bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabis quality assurance program :
Authors: Abdur-Rahman Maryam , Phillips Melissa M , Wilson Walter B
Published: July 2021

NIST launched a CannaQAP in 2020 to improve the comparability of the analytical measurements in forensic and Cannabis (hemp and marijuana) testing laboratories. CannaQAP is an interlaboratory study mechanism that is similar to a proficiency testing scheme; however, the focus is towards education without assigning pass/fail grades to anonymized participants. CannaQAP helps inform NIST about the current measurement capabilities and challenges to assist in the design and characterization of Cannabis RMs. Exercise 1 of CannaQAP focused on the determination of cannabinoids including ?9-THC, THCA, total THC, CBD, CBDA, total CBD, and up to 13 additional cannabinoids in two hemp oils. This report provides a detailed description of the results of this exercise.
Not simply volcanoes – The Geoheritage of the Cretaceous System in the Land of the Extinct Volcanoes Geopark, West Sudetes (SW Poland)
Authors: Migoń Piotr , Pijet-Migoń Edyta
Published: July 2021

Volcanic geoheritage is emphasized as the main asset and distinctive characteristic of the Land of Extinct Volcanoes Geopark in the West Sudetes (SW Poland). However, the geoheritage values of the region are not limited to the legacy of ancient volcanism but include various other elements. This paper explores the contribution of geosites that expose sedimentary rocks of Cretaceous age and landforms developed upon these rocks. Six localities from the Geopark area, included in the comprehensive regional inventory of geosites, are presented. They represent natural and man-made sandstone outcrops and show, among others, lithological variations, small- and large-scale post-sedimentary deformation structures, landforms arising from differential weathering (rock shelters, honeycombs), boulder fields and a sandstone xenolith in volcanic rocks. Next, five localities from outside the Geopark, but still within the Pogórze Kaczawskie region, are described. Qualitative and quantitative evaluation of both groups is attempted, and the results show that, in general, geosites within the Geopark rank higher. However at least two from the other group also have significant geotourist potential. Finally, a brief comparative analysis with other parts of the Sudetes, where Cretaceous sedimentary rocks occur, is offered.
Traumatization of the Past and Martyrological Thinking in the Soviet Union and the Post-Soviet Space
Authors:   Moscow State University, Russia, Anikin Daniil ,   Tomsk State University, Russia
Published: July 2021

The purpose of the article is to analyze the mechanisms of the transformation of martyrological thinking in the Soviet Union and in post-Soviet Russia. The methodological basis of the study is constituted by the works written by the representatives of functionalism (E. Durkheim, M. Halbwachs, P. Bourdieu, J.C. Alexander), who raise the issue of the important role of religious rituals and forms of thinking in social space. Martyrological thinking creates martyrdom cults, performing an ambivalent function. On the one hand, this thinking is a way to maintain a collective identity, and on the other, a way to damage and destroy it. The author concludes that in Soviet society two main stages that formed martyrdom cults can be distinguished: the periods of the Civil War and the Great Patriotic War. In both cases, martyrological thinking was an important factor in the consolidation of the society. In post-Soviet society, martyrological thinking becomes a factor that causes the deconstruction of the symbolic space and a hidden factor in the destabilization of the political organization. The perception of the conservative part of the Russian society is expressed in the formation of the cult of the last Russian emperor, Nicholas II, which, on the one hand, allows to mitigate the historical responsibility, and on the other becomes a moral justification for criticizing the continuity of modern Russian power in relation to the Soviet Union.
HepGentox: a novel promising HepG2 reportergene-assay for the detection of genotoxic substances in complex mixtures
Authors: Pinter Elisabeth , Friedl Christina , Irnesberger Alexandra , Czerny Thomas , Piwonka Tina , Peñarroya Alfonso , Tacker Manfred , Riegel Elisabeth
Published: July 2021

Background

In risk assessment, genotoxicity is a key factor to determine the safety for the consumer. Most in vitro genotoxicity assays were developed for the assessment of pure substances. However, in recent years more attention has been given to complex mixtures, where usually low amounts of a substance are present. For high-throughput screening, a toxicologically sensitive assay should be used, covering a broad range of genotoxic substances and detecting them at low concentrations. HepG2 cells have been recommended as one of the prime candidates for genotoxicity testing, as they are p53 competent, less prone towards cytotoxic effects and tend to have some metabolic activity.

Methods

A HepG2 liver cell line was characterized for its suitability for genotoxicity assessment. For this, a luciferase based reporter gene assay revolving around the p53 pathway was validated for the analysis of pure substances and of complex mixtures. Further, the cell’s capability to detect genotoxins correctly with and without an exogenous metabolizing system, namely rat liver S9, was assessed.

Results

The assay proved to have a high toxicological sensitivity (87.5%) and specificity (94%). Further, the endogenous metabolizing system of the HepG2 cells was able to detect some genotoxins, which are known to depend on an enzymatic system. When complex mixtures were added this did not lead to any adverse effects concerning the assays performance and cytotoxicity was not an issue.

