bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphic variants INSIG2 rs6726538, HLA‐DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women
Authors: Hasan Md. Emtiaz , Matin Maliha , Haque Md. Enamul , Aziz Md. Abdul , Millat Md. Shalahuddin , Uddin Mohammad Sarowar , Moghal Md. Mizanur Rahman , Islam Mohammad Safiqul
Published: February 2021

Objective

Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome‐wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case‐control study to investigate the association of INSIG2 rs6726538 (A; T), HLA‐DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer.

Methods

The present study recruited 234 cervical cancer patients as cases and 212 healthy females as controls. We have applied the tetra‐primer amplification refractory mutation system polymerase chain reaction (T‐ARMS‐PCR) method for genotyping.

Results

The SNP rs6726538 was significantly associated with increased risk of cervical cancer in all genetic models (AT vs. AA: OR = 3.30, 95% CI = 2.19–4.97, p < 0.0001; TT vs. AA: OR = 8.72, 95% CI = 3.87–19.7, p < 0.0001; AT+TT vs. AA: OR = 3.87, 95% CI = 2.61–5.73, p < 0.0001; T vs. A: OR = 2.97, 95% CI = 2.20–4.01, p < 0.0001) except the recessive model which showed a significantly reduced risk (TT vs. AA+AT: OR = 0.20, 95% CI = 0.09–0.44, p = 0.0001). rs9272143 showed significantly reduced risk for the additive model 1, dominant model, and allelic model (TC vs. TT: OR = 0.46, 95% CI = 0.31–0.70, p = 0.0004; TC+CC vs. TT: OR = 0.47 95% CI = 0.32–0.70, p = 0.0002; C vs. T: OR = 0.56, 95% CI = 0.40–0.78, p = 0.0006, respectively). The third variant, rs7780883, was significantly associated with increased risk in additive model 2, dominant, and allelic models (AA vs. GG: OR = 5.08, 95% CI = 2.45–10.5, p < 0.0001; GA+AA vs. GG: OR = 1.54, 95% CI = 1.06–2.24, p = 0.0237; A vs. G: OR = 1.88, 95% CI = 1.34–2.52, p < 0.0001, consecutively), whereas recessive model reduced the risk of cervical cancer (AA vs. GG+GA: OR = 0.20, 95% CI = 0.09–0.41, p < 0.0001). Other models of these SNPs were not associated with cervical cancer. All significant associations for three SNPs withstand after Bonferroni correction except the additive model 2 of rs7780883.

Conclusion

Our study concludes that INSIG2 rs6726538, HLA‐DRB1 rs9272143, and GCNT1P5 rs7780883 polymorphisms may contribute to the development of cervical cancer in the Bangladeshi population.
Testing Graphical Causal Models Using the R Package “dagitty”
Authors: Ankan Ankur , Wortel Inge M. N. , Textor Johannes
Published: February 2021

Causal diagrams such as directed acyclic graphs (DAGs) are used in several scientific fields to help design and analyze studies that aim to infer causal effects from observational data; for example, DAGs can help identify suitable strategies to reduce confounding bias. However, DAGs can be difficult to design, and the validity of any DAG‐derived strategy hinges on the validity of the postulated DAG itself. Researchers should therefore check whether the assumptions encoded in the DAG are consistent with the data before proceeding with the analysis. Here, we explain how the R package ‘dagitty’, based on the web tool dagitty.net, can be used to test the statistical implications of the assumptions encoded in a given DAG. We hope that this will help researchers discover model specification errors, avoid erroneous conclusions, and build better models. © 2021 The Authors.

This article was corrected on 19 July 2022. See the end of the full text for details.

Basic Protocol 1: Constructing and importing DAG models from the dagitty web interface

Support Protocol 1: Installing R, RStudio, and the dagitty package

Basic Protocol 2: Testing DAGs against categorical data

Basic Protocol 3: Testing DAGs against continuous data

Support Protocol 2: Testing DAGs against continuous data with non‐linearities

Basic Protocol 4: Testing DAGs against a combination of categorical and continuous data
A novel mutation in the cathepsin C (CTSC)gene in Iranian family withPapillon‐Lefevresyndrome
Authors: Ghanei Mahmoud , Abbaszadegan Mohammad R. , Forghanifard Mohammad M. , Aarabi Azadeh , Arab Hamidreza
Published: February 2021

Objectives

In this study, we analyzed the whole exomes of CTSC gene in a family with history of PLS.

Materials and methods

Genomic DNA was extracted from peripheral blood and genotype analysis was performed. The mutated protein sequence was used to find the best possible tertiary structure for homology modeling. The homology modeling of the novel mutation was then performed using the online Swiss‐Prot server. The results were also analyzed for to verify its validity.

Results

The analysis of CTSC gene elucidated a novel insertion GAC. The novel mutation was proved by analyzing 50 healthy control volunteers. Modeling of the novel found mutation in CTSC gene revealed structural defects that may have caused the functional abnormalities.

