bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Performance Sustainable Tissue Paper from Agricultural Residue: A Case Study on Fique Fibers from Colombia
Authors: Kumar Rajnish , Zambrano Franklin , Peszlen Ilona , Venditti Richard , Pawlak Joel J. , Jameel Hasan , Gonzalez Ronalds W.
Published: February 2022

Global sustainability megatrends are promoting the utilization of sustainably perceived fibers such as recycled and agricultural residue fibers in hygiene tissue applications. Tissue paper products advertised as sustainable have higher prices and inferior performance than conventional products manufactured from virgin wood fibers. This work demonstrates the feasibility of using agricultural residues from fique plantations (Furcraea microphylla genus) as an alternative to Northern Bleached Softwood Fibers (NBSK) in high-performance hygiene tissue applications. For our study, fiber residues were mechanically cleaned and upgraded to a tissue pulp using a simple pulping and bleaching process. A complete characterization of tissue paper properties (bulk, softness, water absorbency, tensile strength) was performed and compared against the NBSK market pulp. Additionally, fique residue pulp was blended with Bleached Eucalyptus Kraft (BEK) to match the performance of a selected benchmark consisting of 70% BEK and 30% NBSK. Results indicate fique residue bleached pulp has similar fiber morphology and comparable strength properties in terms of the tensile strength (+6%) and tear strength (+10%), but superior bulk (+12%), water absorbency (+28%), and softness (-29 % TS7 values) than NBSK pulp. A fiber blend of 70% BEK and 30% fique residue showed superior tensile strength (+21%), tear strength (+54%), bulk (+ 5.5%), water absorbency (+1.5%), and softness (-8.7% TS7 values) over a similar fiber blend of BEK and NBSK. Our findings demonstrate that fibers from fique residue can substitute NBSK in hygiene tissue applications. Upgrading residues from fique fibers as raw materials for the tissue industry can bridge the gap between sustainability and product performance, simultaneously opening the possibility of new revenue streams for millions of small farmers in the producing countries.
Precisely Translating Computed Tomography Diagnosis Accuracy into Therapeutic Intervention by a Carbon-Iodine Conjugated Polymer
Authors: Yin Mingming , Liu Xiaoming , Lei Ziqiao , Gao Yuting , Liu Jiacheng , Tian Sidan , Liang Zhiwen , Wang Ye , Meng Fanling , Luo Liang
Published: February 2022

The boomed development of precision medicine has underlined an immense need for ultraefficient, multifunctional markers to bridge diagnostic and therapeutic procedures. Particularly, ultraefficient X-ray computed tomography (CT) contrast agents that can precisely translate diagnostic findings into optimal therapeutic intervention represents an unsurmountable clinical challenge. Here, poly(diiododiacetylene) (PIDA), a conjugated polymer composed of only carbon and iodine atoms, is reported as an ultraefficient CT contrast agent to bridge CT diagnostic imaging with therapeutic intervention. PIDA has an unusually high iodine payload (>84 wt%), and the aggregation of nanofibrous PIDA can further amplify CT intensity for over 10 folds with improved geometrical and positional stability in vivo. Moreover, with a highly conjugated backbone, PIDA is in deep blue color, making it dually visible by both CT imaging and naked eyes. The supreme performance of PIDA in CT-guided preoperative planning and visualization-guided surgery has been validated on orthotopic xenograft rat models. More strikingly, PIDA excels clinical fiducial markers of imaging-guided radiotherapy in efficiency and biocompatibility, and exhibits successful guidance of robotic radiotherapy on Beagles, demonstrating great clinical potential to translate CT diagnosis accuracy into therapeutic intervention for precision medicine.
EGFR-Targeted Fluorescent Imaging Using The Da Vinci® Firefly™ Camera For Gallbladder Cancer
Authors: Choi Jung Ha , Kang Chang Moo , Park Jeong Youp
Published: February 2022

Fluorescent imaging may aid with precise diagnosis and treatment of patients with gallbladder cancer. In this study we sought to demonstrate whether the da Vinci® surgical system and Firefly™ camera could detect EGFR-targeted fluorescent images in orthotopic mouse models of gallbladder cancer. An orthotopic mouse model of gallbladder cancer was created by injecting NOZ gallbladder cancer cells mixed with Matrigel into the gallbladder. In vivo imaging of subcutaneous and orthotopic gallbladder tumors was performed after injection of DyLight 650- or 800-conjugated EGFR antibody. Western blotting, flow cytometry, and confocal microscopy showed the presence of EGFR in NOZ cells, but not in HEK cells. Subcutaneous NOZ cell tumors fluoresced after injection with fluorescent EGFR antibody, but subcutaneous HEK tumors did not. Fluorescent EGFR antibody made orthotopic NOZ tumors fluoresce, with an intensity stronger than in surrounding normal tissues. Histochemical examination confirmed the location of the tumors inside the gallbladder and adjacent liver parenchyma. Fluorescent signal was also detected in orthotopic gallbladder tumors with Firefly™ camera. Our study showed that fluorescent EGFR antibodies and the Firefly camera in the da Vinci system can detect fluorescing gallbladder tumors, which demonstrates its potential use for molecular imaging based prevision surgery in near future.
Characterization of ACE2 naturally occurring missense variants: impact on subcellular localization and trafficking
Authors: Badawi Sally , Mohamed Feda E. , Alkhofash Nesreen R. , John Anne , Ali Amanat , Ali Bassam R.
Published: February 2022

