bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic oxidative dehydrogenation of ethane using carbon dioxide as a soft oxidant over Co‐HMS catalysts to ethylene
Authors: Xiao Fei , Guo Dan , Zhao Feigang , Zhao Yujun , Wang Shengping , Ma Xinbin
Published: June 2022

In this work, a series of cobalt doped hexagonal mesoporous silica (Co‐HMS) with the different Co content were prepared by direct hydrothermal method and applied to oxidative dehydrogenation (ODH) reaction of ethane with carbon dioxide. Structural and chemical properties of the catalysts were characterized by nitrogen adsorption, X‐ray powder diffraction (XRD), transmission electron microscopy (TEM), electron dispersive spectroscopy (EDS), X‐ray photoelectron spectroscopy (XPS), and Raman and ultraviolet–visible (UV‐vis) spectroscopy. These characterizations showed that cobalt not only entered the framework of Co‐HMS catalysts but also was evenly dispersed in the bulk. The valence state and coordination mode of cobalt played an important role in the whole ODH reaction system of ethane with carbon dioxide. 2% Co‐HMS with dominant Co2+ had the highest conversion of ethane (26.0%). With the different cobalt content in the catalyst, the proportion of Co2+(Td) and Co2+(Oh) is also different. 1% Co‐HMS with more Co2+(Td) performed the highest ethylene selectivity of 86.7%, which was stable during the 10 h reaction time.
Cr(VI) removal from groundwater by calcium alginate coating microscale zero‐valent iron and activated carbon: Batch and column tests
Authors: Duan Yijun , Meng Fanbin , Li Miao , Hou Xiaoshu , Zhang Shuo , Li Jiacheng , Liu Xiang
Published: June 2022

Although most of the studies focus on the nanoscale zero‐valent iron (nZVI), it still ineffective when comes to in situ utilization due to its intrinsic drawbacks such as rapid aggregation, biotoxicity, high cost, complex preparation process, and so forth. With advantages of lower health risk, lower cost, and simpler fabricate method, microscale zero‐valent iron (mZVI) shows more attractiveness for groundwater remediation than nZVI if its main problem, passivation, can be alleviated. In order to overcome the passivation of mZVI, (mZVI+AC)/CA was produced by encapsulating mZVI and activated carbon (AC) in spherical calcium alginate (CA) matrix in this study. The method effectively solved the passivation of mZVI and showed great long‐effective removal of Cr(VI). The Cr(VI) removal efficiency of (mZVI+AC)/CA could maintain 1.6–2.69 times as much as that of pure mZVI for 0–1500 pore volumes. The maximum Cr(VI) removal capacity reached 100.47 mg/g, which exceeded most of mZVI‐based materials and even some nZVI‐based materials. In addition, mechanism of Cr(VI) removal was revealed by X‐ray diffraction and X‐ray photo‐electron spectroscopy. The results showed that chemisorption, physisorption, reduction, oxidation, and precipitation were involved in the process. Pseudo‐second order model and Freundlich isotherm model were best fitted in kinetics and isotherm experiments, respectively.
Ascorbic acid can alleviate the degradation of levodopa and carbidopa induced by magnesium oxide
Authors: Miyaue Noriyuki , Kubo Madoka , Nagai Masahiro
Published: June 2022

Introduction

Levodopa and carbidopa are reported to be degraded by magnesium oxide (MgO), which is often used as a laxative for patients with Parkinson's disease (PD). Ascorbic acid (AsA) can stabilize levodopa and carbidopa solutions; however, the effect of AsA on the degradation of levodopa and carbidopa induced by MgO has not been fully investigated.

Methods

The effect of AsA was evaluated using in vitro examinations, compared with lemon juice, and by measuring the plasma concentration of levodopa in a patient with PD.

Results

In vitro experiments showed that the relative concentrations of levodopa remained almost constant, and the relative concentrations of carbidopa decreased with time with addition of MgO. AsA mitigated this effect in a concentration‐dependent manner, whereas the addition of lemon juice caused little change, although the pH decreased to the same extent. The results of levodopa pharmacokinetics of the patient showed that the area under the plasma concentration‒time curve values from hour 0 to 8 were 53.00 μmol·h/L with regular administration and 67.27 μmol·h/L with co‐administration of AsA.

Conclusions

AsA can mitigate the degradation of carbidopa induced by MgO and may contribute to improving the bioavailability of levodopa in patients with PD.
Problem‐based learning on household electricity consumption analysis using predictive models and tools
Authors: Ramnath Gaikwad S. , Harikrishnan R.
Published: June 2022

Smart grid (SG) is an emerging subject in power engineering that requires interdisciplinary skills. SG implementation has challenges in accurate prediction of electricity consumption, power stability, power quality, and critical infrastructure security. This study uses predictive modeling and different tools to introduce problem‐based learning techniques through household electricity consumption (HEC) analysis. The problem statement is to understand the effect of the weather conditioning data set on the accuracy of HEC prediction and select the most fitting predictive model for further decision‐making. Five predictive models, namely random forest, linear regression, support vector machine, neural network, and adaptive boosting, are utilized, and their prediction results are compared based on a performance matrix. The paper also briefs the usage of different tools, including Jeffrey's Amazing Statistics Program tool for finding the correlations within variables, the Power Business Intelligence tool for data visualization, and the Orange tool for building predictive modeling. This study focuses on three aspects. Firstly, to demonstrate energy predictive modeling analysis without knowing the coding knowledge. Secondly, to develop the creative thinking of engineering students to solve complex, interdisciplinary engineering problems using tools. Thirdly, to motivate students to be actively involved in their problem‐based research projects.
Synthesis and Antibacterial Evaluation of Rhodanine and Its Related Heterocyclic Compounds against S. aureus and A. baumannii
Authors: Akunuri Ravikumar , Unnissa Tanveer , Kaul Grace , Akhir Abdul , Saxena Deepanshi , Wajidali Mohmadd , Veerareddy Vaishnavi , Yaddanapudi Venkata Madhavi , Chopra Sidharth , Nanduri Srinivas
Published: June 2022

