bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for Xenobiotic Electrophilic Metabolites Using Pulsed Ultrafiltration-Mass Spectrometry
Authors: Nikolic Dejan , Fan Peter W. , Bolton Judy L. , van Breemen Richard B. 
Published: February 2022

Abstract:
A pulsed ultrafiltration-mass spectrometric screening assay has been developed to generate and identify electrophilic metabolites of xenobiotic compounds formed by hepatic cytochrome P450 enzymes. This assay would be suitable for the early identification of potentially toxic compounds during the initial phase of drug development. Rat liver microsomes were trapped by an ultrafiltration membrane in a stirred flow-through chamber, and substrates for microsomal cytochrome P450 including hydroxychavicol, 3-methylindole, cyproheptadine and
2-tert-butyl-4,6-dimethylphenol were flow-injected individually through the chamber along with the cofactors, NADPH and glutathione. Metabolites and glutathione conjugates were detected on-line using electrospray mass spectrometry. Alternatively, the ultrafiltrate was concentrated on a reversed phase HPLC column and analyzed using electrospray LC-MS or LC-MS-MS to separate and characterize isomeric metabolites and metabolites present at low concentration. Enzymatic activation of each xenobiotic substrate produced highly electrophilic metabolites such as quinones, quinone methides and imine methides that reacted with glutathione on-line to produce glutathione conjugates which were detected by using electrospray mass spectrometry. Although epoxides such as cyproheptadine epoxide were generated, it is likely that these compounds were insufficiently reactive to form glutathione conjugates in the absence of cytosolic glutathione S-transferases. Pulsed ultrafiltration-electrospray mass spectrometry offers an efficient method for in vitro formation and mass spectrometric characterization of activated microsomal drug metabolites and is suitable for use during the drug discovery process for the early identification and screening out of potentially toxic lead compounds.
Fluorescence Polarization: An Analytical Tool for Immunoassay and_ Drug Discovery
Authors: Nasir Mohammad Sarwar , Jolley Michael E. 
Published: February 2022

Abstract:
Fluorescence polarization (FP) is an intrinsically powerful technique for the rapid and homogeneous analysis of molecular interactions in biological/chemical systems. The technique has been successfully used to diagnose various viral and infectious diseases in humans and animals, to monitor therapeutic drug levels and substances of abuse in body fluids and to determine food born pathogens, grain mycotoxins and pesticides. It has also been used in monitoring enzyme catalyzed hydrolysis, protein-protein interactions, DNA diagnostics and high throughput screening during the course of drug discovery. Work by various groups, including our own, have demonstrated that the technique can replace a substantial number of solid phase
assays. FP, defined by the equation P = [lv- IH] I [lv + IH] (where V and H are the vertical and
horizontal components of the intensity I of emitted light respectively when exited by vertically plane polarized light), is independent of the intensity of the light and the concentration of the fluorophore. Hence it is functional in colored and cloudy solutions. The FP of a fluorophore is proportional to its rotational relaxation time, which in turn depends upon its molecular volume (or molecular weight) at constant temperature and solution viscosity. When a fluorophore-labeled ligand binds to a larger molecule, equilibrium is established rapidly and the FP increases. This property has been successfully exploited in many fields as described in this review.
Structure-Based Drug Design: Combinatorial Chemistry and Molecular Modeling
Authors: Kirkpatrick D. Lynn , Watson Shawndra , Ulhaq Saraj 
Published: February 2022

Abstract:
Drug discovery efforts are shifting to include the rapid synthetic procedures of combinatorial chemistry and the elegance of rational library design. The wealth of computational methods which explore both the receptor structure and the ultimate pharmacophore complementarity, provide novel avenues for chemists to discover new lead compounds or design virtual libraries for screening prior to the synthetic stage. This mini-review provides an overview of a few current methodologies of library generation, highlighting docking procedures which have utility in both the discovery and optimization stages of drug development. Three specific examples of different approaches to the use of docking are provided. These describe the development of inhibitors to the human A3 adenosine receptor and HIV-1 protease, and the evaluation of the activity of novel inhibitors of the redox regulator protein, human thioredoxin.
Clinical Observation and Genotype-Phenotype Analysis of ABCA4-
Related Hereditary Retinal Degeneration before Gene Therapy
Authors: Zheng Hongmei , Yuan Jiajia , Xiao Xuan , Ye Lin , Chen Changzheng 
Published: February 2022

Background:
Hereditary retinal degeneration (HRD) is an irreversible eye disease that results
in blindness in severe cases. It is most commonly caused by variants in the ABCA4 gene. HRD
presents a high degree of clinical and genetic heterogeneity. We determined genotypic and phenotypic
correlations, in the natural course of clinical observation, of unrelated progenitors of HRD associated
with ABCA4.