Conclusions

The structural analysis of the mutated protein model identifies changes in the stereo‐chemical and the energy level of the mutated protein. Since this protein play a role in the activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, such structural defects may lead to its malfunction causing dysfunctioning of immune defense mechanisms.
Managing ecosystems in a sea of uncertainty: invasive species management and assisted colonizations
Authors: Rendall Anthony R. , Sutherland Duncan R. , Baker Christopher M. , Raymond Ben , Cooke Raylene , White John G.
Published: February 2021

Managing ecosystems in the face of complex species interactions, and the associated uncertainty, presents a considerable ecological challenge. Altering those interactions via actions such as invasive species management or conservation translocations can result in unintended consequences, supporting the need to be able to make more informed decisions in the face of this uncertainty. We demonstrate the utility of ecosystem models to reduce uncertainty and inform future ecosystem management. We use Phillip Island, Australia, as a case study to investigate the impacts of two invasive species management options and consider whether a critically endangered mammal is likely to establish a population in the presence of invasive species. Qualitative models are used to determine the effects of apex predator removal (feral cats) and invasive prey removal (rabbits, rats, and mice). We extend this approach using Ensemble Ecosystem Models to consider how suppression, rather than eradication influences the species community; and consider whether an introduction of the critically endangered eastern barred bandicoot is likely to be successful in the presence of invasive species. Our analysis revealed the potential for unintended outcomes associated with feral cat control operations, with rats and rabbits expected to increase in abundance. A strategy based on managing prey species appeared to have the most ecosystem‐wide benefits, with rodent control showing more favorable responses than a rabbit control strategy. Eastern barred bandicoots were predicted to persist under all feral cat control levels (including no control). Managing ecosystems is a complex and imprecise process. However, qualitative modeling and ensemble ecosystem modeling address uncertainty and are capable of improving and optimizing management practices. Our analysis shows that the best conservation outcomes may not always be associated with the top‐down control of apex predators, and land managers should think more broadly in relation to managing bottom‐up processes as well. Challenges faced in continuing to conserve biodiversity mean new, bolder, conservation actions are needed. We suggest that endangered species are capable of surviving in the presence of feral cats, potentially opening the door for more conservation translocations.
Geographic patterns in seasonal changes of body mass, skull, and brain size of common shrews
Authors: Lázaro Javier , Nováková Lucie , Hertel Moritz , Taylor Jan R. E. , Muturi Marion , Zub Karol , Dechmann Dina K. N.
Published: February 2021

Some small mammals exhibit Dehnel's Phenomenon, a drastic decrease in body mass, braincase, and brain size from summer to winter, followed by a regrowth in spring. This is accompanied by a re‐organization of the brain and changes in other organs. The evolutionary link between these changes and seasonality remains unclear, although the intensity of change varies between locations as the phenomenon is thought to lead to energy savings during winter.

Here we explored geographic variation of the intensity of Dehnel's Phenomenon in Sorex araneus. We compiled literature on seasonal changes in braincase size, brain, and body mass, supplemented by our own data from Poland, Germany, and Czech Republic.

We analyzed the effect of geographic and climate variables on the intensity of change and patterns of brain re‐organization.

From summer to winter, the braincase height decreased by 13%, followed by 10% regrowth in spring. For body mass, the changes were −21%/+82%, respectively. Changes increased toward northeast. Several climate variables were correlated with these transformations, confirming a link of the intensity of the changes with environmental conditions. This relationship differed for the decrease versus regrowth, suggesting that they may have evolved under different selective pressures.

We found no geographic trends explaining variability in the brain mass changes although they were similar (−21%/+10%) to those of the braincase size. Underlying patterns of change in brain organization in northeastern Poland were almost identical to the pattern observed in southern Germany. This indicates that local habitat characteristics may play a more important role in determining brain structure than broad scale geographic conditions.

We discuss the techniques and criteria used for studying this phenomenon, as well as its potential presence in other taxa and the importance of distinguishing it from other kinds of seasonal variation.
High power density inverter utilizing SiC MOSFET and interstitial via hole PCB for motor drive system
Authors: Sato Ikuya , Tanaka Takaaki , Hori Motohito , Yamada Ryuuji , Toba Akio , Kubota Hisao
Published: February 2021

This paper proposes a high power density inverter utilizing SiC metal‐oxide‐semiconductor field‐effect transistor (MOSFET) modules and an interstitial via hole (IVH) printed circuit board (PCB) for a motor drive system. The inverter also includes a power circuit, heatsink, cooling fan, gate drive circuit, and DC capacitors. The output power density of the proposed inverter is 81 kW/L. The inverter outputs 37 kW for motor drive applications. To achieve this superior output power density, this paper explains a prototype SiC MOSFET module without an antiparallel schottky barrier diode, and a unique multilayer laminate IVH PCB to connect the modules and DC capacitors. This paper describes the experimental results to verify the motor drive performance and the increase in temperature under the rated load operation.
Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA‐HF trial
Authors: Butt Jawad H. , Nicolau Jose C. , Verma Subodh , Docherty Kieran F. , Petrie Mark C. , Inzucchi Silvio E. , Schou Morten , Kosiborod Mikhail N. , Langkilde Anna Maria , Martinez Felipe A. , Ponikowski Piotr , Sabatine Marc S. , Sjöstrand Mikaela , Solomon Scott D. , Bengtsson Olof , Jhund Pardeep S. , McMurray John J.V. , Køber Lars
Published: February 2021

Aims

We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF).