Antimicrobial resistance is a serious challenge to modern medicine. Besides imposing high financial burden, multidrug resistant infections are directly responsible for high morbidity and mortality. Even though a number of antibiotics are currently available to treat infections caused by ESKAPE organisms, more and more bacterial strains are becoming resistant to these drugs. Prevailing circumstances pose an urgent unmet need for the development of newer antimicrobials to treat the infections caused by MDR organisms. Rhodanine and structurally related 5‐membered heterocycles possess wide range of pharmacological activities. A number of these derivatives have shown good to potent inhibition against various microorganisms. They are reported to alter the function of DNA gyrase B, metallo‐β‐lactamases, penicillin binding protein (PBP), Mur ligases, RNA polymerase, Enoyl ACP reductases, 1‐deoxy‐d‐xylulose‐5‐phosphate reductoisomerase. etc which are vital in bacterial growth, survival and replication. In this study, we have generated a library of Rhodanine and related 5 membered heterocyclic derivatives and screened them against a panel of pathogens. Among all the compounds, 2a–i, 3a–b, 3g, 4, 6b–c, 6e, 6g, 12a–b and 14b–c have demonstrated good to moderate inhibition against S. aureus (MIC 0.125–8 μg/mL). Further, compound 17b demonstrated moderate activity against A. baumannii (MIC 8 μg/mL). In addition, compounds 2a, 2e, 4, 6c, 6g and 14b have shown good to mild inhibition against MDR S. aureus including VRSA (MIC 0.5–16 μg/mL) with good selectivity index 20–1600. In addition, compound 2e inhibited the growth gradually after 6 h in time kill kinetic studies and not antagonized with the tested FDA approved drugs.
Selective Oxidations Using a Cytochrome P450 Enzyme Variant Driven with Surrogate Oxygen Donors and Light
Authors: Lee Joel H. Z. , Podgorski Matthew N. , Moir Michael , Gee Alecia R. , Bell Stephen G.
Published: June 2022

Cytochrome P450 monooxygenase enzymes are versatile catalysts, which have been adapted for multiple applications in chemical synthesis. Mutation of a highly conserved active site threonine to a glutamate can convert these enzymes into peroxygenases that utilise hydrogen peroxide (H2O2). Here, we use the T252E‐CYP199A4 variant to study peroxide‐driven oxidation activity by using H2O2 and urea‐hydrogen peroxide (UHP). We demonstrate that the T252E variant has a higher stability to H2O2 in the presence of substrate that can undergo carbon‐hydrogen abstraction. This peroxygenase variant could efficiently catalyse O‐demethylation and an enantioselective epoxidation reaction (94 % ee). Neither the monooxygenase nor peroxygenase pathways of the P450 demonstrated a significant kinetic isotope effect (KIE) for the oxidation of deuterated substrates. These new peroxygenase variants offer the possibility of simpler cytochrome P450 systems for selective oxidations. To demonstrate this, a light driven H2O2 generating system was used to support efficient product formation with this peroxygenase enzyme.
A circular dichroism study of the protective role of polyphosphoesters polymer chains in polyphosphoester‐myoglobin conjugates
Authors: Pelosi Chiara , Arrico Lorenzo , Zinna Francesco , Wurm Frederik R. , Di Bari Lorenzo , Tinè Maria R.
Published: June 2022

Protein‐polymer conjugates are a blooming class of hybrid systems with high biomedical potential. Despite a plethora of papers on their biomedical properties, the physical–chemical characterization of many protein‐polymer conjugates is missing. Here, we evaluated the thermal stability of a set of fully‐degradable polyphosphoester‐protein conjugates by variable temperature circular dichroism, a common but powerful technique. We extensively describe their thermodynamic stability in different environments (in physiological buffer or in presence of chemical denaturants, e.g., acid or urea), highlighting the protective role of the polymer in preserving the protein from denaturation. For the first time, we propose a simple but effective protocol to achieve useful information on these systems in vitro, useful to screen new samples in their early stages.
Financial toxicities of cancer in low‐ and middle‐income countries: Perspectives from Southeast Asia
Authors: Eala Michelle Ann B. , Dee Edward Christopher , Ginsburg Ophira , Chua Melvin Lee Kiang , Bhoo‐Pathy Nirmala
Published: June 2022

This commentary draws attention to the financial toxicities associated with cancer in low‐ and middle‐income countries from the perspective of Southeast Asia. It describes interventions at patient–provider, hospital, health care system, and national levels that may mitigate financial toxicity in the region and in similarly resourced parts of the world.
Silver‐Mediated Squaric Acid Reduction as a Facile, Ambient‐temperature and Seedless Route to Tunable Bimetallic Au/Ag Nanostars and Nanosnowflakes
Authors: Kist Jennifer A. , Essner Jeremy B. , Woodward Jonathan D. , Baker Gary A.
Published: June 2022

