bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Structure-based Methods to Analyze Resistance Mutations for Chemically Diverse Non-Nucleoside Reverse Transcriptase Inhibitors
Authors: Tabassum Tasnim , Azeem Syeda M. , Muwonge Alecia N. , Frey Kathleen M. 
Published: June 2020

Background:
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used in combination antiretroviral
therapy to suppress viral loads in HIV patients. The chemical design of NNRTIs has changed in recent years in response
to resistance associated mutations (RAMs) and resistance. NNRTIs are chemically diverse compounds that bind an allosteric site of HIV RT. Resistance-associated mutations (RAMs) identified in HIV patients are associated with NNRTI
resistance. RAMs confer amino acid changes that alter both structural and physiochemical properties of the allosteric site.
Ultimately these changes reduce NNRTI affinity. Previously, we used a combination of computational and experimental
methods to analyze and validate RAMs for 3 diarylpyrimidine (DAPY) NNRTIs.

Objective:
The objective of this study is to apply these methods to other chemically diverse, non-DAPY NNRTIs.

Materials and Methods:
We selected MIV-150 (experimental microbicide) and doravirine for this study. A computational and molecular modeling strategy was used to evaluate the effects of RAMs. Calculated changes in drug affinity and
stability (ΔS + ΔA) were used to determine overall resistance levels: susceptible, low, intermediate, and high. The ΔS +
ΔA values for K101P suggest that this mutation confers intermediate/high-level resistance to MIV-150, but remains susceptible to doravirine. Based on the determined resistance levels, we analyzed the models and used Molecular Dynamics
(MD) to compare the interactions of MIV-150/doravirine with RT wild-type (WT) and RT (K101P). From MD, we found
key interactions were lost with RT (K101P), but are retained with doravirine. To experimentally validate our findings, we
conducted a fluorescence-based reverse transcription assay for MIV-150 with RT (WT) and RT (K101P). IC50 values
determined in assays show a 101-fold change in potency for MIV-150, but essentially no change for doravirine.

Results:
Our computational and experimental results are also consistent with antiviral data reported in the literature.

Conclusion:
We believe that this approach is effective for analyzing mutations to determine resistance profiles for chemically diverse NNRTIs in development.
Disk Battery Ingestion: A Simple User-Guide
Authors: Petruzziello Carmine , Soave Paolo Maurizio 
Published: June 2020

Introduction:
Disk Battery Ingestion (DBI) is a cause of access to the emergency department
(ED), especially in pediatric age. This problem, if not well managed, may lead to serious injuries,
with several complications involving the gastrointestinal and respiratory tract.

Objective:
The aim of this review is to analyze the literature of the last 25 years to make a decisional
flow-chart that may help the emergency physician.

Methods:
For this review, 36 articles have been analyzed (8 articles and 28 case reports), from
1995 to 2019. Data considered from each study included year of publication, type of study, population
studied, type of battery, timing of ingestion, treatment, outcomes, complications.

Results:
A decisional flow-chart has been configured. X-ray should be performed as the first step
in every stable patient, meanwhile CT scan should be performed in unstable patients. When the battery
is still localized in the esophagus, endoscopy should be performed as soon as possible, meanwhile,
when the battery is beyond the esophagus, its diameter should be noted before taking a decision.

Conclusion:
The use of the flow-chart proposed may reduce the risk of worse consequences and severe
injuries for the patients, helping the emergency physician in his decisional process.
Drug Repositioning: Antimalarial Activities of GABA Analogs in Mice Infected with Plasmodium berghei
Authors: Ayankunle Akeem A. , Wakeel Olayemi K. , Kolawole Oyetunji T. , Oyekale Adesola O. , Ojurongbe Olusola , Adeyeba Oluwaseyi A. 
Published: June 2020

Background:
Drug repositioning is becoming popular due to the development of resistance
to almost all the recommended antimalarials. Pregabalin and gabapentin are chemical analogs of gamma-
aminobutyric acid (GABA) approved for the treatment of epilepsy and neuropathic pain.

Objective:
This study investigates acute toxicities and antimalarial activities of pregabalin and
gabapentin in the murine malarial model.