Background:Human angiotensin converting enzyme 2 (ACE2), a type I transmembrane receptor physiologically acting as a carboxypeptidase enzyme within the renin-angiotensin system (RAS), is a critical mediator of infection by several severe acute respiratory syndrome (SARS) corona viruses. For instance, it has been demonstrated that ACE2 is the primary receptor for the SARS-CoV-2 entry to many human cells through binding to the viral spike S protein. Consequently, genetic variability in ACE2 gene has been suggested to contribute to the variable clinical manifestations in COVID-19. Many of those genetic variations result in missense variants within the amino acid sequence of ACE2. The potential effects of those variations on binding to the spike protein has been speculated and, in some case, demonstrated experimentally. However, their effects on ACE2 protein folding, trafficking and subcellular targeting have not been established. Results:In this study we aimed to examine the potential effects of 28 missense variants (V801G, D785N, R768W, I753T, L731F, L731I, I727V, N720D, R710H, R708W, S692P, E668K, V658I, N638S, A627V, F592L, G575V, A501T, I468V, M383I, G173S, N159S, N149S, D38E, N33D, K26R, I21T, S19P) distributed across the ACE2 receptor domains on its subcellular trafficking and targeting through combinatorial approach involving in silico analysis and experimental subcellular localization analysis. Our data show that none of the studied missense variants (including 3 variants predicted to be deleterious R768W, G575V and G173S) has a significant effect on ACE2 intracellular trafficking and subcellular targeting to the plasma membrane. Conclusion: Loss of proper trafficking and targeting of ACE2 is expected to lead to loss of the protein function and therefore our results support the notion that loss of this protein function is not tolerated in humans due to its many essential physiological functions.
Spatiotemporal Analysis of Heat Waves in Jordan
Authors: Alwadi Yazan , Abdulla Fayez
Published: February 2022

Heatwaves are durations of relatively extreme high temperatures. The literature presents multiple methods and criteria of identifying heatwaves based on Temperature exceedance parameter, and a duration parameter. All these presented criteria when applied result in different characteristics measures of heatwaves. Heatwaves are usually studied to identify their impact on one of the affected sectors (Human health, Energy consumption, Ecological conditions, urban air quality, environmental conditions, and any other sector that might be impacted). However, the literature provides little assistance in selecting which criteria to use for which purpose. In this work the idea of using different criterion based on the impacted sector being studied was introduced, we also defined a best fit heatwave criterion to assess the impact of heatwaves on human health based on the existing literature. We then use this criterion to identify heatwaves in 13 stations in Jordan and study the spatial, temporal, and spatiotemporal distributions and development of these heatwaves throughout the study duration (1970-2005). The result of the study shows a dramatic increase in heatwaves characteristics across Jordan. The area subjected to the highest change was the Jordanian capital (Amman), with an increase of 7 folds in number of heatwave days per year, 3 folds in number of heatwaves per year, and a 10% increase in the average temperature in the yearly maximum heatwave. The trends showed no signs of slowing down in the heatwaves’ characteristic change. When projected Amman is expected to have 41 heatwave days and 9.8 heatwaves per year by 2050.
Appropriateness and adherence to guidelines in perioperative antimicrobial prophylaxis in patients undergoing clean surgery: results from a Quality Control Circle intervention
Authors: Zou Jian , Zhong Jia-yun , Liu Yu , Huang Dan , Liu Yan-xin , Li Xi-wen , Gong Wen-jun , Tao Jia
Published: February 2022

Background: Appropriate implementation of perioperative antimicrobial prophylaxis in surgery is considered an effective measure to prevent the incidence of surgical site infection and the emergence of antimicrobial-resistant bacteria. To reduce the emergence of antimicrobial-resistant bacteria, there is a need to improve the correct implementation of PAP. Methods: A QCC activity team was established to grasp the current situation of PAP in clean surgery procedure, set target, formulated corresponding countermeasures and implement and review them in stages. The plan-do-check-act method was cyclically applied. The appropriateness of PAP before (July to December 2018) and after (April to September 2019) the implementation of QCC activities were evaluated based on relevant international and Chinese perioperative antimicrobial prophylaxis guidelines. Results: The appropriate rate of PAP was significantly improved from 68.72% (n=406) before QCC to 93.7% (n=508) post QCC implementation (P＜0.01). A significant improvement (P＜0.05) was also determined for each category: selection (from 78.82 to 96.06%), duration (from 90.15 to 96.46%), indication (from 94.09 to 97.64%), timing of first dose (from 96.55 to 99.21%), antibiotic usage (from 96.8 to 99.41%), re-dosing of antibiotic (from 96.55 to 99.21%). Conclusions: The appropriate application of PAP is improved through QCC activities, providing a useful reference for the prevention of antimicrobial-resistant bacteria and the development of medical quality improvement activities.
cRGD Nanoparticles Loaded with Microbubbles for Enhancing Anti-Proliferation and Anti-Angiogenesis
Authors: Zhang Xia , Xie Rongping , Luo Zhixiong , Liao Haihong , Ouyang Da , Chen Man , Zhou Bing
Published: February 2022