Objective:
To analyze the relationship between the phenotypes and genotypes of ABCA4 variants.

Methods:
A retrospective clinical study of five cases from the ophthalmology department of the People’s
Hospital of Wuhan University from January 2019 to October 2020 was conducted. We tested for
ABCA4 variants in the probands. We performed eye tests, including the best-corrected visual acuity,
super-wide fundus photography and spontaneous fluorescence photography, optical coherence tomography,
and electrophysiological examination.

Results:
Disease-causing variants were identified in the ABCA4 genes of all patients. Among these,
seven ABCA4 variants were novel. All patients were sporadic cases; only one patient had parents who
were relatives, and the other four patients were offspring of unrelated parents. Two patients presented
with Stargardt disease, mainly with macular lesions, two presented with retinitis pigmentosa (cone-rod
type), and one presented with cone dystrophy. The visual acuity and visual field of the five patients
showed varying degrees of deterioration and impairment.

Conclusions:
The same ABCA4 mutation can lead to different clinical phenotypes, and there is variation
in the degree of damage to vision, visual field, and electrophysiology among different clinical
phenotypes. Clinicians must differentiate between and diagnose pathologies resulting from this mutation.
Immune Checkpoint Inhibitors for Advanced Biliary Tract Cancer
Authors: Prager Gerald W. , Taghizadeh Hossein 
Published: February 2022

Abstract:
BTC is a rare and aggressive cancer disease, bearing an overall dismal prognosis with only
finite therapy options. Only combination chemotherapy regimens achieve disease control, which is
often only short-lived since the tumor tissue exhibits high resistance to chemotherapy.
The emergence of immune checkpoint inhibitors in recent years has significantly improved the survival
of cancer patients and thus, has been integrated into the therapeutic management of several solid
tumors, including melanoma, colorectal carcinoma (CRC), hepatocellular carcinoma (HCC), triple-
negative breast cancer (TNBC), and non-small-cell lung cancer (NSCLC).
Investigation of the tumor biology of BTC and results of preliminary studies have shown that BTC
may also be amenable to immunomodulation. In this review, we seek to give a comprehensive overview
of the role, potential, and clinical significance of ICPI in the management of BTC.
Low-level Viremia in Treated HIV-1 Infected Patients: Advances and
Challenges
Authors: Wu Hao , Dai Lili , Bai Ruojing , Lv Shiyun 
Published: February 2022

Abstract:
Antiretroviral therapy (ART) can effectively suppress HIV-1 replication, improving quality
of life and restoring the lifespan of persons living with HIV (PLWH) to near-normal levels. However,
after standardized ART, a low level of HIV-1 RNA, i.e., low-level viremia (LLV), may still be
identified in 3% to 10% of the patients. LLV is capable of impacting the immunological and clinical
outcomes of patients and serves as a risk factor for transmission. The underlying mechanism of LLV
is not yet certain, and the effects of LLV on patient outcomes remain under evaluation. Understanding
LLV will allow effective prevention and control strategies to be designed for the benefit of
PLWH.
Recent Development in the Synthesis of Thiazoles
Authors: Duc Dau Xuan , Chung Nguyen Thi 
Published: February 2022

Background:
Thiazole-containing compounds are widely found in natural products as
well as synthetic sources. Many thiazole-based compounds possess a broad spectrum of
bioactivities, and some of them are well-known drugs in the markets. The use of thiazole
derivatives in other fields such as organic materials, cosmetics, and organic synthesis has also
been widely reported. Due to a wide range of applicability, the synthesis of thiazole-containing
compounds has attracted extensive interest from chemists, and many studies in the synthesis of
thiazole skeleton have been reported recently.

Objective:
This review article will discuss recent studies in the synthesis of thiazoles (from 2012).
Besides the well-established Hantzsch thiazole synthesis, a large number of novel methods have
been developed for the synthesis of thiazole derivatives. In most cases, reaction mechanisms have
also been described.