Methods:
Acute toxicities were assessed using the method of Lorke, while curative activities were
assessed by the administration of serial doses of pregabalin and gabapentin to Plasmodium
berghei infected mice. Pregabalin was further investigated for its prophylactic activity, and curative
potential when combined with either artesunate or amodiaquine. All drugs were freshly prepared
and administered orally. Thin films were collected, stained, and observed under the microscope
for the estimation of parasitemia and calculation of percentage chemoinhibition or chemoprevention.
In pregabalin –artesunate or -amodiaquine combination aspect of this study, survival
day post-infection (SDPI) was recorded, while parasitemia was re-estimated for animals that survived
till day 28.

Results:
The oral LD50 of gabapentin, as well as pregabalin, was >5,000 mg/kg. Gabapentin at 100
and 200 mg/Kg demonstrated 35.64% and -12.78% chemoinhibition, respectively, while pregabalin
demonstrated 75.60% and 100.00% chemoinhibition at doses of 12.5 and 25 mg/Kg, respectively.
Moreover, pregabalin at individual doses of 25, 50 mg/Kg, and in combination with either artesunate
or amodiaquine demonstrated 100.00% chemoinhibition. In its prophylactic study, pregabalin was
found to be 100% chemopreventive at individual doses of 12.5 and 25 mg/Kg.

Conclusion:
Both GABA analogs have antimalarial properties, but pregabalin proved to be more
efficacious.
Evolutive Temporal Footprint of an HIV-1 Envelope Protein in an Epidemiologically Linked Cluster
Authors: de Carvalho Lima Elidamar Nunes , Lima Rodrigo Sucupira Andrade , Arif Muhammad Shoaib , Piqueira José Roberto Castilho , Diaz Ricardo Sobhie 
Published: June 2020

Background:
The C2V3C3 region of gp 120, encoded by the HIV-1 envelope gene (env), is an important antigenic target, a key determinant for viral evolution and essential for determining epitopes for vaccines.

Methods:
The relationships among genetic sequence diversity, selective pressure, constraints on HIV-1 envelope protein were explored and also correlated this analysis with information entropy; hypermutation; HIV tropism; CD4+ T cell counts or HIV viral load. A total of 179 HIV-1 C2V3C3 sequences derived from cell-free plasma were used, determined from serial samples, in four epidemiologically linked individuals (one infected blood donor, two transfusion recipients and a sexual partner infected by one of the recipients) over a maximum period of 8 years. This study is important because it considers the analysis of patterns in genomic sequences, without drugs and over time.

Results:
A temporal relationship among information entropy, hypermutation, tropism switch, viral load, and CD4+ T cell count was determined. Changes in information entropy were time-dependent, and an increase in entropy was observed in the C2V3C3 region at amino acids G313 and F317-I320 (related to the GPGR-motif and coreceptor tropism), and at amino acids A281 in C2 and A346 in C3, related to immune escape.

Conclusion:
The increase of information entropy over time was correlated with hypermutation and the emergence of nonR5- strains, which are both associated with more variable genomes.
Effect of Herbal Aphrodisiac, Dioscorea Bulbifera on Sperm Parameters, Serum Hormonal Levels and Testicular Histology of Wistar Rats
Authors: Msiska Thomson , Mwakikunga Anthony , Tembo David , Lampiao Fanuel 
Published: June 2020

Aim:
The present study was aimed at screening phytochemicals of Dioscorea bulbifera
extracts and evaluating its effects on male rat reproductive system.

Background:
Since ancient times, man has found a lot of health benefits from medicinal plants. According
to the World Health Organisation (WHO), about 80% of the world population depends on
traditional medicine, which is 90% plant-based, for their health needs. In respect of this, men in
Africa use herbal medicines in the management of erectile dysfunction and infertility. Amongst
thousands of herbs, folklore has implicated Dioscorea bulbifera bulbils in the treatment of piles, dysentery,
syphilis, ulcers, cough, leprosy, diabetes, asthma, cancer and infertility. Despite such great
health benefits from D. bulbifera, in vitro studies and clinical data in support of its efficacy as an
aphrodisiac are scanty.

Objective:
The objective of the study was to investigate the effects of Dioscorea bulbifera extracts
on Wistar rat sperm parameters, hormonal levels and histology of the testis.