Background: The inhibition of angiogenesis leads to the degeneration of tumors; thus, anti-angiogenesis therapy is a strategy for the treatment of tumors. Accumulating documents has demonstrated effective anti-angiogenic strategies should simultaneously inhibit endothelium-dependent vessels (EDV) and tumor cell-mediated vasculogenic mimicry (VM). Although cRGD peptide enabling to bind with avb3 integrin can specifically inhibit both EDV and VM, however peptide-based drug delivery platforms have not obtained the expected therapeutic efficacy due to their rapid degradation and low tumor accumulation. Results: Herein, we developed cRGD nanoparticles (cRGD Nano) loaded microbubbles (MB) to enhance their anti-EDV and anti-VM ability for endothelial cells and ovarian cancer cells due to the sonoporation effect from ultrasound (US). Heparin as backbone conjugated with cRGD to prepare cRGD-H conjugate and then loaded with biotin thereby following dialysis to fabricate cRGD Nano. Subsequently, the cRGD Nano were incorporated with MB via avidin-biotin linkage to fabricate cRGD Nano-MB. The enhanced anti-angiogenic effect can take profit of cRGD from cRGD Nano and sonoporation effect from US combined with MB. cRGD Nano has been characterized, and cRGD Nano-MB combined with US exhibited the best intracellular uptake ability than cRGD Nano and cRGD Nano-MB without US by flow cytometry and confocal laser scanning microscopy. Also, cRGD Nano-MB combined with US could efficiently discourage the tube formation of endothelial cells and cancer cells, and presented excellent significant anti-proliferation activity in vivo. Conclusions: The combination of cRGD Nano-MB and US is expected to be a promising strategy for peptide drug delivery and enhancing anti-proliferation and anti-angiogenesis.
Incidence and risk factors for tuberculosis among people living with HIV in Bangui: a cohort study
Authors: Longo Jean De Dieu , Woromogo Sylvain Honoré , Diemer Henri Saint-Clavaire , Tékpa Gaspard , Belec Laurent , Grésenguet Gérard
Published: February 2022

Background. Tuberculosis-HIV co-infection is the leading cause of death for people living with HIV (PLHIV) in the Central African Republic. The objective of this study was to determine the incidence and risk factors of TB among PLHIV in Bangui.Methods: This was a retrospective study carried out on a cohort of PLHIV followed in an HIV infection management center in Bangui. PLHIV aged 18 or older, with no history of TB, enrolled between January 1, 2017 and December 31, 2018 were included in the study. The software, Epi Info 7, made it possible to enter and analyze the data. The chi-square test was used only to compare the proportions at the 5% significance level.Results: A total of 677 patients including 618 (91.28%) on antiretroviral therapy were included in the study. The median age was 34 with extremes ranging from 18 to 57. Of the patients followed, 104 developed TB. The overall incidence of TB was 15.37 (104/677) cases per 100 PLHIV-years. This incidence was 13.10 (81/618) cases per 100 in patients on ART-years and 38.99 (23/59) cases per 100 patients on pre-ART-years. In pre-ART patients the incidence of TB was therefore almost 3 times higher than that of PLHIV on ART (p = 0.03). WHO clinical stages III and IV (p = 0.02), absence of ART (p = 0.03), poor adherence (p = 0.004) and low functional capacity (p = 0.04) were the risk factors associated with the occurrence of TB among PLHIV in Bangui.Conclusions: The high incidence of TB in our context is essentially linked to delay in diagnosis and the quality of care. Early initiation of antiretroviral therapy, systematic screening for TB in PLHIV upon entry into the active queue and better monitoring of patients on ART are strongly recommended.
Mehrsprachige Repertoires in kollaborativen Schreibinteraktionen
Authors:   , Stierwald Mona
Published: February 2022

Die vorliegende Studie widmet sich der Problematik von individueller Mehrsprachigkeit und Mehrschriftigkeit innerhalb kollaborativer Schreibinteraktionen. Individuelle Mehrsprachigkeit/Mehrschriftigkeit wird mittels der Konzepte der sprachlichen Repertoires und Register beleuchtet. Als kollaborative Schreibinteraktion wird ein Face-to-Face-Format definiert, bei dem zwei oder mehrere, am selben Ort befindliche Personen, ein Dokument basierend auf gemeinsamen Ideen anfertigen und hierüber ein Gespräch führen. Von Interesse ist die Forschungsfrage, wie mehrsprachige Studierende der Romanistik an der Goethe-Universität Frankfurt a.M. ihre schriftsprachlichen Ressourcen beim gemeinsamen Formulieren eines akademischen Texts in einer romanischen Zielsprache (Französisch oder Spanisch) einsetzen. Zur Beantwortung der Fragestellung dient ein qualitatives methodenplurales Forschungsdesign, bei dem theoretisch-methodische Forschungsansätze aus Soziolinguistik, Ethnographie und Aktionsforschung zusammenfließen. Die Datenerhebung erfolgte in einem ethnographisch gerahmten Aktionsforschungsseminar, in dem mehrsprachige Studierende über ihre sprachlichen Repertoires schriftlich reflektieren und zum akademischen Schreiben interaktiv in Gruppen zusammenkommen. Das hierbei entstandene Datenmaterial, die Reflexionstexte einerseits sowie die Audio- und Bildschirmaufnahmen der Schreibinteraktionen andererseits, wurde inhalts- und gesprächsanalytisch ausgewertet. Darüber werden Konzepte aus Mehrsprachigkeits- und Textproduktionsforschung miteinbezogen, um einen ganzheitlichen Blick auf Dynamiken beim kollaborativen Formulieren zu gewinnen. Die Studie bietet zahlreiche Anknüpfungspunkte für zukünftige Forschung über Mehrschriftigkeit. Aus theoretischer Sicht ist es relevant, wie strukturelle Mehrschriftigkeit im Format der kollaborativen Schreibinteraktion konzeptualisiert werden kann. Methodisch betrachtet besteht die Notwendigkeit zur Weiterentwicklung des methodenpluralen Forschungsdesigns, um sowohl Daten zu Prozessen und Produkten als auch zu beteiligten Individuen zu triangulieren. In dieser Hinsicht spielt das Verhältnis von Ethnographie und Gesprächsanalyse eine gewichtige Rolle. Aus didaktischer Sicht ist es schließlich bedeutsam, wie die Aneignung zielsprachlicher Kompetenz beim akademischen Schreiben mit einer Integration mehrsprachiger Ressourcen einhergehen kann.
Evaluation of Online-Based Ride-Hailing Services Using Service Quality (Servqual) Method, Refined Kano Model, Importance Performance Analysis (IPA), and Quality Function Deployment (QFD): A Case Study of Grab Bike Indonesia
Authors: Caesaron Dino , Makapedua Jessie , Lukodono Rio Prasetyo
Published: February 2022