Methods and results

Aetiology was investigator‐reported and categorized as ischaemic or non‐ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA‐HF, of whom 2674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13–1.63], but lower risk of HF hospitalization (HR 0.83, 95% CI 0.70–0.98) than non‐ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non‐ischaemic aetiology (HR 0.77, 95% CI 0.65–0.92, and HR 0.71, 95% CI 0.58–0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all‐cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ‐TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology.

Conclusions

Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non‐ischaemic aetiology. In addition, dapagliflozin was safe and well‐tolerated, irrespective of aetiology.
Organocatalytic Amination of Pyrazolones with Azodicarboxylates: Scope and Limitations
Authors: Formánek Bedřich , Šeferna Vít , Meazza Marta , Rios Ramon , Patil Mahendra , Veselý Jan
Published: February 2021

The organocatalytic amination of pyrazol‐5‐ones with azodicarboxylates (catalyzed by quinine) is reported. This asymmetric process furnishes enantiomerically enriched hydrazine adducts containing quaternary stereocenters in high yields (74–96 %) and enantioselectivities (up to ee 97 %). Theoretical calculations allow us to propose the relations between quinine catalyst and reactants leading to observed stereochemical outcome and trends in the effectivity of the reaction.
Thermo‐mechanical modeling of the temperature dependent forming behavior of thermoplastic prepregs
Authors: Ziegs Jean‐Paul , Weck Daniel , Gude Maik , Kästner Markus
Published: February 2021

Numerical optimization of the manufacturing process of hybrid lightweight structures consisting of fiber‐reinforced plastics is of great importance. This article introduces an industry‐oriented modeling approach for the thermoforming process of thermoplastic prepregs. A laminate model combined with established elastic‐plastic constitutive laws is used for the numerical treatment of the temperature dependent material behavior of the composite. The mechanical properties of the Polyamide 66 (PA66) matrix are acquired from a data sheet provided by the manufacturer. Experiments including tensile, shear, and bending tests are performed to characterize the effective deformation behavior of the prepreg in the full temperature range. Appropriate model parameters are determined to represent the temperature dependent deformation behavior of the composite according to the experimental observations. The parameterized material model for the prepreg is eventually applied in the simulation of thermoforming processes to show the influence of process and material parameters on the forming behavior of thermoplastic prepregs.
Performance of unscented Kalman filter for model updating with experimental data
Authors: Cheng Mao , Becker Tracy C.
Published: February 2021

The unscented Kalman filter (UKF) is one of the most widely used algorithms for identifying and updating numerical model parameters. When updating from experimental data, the UKF performs well but it is sensitive to the selection of the initial algorithm variables and vulnerable to the influence of measurement noise. Furthermore, the ability to capture new behavioral features, such as hardening at large displacements, is a challenge. To achieve a more robust algorithm that can learn new features, techniques from the constrained UKF and the adaptive UKF are combined with an additional weighting on learning based on the magnitude of the input. The weighted adaptive constrained unscented Kalman filter (WACUKF) updates the numerical model with adaptive calculation of measurement noise and assigns a different learning rate for measurement data through the weighting function. To confine parameter values in the ranges with physical sense, the WACUKF adopts the sigma points projecting strategy for constrained parameters. Data from two experiments conducted on different structural components, in different laboratories, with different setups are used to validate the effectiveness of the WACUKF and compare against the performance of the UKF. The results demonstrate that the WACUKF can capture and preserve new features during model updating and is more robust and accurate than the UKF.
Prediction of remaining time on site for e‐commerce users: A SOM and long short‐term memory study
Authors: Kao Ling‐Jing , Chiu Chih‐Chou , Wang Hung‐Jui , Ko Chang Yu
Published: February 2021

With the development of information technology, online transactions and e‐commerce are gradually replacing conventional consumption patterns. To obtain a competitive advantage, industries proactively engage in digital transformations and the management of e‐commerce platforms. Faced with changes in market patterns, e‐commerce channels and online advertising firms hope to extend users' website browsing duration/time on site to enhance the effects of product promotion and the likelihood of advertisement clicks. The greatest challenge in predicting time on site is that clickstream data are not mutually independent, and short‐, mid‐, and long‐term data may intervene in a time series. Such timing dependence increases difficulty of capturing or learning the characteristics of website users for ordinary prediction models and leads to confusion and deviation during model construction. Accordingly, this study proposed a prediction method integrating self‐organizing map (SOM) and long short‐term memory (LSTM). The SOM method was initially applied to categorize website members into groups based on similarities in browsing behavior, and the LSTM prediction model was subsequently developed using the webpage browsing data of each group. The performance of the proposed method is evaluated by comparing the prediction with the results of three competing approaches (SOM with support vector regression, SOM with multilayer perceptron, and single LSTM) on the clickstream data provided by a leading online retailer specializing in selling skin care and cosmetics products in Taiwan. The Wilcoxon signed‐rank test validated the proposed SOM‐LSTM model outperforms competing approaches in remaining time‐on‐site prediction. This study serves as a first attempt to systematically predict remaining time on site for e‐commerce users in terms of empirically verifying a hybrid approach which integrates SOM and LSTM techniques.
Intranodal lymphangiography with thoracic duct embolization for the treatment of chyle leaks after head and neck cancer surgery
Authors: Ushinsky Alexander , Guevara Carlos J. , Kim Seung Kwon
Published: February 2021

Background

Thoracic duct injury is a rare complication of head and neck surgery. Thoracic duct embolization (TDE) has been proposed to manage postoperative chyle leaks.