Bimetallic Au/Ag nanoparticles were successfully synthesized using a facile and reproducible method involving rapid, room‐temperature mixing of aqueous solutions of HAuCl4 and AgNO3 in the presence of squaric acid as both the reducing agent and surface capping ligand. Variation in the initial Au : Ag molar ratio yielded a tunable anisotropic shape and affiliated surface plasmon resonance. The nanoparticles displayed excellent stability in water for at least 10 weeks and showed robust catalytic activity in the borohydride‐assisted reduction of the model substrate 4‐nitrophenol.
Review of the Chinese Landscape in Phase 1 Clinical Trials for Noncancer Innovative Drugs Over 2015 to 2020
Authors: Wu Xiaofei , Zhang Fan , Yu Mengyang , Wang Hongyun
Published: June 2022

In recent years, the research and development (R&D) of innovative drugs in China has been dramatically accelerated. And the early clinical study is crucial for drug R&D. However, little is known involving the change of phase I trials for noncancer drugs. We retrieved the data of phase I clinical trials for noncancer innovative drugs on the Registration and Information Disclosure Platform for Drug Clinical Studies on the Center for Drug Evaluation. The number of clinical trials proliferating in recent years and the average annual growth rates of chemical and biological drugs were 55.5% and 42.1%, respectively. Most trials were distributed in Beijing, Shanghai, and other developed coastal cities. Moreover, the clinical trials of innovative drugs in China were focused on the digestive and endocrine systems, whereas the pediatric and orphan drugs were scarce. Based on the data assessment, this work provided comprehensive analysis and suggestions about Chinese drug R&D. Significant advancement has been made in mainland China with the implementation of available policies and the emergence of advanced technologies. Though shortcomings, including uneven geographic distribution and lack of pediatric and orphan drugs, still exist, we believe progress will continue to be made in mainland China.
Ziritaxestat Drug–Drug Interaction with Oral Contraceptives: Role of SULT1E1 Inhibition
Authors: Helmer Eric , Karimian Negin , Van Assche Karen , Seghers Ineke , Le Tallec Sandrine , Cherala Ganesh , Scott Graham , Namour Florence S.
Published: June 2022

In vitro signals indicate that ziritaxestat is a weak cytochrome P450 (CYP) 3A4 inhibitor and inducer. Therefore, potential drug–drug interactions (DDIs) with oral contraceptives were examined at a time when ziritaxestat was under development for treatment of fibrotic diseases. This open‐label, crossover (fixed sequence) DDI study enrolled healthy, nonpregnant women aged 18–65 years (n = 15) who were using highly effective contraception, such as a nonhormonal intrauterine device, bilateral tubal occlusion, or sexual abstinence. A single dose of oral contraceptive (0.03 mg ethinyl estradiol (EE) and 3 mg drospirenone (DRSP)) was administered on days 1, 8, and 18, and ziritaxestat 600 mg once daily was administered from days 8 to 23. Co‐administration resulted in a 2.8‐fold and 2.4‐fold increase in EE maximum plasma concentration (Cmax) and area under the plasma drug concentration–time curve from time zero to infinity (AUC0–inf), respectively (day 18 vs. day 1). DRSP Cmax and AUC0–inf increased by 1.1‐fold and 1.2‐fold, respectively. DRSP is a CYP3A4 substrate, meaning increased EE exposure with ziritaxestat was not due to CYP3A4 inhibition. Ziritaxestat inhibition of EE glucuronidation and sulfation was quantified by liquid chromatography with tandem mass spectrometry in day 1 and day 18 plasma samples after EE conjugate hydrolysis. The ratio of EE AUC from time of administration up to the time of the last quantifiable concentration (AUClast) with/without hydrolysis by arylsulfatase was substantially lower on day 18 vs. day 1, suggesting ziritaxestat is a potent inhibitor of sulfation; EE glucuronidation was largely unaffected by ziritaxestat. In vitro assessment confirmed ziritaxestat is a potent inhibitor of sulfotransferase family 1E member 1 (half‐maximal inhibitory concentration < 0.8 μM). These findings highlight the importance of assessing enzymes other than CYP3A4 when investigating potential DDIs with oral contraceptives.
CUT&RUN for Chromatin Profiling in Caenorhabditis elegans
Authors: Emerson Felicity J. , Lee Siu Sylvia
Published: June 2022

Cleavage under targets and release using nuclease (CUT&RUN) is a recently developed chromatin profiling technique that uses a targeted micrococcal nuclease cleavage strategy to obtain high‐resolution binding profiles of protein factors or to map histones with specific post‐translational modifications. Due to its high sensitivity, CUT&RUN allows quality binding profiles to be obtained with only a fraction of the starting material and sequencing depth typically required for other chromatin profiling techniques such as chromatin immunoprecipitation. Although CUT&RUN has been widely adopted in multiple model systems, it has rarely been utilized in Caenorhabditis elegans, a model system of great importance to genomic research. Cell dissociation techniques, which are required for this approach, can be challenging in C. elegans due to the toughness of the worm's cuticle and the sensitivity of the cells themselves. Here, we describe a robust CUT&RUN protocol for use in C. elegans to determine the genome‐wide localization of protein factors and specific histone marks. With a simple protocol utilizing live, uncrosslinked tissue as the starting material, performing CUT&RUN in worms has the potential to produce physiologically relevant data at a higher resolution than chromatin immunoprecipitation. This protocol involves a simple dissociation step to uniformly permeabilize worms while avoiding sample loss or cell damage, resulting in high‐quality CUT&RUN profiles with as few as 100 worms and detectable signal with as few as 10 worms. This represents a significant advancement over chromatin immunoprecipitation, which typically uses thousands or hundreds of thousands of worms for a single experiment. The protocols presented here provide a detailed description of worm growth, sample preparation, CUT&RUN workflow, library preparation for high‐throughput sequencing, and a basic overview of data analysis, making CUT&RUN simple and accessible for any worm lab. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Growth and synchronization of C. elegans