Discussion

The HepGentox proved to have a high toxicological sensitivity and specificity for the tested substances, with similar or even lower lowest effective concentration (LEC) values, compared to other regulatory mammalian assays. This combines some important aspects in one test system, while also being less time and material consuming and covering several genotoxicity endpoints. As the assay performs well with and without an exogenous metabolizing system, no animal liver fractions have to be used, which application is discussed controversially and is considered to be expensive and laborious in sample testing. Because of this, the HepGentox is suitable for a cost-efficient first screening approach to obtain important information with human cells for further approaches, with a relatively fast and easy method. Therefore, the HepGentox is a promising assay to detect genotoxic substances correctly in complex mixtures even at low concentrations, with the potential for a high throughput application. In a nutshell, as part of an in vitro bioassay test battery, this assay could provide valuable information for complex mixtures.
COVID-19 Pandemic - Clinical Features, Recent Investigations, Diagnosis, Modes of Transmission, and Role of WHO
Authors: Motwani Neelam Vinod , Dudhekar Abhilash Ulhas , Muntode Pramita Ambadas
Published: July 2021

In 2019 December, a bunch of respiratory disorder cases associated with city’s South China seller spot for sea food of unknown pathology was identified by the health authorities of Wuhan, China. And has been designated a public health emergency of international concern. Consequently, it was concluded that the virus spreads from individual-to-individual, and carriers are the most common source of Coronavirus growth. Novel Coronavirus, SARS–COV-2, was revealed by subsequent investigations and that was the initiative agent now at the core of a major outburst. To prevent or to reduce transmission, special focus and efforts were applied to vulnerable population including elderly people, children and health workers. And large scale measures were taken to lower communicable spread of COVID-19 from surveying a relation of (SARS) Severe Acute Respiratory Syndrome and (MERS) Middle East Respiratory Syndrome, where beta corona virus, which strike the lower respiratory tract and shows pneumonia in human being, was the causative agent. WHO announced outbreak of COVID-19 in the early First light of January 31, 2020 (Korea Standard Time) as “Public Health Emergency of International Concern” (PHEIC).An important collective goal was to reduce the outbreak and to flatten the peak of the outbreak curve. Delays result in significantly higher death tolls. In this review, we are trying to highlight the clinical features, investigations, WHO declaration of PHEIC, mode of transmission, effective Infection protocol to prevent this virulent infection from expansion and WHO 5 Movements because Hand Washing is a way of disinfecting a person’s hands that considerably decreases likely pathogens (deadly germs) on the palms.
COVID 19 in Geriatric Patients in Vidharbha Region
Authors: Chamat Ayush , Nagrale Ninad , Bankar Nandkishor
Published: July 2021

Introduction: Although all age groups are at risk of getting COVID-19, older people are at greater risk of developing serious illnesses as a result of the physical changes that come with aging and the onset of health symptoms Symptoms: Fever Cough Throat Throat Tiredness According to the current epidemiological evidence, patients with SARS-coV2 virus over the age of 80 are at greater risk of dying than younger patients, according to a study of Coronavirus 2019 (COVID-19) is a highly contagious disease caused by a novel coronavirus from Wuhan, China, was also recognized by the International Committee on Taxonomy of Viruses as acute acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ICTV).

Aim: Covid-19 in geriatric patients in vidharbha region

Materials and Methods: Covid 19 positive Patients went directly to the Observed Treatment in the Dept. of Medicine and Dept. of Respiratory, DMMC and SMHRC, Nagpur.

Results: Recovery is usually slower and more difficult. Most of us are concerned about our elderly relatives who live far away from us. They can experience anxiety as a result of living alone, being on a fixed income or pension, no longer driving and unable to use public transportation, and having their regular health checkups postponed. They may also be suffering from undiagnosed or poorly treated depression. COVID-19 has exacerbated the concerns of millions of elderly people.

Conclusion: We may also assist them by following the steps below. Ensure their medical supplies are stocked up.
Clinical Feature, Cause and Outcome in Female Paediatric Child with Osseomuscular Type of Wilson’s Disease
Authors: Yelekar Mayuri , Pahune Lina , Alwadkar Indu , Kawale Aparna
Published: July 2021

Introduction: Genetically inherited diseases have grown in the last few decades. Wilson’s disease is one of those, named after the U.S.-born British neurologist Dr. Samuel Alexander Kinnier Wilson.

Case Presentation: A 12 years old female child was admitted in A.V.B.R. hospital with the chief complaints of altered behaviour, speech disturbances, no physical coordination, uncontrolled movement since 2 to 3 months and fever since 2-3 days. Golden brown eye discoloration was present. After physical examination and investigation doctor diagnosed it as a case of Wilson’s disease.

The Main Diagnosis, Therapeutic Intervention and Outcomes: After physical examination and investigation doctor diagnosed this as a case of Wilson’s disease.  Zinc and vitamin supplements were given for 7 days to enhance immunity.  Beta-blocker was given For 7days twice a day, Tab. Trietinine 250 mg was given once a day for 7 days to remove the heavy metal i.e. copper. She took all treatment and outcome was good. Her signs and symptoms got reduced and she was able to do her routine activities.