Conclusion:
The synthesis of thiazole derivatives has drawn great attention from chemists, and
many studies in the synthesis of these heterocycles have been reported recently. The classical
method, the Hantzsch thiazole synthesis has received great research interest from chemists.
Moreover, many new methods have been established to synthesize thiazole-derived compounds.
Unquestionably, more and more approaches to access thiazole skeleton will appear in the
literature. The application of well-established thiazole synthesis methods to the synthesis of
drugs, organic materials, and natural products will almost certainly be studied.
A Seven-Joint Ultrasound Score for Differentiating Between Rheumatoid
and Psoriatic Arthritis
Authors: Sapundzhieva Tanya , Sapundzhiev Lyubomir , Karalilova Rositsa , Batalov Anastas 
Published: February 2022

Background:
Differentiating between seronegative rheumatoid arthritis (RA) and psori-atic arthritis (PsA) presenting only with the involvement of the small joints of the hands can be challenging. Implementing musculoskeletal ultrasound (US) to reveal specific patterns of joint and tendon involvement may have an added value in the management of early arthritis.

Objective:
The aim was to investigate whether a seven-joint US score was able to distinguish be-tween patients with RA and PsA.

Materials and Methods:
One hundred and forty-one patients with RA, 65 patients with PsA, and 45 healthy controls (HC) were included in the current study. US assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth meta-tarsophalangeal joint was performed, and the following scores were calculated: synovitis and teno-synovitis/paratenonitis scores on grayscale ultrasound (GSUS) and on power Doppler (PD) US, ero-sion score, US7 score.

Results:
RA patients had significantly higher median scores of GS synovitis, PD synovitis, ero-sions, and US7 than PsA patients (p < 0.001). PsA patients had significantly higher median scores of GS tenosynovitis/paratenonitis and PD tenosynovitis/paratenonitis (p < 0.001). All US scores were significantly higher for both patient groups as compared to the HC group (p < 0.001).

Conclusion::
Sonographic evaluation by a seven-joint score can be helpful in the differentiation be-tween rheumatoid and psoriatic arthritis.
Developing and Implementing an mHealth Heart Failure Self-care Program to Reduce Readmissions: Randomized Controlled Trial
Authors: Johnson Amber E , Routh Shuvodra , Taylor Christy N , Leopold Meagan , Beatty Kathryn , McNamara Dennis M , Davis Esa M 
Published: February 2022

Background
Patients admitted with decompensated heart failure (HF) are at risk for hospital readmission and poor quality of life during the discharge period. Lifestyle behavior modifications that promote the self-management of chronic cardiac diseases have been associated with an improved quality of life. However, whether a mobile health (mHealth) program can assist patients in the self-management of HF during the acute posthospital discharge period is unknown.

Objective
We aimed to develop an mHealth program designed to enhance patients’ self-management of HF by increasing knowledge, self-efficacy, and symptom detection. We hypothesized that patients hospitalized with HF would be willing to use a feasibly deployed mHealth program after their hospital discharge.

Methods
We employed a patient-centered outcomes research methodology to design a stakeholder-informed mHealth program. Adult patients with HF admitted to a large academic hospital were enrolled and randomized to receive the mHealth intervention versus usual care. Our feasibility outcomes included ease of program deployment, use of the clinical escalation process, duration of participant recruitment, and participant attrition. Surveys assessing the demographics and clinical characteristics of HF were measured at baseline and at 30 and 90 days after discharge.

Results
The study period was between July 1, 2019, and April 7, 2020. The mean cohort (N=31) age was 60.4 (range 22-85) years. Over half of the participants were men (n=18, 58%) and 77% (n=24) were White. There were no significant differences in baseline measures. We determined that an educational mHealth program tailored for patients with HF is feasibly deployed and acceptable by patients. Though not significant, we found notable trends including a higher mean quality of life at 30 days posthospitalization among program users and a longer duration before rehospitalization, which are suggestive of better HF prognosis.

Conclusions
Our mHealth tool should be further assessed in a larger comparative effectiveness trial. Our pilot intervention offers promise as an innovative means to help HF patients lead healthy, independent lives. These preliminary data suggest that patient-centered mHealth tools can enable high-risk patients to play a role in the management of their HF after discharge.