Basic Protocol 2: Worm dissociation, sample preparation, and optimization

Basic Protocol 3: CUT&RUN chromatin profiling

Alternate Protocol: Improving CUT&RUN signal using a secondary antibody

Basic Protocol 4: CUT&RUN library preparation for Illumina high‐throughput sequencing

Basic Protocol 5: Basic data analysis using Linux
Promoting lab culture to enhance academic resilience during crises
Authors: Arranz Ignasi , Nobre Regina , Cucherousset Julien , Reis de Carvalho Aline , Cantarute‐Rodrigues Amanda , Favriou Pierre , Garcia Flavien , Gimenez Marie , Imbert Alexis , Marin Valentin , Paz‐Vinas Ivan
Published: June 2022

The COVID‐19 pandemic has heavily impacted academics’ professional and personal lives, forcing many research groups (labs) to shift from an academic system primarily based on in‐person work to an almost full‐time remote workforce during lockdowns. Labs are generally characterized by a strong lab culture that underpins all research and social activities of its members. Lab culture traditionally builds on the pillars of in‐person communication, knowledge sharing, and all social and professional activities that promote collaboration, team building, scientific productivity, and well‐being. Here, we use the experience of our research group facing the COVID‐19 pandemic to illustrate how proactively reinforcing lab culture and its positive outcomes have been essential to our lab when transitioning from an in‐person to a remote lab environment, and through its ongoing evolution toward a hybrid remote/in‐person model. We argue that the proactive promotion of lab culture in research groups can foster academic resilience during crises, helping research groups to maintain their capacity to conduct scientific activities while preserving a sustainable life/work balance and a healthy mental condition.
COVID‐19 lockdown measures impacted citizen science hedgehog observation numbers in Bavaria, Germany
Authors: Sweet Fabio S. T. , Rödl Thomas , Weisser Wolfgang W.
Published: June 2022

The COVID‐19 pandemic has led to temporary changes in human–animal interactions due to changes in human activities. Here, we report on a surge in hedgehog observations during the first COVID‐19 lockdown in Germany in 2020, on the citizen science Web portal “Igel in Bayern” (Hedgehogs in Bavaria) in Germany. This increase in comparison with previous years was attributed to an increase in the number of people reporting hedgehog observations, rather than an increase in the number of hedgehog observations made by each observer. Additionally, in contrast to other studies on the effects of a COVID‐19 lockdown on observations recorded by citizen science projects, the share of observations made in more urbanized areas during the lockdown time was not higher than the change observed in less urbanized areas. This is possibly a result of the differences in COVID‐19 measures between Germany and other countries where preceding studies were carried out, in particular the lack of measures limiting traveling outdoor activities for citizens.
Nematode communities indicate diverse soil functioning across a fog gradient in the Namib Desert gravel plains
Authors: Treonis Amy M. , Marais Eugene , Maggs‐Kölling Gillian
Published: June 2022

Soil nematodes are fundamentally aquatic animals, requiring water to move, feed, and reproduce. Nonetheless, they are ubiquitous in desert soils because they can enter an anhydrobiotic state that allows them to persist when water is biologically unavailable. In the hyper‐arid Namib Desert of Namibia, rain is rare, but fog routinely moves inland from the coast and supports plant and animal life. Very little is understood about how this fog may affect soil organisms. We investigated the role of fog moisture in the ecology of free‐living, soil nematodes across an 87‐km fog gradient in the gravel plains of the Namib Desert. We found that nematodes emerged from anhydrobiosis and became active during a fog event, suggesting that they can utilize fog moisture to survive. Nematode abundance did not differ significantly across the fog gradient and was similar under shrubs and in interplant spaces. Interplant soils harbor biological soil crusts that may sustain nematode communities. As fog declined along the gradient, nematode diversity increased in interplant soils. In areas where fog is rare, sporadic rainfall events can stimulate the germination and growth of desert ephemerals that may have a lasting effect on nematode diversity. In a 30‐day incubation experiment, nematode abundance increased when soils were amended with water and organic matter. However, these responses were not evident in field samples, which show no correlations among nematode abundance, location in the fog gradient, and soil organic matter content. Soil nematodes are found throughout the Namib Desert gravel plains under a variety of conditions. Although shown to be moisture‐ and organic matter‐limited and able to use moisture from the fog for activity, variation in fog frequency and soil organic matter across this unique ecosystem may be biologically irrelevant to soil nematodes in situ.
Critical considerations for enacting student success
Authors: Taylor Leonard
Published: June 2022

Higher education institutions and the actors therein are still grappling with disparities in student outcomes and disparate student experiences. Although diligent efforts have been made, institutions have yet to transform in any substantial way to overcome these issues. Rather than offering new student success practices, the focus of this chapter is on how to support those who work to support students. To support the enactment of collective and specific student success commitments, I provide four critical considerations for senior leaders and student success decision‐makers, focused on the necessary institutional conditions for those carrying out student success work. The perspectives presented are largely shaped by discussions of the gaps between research knowledge and theories generated related to student success, perspectives on what happens in practice, the complexities of institutional environments and how they change, and how these constitute, relate to, and mitigate one another.
Critical perspectives on Black students’ success
Authors: Blockett Reginald A. , Ross Taylor J. , Todd Phillip A.
Published: June 2022