Conclusion: The diagnosis of Wilson's disease relies largely on clinical examination and laboratory confirmation of abnormal metabolism of copper. This case responded well to all treatment and her recovery was good.
The root cause analysis on failed patient‐specific measurements of pencil beam scanning protons using a 2D detection array with finite size ionization chambers
Authors: Ricci Jacob C. , Hsi Wen C. , Su Zhong , Mund Karl , Dawson Robert , Indelicato Daniel J.
Published: July 2021

The aim of this report is to present the root cause analysis on failed patient‐specific quality assurance (QA) measurements of pencil beam scanning (PBS) protons; referred to as PBS‐QA measurement. A criterion to fail a PBS‐QA measurement is having a <95% passing rate in a 3.0%‐3.0 mm gamma index analysis. Clinically, we use a two‐dimensional (2D) gamma index analysis to obtain the passing rate. The IBA MatriXX PT 2D detection array with finite size ionization chamber was utilized. A total of 2488 measurements performed in our PBS beamline were cataloged. The percentage of measurements for the sites of head/neck, breast, prostate, and other are 53.3%, 22.7%, 10.5%, and 13.5%, respectively. The measurements with a passing rate of 100 to >94%, 94 to >88%, and <88% were 93.6%, 5.6%, and 0.8%, respectively. The percentage of failed measurements with a <95% passing rate was 10.9%. After removed the user errors of either re‐measurement or re‐analysis, 8.1% became acceptable. We observed a feature of >3% per mm dose gradient with respect to depth on the failed measurements. We utilized a 2D/three‐dimensional (3D) gamma index analysis toolkit to investigate the effect of depth dose gradient. By utilizing this 3D toolkit, 43.1% of the failed measurements were improved. A feature among measurements that remained sub‐optimal after re‐analysis was a sharp >3% per mm lateral dose gradient that may not be well handled using the detector size of 5.0 mm in‐diameter. An analysis of the sampling of finite size detectors using one‐dimensional (1D) error function showed a large dose deviation at locations of low‐dose areas between two high‐dose plateaus. User error, large depth dose gradient, and the effect of detector size are identified as root causes. With the mitigation of the root causes, the goals of patient‐specific QA, specifically detecting actual deviation of beam delivery or identifying limitations of the dose calculation algorithm of the treatment planning system, can be directly related to failure of the PBS‐QA measurements.
Low‐Dimensional Embeddings for Interaction Design
Authors: Rusu Marius Mihai , Schött Svenja Yvonne , Williamson John H. , Schmidt Albrecht , Murray-Smith Roderick
Published: July 2021

Physical interactions with the real world have many degrees of freedom, which has led to the development of novel input devices with a multitude of sensors to capture increasingly high‐dimensional data. This high dimensionality makes the design of interactive systems more complex. Herein, the use of autoencoder‐based dimensionality reduction is explored to simplify the design process. For this purpose, a data glove equipped with accelerometers is used to record high‐dimensional hand movement data that are thereafter reduced to 2D embeddings using autoencoders. The exploration and evaluation of the resulting embeddings suggest that autoencoders can be used to create meaningful low‐dimensional representations of complex human movement. The characteristics generality, variability, connectivity, and distinguishability are established and a guideline is provided for assessing low‐dimensional embeddings. Referring to these characteristics, system engineers can evaluate different input modalities and gestures for their specific interaction task. Further, a framework is outlined for designing and evaluating gesture interaction in the low‐dimensional space. By demonstrating the exemplary design of the interaction with a virtual lever, this research gives system engineers a template for interaction design in the low‐dimensional space.
Youth Mentoring Relationships and College Social and Academic Functioning: The Role of Mentoring Relationship Quality, Duration, and Type
Authors: McClain Cara M. , Kelner William C. , Elledge L. Christian
Published: July 2021

The aim of the present study was to examine how college students’ retrospective reports of youth‐mentoring experiences were associated with current sense of belonging and community, academic motivation, and college self‐efficacy, and to determine hows these outcomes vary as a function of mentoring relationship quality, duration, and type (e.g., natural versus program‐sponsored). Analyses were conducted in Mplus 8.0 on a sample of 400 college students. Our findings suggest that most college students endorse a mentoring relationship. We found that having a mentor was associated with increased college self‐efficacy. Among those with a youth mentor, relationship quality was positively associated with sense of belonging and college self‐efficacy while duration of the mentoring relationship and relationship type were not associated with college‐related outcomes. Further analyses were conducted to assess how the associations between relationship quality and the college‐related outcomes varied as a function of mentoring duration and type. Relationship quality was uniquely associated with these college‐related outcomes over and above student gender, race, and first‐generation status. Our findings suggest it may be important to prioritize the enhancement of mentor relationship quality as a mechanism to affect change in academic‐related outcomes.
Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride
Authors: Zhang Kun , Rombach David , Nötel Nicolas Yannick , Jeschke Gunnar , Katayev Dmitry
Published: July 2021