The rapid development of the service industry in Indonesia is seen from the emergence of several companies in the transportation sector based on online applications. To compensate for the public needs of these services, the company needs to maintain customer satisfaction from the service performance. The research aimed to evaluate the quality of transportation services at Grab Bike Indonesia. By using quantitative and qualitative approach, the research applied Service Quality (Servqual) analysis for the level of perceived satisfaction, Refined Kano model for the role of each attribute to customer satisfaction, Importance Performance Analysis (IPA) for the priority of improvements, and Quality Function Deployment (QFD) for the technical steps of improvement. Servqual analysis shows 36 service attributes that need to be improved, particularly 16 service attributes with high gap scores. Furthermore, there are 5 attributes classified as major influencing attributes on customer satisfaction based on Refined Kano analysis. These factors also need to be improved in the IPA category. From the results of QFD, it suggests that the company should consider the technical steps of improvement. For example, the company should provide regulations that drivers must obey, have driving standards, strict sanctions for every violation of rules, initial training for drivers, and utilization of GPS properly, provide an easy way for customer feedback, and others.
Clustering Regency and City in East Java Based on Population Density and Cumulative Confirmed COVID-19 Cases
Authors: Khikmah Khusnia Nurul , Sofro A'yunin
Published: February 2022

Coronavirus is a big family of viruses that causes acute respiratory syndrome and mediates human-to-human by the environment. A factor that affects the spread of infectious diseases is population density. Therefore, it is necessary to study the effect of population density on infectious diseases like COVID-19. The research analyzed the effect of the population density of each regency in East Java on cumulative confirmed COVID-19 cases until December 9, 2020. The research applied quantitative method using the agglomerative hierarchical clustering method. The clustering method included single, average, and complete linkages. The results of clustering using single linkage and average linkages have the same results for the population density of Jember Regency. This regency has the lowest effect for the cumulative confirmed COVID-19 cases. Then, complete linkage obtains that Banyuwangi Regency and Gresik Regency has the population density with the lowest effect for the cumulative number of confirmed COVID-19 cases. The results of clustering with single, average, and complete linkages have the same results for population density with a big effect on the cumulative number of confirmed COVID-19 cases in Surabaya City. The results of best clustering regencies or cities that population density affects the number of
KNOWLEDGE RETENTION STRATEGY EVALUATION & KNOWLEDGE MANAGEMENT SYSTEM DESIGN AT PLASTIC INJECTION COMPANY IN INDONESIA
Authors: Anggoro Leo Adi , Simamora Bachtiar H.
Published: February 2022

The potential of knowledge loss when an employee retires or resigns is high at PT. XYZ a plastic injection company in Indonesia. Therefore, it is required to evaluate their knowledge retention strategy (KRS) and developing a knowledge management system (KMS). The evaluation of KRS using Organizational Knowledge Retention Framework developed by David DeLong and for designing KMS model using the 10-Step KM Roadmap method developed by Amrit Tiwana. Through a well-developed KRS and KMS design model, PT. XYZ can overcome the problem of losing the knowledge that occurs because employees retire or resign.
EXPLORING ENABLERS, BARRIERS AND OPPORTUNITIES TO DIGITAL SUPPLY CHAIN MANAGEMENT IN VIETNAMESE MANUFACTURING SMES
Authors: Linh Nguyen Phuc Khanh , Kumar Vikas , Ruan Ximing
Published: February 2022

This paper examines the enablers, barriers and opportunities of digital supply chain management (DSCM) in manufacturing Small and Medium-sized Enterprises (SMEs) in Vietnam fromexpert’s perspective. The study is a foundational effort to contribute to the establishment of new digital management era in many emerging economies. Applying a systematic literature review (SLR) of relevant studies and a qualitative data methodology this research also aims to explore the factors affecting technology adoption in supplychain management from managerial perspective of Vietnamese manufacturing SMEs. Findings of the research reveal that the enablers and barriers are classified into four main dimensions which are Organisational, Technological, Strategic and Legal –Ethical issues. In addition, our findings also reveal that external factors deeply influence the adoption intention in Vietnamese manufacturing SMEs. The development of digital SCM could be different in each case according to companies’ characteristics and business environment. Our study therefore adds to the limited research in the domain of digital technology adoption in SMEs in developing country context.
Millennials’ Service Quality Preferences: Evidence from Large Retail Outlets in South Africa
Authors: Adam Shaheen , Ogunlela Oyebanjo , Tengeh Robertson , Cupido Chris
Published: February 2022