Methods:
Thirty healthy adult male Wistar rats were divided into 5 groups of 6 rats each and were
given different treatments of Dioscorea bulbifera extracts by oral gavage at 200 and 400 mg kg-1
body weight. After 8 weeks, body and reproductive organ weights, sperm concentration, hormonal
levels and histological structure of the testis were evaluated. A calorimetric method was used to assess
the quantity of phytochemical constituents.

Results:
Testosterone, luteinizing hormone, estradiol and follicle-stimulating hormone levels were
significantly (p<0.05) enhanced whereas prolactin levels were significantly (p<0.05) down-regulated
in the treated groups. Total sperm motility, sperm concentration and the percentage of progressively
motile cells increased compared to the control. All the treated animals showed an increase in
body weight, seminiferous tubule diameter and germinal epithelial height with the testes showing
all the stages of spermatogenesis.
Phytochemical screening of the methanol extracts revealed the presence of alkaloids, steroids,
flavonoids, phenols and saponins.

Conclusion:
Dioscorea bulbifera has secondary metabolites that seem to stimulate androgenic and
anabolic effects. These secondary metabolites appear to be responsible for the positive changes in
testicular architecture, serum hormonal levels, caudal sperm concentration and motility parameters.
This study supports the ethno-aphrodisiac claims that have been made against it.
Team-Based Learning on Teaching Medical and Health Terminology
Authors: Azizam Nor Azmaniza , Maon Siti Noorsuriani , Ali Husin Liatul Izian , Ahmad Siti Nurul Akma , Mat Som Rohana 
Published: June 2020

This study aimed at evaluating the effectiveness of TBL teaching and learning Medical and Health Terminology subject. The TBL session has been undertaken in two phases, commencing with the Individual Readiness Test (IRT), and followed the Group Readiness Test (GRT). The outcomes indicated the significance of scoring between the two phases for both components, which are suggestive of TBL implementation, showing a positive response from students. The statistical analysis has also revealed score differences between the Medical and Health Terminology subjects, according to student background. TBL should advocate and actively promoted in all issues for the Health Administration program.
Keywords: Team-Based Learning, Academic Performance, Universiti Teknologi MARA.
eISSN: 2398-4287 © 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.DOI: https://doi.org/10.21834/ebpj.v5iSI1.2317
How Situational Factors at the Workplace Affect Work Engagement among Public Administrators: A mediation moderated framework
Authors: Husain Nor Azmawati , Sulaiman Mira Maisarah 
Published: June 2020

Situational factors at work may influence work engagement among employees. With 169 respondents from public administrators in the Johor Bahru Tengah Municipal Council, Malaysia, the findings were derived. The survey data from respondents were analyses using hierarchical multiple regression analysis. Findings showed that ambiguity and imbalance impaired work engagement. Meanwhile, distributive fairness significantly influences work engagement directly and indirectly. The results suggest that the influence of an ambiguous situation at work decreased work engagement, but can be improved, mainly through distributive fairness. Distributive fairness also moderated the linkage between ambiguous situational at work and work engagement.
Keywords: Work engagement, Public administrators, Situational factors, Ambiguity, Imbalance, Distributive fairness.
eISSN: 2398-4287 © 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v5iSI1.2330
Internet Use, Risk Awareness, and Demographic Characteristics Associated With Engagement in Preventive Behaviors and Testing: Cross-Sectional Survey on COVID-19 in the United States
Authors: Li Siyue , Feng Bo , Liao Wang , Pan Wenjing 
Published: June 2020

Background
During the coronavirus disease (COVID-19) pandemic, engagement in preventive behaviors and getting tested for the virus play a crucial role in protecting people from contracting the new coronavirus.

Objective
This study aims to examine how internet use, risk awareness, and demographic characteristics are associated with engagement in preventative behaviors and testing during the COVID-19 pandemic in the United States.

Methods
A cross-sectional survey was conducted on Amazon Mechanical Turk from April 10, 2020, to April 14, 2020. Participants’ internet use (in terms of the extent of receiving information pertaining to COVID-19), risk awareness (whether any immediate family members, close friends or relatives, or people in local communities tested positive for COVID-19), demographics (sex, age, ethnicity, income, education level, marital status, and employment status), as well as their engagement in preventative behaviors and testing were assessed.

