aussehen?
Zwanzig Jahre Science of Synthesis
Authors: Fürstner Alois , Hopf Henning , Schaumann Ernst , Shortt de Hernandez Fiona
Published: November 2020

Die Reaktionsdatenbank, Nachfolgerin des Houben‐Weyl, feiert Jubiläum.
Elektronische Resonanzzustände – warum die Energie komplex sein kann, Trendbericht Theoretische Chemie 2020, Teil 1
Authors: Jagau Thomas
Published: November 2020

Bedingt durch die steigende Relevanz elektronischer Resonanzen gewinnen nichthermitesche Me‐thoden zunehmende Bedeutung für die Quantenchemie. Außerdem: Da magnetische Wechselwirkungen jenseits des Ferromagnetismus komplex sein können, ist ein Verständnis für die zugrundeliegenden physikalischen Prinzipien und chemischen Konzepte zu entwickeln. Dabei helfen beispielsweise Dichtefunktionaltheorie und Multireferenzmethoden. Und um die Spinzustände zu analysieren, die aus magnetischer Kopplung entstehen, eignen sich etwa Orbitalentropiemaße.
Biochemikerin trifft Mikrobiologin
Authors: Osterath Brigitte , Leusmann Eliza , Zbikowski Frauke
Published: November 2020

Die Französin Emmanuelle Charpentier und die US‐Amerikanerin Jennifer A. Doudna haben das Crispr‐Cas‐System erforscht und zu einem universell einsetzbaren Gentechnikwerkzeug weiter entwickelt. Dafür erhalten sie nun den Chemienobelpreis. Schlüssel zum Erfolg war die Kooperation zwischen zwei Frauen, die ihre Fachgebiete zusammenfügten.
Stoffströme: Kunststoffe
Authors: Bulmahn Maren
Published: November 2020

Alle zwei Jahre zeigt eine Studie den Lebensweg von Plastik in Deutschland und unterstützt die Entwicklung von Kreisläufen.
FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA-Mutated Metastatic Castrate-Resistant Prostate Cancer
Authors: Anscher Mitchell S. , Chang Elaine , Gao Xin , Gong Yutao , Weinstock Chana , Bloomquist Erik , Adeniyi Oluseyi , Charlab Rosane , Zimmerman Sarah , Serlemitsos-Day Maritsa , Ning Yang Min , Mayrosh Ruth , Fuller Barbara , Trentacosti Ann Marie , Gallagher Pamela , Bijwaard Karen , Philip Reena , Ghosh Soma , Fahnbulleh Frances , Diggs Felicia , Arora Shaily , Goldberg Kirsten B. , Tang Shenghui , Amiri-Kordestani Laleh , Pazdur Richard , Ibrahim Amna , Beaver Julia A.
Published: November 2020

The U.S. Food and Drug Administration (FDA) granted accelerated approval to rucaparib in May 2020 for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane. This approval was based on data from the ongoing multicenter, open-label single-arm trial TRITON2. The primary endpoint, confirmed objective response rate, in the 62 patients who met the above criteria, was 44% (95% confidence interval [CI]: 31%–57%). The median duration of response was not estimable (95% CI: 6.4 to not estimable). Fifty-six percent of patients had a response duration of >6 months and 15% >12 months. The safety profile of rucaparib was generally consistent with that of the class of poly-(ADP-ribose) polymerase enzyme inhibitors and other trials of rucaparib in the treatment of ovarian cancer. Deaths due to adverse events (AEs) occurred in 1.7% of patients, and 8% discontinued rucaparib because of an AE. Grade 3–4 AEs occurred in 59% of patients. No patients with prostate cancer developed myelodysplastic syndrome or acute myeloid leukemia. The trial TRITON3 in patients with mCRPC is ongoing and is planned to verify the clinical benefit of rucaparib in mCRPC. This article summarizes the FDA thought process and data supporting this accelerated approval.

Implications for Practice

The accelerated approval of rucaparib for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane represents the first approved therapy for this selected patient population. This approval was based on a single-arm trial demonstrating a confirmed objective response rate greater than that of available therapy with a favorable duration of response and an acceptable toxicity profile. The ongoing trial TRITON3 is verifying the clinical benefit of this drug.