Service quality and customer perception vary across business sectors. The youth plays a vital role in determining the quality of service in large food retail outlets in South Africa in general and most notably in the Cape Metropolis. This study investigated the most critical factors of service quality that are significant in the Millennials perception, used to measure quality in the large food retail sector. The quantitative method was adopted to measure the relationship amongst the variables of a retail service quality scale (RSQS), with the sample of 220 purposively drawn from second and third-year students at a university of technology. Findings indicate the coefficient of determination R2 of 88% and a Durbin-Watson (DW) coefficient of 0.25, as well as an F statistics (f-stat) of 63.92, this show that the physical aspect (ease of accessibility to products) will contribute positively to overall service quality of retail food outlets.
Current Mass Spectrometric Methods in Organic Chemistry
Authors: Mosi A.A. , Eigendorf G.K.
Published: February 2022

This review is intended to provide an outline of the basic principles of operation and current developments of mass spectrometric techniques applicable to the field of organic chemistry. New ionization techniques, particu.larly useful for the analysis of polar and high molecular
weight materials, introduced during the past few years are reported together with mo re
traditional methods of ion formation. Various mass analyzers, suitable for single or multiple mass identification processes are described.

Applications of mass spectrometry to certain classes of organic compounds, such as steroids, alkaloids, carbohydrates and porphyrins are illustrated with examples.

All spectral data reported here have been obtained in the authors' laboratory.
Recent Developments and Applications of High-Performance Liquid Chromatography-Eiectrospray Ionization Mass Spectrometry
Authors: Dass Chhabil
Published: February 2022

The technique of high-performance liquid chromatography (HPLC)/electrosprayionization (ESI)/mass spectrometry (MS) is one of the most exciting developments of recent times in analytical methodology. With this combination, a variety of thermally labile, polar, and nonvolatile compounds present in a complex matrix can be separated and characterized unambiguously. This review will discuss the basics of ESI process, key issues of primary concern in the use of HPLC/ESI/MS, and various HPLC/ESI systems. An overview of timely applications of HPLC/ESI/MS in characterization of proteins, peptides , and oligosaccharides, analysis of combinatorial libraries, detection of posttranslational modifications in proteins, degradation of bioactive peptides, and quantification of peptides, pharmaceutical drugs, toxins and their metabolites, will be presented.
Bicyclic Acetals-'in System-s of Chemical Communication
Authors: Francke W. , Schroder W.
Published: February 2022

Bicyclic acetals play an important role as volatile signals in systems of chemical communication among many insect species, i.e. bark beetles, weevils, and moths. They represent cryptic ketodiols with a glycol- and 1,3- diol-substructure. Alkylated members of four different systems are known, namely derivatives of 2,7-dioxabicyclo[2.2.1]heptane, 2,8-dioxabicyclo [3.2.1]octane, 6,8-dioxabicyclo[3.2.1]octane, and 2,9-dioxabicyclo[3.3.1]
nonane. Some of the compounds carry an additional oxygen function. A couple of structures have been extensively used as model compounds for studies in synthetic organic chemistry. Brevicomin, 7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane as well as frontalin, 1,5-dimethyl-
6,8-dioxabicyclo[3.2.1]octane, have been most frequently prepared. Both pheromones are components of a kind of dialog between males and females of Dendroctonus bark beetles. Also, predators use them as kairomones. Frontalin and 1,3,3-trimethyl-2,7- dioxabicyclo[2.2.1]heptane have been found in volatiles of elephants and men, respectively, however, their biological significance is unknown in these cases. This review will provide an overview over structures of bicyclic acetals which are used as pheromones. It will comprise present knowledge on their occurrence and biological function and include facts and speculations concerning their biosynthesis. Furtheron, analytical aspects, especially mass spectrometry will be discussed, and plotted spectra will be shown. Syntheses, especially those providing optically active products carried out during the last eight years, will be reviewed.
Combinatorial Libraries by Portioning and Mixing
Authors: Furka A. , Bennett W. D.
Published: February 2022

Combinatorial chemistry - due to its radically new synthetic methods - can be considered a forerunner of chemistry in the next century. One of the most important methods is the portioning-mixing (split-mix) synthesis which embodies the combinatorial principle. It is easily realized. Both manual and automatic devices have been described. Some features that contribute to its popularity include: it produces all possible structural combinations of the monomers, it has outstanding productivity, it leads to the formation of individual compounds in nearly equimolar quantities (affected by statistics and incomplete reactions), and it can be applied to all classes of organic compounds. Since an enormously large number of compounds can be produced in principle in a relatively short time, some practical considerations are discussed that can be useful in library design. Encoding organic libraries by peptide or nucleotide sequences or with binary tags are also described together with methods for tagging macroscopic support units with electronic chips, two dimensional bar codes or colored resin and capsule caps. Among the deconvolution strategies, the iteration method, positional scanning, omission libraries, the Selectide and the Pharmacopeia methods are mentioned. A collection of libraries prepared by portioning-mixing is also included in graphical format.
Recent Advances in the Solid Phase Synthesis of Drug Heterocyclic Small Molecules
Authors: Andres C. J. , Denhart Derek J. , Deshpande Milind S. , Gillman Kevin W.
Published: February 2022

Because of their synthetic challenge, broad range of physical I chemical properties, and diverse biological activities, heterocycles continue to be of interest to both the academic and industrial chemist. This review covers recent advances in the solid phase synthesis of drug-like heterocyclic small molecules. Syntheses which form the heterocycle on the solid phase are emphasized; syntheses in which a preformed heterocycle is functionalized on the solid support have been omitted. The majority of references are from publication year 1999. This review should be of interest to anyone involved in, or contemplating the solid phase synthesis of small molecule drug-like heterocycles, especially for combinatorial chemistry applications.
A High Throughput Platform for Systematic Evolution of Ligands by Exponential Enrichment (SELEX™)
Authors: Drolet D. W. , Jenison R. D. , Smith D. E. , Pratt D. , Hicke B. J.
Published: February 2022