Results
Our data included 979 valid responses from the United States. Participants who received more COVID-19–related health information online reported more frequent effort to engage in all types of preventive behaviors: wearing a facemask in public (odds ratio [OR] 1.55, 95% CI 1.34-1.79, P<.001), washing hands (OR 1.58, 95% CI 1.35-1.85, P<.001), covering nose and mouth when sneezing and coughing (OR 1.78, 95% CI 1.52-2.10, P<.001), keeping social distance with others (OR 1.41, 95% CI 1.21-1.65, P<.001), staying home (OR 1.40, 95% CI 1.20-1.62, P<.001), avoiding using public transportation (OR 1.57, 95% CI 1.32-1.88, P<.001), and cleaning frequently used surfaces (OR 1.55, 95% CI 1.34-1.79, P<.001). Compared with participants who did not have positive cases in their social circles, those who had immediate family members (OR 1.48, 95% CI 8.28-26.44, P<.001) or close friends and relatives (OR 2.52, 95% CI 1.58-4.03, P<.001) who tested positive were more likely to get tested. Participants’ sex, age, ethnicity, marital status, and employment status were also associated with preventive behaviors and testing.

Conclusions
Our findings revealed that the extent of receiving COVID-19–related information online, risk awareness, and demographic characteristics including sex, ethnicity, age, marital status, and employment status are key factors associated with US residents’ engagement in various preventive behaviors and testing for COVID-19.
Seeing Double: Peace, Order, and Good Government, and the Impact of Federal Greenhouse Emissions Legislation on Provincial Jurisdiction
Authors: Leach Andrew , Adams Eric 
Published: June 2020

Federal regulation of greenhouse gas (GHG) emissions presents a difficult challenge for Canadian constitutional law. The federal government’s legislation to implement a national minimum standard of GHG emissions pricing, the Greenhouse Gas Pollution Pricing Act (GGPPA), and the trio of reference cases launched by Saskatchewan, Ontario, and Alberta questioning its constitutional validity, have brought the law and politics of GHG emissions pricing to the forefront of Canadian federalism. In the two appellate court decisions delivered to date, the legislation has been sustained as a valid exercise of Parliament’s power to legislate for the Peace, Order, and Good Government (POGG) of Canada. In each case, however, judges have expressed significant concern with respect to the impact of the legislation on provincial jurisdiction.
We draw on recent and historic jurisprudence to characterize conceptual errors that have bedevilled POGG, specifically in the tendency to overestimate its impact on provincial jurisdiction. We then examine the existing interpretive principles that limit POGG’s ability to upend the critical balance inherent in the division of powers. Finally, we discuss how a properly empowered, calibrated, and constrained POGG relates to the GGPPA. We argue that the reduction of national GHG emissions constitutes a valid federal subject under the national concern branch of POGG, and that the GGPPA is a valid exercise of federal jurisdiction. We see no reason under the double aspect doctrine and cooperative federalism why provinces would lose any existing provincial jurisdiction as a result of the implementation of the GGPPA. Rather, a restrained approach to paramountcy, and the mechanics of the GGPPA itself suggest that provincial and federal legislation will work concurrently on GHGs. That seems entirely appropriate given the nature of the climate change crisis before us. In the legislative challenge of our time, we believe Canada’s Constitution is up to the task.
The Toronto Municipal Election: Judicial Failure to Protect the Structure of the Canadian Constitution
Authors: Johnson* (Alyn) James 
Published: June 2020