Methods

Twelve patients who underwent lymphangiography for a chyle leak after head and neck surgery (M:F = 5:7, mean 55 years) were retrospectively reviewed. Lymphangiographic findings, technical success, complications, and clinical outcomes were analyzed.

Results

Chyle leak was identified and TDE attempted in 11 of 12 patients. Three patients required repeat TDE. Technical success of TDE was 86% (12/14). Clinical success for patients with technically successful TDE was 90% (9/10). Median time until drain removal was 2.1 days in nine patients with clinical success. Two major complications were encountered, chylothorax after initial TDE, requiring additional TDE and in one case surgical TD ligation.

Conclusions

TDE is a safe treatment for chyle leaks after head and neck surgery with high technical and clinical success rates.
Examining the factor structure, reliability, and validity of the main outcome measure used in mentalization‐based therapy skills training
Authors: Polnay Adam , McIntosh Lindsey G. , Burnett Aileen , Williams Andrea , Cahill Catherine , Wilkinson Peter , Mohammad Fiona , Patrick Jon
Published: February 2021

Background and Aims

Multiple national guidelines stress the importance for clinicians to possess good therapeutic skills for working with patients with significant relational difficulties (who may receive a diagnosis of personality disorder). Training clinicians in mentalization‐based treatment skills (MBT‐S) is one approach to address this. The main outcome measure used in MBT‐S studies is the Knowledge and Application of MBT Questionnaire (KAMQ). However, an absence of research into the properties and validity of the KAMQ has limited the methodological quality of MBT‐S evaluations so far. The aim of this study was therefore to investigate the factor structure, internal consistency, reliability, and validity of the KAMQ.

Methods

Using an existing multiprofessional sample of 217 clinicians from 2014 to 2016, we undertook exploratory factor analysis to determine the factor structure and internal consistency of the KAMQ. Convergent validity of the measure with the Attitudes to Personality Disorder Questionnaire (APDQ) was assessed in a subset of this dataset where both questionnaires had been administered (n = 92). Additionally, by recruiting a new sample of 70 clinicians, we assessed the measure's test‐retest reliability.

Results

Factor analysis found three factors underlying 17 of the 20 KAMQ items, relating to therapeutic skills in mentalizing, beliefs about applying MBT in practice, and specific MBT knowledge. The KAMQ was revised following the factor analysis to form the KAMQ‐2 with 17 items. Internal consistency (α = .85, 95% confidence interval [CI] = 0.80‐0.89) and test‐retest reliability (ICC = 0.84, 95% CI = 0.73‐0.91) were good. In correlation analyses, the KAMQ‐2 showed convergent validity with the main factor from the APDQ (n = 48; rs = 0.39, P < .01).

Conclusion

The KAMQ‐2 provides a short, reliable self‐report instrument which probes clinicians' knowledge about mentalizing skills, and beliefs about using these. There was preliminary evidence for validity. The properties of the KAMQ‐2 mean that more robust evaluation and development of MBT‐S is now possible.
Three‐class classification of brain magnetic resonance images using average‐pooling convolutional neural network
Authors: Kakarla Jagadeesh , Isunuri Bala Venkateswarlu , Doppalapudi Krishna Sai , Bylapudi Karthik Satya Raghuram
Published: February 2021

Brain tumor image classification is one of the predominant tasks of brain image processing. The three‐class brain tumor classification becomes a trivial task for researchers as each tumor exhibit distinct characteristics. Existing classification models use deep neural networks and suffer from high computational cost. We have proposed an eight‐layer average‐pooling convolutional neural network to address three‐class brain tumor classification. The proposed model uses three convolution blocks along with a dense layer and a softmax layer. We have utilized N‐adam optimizer with a sparse‐categorical cross‐entropy loss function to improve the learning rate. The proposed model has been evaluated using a dataset consists of 3064 brain tumor magnetic resonance images. The proposed model outperforms state‐of‐the‐art models with 97.42% accuracy and takes lesser computation time than its competitive models.
Coordinated development of agricultural water resources and the socio‐economy in Shanxi province considering uncertainty*
Authors: Yang Gaiqiang , Ding Lirui , Huo Lijuan , Hu Yuxian
Published: February 2021