The systematic evolution of ligands by exponential enrichment (SELEX™) process is a combinatorial chemistry method for the isolation of nucleic acid ligands (aptamers) that bind to a desired target molecule with high affinity. In order to increase throughput via automation, we have adapted the SELEX process for protein targets to a robotics-compatible microtiter plate format. A remarkable feature of the platform is that targets are immobilized by hydrophobic adsorption onto the plate surface. Hydrophobic immobilization procedures are simple and require no specialized modification of the protein target. This format was tested by manually performing four independent SELEX experiments. All were concluded within 8 rounds of selection and yielded aptamers that bind in solution to their respective protein target, calf intestinal alkaline phosphatase, human a-thrombin or human platelet derived growth factor, with
equilibrium dissociation constants below 3 x 1o-10 M.
A Rational Approach to Anticancer Drug Design: 2D and 3D- QSAR,
Molecular Docking and Prediction of ADME Properties using Silico
Studies of Thymidine Phosphorylase Inhibitors
Authors: Raut Vaibhav V. , Bhandari Shashikant V. , Patil Shital M. , Sarkate Aniket P.
Published: February 2022

Background:

Cancer is the most prevalent disease seen nowadays. Thymidine phosphorylase
(TP) is an angiogenic enzyme that is overexpressed in many solid tumors. Over the years, Thymidine
phosphorylase has emerged as a novel target for anticancer drug development as an inhibitor.

Objective:

To design novel oxadiazole-isatin pharmacophore-containing molecules and explore their
structural requirements related to the anticancer activity.

Methods:

Pharmacophore optimisation was carried out for oxadiazole-isatin hybrid molecules using molecular
modeling studies (2D and 3D QSAR). Further, the new chemical entities were designed using the
combilib tool of V life software. To have a better understanding of the binding interactions, the newly
designed molecules were docked. To achieve a drug-like pharmacokinetic profile, molecules were also
tested for ADME prediction.

Results:

Two-Dimensional Quantitative Structure-Activity Relationship (2D-QSAR) model was generated
using the multiple regression method with r2 = 0.84 and q2 = 0.76. Three-Dimensional Quantitative
Structure-Activity Relationship (3D-QSAR) model was obtained by simulated annealing k nearest near
(SA kNN) method with q2 = 0.8099. Molecular docking studies showed promising results. Compound 5
was found to be with the best dock score and the best fit to the active site pocket of the thymidylate phosphorylase
enzyme. The compounds have notable absorption, distribution, metabolism, and excretion
(ADME) properties that can be predicted to assure a drug-like pharmacokinetic profile.

Conclusion:

One of the most successful and fast-increasing methodologies is molecular modeling. It not
only aids in the prediction of specific target compounds but also aids in the cost reduction of valuable
substances. The successful use of molecular modeling was done in this study, with caution taken to avoid
any chance co-relation. Optimised pharmacophore was obtained and new chemical entities were designed.
Docking studies revealed that Compound 5 has shown better H-bond interaction with Lys 221 and Thr
151 with bond distances 2.0 Α° and 1.8 Α° which is the most active molecule. ADME tests discovered
that the majority of the newly designed compounds were within a reasonable range as required in a druglike
pharmacokinetic profile. Molecules 2, 4, 5, 6 can be considered as a lead for future synthesis and
biological screening.
Assessment of Rheumatoid Hand Function as a Characteristic Feature of
Rheumatoid Arthritis in Patients Treated with Methotrexate or Methotrexate
with Biological Agents with or without Deformation of Hands
Authors: Wisłowska Małgorzata , Chruściak Tomasz
Published: February 2022

Background:

The hand is an excellent work tool that provides the functional ability to mechanical work. The hand is affected in rheumatoid arthritis (RA) patients, it is a significant prob-lem in the functional sphere as a result of deformities, the grasping function limitation and muscle strength.

Objectives:

The aim of the study was the assessment of grip strength, endurance and manipulation abilities of rheumatoid hands with or without deformities treated with methotrexate (MTX) or MTX plus biologics (MTX+BIO).

Material and Methods:

The study involved 80 RA women, (40 received MTX+BIO, 40 MTX), treated at the Rheumatology Department of the Central Clinical Hospital of Interior Affairs in War-saw. VAS-pain, DAS28, SDAI, HAQ, HAQ hands, estimation of hand grip strength, endurance, and manipulation ability were analyzed.

Results:

In group MTX+BIO, values of DAS28 (3.7±1.3 vs. 4.3±1.2, p=0.019), HAQ (0.72 ± 0.57 vs. 1.08± 0.87, p=0.011) and HAQ-hand (0.85±0.65 vs. 1.19±0.68, p=0.024) were statistically lower than in MTX group. Hand deformations were recorded in 35 (43.7 %) cases, 16 (40 %) in MTX group, 19 (47.5 %) in MTX+BIO. Comparison of grip strength, endurance, and manipulation ability showed better results in MTX+BIO group with deformities (significance level from 0.013 to 0.046) than in MTX group. Relative differences in hand function in MTX + BIO group ranged from 10.8 % (maximal power grip strength) to 127.6 % (minimal hand endurance), after disease duration ad-justment - from 28.2 % (maximal power grip strength) to 148.4 % (minimal hand endurance).