We report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low‐cost and readily available reagent. This light‐mediated process is fundamentally different from conventional methodologies and occurs through a trifluoroacyl radical mechanism promoted by a photocatalyst, which triggers a C−O bond fragmentation. Mechanistic studies (kinetic isotope effects, spectroelectrochemistry, optical spectroscopy, theoretical investigations) highlight the evidence of a fleeting CF3CO radical under photoredox conditions. The trifluoroacyl radical can be stabilized under CO atmosphere, delivering the trifluoroacetylation product with higher chemical efficiency. Furthermore, the method can be turned into a trifluoromethylation protocol by simply changing the reaction parameters. Beyond simple alkenes, this method allows for chemo‐ and regioselective functionalization of small‐molecule drugs and common pharmacophores.
Instrument Set Decontamination Workflows Designed for Success in Sterile Processing
Authors: Mace Davis Courtney , Spear Joan M.
Published: July 2021

In sterile processing, several factors can result in confusion and unpredictable quality outcomes in surgical instrument sets, including the large number of instruments to manage, the complexity of certain instruments, and the multiple instructions for cleaning solutions and cleaning equipment for use. At a multihospital health system, the director of sterile processing had a vision that involved designing standard decontamination workflows and standardized cleaning pathways based on quality concepts to support patient safety. When there was a pause in elective surgeries in the spring of 2020 as a result of the spread of coronavirus disease 2019, sterile processing personnel became available to participate in a project to create and test these new standardized cleaning pathways and decontamination workflows. This article provides an overview of the inception and execution of this project and how instrument cleaning and decontamination was streamlined to promote a more efficient workflow for sterile processing.
A Systematic Review of Interventions Used to Enhance Implementation of and Compliance With the World Health Organization Surgical Safety Checklist in Adult Surgery
Authors: Liu Liang Qin , Mehigan Sinead
Published: July 2021

The focus of this systematic review is to identify and synthesize the evidence for effectiveness of interventions to increase compliance with the World Health Organization Surgical Safety Checklist (SSC) for adult surgery. We searched a variety of databases and identified 24 peer‐reviewed articles of either a quantitative (n = 17), qualitative (n = 4), or mixed‐methods design (n = 3) published in English from January 1, 2008, to July 8, 2020. Interventions included modifying the ways of delivering the SSC, integrating or tailoring the SSC to local context or existing practice, promoting clinician awareness and engagement, and managing policies. Despite a lack of common outcome measures, all quantitative and mixed‐methods study results showed a significant positive effect on SSC compliance. A few researchers reported nonsignificant or negative changes in certain aspects with the interventions. Additional research is needed to address SSC compliance measures globally and outcomes in developing countries.
Synthesis of new 7‐amino‐3,4‐dihydroquinolin‐2(1H)‐one‐peptide derivatives and their carbonic anhydrase enzyme inhibition, antioxidant, and cytotoxic activities
Authors: Küçükbay Hasan , Gönül Zeynep , Küçükbay Fatümetüzzehra Zehra , Tekin Zehra , Angeli Andrea , Bartolucci Gianluca , Supuran Claudiu T. , Tatlıcı Eray , Apohan Elif , Yeşilada Özfer
Published: July 2021

Six new monopeptides, seven new dipeptides, and two deprotected monopeptide dihydroquinolinone conjugates were prepared by the benzothiazole‐mediated method and their structures were confirmed by nuclear magnetic resonance, mass, infrared spectroscopy, and elemental analysis methods. The human carbonic anhydrase (hCA) I and hCA II enzyme inhibition activities of the compounds were determined using the stopped‐flow instrument. The synthesized peptide–dihydroquinolinone conjugates 2, 3, 6, 10, 13, and 15 showed inhibition against the hCA II enzyme in the range of 15.7–65.7 µM. However, none of the compounds showed inhibition of hCA I at a concentration of 100 µM. The antioxidant activities of the compounds were also examined using the DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging method at concentrations of 12.5–125 µg/ml, but when compared with the standard antioxidant compounds α‐tocopherol and butylated hydroxyanisole (BHA), weak antioxidant activities were detected. The cytotoxic effects of four compounds against the A549 and BEAS‐2B cell lines were also investigated. Among the compounds studied, compound 7 was found to be most effective, with the IC50 values on the A549 cells for 48 and 72 h being 26.87 and 9.979 µg/ml, respectively, and the IC50 values on the BEAS‐2B cells being >100 µg/ml. None of the tested compounds showed antimicrobial activity in the concentration range (800–1.56 µg/ml) studied.
An engineered microfluidic blood‐brain barrier model to evaluate the anti‐metastatic activity of β‐boswellic acid
Authors: Vakilian Saeid , Alam Khurshid , Al‐Kindi Juhaina , Jamshidi‐Adegani Fatemeh , Rehman Najeeb Ur , Tavakoli Rezvan , Al‐Riyami Khamis , Hasan Anwarul , Zadjali Fahad , Csuk Rene , Al‐Harrasi Ahmed , Al‐Hashmi Sulaiman
Published: July 2021

Background

The development of anti‐cancer drugs with the ability to inhibit brain metastasis through the blood‐brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models.