In this chapter, we explore the research literature on Black college students’ success and apply critical theoretical frameworks to reimagine how college student educators and administrators can promote a more holistic approach to student success. Scholars and researchers have focused on identifying how and why Black students succeed or not, and have illustrated a number of common experiences Black students endure in traditionally white institutions (TWIs). Less common but centrally important, however, are accounts and interpretations of Black students’ experiences that center Blackness, especially in intersectional ways. We offer three recommendations that stand to inform institutional practices and perhaps inspire continued scholarship related to Black students and their postsecondary success.
Student success at historically Black colleges and universities: Early findings and promising practices from the UNCF® Career Pathway Initiative
Authors: Njoku Nadrea R. , Owens LaToya
Published: June 2022

The Institute for Capacity Building (ICB) and the Frederick D. Patterson Research Institute (FDPRI) found that there is a notable gap in institutions’ readiness to drive transformative change on campus. Early lessons from the UNCF® Career Pathways Initiative (CPI) ICB and FDPRI generated insights that indicate overall institutional health is as core to student success as student experience. This chapter provides an overview of how to scale student success initiatives that address institutional core functioning and focus on producing career‐ready graduates. Through this use of culturally relevant research practices, this chapter highlights the necessity of a culturally relevant approach in creating equity‐centered student success interventions and shifting institutional culture, while maintaining mission‐aligned practices.
Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature
Authors: Kim Myung‐Ho , Kim Mi‐Young , Salloum Shadi , Qian Tongqi , Wong Lai Ping , Xu Min , Lee Yoojin , Shroff Stuti G. , Sadreyev Ruslan I. , Corey Kathleen E. , Baumert Thomas F. , Hoshida Yujin , Chung Raymond T.
Published: June 2022

Lipophilic but not hydrophilic statins have been shown to be associated with reduced risk for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. We investigated differential actions of lipophilic and hydrophilic statins and their ability to modulate a clinical prognostic liver signature (PLS) predicting HCC risk in patients with liver disease. Hepatitis C virus (HCV)–infected Huh7.5.1 cells, recently developed as a model to screen HCC chemopreventive agents, were treated with lipophilic statins (atorvastatin and simvastatin) and hydrophilic statins (rosuvastatin and pravastatin), and then analyzed by RNA sequencing and PLS. Lipophilic statins, particularly atorvastatin, more significantly suppressed the HCV‐induced high‐risk pattern of PLS and genes in YAP and AKT pathway implicated in fibrogenesis and carcinogenesis, compared with the hydrophilic statins. While atorvastatin inhibited YAP activation through the mevalonate pathway, the distinctive AKT inhibition of atorvastatin was mediated by stabilizing truncated retinoid X receptor alpha, which has been known to enhance AKT activation, representing a target for HCC chemoprevention. In addition, atorvastatin modulated the high‐risk PLS in an in vitro model of nonalcoholic fatty liver disease (NAFLD). Conclusion: Atorvastatin distinctively inhibits YAP and AKT activation, which are biologically implicated in HCC development, and attenuates a high‐risk PLS in an in vitro model of HCV infection and NAFLD. These findings suggest that atorvastatin is the most potent statin to reduce HCC risk in patients with viral and metabolic liver diseases.
Report of a family with Huntington's disease
Authors: Luo Zhong , Wang Jian , Cao Piao , Zhang Lin‐Hai , Hao Ren‐Fang , Liang Tao
Published: June 2022

The aim of this article was to analyze the clinical and genetic characteristics of a patient with Huntington's disease and her family. We analyzed the clinical data of a patient with Huntington's disease and her family members in the Department of Neurology of our hospital, drew the genetic pedigree, and used gene fragment analysis to detect and analyze the genes of three people in the family according to the principle of informed consent. The genetic pedigree of the family was consistent with that of autosomal dominant diseases. A total of five people in this family developed the disease, two died, and the main clinical manifestations were dystonia, ataxia, and cognitive impairment. Three people in this family underwent genetic testing, and two exhibited normal genotypes. The cytosine–adenine–guanine trinucleotide (CAG) repeats of the proband were abnormally amplified, and the number of repeats reached 43. The main clinical features of the patient included chronic obscure onset, obvious positive family genetic history, clinical features of involuntary limb movement with cognitive impairment, rapid disease progression, poor treatment effect, and abnormal amplification of CAG repeats as shown through genetic testing. All the above features met the diagnostic criteria of Huntington's disease.
The downregulation of miR‐22 and miR‐372 may contribute to gestational diabetes mellitus through regulating glucose metabolism via the PI3K/AKT/GLUT4 pathway
Authors: Li Wei , Yuan Xianlin , He Xin , Yang Li , Wu Yingyuan , Deng Xiaofeng , Zeng Yiwen , Hu Kesheng , Tang Bo
Published: June 2022

Background

Identifying effective regulatory mechanisms will be significant for Gestational diabetes mellitus (GDM) diagnosis and treatment.

Methods

The expressions of miR‐22 and miR‐372 in placenta tissues from 75 pregnant women with GDM and 75 matched healthy controls and HRT8/SVneo cells (a model of insulin resistance) were analyzed by qPCR. The expressions of PI3K, AKT, IRS, and GLUT4 in high glucose‐treated HRT8/SVneo cells transfected with miR‐22 or miR‐372 mimics or inhibitors was assessed by Western blot. A luciferase gene reporter assay was employed to verify miRNAs' target genes.