The conflict between agricultural water resources and socio‐economic development is a global problem. Accurate evaluation of coordinated development of agricultural water resources and socio‐economic factors and risk mitigation is necessary for sustainable development under uncertainty. In order to accurately evaluate the coordination between agricultural water resources and socio‐economic development under uncertainty, an evaluation method was applied in this study by coupling an analytic hierarchy process method with an uncertainty analysis method. The evaluation method, including selection of criteria, data collection, determination of indicator weights, evaluation of coordinated development, prediction of parameters, and judgment of coordinated development state, has been proposed to study the degree of coordinated development. To deal with uncertainties, the Monte Carlo method and the fuzzy set method were used. The overall method was demonstrated to solve a real‐world evaluation problem in Shanxi province, China. Results showed that degrees of coordinated development were (0.7, 0.8) for most of the cities in Shanxi in 2015, indicating that the state of coordinated development was intermediate. In 2020, the degree of coordinated development was expected to markedly decrease, the state of coordinated development to be minimal, and agricultural water resources utilization to lag behind socio‐economic development.
Biotransformation and toxicity evaluation of functionalized manganese doped iron oxide nanoparticles
Authors: Akhtar Kanwal , Javed Yasir , Muhammad Faqir , Akhtar Bushra , Shad Naveed Akhtar , Sajid Muhammad Munir , Jamil Yasir , Sharif Ali , Abbas Wasim
Published: February 2021

Safe inorganic nanomaterials are tremendously used for diagnosis and therapies. However, essential processing in the microbiological environment changed the physical properties and in situ degradability, which is evaluated meticulously. In this research article, bare, Polyethylene glycol, and citrate coated manganese doped iron oxide nanoparticles are synthesized through the coprecipitation route. Structural, magnetic, optical, and morphological analyses are performed through different characterization tools. X‐ray diffraction confirmed the formation of single‐phase FeMnO3 with a crystallite size of 48.91 nm. Vibrating sample magnetometer analysis confirmed the formation of soft ferromagnetic behavior of bare and coated nanoparticles (NPs). Scanning electron microscopy and transmission electron microscopy confirmed the formation of spherical shaped nanoparticles. Single‐dose in vivo acute toxicity testing is performed through the intraperitoneal route of administration on groups of healthy albino rats. Elevated enzyme levels of kidney and liver are observed at day 1 but a transient decrease is observed at later stages. Through optical follow‐up, degradation effects are studied by adding prepared NPs in lysosomal like medium. Finally, metabolization of degraded products based on manganese/iron ions is studied by adding apoferritin into a lysosome like solution. These studies showed partial storage of manganese ions from NPs, while no substantial transfer is observed in the case of manganese salt.
The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model
Authors: Noonan Megan L , Ni Pu , Agoro Rafiou , Sacks Spencer A , Swallow Elizabeth A , Wheeler Jonathan A , Clinkenbeard Erica L , Capitano Maegan L , Prideaux Matthew , Atkins Gerald J , Thompson William R , Allen Matthew R , Broxmeyer Hal E , White Kenneth E
Published: February 2021

Fibroblast growth factor-23 (FGF23) is a critical factor in chronic kidney disease (CKD), with elevated levels causing alterations in mineral metabolism and increased odds for mortality. Patients with CKD develop anemia as the kidneys progressively lose the ability to produce erythropoietin (EPO). Anemia is a potent driver of FGF23 secretion; therefore, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) currently in clinical trials to elevate endogenous EPO to resolve anemia was tested for effects on iron utilization and FGF23-related parameters in a CKD mouse model. Mice were fed either a casein control diet or an adenine-containing diet to induce CKD. The CKD mice had markedly elevated iFGF23 and blood urea nitrogen (BUN), hyperphosphatemia, and anemia. Cohorts of mice were then treated with a patient-equivalent dose of BAY 85-3934 (BAY; Molidustat), which elevated EPO and completely resolved aberrant complete blood counts (CBCs) in the CKD mice. iFGF23 was elevated in vehicle-treated CKD mice (120-fold), whereas circulating iFGF23 was significantly attenuated (>60%) in the BAY-treated CKD mice. The BAY-treated mice with CKD also had reduced BUN, but there was no effect on renal vitamin D metabolic enzyme expression. Consistent with increased EPO, bone marrow Erfe, Transferrin receptor (Tfrc), and EpoR mRNAs were increased in BAY-treated CKD mice, and in vitro hypoxic marrow cultures increased FGF23 with direct EPO treatment. Liver Bmp-6 and hepcidin expression were downregulated in all BAY-treated groups. Femur trabecular parameters and cortical porosity were not worsened with BAY administration. In vitro, differentiated osteocyte-like cells exposed to an iron chelator to simulate iron depletion/hypoxia increased FGF23; repletion with holo-transferrin completely suppressed FGF23 and normalized Tfrc1. Collectively, these results support that resolving anemia using a HIF-PHI during CKD was associated with lower BUN and reduced FGF23, potentially through direct restoration of iron utilization, thus providing modifiable outcomes beyond improving anemia for this patient population. © 2021 American Society for Bone and Mineral Research (ASBMR).
Purchase task sensitivity to drug and nondrug reinforcers in opioid‐agonist treatment patients
Authors: Schwartz Lindsay P. , Silberberg Alan , Hursh Steven R.
Published: February 2021