Conclusion::

Measuring grip strength, hand endurance, manipulation abilities are useful in RA pa-tients with hand deformities.
Effectiveness of Dental Pulp-derived Stem Cells and Bone Marrowderived
Mesenchymal Stromal Cells Implanted into a Murine Critical
Bone Defect
Authors: Vater Corina , Männel Christian , Bolte Julia , Tian Xinggui , Goodman Stuart B. , Zwingenberger Stefan
Published: February 2022

Background:

While bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been
used for many years in bone tissue engineering applications, the procedure still has drawbacks such as
painful collection methods and damage to the donor site. Dental pulp-derived stem cells (DPSCs) are
readily accessible, occur in high amounts, and show a high proliferation and differentiation capability.
Therefore, DPSCs may be a promising alternative for BM-MSCs to repair bone defects.

Objective:

The aim of this study was to investigate the bone regenerative potential of DPSCs in comparison
to BM-MSCs in vitro and in vivo.

Methods:

In vitro investigations included analysis of cell doubling time as well as proliferation and osteogenic
differentiation. For the in vivo study, 36 male NMRI nude mice were randomized into 3 groups: 1)
control (cell-free mineralized collagen matrix (MCM) scaffold), 2) MCM + DPSCs, and 3) MCM + BMMSCs.
Critical size 2 mm bone defects were created at the right femur of each mouse and stabilized by an
external fixator. After 6 weeks, animals were euthanized, and microcomputed tomography scans (μCT)
and histological analyses were performed.

Results:

In vitro DPSCs showed a 2-fold lower population doubling time and a 9-fold higher increase in
proliferation when seeded onto MCM scaffolds as compared to BM-MSCs, but DPSCs showed a significantly
lower osteogenic capability than BM-MSCs. In vivo, the healing of the critical bone defect in
NMRI nude mice was comparable among all groups.

Conclusions:

Pre-seeding of MCM scaffolds with DPSCs and BM-MSCs did not enhance bone defect
healing.
Usability of Wearable Multiparameter Technology to Continuously Monitor Free-Living Vital Signs in People Living With Chronic Obstructive Pulmonary Disease: Prospective Observational Study (Preprint)
Authors: Hawthorne Grace , Greening Neil , Esliger Dale , Briggs-Price Samuel , Richardson Matthew , Chaplin Emma , Clinch Lisa , Steiner Michael C , Singh Sally J , Orme Mark W
Published: February 2022

BACKGROUND

Vital signs monitoring (VSM) is routine for inpatients, but monitoring during free-living conditions is largely untested in chronic obstructive pulmonary disease (COPD).

OBJECTIVE

This study investigated the usability and acceptability of continuous VSM for people with COPD using wearable multiparameter technology.

METHODS

In total, 50 people following hospitalization for an acute exacerbation of COPD (AECOPD) and 50 people with stable COPD symptoms were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks (42 days). The device recorded heart rate (HR), respiratory rate (RR), skin temperature, and physical activity. Adherence was defined by the number of days the vest was worn and daily wear time. Signal quality was examined, with thresholds of ≥85% for HR and ≥80% for RR, based on the device’s proprietary confidence algorithm. Data quality was calculated as the percentage of wear time with acceptable signal quality. Participant feedback was assessed during follow-up phone calls.

RESULTS

In total, 84% of participants provided data, with average daily wear time of 11.8 (SD 2.2) hours for 32 (SD 11) days (average of study duration 76%, SD 26%). There was greater adherence in the stable group than in the post-AECOPD group (≥5 weeks wear: 71.4% vs 45.7%; P=.02). For all 84 participants, the median HR signal quality was 90% (IQR 80%-94%) and the median RR signal quality was 93% (IQR 92%-95%). The median HR data quality was 81% (IQR 58%-91%), and the median RR data quality was 85% (IQR 77%-91%). Stable group BMI was associated with HR signal quality (rs=0.45, P=.008) and HR data quality (rs=0.44, P=.008). For the AECOPD group, RR data quality was associated with waist circumference and BMI (rs=–0.49, P=.009; rs=–0.44, P=.02). In total, 36 (74%) participants in the Stable group and 21 (60%) participants in the AECOPD group accepted the technology, but 10 participants (12%) expressed concerns with wearing a device around their chest.

CONCLUSIONS

This wearable multiparametric technology showed good user acceptance and was able to measure vital signs in a COPD population. Data quality was generally high but was influenced by body composition. Overall, it was feasible to continuously measure vital signs during free-living conditions in people with COPD symptoms but with additional challenges in the post-AECOPD context.
Comparison of the Erectile Dysfunction Drugs Sildenafil and Tadalafil Using Patient Medication Reviews: Topic Modeling Study (Preprint)
Authors: Kim Maryanne , Noh Youran , Yamada Akihiko , Hong Song Hee
Published: February 2022

BACKGROUND

Topic modeling of patient medication reviews of erectile dysfunction (ED) drugs can help identify patient preferences regarding ED treatment options. The identification of a set of topics important to the patient from social network service drug reviews would inform the design of patient-centered medication counseling.

OBJECTIVE

This study aimed to (1) identify the distinctive topics from patient medication reviews unique to tadalafil versus sildenafil; (2) determine if the primary topics are distributed differently for each drug and for each patient characteristic (age and time on ED drug therapy); and (3) test if the primary topics affect satisfaction with ED drug therapy controlling for patient characteristics.