Results

The expressions of miR‐22 and miR‐372 in placental tissues from GDM patients and HRT8/SVneo cells were significantly decreased compared with the respective controls. The GLUT4 expression was significantly decreased in the placenta tissues of GDM and HRT8/SVneo cells with high glucose transfected with miR‐22 and miR‐372 inhibitors. We confirmed that SLC2A4, the gene encoding GLUT4, was a direct target of miR‐22 and miR‐372. In this study, we report that the lower expressions of miR‐22 and miR‐372 in placental tissue from GDM patients.

Conclusion

Our results further suggested that the downregulations of miR‐22 and miR‐372 may contribute to GDM through regulating the PI3K/GLUT4 pathway.
Deep Learning Staging of Liver Iron Content From Multiecho MR Images
Authors: Positano Vincenzo , Meloni Antonella , Santarelli Maria Filomena , Pistoia Laura , Spasiano Anna , Cuccia Liana , Casini Tommaso , Gamberini Maria Rita , Allò Massimo , Bitti Pier Paolo , Pepe Alessia , Cademartiri Filippo
Published: June 2022

Background

MRI represents the most established liver iron content (LIC) evaluation approach by estimation of liver T2* value, but it is dependent on the choice of the measurement region and the software used for image analysis.

Purpose

To develop a deep‐learning method for unsupervised classification of LIC from magnitude T2* multiecho MR images.

Study Type

Retrospective.

Population/Subjects

A total of 1069 thalassemia major patients enrolled in the core laboratory of the Myocardial Iron Overload in Thalassemia (MIOT) network, which were included in the training (80%) and test (20%) sets. Twenty patients from different MRI vendors included in the external test set.

Field Strength/Sequence

A5 T, T2* multiecho magnitude images.

Assessment

Four deep‐learning convolutional neural networks (HippoNet‐2D, HippoNet‐3D, HippoNet‐LSTM, and an ensemble network HippoNet‐Ensemble) were used to achieve unsupervised staging of LIC using five classes (normal, borderline, middle, moderate, severe). The training set was employed to construct the deep‐learning model. The performance of the LIC staging model was evaluated in the test set and in the external test set. The model's performances were assessed by evaluating the accuracy, sensitivity, and specificity with respect to the ground truth labels obtained by T2* measurements and by comparison with operator‐induced variability originating from different region of interest (ROI) placements.

Statistical Tests

The network's performances were evaluated by single‐class accuracy, specificity, and sensitivity and compared by one‐way repeated measures analysis of variance (ANOVA) and one‐way ANOVA.

Results

HippoNet‐Ensemble reached an accuracy significantly higher than the other networks, and a sensitivity and specificity higher than HippoNet‐LSTM. Accuracy, sensitivity, and specificity values for the LIC stages were: normal: 0.96/0.93/0.97, borderline: 0.95/0.85/0.98, mild: 0.96/0.88/0.98, moderate: 0.95/0.89/0.97, severe: 0.97/0.95/0.98. Correctly staging of cases was in the range of 85%–95%, depending on the LIC class. Multiclass accuracy was 0.90 against 0.92 for the interobserver variability.

Data Conclusion

The proposed HippoNet‐Ensemble network can perform unsupervised LIC staging and achieves good prognostic performance.

Evidence Level

4

Technical Efficacy

Stage 2
Postsplenectomy morbidity and mortality in patients with immune thrombocytopenic purpura: A national cohort study
Authors: Sharon Cimarron E. , Straker Richard J. , Perry Nikhita , Miura John T. , Karakousis Giorgos C.
Published: June 2022

Background

We sought to identify factors associated with 30‐day morbidity, and their impact on 30‐day mortality, among patients undergoing splenectomy for immune thrombocytopenic purpura (ITP).

Methods

Using the ACS‐NSQIP database, patients undergoing splenectomy for ITP were identified (2005–2019), and those with and without postoperative complications within 30 days of surgery were compared.

Results

Of 2483 patients evaluated, 280 (11.3%) developed 30‐day morbidity: infection (n= 145 [5.8%]), venous thromboembolism (n = 71 [2.9%]), acute renal failure (n = 7 [0.3%]), respiratory failure (n = 40 [1.6%]), cardiac arrest/myocardial infarction (n = 16 [0.6%]), cerebrovascular accident (n = 4 [0.2%]), or postoperative blood transfusion (n = 62 [2.5%]). Risk‐factors for 30‐day morbidity included age ≥50 years (odds ratio [OR] 1.50, p = 0.020), body mass index ≥30 kg/m2 (OR 1.45, p = 0.023), functional dependence (OR 2.90, p = 0.009), preoperative albumin <3.5 g/dL (OR 2.10, p < 0.001), preoperative platelets <30 000/μL (OR 1.54, p = 0.020), open surgical approach (OR 2.32, p < 0.001), and inpatient status before surgery (OR 1.85, p = 0.040). Among patients at low‐risk for 30‐day morbidity (no risk‐factors present), the 30‐day morbidity rate was 5.0% versus 41.5% for ≥5 risk‐factors (p < 0.001). Thirty‐day mortality was 1.2%.

Conclusions

Thirty‐day morbidity and mortality are low with splenectomy for ITP. Select patients have particularly low perioperative risk and may benefit from early splenectomy if initial medical therapy fails.
Leveraging web search data to explore public interest in psoriasis in Germany
Authors: Wallnöfer Fabian , Erbas Mert E. , Tizek Linda , Schuster Barbara , Wecker Hannah , Biedermann Tilo , Zink Alexander
Published: June 2022

Background

Little is known about what people are interested in when they search the web for psoriasis. The monitoring of online search behaviour allows the assessment of interest in a disease on a more representative level by including people outside of medical settings.