The behavioral economics of substance abuse has been increasingly recognized as a method of determining the value of abused substances for individuals who use those substances. It has been hypothesized that such analyses could serve as a clinical tool and that demand functions can be targeted predictors for the level of intervention necessary. This study evaluated the sensitivity of a demand task in 2 patient groups in a medication assisted treatment program (methadone maintenance), those who had used opioids in the last 2 months and those who had not used opioids in at least 18 months. Demand for 7 drugs and a control was assessed using hypothetical purchase tasks. Participants maintaining long‐term abstinence had significantly higher α (sensitivity to price) and lower Q0 (intensity of demand) for heroin than participants who had recently used opioids. Further research is necessary to illustrate if treatment is responsible for this reduction in demand. If so, demand analyses may provide clinical utility as an aid for treatment planning or as a target for treatment.
Clinical diagnostic criteria for IgG4‐related sclerosing cholangitis 2020
Authors: Nakazawa Takahiro , Kamisawa Terumi , Okazaki Kazuichi , Kawa Shigeyuki , Tazuma Susumu , Nishino Takayoshi , Inoue Dai , Naitoh Itaru , Watanabe Takayuki , Notohara Kenji , Kubota Kensuke , Ohara Hirotaka , Tanaka Atsushi , Takikawa Hajime , Masamune Atsushi , Unno Michiaki
Published: February 2021

Several years have passed since the clinical diagnostic criteria for IgG4‐related sclerosing cholangitis 2012 were published. New findings and knowledge have accumulated since then.

The Research Committees for IgG4‐related Diseases and for Intractable Diseases of the Liver and Biliary Tract, in association with the Ministry of Health, Labor, and Welfare of Japan and the Japan Biliary Association, have established a working group consisting of researchers specializing in IgG4‐SC and have drawn up new clinical diagnostic criteria for IgG4‐SC 2020.

The diagnosis of IgG4‐SC is based on a combination of the following six criteria: (a) narrowing of the intra‐ or extrahepatic bile duct; (b) thickening of the bile duct wall; (c) serological findings; (d) pathological findings; (e) other organ involvement; and (f) effectiveness of steroid therapy.

These new diagnostic criteria for IgG4‐SC are useful in practice for general physicians and other non‐specialists.
Magnetic Resonance Iron Imaging in Amyotrophic Lateral Sclerosis
Authors: Bhattarai Anjan , Egan Gary F. , Talman Paul , Chua Phyllis , Chen Zhaolin
Published: February 2021

Amyotrophic lateral sclerosis (ALS) results in progressive impairment of upper and lower motor neurons. Increasing evidence from both in vivo and ex vivo studies suggest that iron accumulation in the motor cortex is a neuropathological hallmark in ALS. An in vivo neuroimaging marker of iron dysregulation in ALS would be useful in disease diagnosis and prognosis. Magnetic resonance imaging (MRI), with its unique capability to generate a variety of soft tissue contrasts, provides opportunities to image iron distribution in the human brain with millimeter to sub‐millimeter anatomical resolution. Conventionally, MRI T1‐weighted, T2‐weighted, and T2*‐weighted images have been used to investigate iron dysregulation in the brain in vivo. Susceptibility weighted imaging has enhanced contrast for para‐magnetic materials that provides superior sensitivity to iron in vivo. Recently, the development of quantitative susceptibility mapping (QSM) has realized the possibility of using quantitative assessments of magnetic susceptibility measures in brain tissues as a surrogate measurement of in vivo brain iron. In this review, we provide an overview of MRI techniques that have been used to investigate iron dysregulation in ALS in vivo. The potential uses, strengths, and limitations of these techniques in clinical trials, disease diagnosis, and prognosis are presented and discussed. We recommend further longitudinal studies with appropriate cohort characterization to validate the efficacy of these techniques. We conclude that quantitative iron assessment using recent advances in MRI including QSM holds great potential to be a sensitive diagnostic and prognostic marker in ALS. The use of multimodal neuroimaging markers in combination with iron imaging may also offer improved sensitivity in ALS diagnosis and prognosis that could make a major contribution to clinical care and treatment trials.

Level of Evidence

2

Technical Efficacy

Stage 3
Solid‐phase microextraction of methadone by using a chitosan nanocomposite incorporated with Polyoxomolibdate nanocluster/Graphene oxide
Authors: Abedi Hamid
Published: February 2021

In the present study, we report on the simple sol–gel preparation of a nanocomposite composed of chitosan/ polyoxometalate /graphene oxide, and its application in the headspace solid‐phase microextraction combined with the ion mobility spectrometry for the analysis of methadone in biological matrices. The developed nanocomposite was characterized through the infrared spectroscopy and thermogravimetric analyses. The ternary nanocomposite coating offers good mechanical and thermal stability and high extraction efficiency thanks to its large specific surface. A central composite statistical design was used to study the main variables affecting the extraction efficiency. Afterward, to study the relationship between different input and output variables as well as to identify the optimal operating conditions, response surface methodology was used, whereby a second‐order polynomial equation was fit to the experimental data. The optimized extraction conditions were as follows: temperature, 70°C; extraction time, 15 min; and concentration of NaCl, 5%w/v. The detection limit of 0.12 ng/mL was obtained at the optimized extraction conditions, and the calibration plot was linear in the concentration range of 0.30–200 ng/mL. With relatively low limit of detection and good precisions, the proposed method has the potential for the extraction and determination of methadone in biological samples.
Sol‐Gel Synthesis and Antibacterial Characterization of Bioactive Ferrous Citrate‐Silica Hybrid Materials
Authors: Fusco Alessandra , Donnarumma Giovanna , Caputo Pina , Gallo Monica. , Catauro Michelina
Published: February 2021