Main Methods

In this study, the Geltrex‐based Transwell and microfluidic BBB models were applied to screen the effect of β‐boswellic acid (β‐BA) on the metastasis of MDA‐MB‐231 cells through the BBB in static and dynamic conditions, respectively.

Major Results

The toxicity assay revealed that β‐BA deteriorates MDA‐MB‐231 cells, while β‐BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans‐endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β‐BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β‐BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β‐BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β‐BA‐mediated metastasis inhibition was significantly higher than that mediated by Cis.

Conclusions and Implications

 In summary, the current study proved the anti‐metastatic potential of β‐BA in both static and dynamic BBB models.
Recent Research Trends of Two‐Photon Photosensitizer for Simultaneous Imaging and Photodynamic Therapy
Authors: Lee Hyo Won , Lee Dong Joon , Lim Chang Su
Published: July 2021

Imaging and photodynamic therapy through two‐photon excitation can be applied to medical application of deep inside the tissue by minimizing light absorption by the tissue. It is the best solution that can complement the shortcomings of conventional photodynamic therapy. In addition, auto‐fluorescence can be minimized, and damage to normal cells can be avoided through spatial and temporal control. To maximize the image realization and the effect of treatment, a single photosensitizer with high fluorescence quantum yields, two‐photon absorption value, and good1O2or reactive oxygen species production performance must be developed. Therefore, recent research related to this topic is summarized. In addition, two‐photon photosensitizers that approach selective imaging and treatment for target diseases and future challenges were discussed.
Ultrasensitive Capsaicin Sensor Based on Endogenous Single‐Molecule Fluorophore Enhancement and Quenching Interface on Gold Nanoislands
Authors: Chakkarapani Suresh Kumar , Lee Seungah , Kang Seong Ho
Published: July 2021

Ultrasensitive capsaicin sensor based on endogenous single‐molecule fluorophore enhancement and quenching interface on gold nanoislands (GNIs) was developed by correlative fluorescence fluctuation optical spectroscopy. Endogenous fluorescence of capsaicinoids was enhanced by plasmon resonance energy transfer in the proximity of GNIs. The enhanced fluorescence signals exhibited large fluctuation from the average intensity reflecting the characteristic to‐and‐fro Brownian motion of fluorophores to the proximity of GNIs. The fluctuation of fluorophores showed enhancement, quenching, and equilibrium lifetimes depending on fluorophore‐GNI distance. The correlation diffusion of fluorophore signal decreased with increasing concentration of capsaicinoids. In the cross‐correlative quantification of capsaicinoids using the GNI array chip, the method showed excellent detection limits of 290 zM for capsaicin and 467 zM for dihydrocapsaicin. This method consisting of fluorophore fluctuation analysis and correlation diffusion‐based quantification has potential application to the study of label‐free single‐molecule interactions.
Differential expression of microRNAs associated with neurodegenerative diseases and diabetic nephropathy in proteinl‐isoaspartyl methyltransferase‐deficient mice
Authors: Su Zhonghao , Ren Na , Ling Zicheng , Sheng Lanyue , Zhou Sirui , Guo Chunxia , Ke Zunji , Xu Tiefeng , Qin Zhenxia
Published: July 2021

Proteinl‐isoaspartyl methyltransferase (PIMT/PCMT1), an enzyme repairing isoaspartate residues in peptides and proteins that result from the spontaneous decomposition of normall‐aspartyl andl‐asparaginyl residues during aging, has been revealed to be involved in neurodegenerative diseases (NDDs) and diabetes. However, the molecular mechanisms for a putative association of PIMT dysfunction with these diseases have not been clarified. Our study aimed to identify differentially expressed microRNAs (miRNAs) in the brain and kidneys of PIMT‐deficient mice and uncover the epigenetic mechanism of PIMT‐involved NDDs and diabetic nephropathy (DN). Differentially expressed miRNAs by sequencing underwent target prediction and enrichment analysis in the brain and kidney of PIMT knockout (KO) mice and age‐matched wild‐type (WT) littermates. Sequence analysis revealed 40 differentially expressed miRNAs in the PIMT KO mouse brain including 25 upregulated miRNAs and 15 downregulated miRNAs. In the PIMT KO mouse kidney, there were 80 differentially expressed miRNAs including 40 upregulated miRNAs and 40 downregulated miRNAs. Enrichment analysis and a systematic literature review of differentially expressed miRNAs indicated the involvement of PIMT deficiency in the pathogenesis in NDDs and DN. Some overlapped differentially expressed miRNAs between the brain and kidney were quantitatively assessed in the brain, kidney, and serum‐derived exosomes, respectively. Despite being preliminary, these results may aid in investigating the pathological hallmarks and identify the potential therapeutic targets and biomarkers for PIMT dysfunction‐related NDDs and DN.
Immobilisation of Iron Porphyrin from an Equilibrium Solution with Diazonium‐Functionalised Axial Ligand: Dependence of Film Composition on Grafting Potential
Authors: Wu Ting , Brooksby Paula A. , Fitchett Christopher M. , Downard Alison J.
Published: July 2021