Trial Registration
ClinicalTrials.gov NCT03982017; https://clinicaltrials.gov/ct2/show/NCT03982017
The establishment of a reference geodetic network made of closed polygonometric quadrangles and designated for landslide slopes
Authors: Simonyan Vladimir V. , Volkov Victor V. 
Published: February 2022

Introduction. A reference geodetic network in the form of a closed polygonometric quadrangle is established at the Karamyshevsky landslide slope in Moscow for the purpose of repeated geodetic observations of landslide displacements. The purpose of the study is to show that the reference geodetic network in the form of closed polygonometric quadrangles can be implemented for landslide slopes along with other linear and angular methods.
Materials and methods. Accurate or high-precision electronic total stations, such as Leica, Sokkia, Topcon, etc. are used to take field measurements. In this case, all four corners and all four sides are to be measured. There are three redundant measurements in this polygon of polygonometry to ensure the reliable control of the field work quality. It is advisable to equalize this polygon using the correlate type of the least squares method for the two reasons. First, to calculate the acceptable residuals, it is necessary to make an appropriate conditional equation, i.e. implement the most important and time-consuming part of the correlate method algorithm. Second, in the process of the algorithm implementation, the correlate method allows to obtain the inverse weights of equalized measurements, whose comparison with the inverse weights of unbalanced measurements provides a visual representation of the quality of the geometry of the designed network.
Results. The mathematical processing of the results of geodetic measurements of the reference network in the form of closed polygonometric quadrangles using the method of least squares is quite complex and requires a computer technology and appropriate software. However if they are available, the problem is solved unambiguously and very accurately, which particularly important.
Conclusions. The construction of reference geodetic networks in the form of closed polygonometric quadrangles for observing landslide displacements can be recommended for other landslide slopes.
Editorial
Authors: Da Silva Lucas , Ferreira António 
Published: February 2022

This special issue of University of Porto Journal of Engineering contains selected papers presented at the 2nd International Conference on Science and Technology Education STE 2021, held at Faculty of Engineering of the University of Porto (FEUP), Portugal, during 7-8 October 2021.
This conference is held every two years. The conference is co-chaired by António Ferreira (University of Porto, Portugal) and Lucas F. M. da Silva (University of Porto, Portugal). The goal of the conference is to provide an international forum for the sharing, dissemination and discussion of research, experience and perspectives across a wide range of teaching and learning issues. About 50 papers were presented by researchers from nearly 20 countries.
In order to disseminate the work presented at STE 2021, selected papers were prepared which resulted in the present special issue. Various topics are covered resulting in seven papers dealing with learning mechanisms (first two papers), learning systems (one paper) and diversity and inclusiveness (last four papers). The papers presented here are good examples of the latest trends related to science and technology education.
The editors wish to thank all the authors for their participation and cooperation, which made this volume possible. Finally, they would like to thank the team of FEUP library, especially Luís Miguel Costa and Palmira Seixas, for the excellent cooperation during the preparation of this issue.
Fobia social em estudantes de medicina submetidos ao método de ensinoaprendizagem baseada em problemas no estado de Sergipe
Authors: Andrade Mayana Lula , Silveira Kamila Maria de Andrade Santos , Santos Júnior Eusébio Lino dos , Ferro Neto Paulo Milhomem , Pimentel Deborah 
Published: February 2022

Objetivo: Identificar a prevalência de fobia social e das principais situações sociais que a caracterizam e que cursam com sintomas de ansiedade, medo ou evitação em estudantes de medicina submetidos à metodologia de ensino aprendizagem baseada em problemas (ABP) no estado de Sergipe. Métodos: Trata-se de um recorte de um estudo clínico não experimental, exploratório, transversal, descritivo e de abordagem analítica quantitativa. Obtivemos uma amostra de 323 alunos, sendo o nosso universo todos os estudantes de medicina do estado de Sergipe cuja instituição de ensino adote o método de ABP. Para avaliação dos alunos, utilizamos um questionário específico e a Escala de Fobia Social de Liebowitz. Resultados: A fobia social foi detectada em 30,7% dos estudantes, com maior prevalência para a gravidade moderada. Dentro do perfil epidemiológico, o sexo feminino, os solteiros e os alunos com idade entre 18 e 25 anos foram aqueles com maior prevalência da doença. As principais situações sociais temidas no que se refere a medo ou ansiedade foram expressar discordância ou desaprovação para alguém e o de falar com alguém que não conhece. As situações sociais mais frequentemente evitadas foram expressar discordância ou desaprovação, falar com pessoas desconhecidas e ser o centro das atenções. Conclusão: A fobia social teve uma alta prevalência entre a amostra de universitários do curso de medicinasubmetidos à metodologia ABP, em Sergipe, com maior destaque para a gravidade moderada do transtorno. Com este estudo, pretendemos colocar o tema em evidência e incentivar novos trabalhos sobre o mesmo.
Analisa Perilaku Konsumen Dalam Pengambilan Keputusan Pembelian Jajanan Pasar Pada Masa Pandemi Covid-19 Di Kecamatan Delta Pawan Kabupaten Ketapang
Authors: Rian Irianto , Fitriani Dian , Arahman Emi 
Published: February 2022