In Toronto (City) v Ontario (AG),1 a recent decision on the legality of legislative interference in the Toronto 2018 municipal election, the Ontario Court of Appeal makes an alarming attempt to rewrite the Canadian Constitution. The subject of this revision is the legitimate role of unwritten principles in constitutional interpretation. Robin Elliot maintains, in a leading scholarly treatment of the subject, that unwritten principles can inform constitutional interpretation in two main ways: first, they can provide an independent basis on which to overrule impugned legislation; second, they can assist in interpreting constitutional text.2 Elliot qualifies the former usage by limiting it to those principles that “can fairly be said to arise by necessary implication from provisions of the text of the Constitution … since they have the same legal status as the text.”3 The Court of Appeal, however, states that unwritten principles cannot be used as a stand-alone basis on which to overrule legislation.4
In this article, I draw on numerous Supreme Court of Canada decisions to argue that the Ontario Court of Appeal’s view of the Constitution is, with respect, fundamentally flawed. Unwritten principles inform the structure of a democratic constitution and thereby provide legislation with its claim to legitimacy. Legislation that violates foundational unwritten principles is, of necessity, subject to judicial challenge. I also argue that the Court of Appeal’s doctrinally unsustainable approach to unwritten principles led to a flawed ruling on the legality of Ontario’s interference in the 2018 Toronto election. In Reference re Senate Reform, the Supreme Court of Canada unanimously states that “constitutional interpretation must be informed by the foundational principles of the Constitution.”5 The Court of Appeal failed to provide any detailed consideration of the democratic principle, and thereby failed to recognize the constitutional imperative that protects the integrity of the electoral process.
*PhD in Constitutional and Administrative Law, Queen’s University. Principal of Public Law Solutions, a research firm in Toronto.[1] 2019 ONCA 732 [Toronto v Ontario (CA 2019)].[2] “References, Structural Argumentation and the Organizing Principles of Canada’s Constitution” (2001) 80 Can Bar Rev 67 at 83-86, 141-42, and generally 86-98.[3] Ibid at 95. See also 83-84.0[4] Toronto v Ontario (CA 2019), supra note 1 at para 89.[5] 2014 SCC 32 at para 25 [Senate Reference].
Dialysis Regret
Authors: Saeed Fahad , Ladwig Susan A. , Epstein Ronald M. , Monk Rebeca D. , Duberstein Paul R. 
Published: June 2020

Background and objectives
Although some patients regret the decision to start dialysis, modifiable factors associated with regret have rarely been studied. We aimed to identify factors associated with patients’ regret to initiate dialysis.

Design, setting, participants, & measurements
A 41-item questionnaire was administered to adult patients receiving maintenance dialysis in seven dialysis units located in Cleveland, Ohio, and its suburbs. Of the 450 patients asked to participate in the study, 423 agreed and 397 provided data on decisional regret. We used multivariable logistic regression to identify predictors of regret, which was assessed using a single item, “Do you regret your decision to start dialysis?” We report adjusted odd ratios (ORs) and 95% confidence intervals (95% CIs) for the following candidate predictors: knowledge of CKD, attitudes toward CKD treatment, and preference for end-of-life care.

Results
Eighty-two of 397 respondents (21%) reported decisional regret. There were no significant demographic correlates of regret. Regret was more common when patients reported choosing dialysis to please doctors or family members (OR, 2.34; 95% CI, 1.27 to 4.31; P<0.001). Patients who reported having a prognostic discussion about life expectancy with their doctors (OR, 0.42; 95% CI, 0.18 to 0.98; P=0.03) and those who had completed a living will (OR, 0.48; 95% CI, 0.25 to 0.95; P=0.03) were less likely to report regret with dialysis initiation.

Conclusions
Dialysis regret was common in this sample. Demographic factors (age, sex, marital status, race, or educational attainment) were not significantly associated with regret, but modifiable care processes were.

Podcast
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_06_09_CJN13781119.mp3
Types and outcomes of cytopenia in critically ill patients
Authors: Bagheri Zahra , Labbani-Motlagh Zohreh , Mirjalili Mahtabalsadat , Karimzadeh Iman , Khalili Hossein 
Published: June 2020

Cytopenia is common complication in critically ill patients.
Aim:
Incidence and pattern of different types of cytopenia as well as its impact on mortality and length of stay in critically ill patients were evaluated.
Methods:
Critically ill patients with any kind of cytopenia for more than 2 days were evaluated.
Results:
Anemia was the most common type of cytopenia in the patients (99.14%), followed by lymphocytopenia (32.17%), thrombocytopenia (27.82%), and leukopenia (19.13%). Mortality rate was significantly higher in patients with anemia (p < 0.0001), thrombocytopenia (p < 0.0001), leukopenia (p < 0.0001), neutropenia (p = 0.004), lymphopenia (p = 0.002) and pancytopenia (p < 0.0001). Higher duration of anemia, lymphopenia and thrombocytopenia were associated with longer intensive care unit stay (p < 0.0001, p < 0.0001 and p < 0.001, respectively).
Conclusion:
Among all assessed variables, incidence of thrombocytopenia could independently predict the mortality.