In dichloromethane solution, tetraphenylporphyrin iron (III) chloride (FeTPPCl) and 4‐(1H‐Imidazol‐1‐yl)aniline (Im‐Ph‐NH2) exist in equilibrium with axially‐coordinated [FeTPP(Im‐Ph‐NH2)n]+ (n=1 and 2). After in situ diazotisation of Im‐Ph‐NH2, electroreduction of the diazonium ion leads to deposition of a film incorporating [FeTPP(Im‐Ph)2]+ and uncoordinated Im‐Ph. In the 1 : 1 FeTPPCl:Im‐Ph‐NH2 grafting solution used in this work, Im‐Ph‐NH2 is mostly uncoordinated. However, the formation constant for axially coordinated Fe(II)TPP is significantly greater than for Fe(III)TPP+. Consequently, the relative amounts of coordinated and uncoordinated Im‐Ph in the films depends on whether the grafting scans traverse the potential for reduction of FeTPPCl. In addition, redox grafting can occur based on the Fe(III)/(II) couple of solution‐ and film‐based porphyrin. Electrochemistry, atomic force microscopy and X‐ray photoelectron spectroscopy reveal that the relative amount of free and coordinated Im‐Ph, and concentration of [FeTPP(Im‐Ph)2]+ in the films depend on the negative potential limit during grafting.
The Impact of C2 Insertion into a Carbazole Donor on the Physicochemical Properties of Dibenzo[a,j]phenazine‐Cored Donor–Acceptor–Donor Triads
Authors: Zimmermann Crocomo Paola , Kaihara Takahito , Kawaguchi. Soki , Stachelek Patrycja , Minakata Satoshi , de Silva Piotr , Data Przemyslaw , Takeda Youhei
Published: July 2021

Novel electron donor–acceptor–donor (D‐A‐D) compounds comprising dibenzo[a,j]phenazine as the central acceptor core and two 7‐membered diarylamines (iminodibenzyl and iminostilbene) as the donors have been designed and synthesized. Investigation of their physicochemical properties revealed the impact of C2 insertion into well‐known carbazole electron donors on the properties of previously reported twisted dibenzo[a,j]phenazine‐core D‐A‐D triads. Slight structural modification caused a drastic change in conformational preference, allowing unique photophysical behavior of dual emission derived from room‐temperature phosphorescence and triplet–triplet annihilation. Furthermore, electrochemical analysis suggested sigma‐dimer formation and electrochemical polymerization on the electrode. Quantum chemical calculations also rationalized the experimental results.
Modeling of Single Droplet Mass Transfer of Acetic Acid with Triisooctylamine‐Based Solvent
Authors: Rudelstorfer Georg , Siebenhofer Matthäus , Grafschafter Annika
Published: July 2021

The design of mass transfer equipment based on single droplet mass transfer data is still a great challenge, although having been subject of intensive discussion for decades already. Extraction with chemical reaction may rather contribute to additional problems when modeling single droplet mass transfer. Single droplet mass transfer of acetic acid from aqueous carrier into triisooctylamine based solvents modified with the Lewis acid modifier isodecanol and the diluent Shellsol T has been investigated. Mass transfer of acetic acid into triisooctylamine‐based solvent droplets is strictly controlled (actually limited) by diffusion of the laden solvent from the interface into the droplet bulk phase.
Longer term outcomes with single‐agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13‐month follow‐up from the pivotal DREAMM‐2 study
Authors: Lonial Sagar , Lee Hans C. , Badros Ashraf , Trudel Suzanne , Nooka Ajay K. , Chari Ajai , Abdallah Al‐Ola , Callander Natalie , Sborov Douglas , Suvannasankha Attaya , Weisel Katja , Voorhees Peter M. , Womersley Lynsey , Baron January , Piontek Trisha , Lewis Eric , Opalinska Joanna , Gupta Ira , Cohen Adam D.
Published: July 2021

Background

On the basis of the DREAMM‐2 study (ClinicalTrials.gov identifier NCT03525678), single‐agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti‐CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM‐2 after 13 months of follow‐up among patients who received belamaf 2.5 mg/kg.

Methods

DREAMM‐2 is an ongoing, phase 2, open‐label, 2‐arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti‐CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee.

Results

As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty‐one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%‐43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression‐free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6‐3.6 months), respectively. Response and survival outcomes in patients who had high‐risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow‐up.