Objectives

This study aims to reveal relevant aspects regarding psoriasis for people consulting the web.

Methods

Google Ads Keyword Planner was used to select and evaluate relevant German keywords for ‘psoriasis' in the study period from September 2016 to August 2020 on German territory. All keywords were qualitatively reviewed and descriptively analysed in 11 categories. One‐way analysis of variance, Welch test and Pearson's correlation coefficient were used to assess differences within Germany, annual search volumes and seasons.

Results

Overall, 11,170,740 German language Google searches on the topic of psoriasis were made. In the general category, the most commonly searched disease aspect was related to the possible contagiousness of psoriasis (n = 122,040). ‘Head’ (51.1%), followed by ‘nails’ (15.9%), ‘hands’ (8.8%), ‘feet’ (7.8%), and ‘genital/anal area’ (6.1%), was the most frequently searched for localization. Pustular forms of psoriasis were overrepresented in the search volume. Almost half of the search terms for therapy were represented by keywords related to alternative care and phytotherapy, while less than 1% related to biologics. Differences between the federal states for search volume on treatment options (p < 0.001) and between annual search volumes (p < 0.001) were found.

Conclusions

Queries on pustular forms and difficult‐to‐treat areas gained high online interest, which suggests higher disease impact or underdiagnosis. The high interest in alternative therapy options suggests possible therapy dissatisfaction, lack of patient information or lack of access to guideline‐conform therapy options. The possible infectiousness of psoriasis seems to remain an issue in the general population and should be addressed accordingly.
Reinke's edema management and voice outcomes
Authors: Dewan Karuna , Chhetri Dinesh K. , Hoffman Henry
Published: June 2022

Objectives

Reinke's edema is a chronic disease of the respiratory tract that occurs in adults with a history of chronic smoke exposure. Also known as polypoid corditis, polypoid laryngitis, and polypoid degeneration of the vocal fold, it is strongly associated with smoking, frequently with vocal misuse/abuse, and occasionally with laryngopharyngeal reflux. Reinke's edema remains a cause of chronic dysphonia that is difficult to manage. This review provides perspectives on current and future management of Reinke's edema.

Results

Reinke's edema impacts <1% of the population. The excessive mass is seen in polypoid degeneration results in a loss of pitch control and a rough voice. Women are more likely to present for treatment as the characteristic lowering of vocal pitch is more noticeable in women than men. Multiple grading systems have been proposed within the literature. The current standard of care is surgical excision, after smoking cessation. The microflap technique remains the approach of choice for bulky lesions. Surgical management of Reinke's edema has evolved with the introduction of various lasers into otolaryngologic practice; some which can now be used in the office setting. While many management approaches have been described within the literature, there is a little direct comparison and no obvious superior method of Reinke's edema management.

Conclusion

To date, the biology of Reinke's edema is not well understood. Additional research is needed further elucidate the role of uncontrolled reflux in the development and recurrence of Reinke's edema.
Formulation of Dermal Tissue Matrix Bioink by a Facile Decellularization Method and Process Optimization for 3D Bioprinting toward Translation Research
Authors: Bera Ashis Kumar , Sriya Yeleswarapu , Pati Falguni
Published: June 2022

Decellularized extracellular matrices (ECMs) are being extensively used for tissue engineering purposes and detergents are predominantly used for this. A facile detergent‐free decellularization method is developed for dermal matrix and compared it with the most used detergent‐based decellularization methods. An optimized, single‐step, cost‐effective Hypotonic/Hypertonic (H/H) Sodium Chloride (NaCl) solutions‐based method is employed to decellularize goat skin that resulted in much higher yield than other methods. The ECM composition, mechanical property, and cytocompatibility are evaluated and compared with other decellularization methods. Furthermore, this H/H‐treated decellularized dermal ECM (ddECM) exhibits a residual DNA content of <50 ng mg−1 of dry tissue. Moreover, 85.64 ± 3.01% of glycosaminoglycans and 65.53 ± 2.9% collagen are retained compared to the native tissue, which is higher than the ddECMs prepared by other methods. The cellular response is superior in ddECM (H/H) than other ddECMs prepared by detergent‐based methods. Additionally, a bioink is formulated with the ddECM (H/H), showing good shear thinning and shear recovery properties. Process optimization in terms of print speed, flow rate, and viscosity is done to obtain a bioprinting window for ddECM bioink. The printed constructs with optimized parameters have adequate mechanical and cell adhesive properties and excellent isotropic cellular alignment.
Parameter‐uniform numerical methods for singularly perturbed linear transport problems
Authors: Gracia José Luis , Navas‐Montilla Adrian , O'Riordan Eugene
Published: June 2022

Pointwise accurate numerical methods are constructed and analysed for three classes of singularly perturbed first order transport problems. The methods involve piecewise‐uniform Shishkin meshes and the numerical approximations are shown to be parameter‐uniformly convergent in the maximum norm. A transport problem from the modelling of fluid–particle interaction is formulated and used as a test problem for these numerical methods. Numerical results are presented to illustrate the performance of the numerical methods and to confirm the theoretical error bounds established in the paper.
Global classical solutions to the compressible micropolar viscous fluids with large oscillations and vacuum
Authors: Zhu Canze , Tao Qiang
Published: June 2022

In this paper, we consider the three dimensional Cauchy problem of the compressible micropolar viscous flows. We prove the existence of unique global classical solution for smooth initial data with small initial energy but possibly large oscillations and the initial density may allowed to contain the interior and far field vacuum states. Furthermore, the large time behavior of the solution is obtained as well.
Multicenter Repeatability and Reproducibility of MR Fingerprinting in Phantoms and in Prostatic Tissue
Authors: Lo Wei‐Ching , Bittencourt Leonardo Kayat , Panda Ananya , Jiang Yun , Tokuda Junichi , Seethamraju Ravi , Tempany‐Afdhal Clare , Obmann Verena , Wright Katherine , Griswold Mark , Seiberlich Nicole , Gulani Vikas
Published: June 2022

Purpose

To evaluate multicenter repeatability and reproducibility of T1 and T2 maps generated using MR fingerprinting (MRF) in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom and in prostatic tissues.