The aim of this work is the synthesis of therapeutic systems, iron (II) based, by sol‐gel method. In a SiO2 matrix, different weight percentages of ferrous citrate (Fe(II)C are embedded. Fourier Transform Infrared (FTIR) spectroscopy is used to study the interactions among different components in the hybrid materials. The bioactivity of the synthesized hybrid materials is evaluated by the formation of a layer of hydroxyapatite on the surface of samples soaked in SBF using FTIR spectroscopy. Finally, also, the potential antibacterial properties of the different materials against two different bacteria, Staphylococcus epidermidis and Pseudomonas aeruginosa, are investigated.
Kinetics of Formation of Flavano‐C‐Glycosidic Ellagitannins (Acutissimin A and B) in Model Solutions Containing Medium Toasted Oak Chips and Catechin for Wine Aging
Authors: Gallo Monica , Montesano Domenico , Ciaravolo Martina , De Paola Fulvio , Poggetto Giovanni Dal , Naviglio Daniele
Published: February 2021

The aging process of wine goes beyond conservation and involves the use of wood, which is capable of containing and protecting, and allows a limited passage of oxygen, sufficient to promote slow maturation of the wine, thanks to which it reaches the maximum of its organoleptic qualities. The most used wood is oak and during aging, the wine extracts from the wood of the barrels an abundant quantity of aromatic substances, due to the contact between the wine and the matrix of the wood. Among the newly formed compounds, the flavano‐ellagitannins, namely the acutissimin A and B, are the minor compounds found in wood aged wine. They are formed during the aging process through the condensation of tannins, such as vescalagin, extracted from the wood matrix and flavonoids, such as catechins contained in wine. The aim of the study is to verify the formation of acutissimins after 28 days in model solutions that simulated aged wine in the presence of 1%, 5%, and 10% w/v percentages of wood chips obtained from Quercus alba and with variable concentrations of catechin (100 and 500 mg L−1). The formation of compounds, including acutissimin A and B, and the disappearance of catechin are identified by high‐performance liquid chromatography/electrospray ionization/mass spectrometry. Acutissimins A and B are validated by comparison with the characteristic m/z reported in the literature. Based on the results obtained, the model system prepared with 500 mg L−1 of catechin and 10% w/v oak chips showed the highest content of acutissimin A and B.
Chiral Separation of Diastereomeric and Enantiomeric Products Obtained by an Organic Reaction in Aqueous Media between Cyclohexanone and p‐nitrobenzaldehyde by HPLC on Chiral Stationary Phase
Authors: Naviglio Daniele , Poggetto Giovanni Dal , Montesano Domenico , Ciaravolo Martina , De Paola Fulvio , Gallo Monica
Published: February 2021

To understand the intimate essence of the phenomena that occur around us and in us, it is necessary to go down to the atomic and molecular level. From the scale of atoms to the human one, nature is chiral (the term derives from the Greek χείρ, “hand,” that are not superimposable). A chiral chemical compound exists as two isomeric forms, called enantiomers, which are the mirror image of each other and cannot be superimposed on each other. It is important to understand the cause‐effect correlations of this asymmetry, which seems to be universal feature of many natural substances; in fact, many drugs, food additives, flavors, cosmetics, agrochemicals, and so on show chirality and surprisingly the biological activity of the two enantiomers is often different (for example one is biologically active, while the other is not active). To separate enanatiomers, an interaction with an entity that is also chiral with the formation of special interactions is required. This work describes the development of the separation method of four diastereoisomers obtained as products (adducts) of an organic reaction between cyclohexanone and benzaldehyde variously substituted in aromatic ring. The chiral separation of the two geometric isomers syn and anti adducts produced by the reaction is obtained by high performance chromatography with a diode detector (HPLC‐DAD), using a chiral column and a ternary mixture composed of n‐hexane, dichloromethane and ethanol.
Kinetics of the Non‐isothermal Degradation of POSS/EPDM Hybrids Composites
Authors: Zaharescu Traian , Catauro Michelina , Blanco Ignazio
Published: February 2021