Conclusions

Extended follow‐up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM.
Web service selection and composition based on uncertain quality of service
Authors: Zeyneb Yasmina Remaci , Fethallah Hadjila , Fadoua Lahfa
Published: July 2021

Web services are becoming a major utility for accomplishing complex tasks over the Internet. In practice, the end‐users usually search for Web service compositions that best meet the quality of service (QoS) requirements (i.e., QoS global constraints). Since the number of services is constantly increasing and their respective QoS is inherently uncertain (due to environmental conditions), the task of selecting optimal compositions becomes more challenging. To tackle this problem, we propose a heuristic based on majority judgment that allows for reducing the search space. In addition, we perform a constraint programming search to select the Top K compositions that fulfill the QoS global constraints. The experimental results demonstrate the high performance of our approach.
Mapping the miRNA‐mRNA Interactome in Human Hepatocytes and Identification of Functional mirSNPs in Pharmacogenes
Authors: Powell Nicholas R. , Zhao Harrison , Ipe Joseph , Liu Yunlong , Skaar Todd C.
Published: July 2021

MiRNAs regulate the expression of hepatic genes involved in pharmacokinetics and pharmacodynamics. Genetic variants affecting miRNA binding (mirSNPs) have been associated with altered drug response, but previously used methods to identify miRNA binding sites and functional mirSNPs in pharmacogenes are indirect and limited by low throughput. We utilized the high‐throughput chimeric‐eCLIP assay to directly map thousands of miRNA‐mRNA interactions and define the miRNA binding sites in primary hepatocytes. We then used the high‐throughput PASSPORT‐seq assay to functionally test 262 potential mirSNPs with coordinates overlapping the identified miRNA binding sites. Using chimeric‐eCLIP, we identified a network of 448 miRNAs that collectively target 11,263 unique genes in primary hepatocytes pooled from 100 donors. Our data provide an extensive map of miRNA binding of each gene, including pharmacogenes, expressed in primary hepatocytes. For example, we identified the hsa‐mir‐27b‐DPYD interaction at a previously validated binding site. A second example is our identification of 19 unique miRNAs that bind to CYP2B6 across 20 putative binding sites on the transcript. Using PASSPORT‐seq, we then identified 24 mirSNPs that functionally impacted reporter mRNA levels. To our knowledge, this is the most comprehensive identification of miRNA binding sites in pharmacogenes. Combining chimeric‐eCLIP with PASSPORT‐seq successfully identified functional mirSNPs in pharmacogenes that may affect transcript levels through altered miRNA binding. These results provide additional insights into potential mechanisms contributing to interindividual variability in drug response.
Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) and Ductus Arteriosus Closure After Premature Birth
Authors: Bouazza Naïm , Treluyer Jean‐Marc , Foissac Frantz , Urien Saïk , Aikio Outi , Roze Jean‐Christophe , Hallman Mikko
Published: July 2021

In preterm infants, a high risk of hemodynamically significant patent ductus arteriosus (PDA) exists and its persistence is associated with an increased risk of severe morbidity. Current pharmacological options include ibuprofen or indomethacin. However, treatment by indomethacin or ibuprofen of a large PDA was shown to reduce early pulmonary hemorrhage and later medical treatment but had no effect on neonatal death or morbidity. Early prophylactic treatment of ductus arteriosus by paracetamol seems to be an attractive opportunity to reduce life‐threatening morbidity. However, there are currently no data regarding the pharmacokinetics (PK) and pharmacodynamics of paracetamol in preterm neonates in this potential new indication. In this study, we aimed to develop a population PK model for paracetamol and investigate the relationship between paracetamol exposure levels and time to contraction of the ductus. Data were modeled using Monolix software. A one‐compartment model adequately described the paracetamol concentration‐time course. A Weibull model adequately described the time to contraction of the ductus. Our results suggest that the dosage used in this study (i.e., first day 42.5 mg/kg, then 30 mg/kg/day) allows for reaching the maximum inhibition response from paracetamol regarding the time to close the ductus. However, this study pointed out a lower effect of paracetamol on extremely preterm neonates (below 27 weeks). Therefore, a dose‐finding study focusing specifically on extremely preterm neonates with treatment efficacy and toxicity is strongly needed.
Oral health related quality of life and reasons for non‐dental attendance among patients with substance use disorders in withdrawal rehabilitation
Authors: Åstrøm Anne Nordrehaug , Virtanen Jorma , Özkaya Ferda , Fadnes Lars Thore
Published: July 2021

No study has assessed the socio‐behavioral distribution of oral health related quality of life (OHRQoL) among patients with substance use disorders receiving medically assisted rehabilitation therapy (MAR) in Norway.

Objectives

To examine the prevalence of oral impacts on daily performances (OIDP) and its distribution among MAR patients in western Norway. We also examined whether oral impacts discriminate with different reasons for non‐dental attendance.

Material and Methods

A cross‐sectional study focusing OHRQoL was nested to the INTRO‐HCV study and implemented in six rehabilitation clinics for people with substance use disorders. A total of 167 MAR patients completed personal interviews and oral clinical examination upon entering the clinic for their MAR medication.

Results

The prevalence of oral impacts (OIDP > 0) was 61%. Logistic regression, adjusted for sex and age presented with odds ratios (OR) with 95% confidence intervals (CI) revealed that less than 20 remaining teeth (OR = 5.3 95% CI: 1.6–23.3) and dissatisfaction with dental care (OR = 5.1 95% CI: 1.3–19.0) increased the odds of having OIDP > 0. OIDP > 0 was also associated with insufficient dental follow‐up due to dental anxiety and poor experiences with perceived attitudes of dental workers. Means OIDP among people with negative experiences with attitudes of dental care workers were 3.1 (SD 0.8) compared to 1.4 (SD 0.7) among those without negative experiences, and 2.8 (SD) for those with dental anxiety compared to 1.8 (SD) among those without.