Methods

MRF experiments were performed on 5 different 3 Tesla MRI scanners at 3 different institutions: University Hospitals Cleveland Medical Center (Cleveland, OH), Brigham and Women's Hospital (Boston, MA) in the United States, and Diagnosticos da America (Rio de Janeiro, RJ) in Brazil. Raw MRF data were reconstructed using a Gadgetron‐based MRF online reconstruction pipeline to yield quantitative T1 and T2 maps. The repeatability of T1 and T2 values over 6 measurements in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom was assessed to demonstrate intrascanner variation. The reproducibility between the 4 clinical scanners was assessed to demonstrate interscanner variation. The same‐day test–retest normal prostate mean T1 and T2 values from peripheral zone and transitional zone were also compared using the intraclass correlation coefficient and Bland–Altman analysis.

Results

The intrascanner variation of values measured using MRF was less than 2% for T1 and 4.7% for T2 for relaxation values, within the range of 307.7 to 2360 ms for T1 and 19.1 to 248.5 ms for T2. Interscanner measurements showed that the T1 variation was less than 4.9%, and T2 variation was less than 8.1% between multicenter scanners. Both T1 and T2 values in in vivo prostatic tissue demonstrated high test–retest reliability (intraclass correlation coefficient > 0.92) and strong linear correlation (R2 > 0.840).

Conclusion

Prostate MRF measurements of T1 and T2 are repeatable and reproducible between MRI scanners at different centers on different continents for the above measurement ranges.
Development of a training programme for professional nurses in South Africa – An educational response to the COVID‐19 pandemic
Authors: Jordan Portia , Iwu‐Jaja Chinwe , Mokoka Elizabeth , Kearns Irene , Oamen Benedict , de Lange Santel , Schutte Loraine , Naidoo Vasanthrie
Published: June 2022

Aim

This paper describes the development of the training programme for South African professional nurses on how to manage critically ill COVID‐19 patients in intensive care units and repurposed general wards.

Design and methods

The Analysis, Design, Development, Implementation and Evaluation educational instructional design model guided the development of the training programme. A case‐based study approach and blended learning were used to deliver the six modules.

Results

The training programme was developed, reviewed and validated by the coordinating team of facilitators involved in the initiative. Implementation of the training programme and the result thereof will not be discussed as part of this manuscript.

Conclusion

The training programme aimed to enhance the knowledge of professional nurses in the management of critically ill patients with COVID‐19. As the pandemic evolves, a need for training and ongoing support was identified, which might address the need for surge capacity and hospital readiness planning.
Correlating measured radiotherapy dose with patterns of endocrinopathy: The importance of minimizing pituitary dose
Authors: Fraser Olivia , Crowne Elizabeth , Tacey Mark , Cramer Rebecca , Cameron Alison
Published: June 2022

Background

Pituitary insufficiency is a common toxicity of cranial radiotherapy received in childhood for central nervous system, head and neck, and hematological malignancies. There is a recognized deficiency pattern and correlation with prescribed radiotherapy dose; however, correlation with measured pituitary dose (which can be minimized with modern radiotherapy techniques) has not previously been assessed.

Procedure

Retrospective analysis was carried out of measured pituitary dose and endocrine outcomes of patients receiving cranial, total body, or head and neck photon beam radiotherapy at a tertiary center from July 2008 to October 2019.

Results

Complete data for 102 patients were available. Median (IQR) age at radiotherapy was 9.0 (6.0‐12.0) and follow‐up 5.7 years (3.5‐9.1). Most patients received focal brain radiotherapy (36.3%) or total body irradiation (32.4%); most frequent diagnoses were acute lymphoblastic leukemia (25.5%) and medulloblastoma (17.6%). The majority developed pituitary insufficiency (64; 62.7%); 41% had one and 38% had two hormone deficiencies. Growth hormone deficiency (GHD) (58; 56.9%) and thyroid‐stimulating hormone deficiency (TSHD) (32; 31.4%) were most common. Patients who developed pituitary insufficiency received higher maximum pituitary dose—median (IQR) Gy, 44.0 (20.4‐54.0) vs 18.2 (14.4‐52.6); P = 0.008. Doses of 40‐49 Gy or >50 Gy led to a higher cumulative incident rate than <20 Gy (HR 4.07, P < 0.001 and HR 3.04, P < 0.001, respectively). However, even at lower dose bands, levels of pituitary insufficiency were significant with a five‐year cumulative incidence of GHD for <20 Gy and TSHD for 20‐29 Gy reaching >30%.

Conclusions

Our findings confirm a correlation between measured pituitary dose and risk of insufficiency even at lower doses, despite modern radiotherapy techniques. These data highlight the importance of minimizing pituitary dose and early specialist endocrine follow‐up.