Polyhedral Oligomeric Silsesquioxane (POSS)/Ethylene‐propylene‐diene monomer (EPDM) composite, at 3% wt of POSS, is prepared by the evaporation of solvent (CHCl3) from polymer/filler system at room temperature and is investigated, by the means of thermogravimetric analysis (TGA), and the obtained TGA data are treated by the Kissinger method to get the apparent activation energy (Ea) of degradation. The results obtained for the composites, at different levels of irradiation, are discussed and compared with each other and with those obtained for pristine EPDM. A good improvement of the thermal stability, with respect to the neat polymer, is found showing the effect of the POSS molecules on the degradation rate. A classification among the samples at different levels of radiations is also drawn up, showing also in this case, the beneficial effect of the POSSs presence.
Structural and Elastic Characterization of Biopolymers Hydrolysis by Acoustic Microscopy
Authors: Morokov Egor , Demina Varvara , Sedush Nikita , Kalinin Kirill , Dmitryakov Petr , Krasheninnikov Sergei , Khramtsova Elena , Grigoriev Timofei , Chvalun Sergei , Levin Vadim
Published: February 2021

In this work, the high‐frequency acoustic microscopy is applied for imaging of internal microstructure and measurement of elastic characteristics of the biodegradable polymers based on D,L‐lactide, L‐lactide, ε‐caprolactone, and their copolymers. Acoustic microscopy results (images of microstructure in the volume and values of sound speed) have been supplemented by data on gel permeation chromatography, differential scanning calorimetry, and mechanical tensile test obtained on the polymers under the hydrolysis range from initial state to 8 weeks with step of 2 weeks. The features of ultrasound visualization and elastic characterization of each the polymer type have been discussed. The changes of the ultrasound characteristics have been detected in the high‐rate degradation polymers.
Organic Inhibitors to Prevent Chloride‐Induced Corrosion in Concrete: Atomistic Simulations of Triethylenetetramine‐Based Inhibitor Film
Authors: Raffaini Giuseppina , Catauro Michelina , Ganazzoli Fabio , Bolzoni Fabio , Ormellese Marco
Published: February 2021

Inhibitors are largely used to prevent chloride‐induced corrosion in reinforced concrete structures thanks to both a barrier effect on chloride penetration and a competition with the adsorption of the inhibitor. The interaction mechanisms between passive film on carbon steel, the inhibitor molecule, and chlorides still require deeper understanding. Theoretical studies based on molecular mechanics (MM) and molecular dynamics (MD) methods can be useful to better understand the passive film formation and its interaction with chlorides. In this work, the interaction between a triethylenetetramine (TETA) inhibitor film on γ‐FeOOH surface and chlorides is studied using MD methods. After MM optimization in the initial adsorption stage, some chlorides are close to protective TETA film. After MD run at room temperature effectively, chlorides remain close to the protective film. In order to have an effective barrier on chloride attack, the metal oxide must remain wholly covered by the protective film. The TETA film well covers the lepidocrocite surface but cannot kinetically efficiently prevent the chloride‐induced corrosion compared to other organic films exposing COO− groups because it does not exert any repulsion to chlorides.
Research of Impregnated Carbon Fiber Tow Quality for 3D Composites Printing
Authors: Kuncius Tomas , Rimašauskas Marius
Published: February 2021

Time nowadays becoming more and more important resource in the life. Additive manufacturing technologies allow to produce very complex shapes of products reducing product development time. Moreover, additive manufacturing of composite parts allows to produce structural parts with perfect mechanical properties. Though production of composites is still very complicated because reinforcement material needs to be prepared for the process. Moreover, preparation process can significantly influence on quality of produced part. This article focusing on preparation procedure of continuous carbon fiber (CCF) tow for 3D printing of composite structures. Visual analysis of impregnated CCF showed that internal air voids area in the analyzed cross‐sections fluctuates from 11.1% to 22.8%. Meanwhile, after pull‐out test, significant effect of impregnation on adhesion is observed. Not impregnated CCF is pulled‐out from matrix material with the tensile force 38 N, however impregnated CCF is not even pulled‐out with the force 138 N.
Investigation of Specific FDM Process Parameters to Optimize the Polymer Discharge of Carbon Fiber Reinforced PEEK
Authors: Wächter Julian , Elsner Christian Lennart , Moritzer Elmar
Published: February 2021

Fused deposition modeling (FDM) is a widely used manufacturing process and the materials market is growing due to the increased requirements on materials. In particular, processing of high‐temperature materials such as PEEK is challenging. The aim of these studies is to investigate and improve the processability of a carbon fiber reinforced polyether ether ketone (PEEK) material in the FDM process. The first step is to define the relevant process parameters, which remain constant over the entire investigation. In particular, the material‐specific temperatures must be defined. Based on previous investigations regarding the weld seam strength and the warpage of the selected PEEK materials, a method to determine and adjust essential process parameters should be developed. One approach is the consideration of the volumetric polymer discharge at a stationary filament feed rate. The optimized adjustment of the feed rate ensures increased component densities and an improved process reliability. In this context, the component areas with non‐stationary extruder movement, such as in corner areas, have got a huge influence on the component quality. The acceleration and deceleration processes do not result in a desired uniform strand geometry due to the pressure changes within the nozzle. The acceleration can result in thinner strands while the deceleration can lead to a thickening of the polymer discharge. The aim is to adjust the pressure inside the nozzle depending on the acceleration profile to enable a homogenous strand geometry. The method should therefore allow the improvement of the processability of PEEK materials.