Conclusion

OHRQoL among MAR patients was generally poor. To reach those with a need for dental care, modification of the existing rehabilitation approach toward closer collaboration between dental health care workers and others in contact with drug users might be necessary.
Models of mediation: Theoretical and legal analysis
Authors: Lohvinenko Mykola , Starynskyi Mykola , Rudenko Lyudmila , Kordunian Iryna
Published: July 2021

The research is relevant since the success of mediation largely depends on the model of the process chosen by the mediator at the stage of preparation. This article aims to study different models of mediation, such as facilitative mediation, evaluative, transformative, e‐mediation, mixed mediation, mediation‐arbitration, narrative mediation, “Shuttle” mediation, court‐mandated mediation, and a lot of others. The key method of research on this issue is the method of analysis, which was used to characterize and determine the characteristics of different models of mediation, and to classify these models according to different criteria. The results showed that among all the studied models, facilitative mediation is the most popular in use. It focuses on the interests of the parties, reflecting the main goal of this procedure, which is to achieve a solution that meets the interests of all parties, and mixed mediation, when the mediator combines different mediation models, using the benefits of each. The study concluded that the mediator should take into account the content of the dispute, the interests of the parties, and the relationship between them, and choose the style of the process that best suits the specific situation. The materials of the article can be used to develop legislation regulating mediation in Ukraine. The results of this study can be used by scientists to conduct theoretical and practical research in the field of alternative dispute resolution, as well as mediators to increase the level of knowledge in the preparation for mediation.
Decline in neutralising antibody responses, but sustained T‐cell immunity, in COVID‐19 patients at 7 months post‐infection
Authors: Chen Jun , Liu Xiaomin , Zhang Xinyu , Lin Yixiao , Liu Danping , Xun Jingna , Wang Zhenyan , Gu Ling , Li Qian , Yin Dan , Yang Junyang , Lu Hongzhou
Published: July 2021

Objectives

This study aimed to explore the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐specific humoral responses and T‐cell responses in patients who have recovered from coronavirus disease 2019 (COVID‐19) to understand the natural protective immune responses and to facilitate the development of vaccines.

Methods

We conducted a combined assessment of the changes in neutralising antibody levels and SARS‐CoV‐2‐specific T‐cell responses over time in 27 patients up to 7 months after infection.

Results

The neutralising antibody remained detectable in 96.3% of the patients at their second visit at about 7 months post‐onset of symptoms. However, their humoral responses, including titres of the spike receptor‐binding domain IgG and neutralising antibody, decreased significantly compared with those at first clinic visit. By contrast, the proportions of spike‐specific CD4+ T cells, but not CD8+ T cells, in COVID‐19 patients after recovery were persistently higher than those in healthy controls. No significant change was observed in the proportion of spike‐specific CD4+ T cells in patients who had recovered from COVID‐19 within 7 months.

Conclusion

The SARS‐CoV‐2‐specific T‐cell immune responses persisted, while the neutralising antibodies decayed. Further studies are needed to extend the longevity of neutralising antibodies and to evaluate whether these T cells are sufficient to protect patients from reinfection.
Paternal biopsychosocial resilience in triadic interactions among African American/Black families exposed to trauma and socioeconomic adversity
Authors: Bocknek Erika London , Lozada Fantasy T. , Richardson Patricia , Brown Deon , McGoron Lucy , Rajagopalan Adithi
Published: July 2021

Fathers have a distinct and unique effect on child development, but little is known about fathering beyond White or majority White families. The current study includes African American/Black biological fathers (N = 88) and their two‐year‐old children. Fathers reported low incomes and high rates of depression and posttraumatic stress disorder (PTSD). Parenting behaviors were observed in high‐stress and low‐stress triadic contexts. In the high‐stress condition, we assessed paternal responses to children's bids after the family was reunited following a separation paradigm. In the low‐stress condition, we assessed parenting behaviors during a teaching task. Fathers’ social baseline respiratory sinus arrhythmia (RSA) was obtained as an index of parasympathetic arousal. RSA moderated the association between PTSD and fathers’ responsiveness (F = 6.90,p = .00,R2 = .30), with no association between PTSD and responsiveness demonstrated among fathers with the highest levels of RSA relative to the sample (effect = .04,p = .00; CI [0.02, 0.06]). RSA did not moderate the association between paternal depression and parenting behaviors (p > .05). Furthermore, responsiveness was only significantly associated with low‐stress paternal teaching behaviors for fathers with lower RSA (F = 4.34,p = .01,R2 = .21; effect = –.19,p = .00; CI [0.06, 0.32]). Findings demonstrate significant relationships among RSA, PTSD, and parenting for African American/Black men in contexts of economic adversity.