The world is currently experiencing a crisis caused by the Corona pandemic. The virus which has another name COVID-19 has also succeeded in changing people's behavior. Such as social distancing, for example, which affects changes in consumer behavior. Jajanan pasar are traditional Indonesian foods that are traded in markets, especially in traditional markets, usually made with unique tastes and attractive shapes. The purpose of this study is to determine the influence of consumer behavior factors (occupation, income, number of dependents, education level and age) in making decisions to purchase market snacks during the Covid 19 pandemic.The analytical method used is logistic regression analysis, which is one of the mathematical model approaches used to analyze the relationship of one or more independent variables with a dichotomous / binary categorical dependent variable. The results of the study explained that during the Covid pandemic 19 factors - consumer behavior factors in making decisions on buying market snacks in Delta Pawan District, Ketapang Regency, namely work, income, number of dependents, level of education and age did not have a significant effect on consumer behavior in making snack buying decisions. market in Delta Pawan District. Keywords: Covid 19, jajanan pasar, logistic regression
Fatores de risco da sepse neonatal tardia: uma revisão narrativa
Authors: Malaquias Clara Feitosa Vieira , Araujo Maycon Alves , Donato Carolina Silva , Silva Gilson Freitas Rodrigues da , Belo Fernanda Fabrícia Resende , Diniz Maria Luísa Prado , Souza Juliano Chaves Cotrim de , Antunes Ana Luiza Dias , Oliveira Ana Clara Fonseca , Cavalcante Thainá Souza Andrade 
Published: February 2022

Objetivo: Compreender quais são os principais fatores de risco para a sepse de início tardio que acometem os neonatos. Revisão bibliográfica: A sepse neonatal, pode ser dividida em duas categorias: sepse precoce, adquirida nas primeiras 72 horas de vida, e sepse de início tardio, também conhecida como sepse hospitalar, que ocorre após as 72 horas. Desse modo, a sepse neonatal tardia frequentemente ocorre pela transmissão horizontal, por fatores ambientais ou nosocomiais. Os principais fatores documentados são o uso de Cateter Central de Inserção Periférica (PICC), nutrição parenteral, ventilação mecânica, uso de antibióticos de largo espectro, monitorização invasiva, uso de incubadora, tempo de internação superior a 21 dias na Unidade de Terapia Intensiva Neonatal (UTIN) e o uso de bloqueadores de receptores H2. Considerações finais: Considerando sua gravidade, evidencia-se a importância de entender de forma detalhada e sistematizada os principais fatores de risco para a ocorrência da sepse, durante internamento nas UTIN e externamente a ela, tendo em vista que, além de toda a fisiopatologia complexa, ela também está associada a sequelas neurocognitivas que afetarão o desenvolvimento e ao alto índice de morbimortalidade.
IMPROVING THE ENERGY CHARACTERISTICS OF PHOTOVOLTAIC MODULES DUE TO REFLECTED RADIATION
Authors: Кувшинов В.В. , Гусева Е.В. , Ивантеев И.С. 
Published: February 2022

В статье рассмотрена конструкция фотоэлектрической кремниевой панели повышенной эффективности, которая достигается за счет использования модулей с двухсторонним расположением солнечных элементов на лицевой и тыльной стороне.
The article discusses the design of a photovoltaic silicon panel with increased efficiency, which is achieved through the use of modules with two-sided arrangement of solar cells on the front and back sides.