METHODS

Data were collected from the patient medication reviews of sildenafil and tadalafil posted on WebMD and Ask a Patient. The latent Dirichlet allocation method of natural language processing was used to identify 5 distinctive topics from the patient medication reviews on each drug. Analysis of variance and a 2-sample t test were conducted to compare the topic distribution and assess whether patient satisfaction varies with the primary topics, age, and time on medication for each ED drug. Statistical significance was tested at an alpha of .05.

RESULTS

The patient medication reviews of sildenafil (N=463) had 2 topics on treatment benefit and 1 each on medication safety, marketing claim, and treatment comparison, while the patient medication reviews of tadalafil (N=919) had 2 topics on medication safety and 1 each on the remaining subjects. Sildenafil’s reviewers quite frequently (94/463, 20.4%) mentioned erection sustainability as their primary topic, whereas tadalafil’s reviewers were more concerned about severe medication safety. Those who mentioned erection sustainability as their primary topic were quite satisfied with their treatment as opposed to those who mentioned severe medication safety as their primary topic (score 3.85 vs 2.44). The discovered topics reflected the marketing claims of blue magic and amber romance for sildenafil and tadalafil, respectively. The topic of blue magic was preferred among younger patients, while the topic of amber romance was preferred among older patients. The topic alternative choices, which appeared for both the ED drugs, reflected patient interest in the comparative effectiveness and price outside the drug labeling information.

CONCLUSIONS

The patient medication reviews of ED drugs reflect patient preferences regarding drug labeling information, marketing claims, and alternative treatment choices. The patient preferences concerning ED treatment attributes inform the design of patient-centered communication for improved ED drug therapy.
Control Centre for Intensive Care as a Tool for Effective Coordination, Real-Time Monitoring, and Strategic Planning During the COVID-19 Pandemic (Preprint)
Authors: Komenda Martin , Černý Vladimír , Šnajdárek Petr , Karolyi Matěj , Hejný Miloš , Panoška Petr , Jarkovský Jiří , Gregor Jakub , Bulhart Vojtěch , Šnajdrová Lenka , Májek Ondřej , Vymazal Tomáš , Blatný Jan , Dušek Ladislav
Published: February 2022

UNSTRUCTURED

In the Czech Republic, the strategic data-based and organizational support for individual regions and for providers of acute care at the nationwide level is coordinated by the Ministry of Health. At the beginning of the COVID-19 pandemic, the country needed to very quickly implement a system for the monitoring, reporting, and overall management of hospital capacities. The aim of this viewpoint is to describe the purpose and basic functions of a web-based application named “Control Centre for Intensive Care,” which was developed and made available to meet the needs of systematic online technical support for the management of intensive inpatient care across the Czech Republic during the first wave of the pandemic in spring 2020. Two tools of key importance are described in the context of national methodology: one module for regular online updates and overall monitoring of currently free capacities of intensive care in real time, and a second module for online entering and overall record-keeping of requirements on medications for COVID-19 patients. A total of 134 intensive care providers and 927 users from hospitals across all 14 regions of the Czech Republic were registered in the central Control Centre for Intensive Care database as of March 31, 2021. This web-based application enabled continuous monitoring and decision-making during the mass surge of critical care from autumn 2020 to spring 2021. The Control Center for Intensive Care has become an indispensable part of a set of online tools that are employed on a regular basis for crisis management at the time of the COVID-19 pandemic.
Process evaluation of an interactive mHealth adherence support intervention for HIV patients: lessons learned in the Philippines Connect for Life Study (Preprint)
Authors: O'Connor Cara , Leyritana Katerina , Doyle Aoife M. , Birdthistle Isolde , Lewis James J. , Gill Randeep , Salvaña Edsel Maurice
Published: February 2022

BACKGROUND

The Philippines HIV epidemic is one of the fastest growing globally, and infections among men who have sex with men (MSM) are rising at an alarming rate. Connect for Life Philippines is a mobile health intervention to support ART adherence in this key population through individualized voice calls and short message services (SMS).

OBJECTIVE

The objective of this process evaluation was to assess the reach, dose delivered and received, fidelity, acceptability of the intervention and to describe contextual factors affecting implementation.

METHODS

Participants received a personalized combination of automated pill reminders, appointment reminders, health tips, and adherence feedback messages delivered by voice call or SMS at the patient’s preferred time/day. To measure the fidelity and dose of the intervention, call and SMS logs from the mHealth platform were analyzed. Usability and acceptability information was collected via questionnaires at three time points during the 48-week study. Qualitative feedback was collected in monthly process reports, comments fields in the questionnaires, and in focus group discussions.

RESULTS

The 462 study participants received 25,375 IVRS calls and 8,234 SMS during the study. Due to technical issues, intervention fidelity was low, with only 18.8% of participants receiving the pill reminders via voice call and others receiving a scaled-back SMS intervention.
After 48 weeks in the study, 64% of participants reported that they would be quite likely or very likely to recommend the program to a friend and 53% of participants reported that they benefitted quite a bit or very much from the intervention. Participants who were on ART for less than 6 months at the start of the study and participants who received the daily or weekly pill reminder feature were more likely to report that they benefitted from the intervention (p=0.02 and p=0.013, respectively).

CONCLUSIONS

Mobile health interventions are useful to support adherence as they have low replication costs and are highly adaptable to specific cultural contexts. The Connect for Life intervention had high participant satisfaction and acceptability. However, poor reliability of local telecommunications networks had a large impact the intervention usability, fidelity and dose received.