bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj Hospital, Bangkok, Thailand from 2015 to 2017
Authors: Boonyasiri Adhiratha , Jauneikaite Elita , Brinkac Lauren M. , Greco Chris , Lerdlamyong Kanokorn , Tangkoskul Teerawit , Nguyen Kevin , Thamlikitkul Visanu , Fouts Derrick E. 
Published: January 2021

Abstract
Background: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data.Methods: The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes.Results: Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n=18) and CPE-colonised patients who developed CPE infections during the study (n=3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 (n=15) and ST231 (n=14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes.Conclusions: This study has revealed the genomic features of disease-causing or colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.
Genetic characterization of G12P[6] and G12P[8] rotavirus strains collected in six African countries between 2010 and 2014
Authors: Rakau Kebareng G. , Nyaga Martin M. , Gededzha Maemu P. , Mwenda Jason M. , Mphahlele M. Jeffrey , Seheri L. Mapaseka , Steele Duncan 
Published: January 2021

Abstract
Background: G12 rotaviruses were first observed in sub-Saharan Africa in 2004 and since then have continued to emerge and spread across the continent and are reported as a significant human rotavirus genotype in several African countries, both prior to and after rotavirus vaccine introduction. This study investigated the genetic variability of 15 G12 rotavirus strains associated with either P[6] or P[8] identified between 2010 and 2014 from Ethiopia, Kenya, Rwanda, Tanzania, Togo and Zambia.Methods: The investigation was carried out by comparing partial VP7 and partial VP4 sequences of the African G12P[6] and G12P[8] strains with the available GenBank sequences and exploring the recognized neutralization epitopes of these strains. Additionally, Bayesian evolutionary analysis was carried out using Markov Chain Monte Carlo (MCMC) implemented in BEAST to estimate the time to the most recent ancestor and evolutionary rate for these G12 rotavirus strains.Results: The findings suggested that the VP7 and VP4 nucleotide and amino acid sequences of the G12 strains circulating in African countries are closely related, irrespective of country of origin and year of detection, with the exception of the Ethiopian strains that clustered distinctly. Neutralization epitope analysis revealed that rotavirus VP4 P[8] genes associated with G12 had amino acid sequences similar to those reported globally including the vaccine strains in RotaTeq and Rotarix. The estimated evolutionary rate of the G12 strains was 1.016 x10−3 substitutions/site/year and was comparable to what has been previously reported. Three sub-clusters formed within the current circulating lineage III shows the diversification of G12 from three independent ancestries within a similar time frame in the late 1990s.Conclusions: At present it appears to be unlikely that widespread vaccine use has driven the molecular evolution and sustainability of G12 strains in Africa. Continuous monitoring of rotavirus genotypes is recommended to assess the long-term impact of rotavirus vaccination on the dynamic nature of rotavirus evolution on the continent.
Gender Intentional Approaches to Enhance Health Social Enterprises in Africa: A Qualitative Study of Constraints and Strategies
Authors: McKague Kevin , Harrison Sarah , Musoke Jenipher 
Published: January 2021

Abstract
Background: Health social enterprises are experimenting with community health worker (CHW) models that allow for various income-generating opportunities to motivate and incentivize CHWs. Although evidence shows that improving gender equality contributes to the achievement of health outcomes, gender-based constraints faced by CHWs working with social enterprises in Africa have not yet been empirically studied. This study is the first of its kind to address this important gap in knowledge. Methods: We conducted 36 key informant interviews and 21 focus group discussions between 2016 and 2019 (for a total of 175 individuals: 106 women and 69 men) with four health social enterprises in Uganda and Kenya and other related key stakeholders and domain experts. Interview and focus group transcripts were coded according to gender-based constraints and strategies for enhanced performance as well as key sites for intervention. Results: We found that CHW programs can be more gender responsive. We introduce the Gender Integration Continuum for Health Social Enterprises as a tool that can help guide gender equality efforts. Data revealed female CHWs face seven unique gender-based constraints (compared to male CHWs): 1) higher time burden and lack of economic empowerment; 2) risks to personal safety; 3) lack of career advancement and leadership opportunities; 4) lack of access to needed equipment, medicines and transport; 5) lack of access to capital; 6) lack of access to social support and networking opportunities; and 7) insufficient financial and non-financial incentives. Data also revealed four key areas of intervention: the health social enterprise, the CHW, the CHW’s partner, and the CHW’s patients. In each of the four areas, gender responsive strategies were identified to overcome constraints and contribute to improved gender equality and community health outcomes. Conclusions: This is the first study of its kind to identify the key gender-based constraints and gender responsive strategies for health social enterprises in Africa using CHWs. Findings can assist organizations working with CHWs in Africa (social enterprises, governments or non-governmental organizations) to develop gender responsive strategies that increase the gender and health outcomes while improving gender equality for CHWs, their families, and their communities.
A thermodynamic modeling of 2-bed adsorption desalination to promote main equipment performance
Authors: Amirfakhraei Amirhossein , Khorshidi Jamshid , Zarei Taleb 
Published: January 2021

Abstract
Adsorption desalination utilizes the discrete adsorption of the water vapor from the evaporator, and is capable of being discharged to the condenser. This study illuminated an advanced cycle of mass and heat recovery among beds, condensers, and evaporators. Morover, the thermodynamic modeling of adsorption desalination systems (ADS) under different operating conditions was investigated. Furthermore, its effect on the evaporator vapor production and the water vapor adsorption and desorption in the adsorption beds were accounted for. Parenthetically, the mathematical model of ADS thermodynamics was validated with the experimental data. Besides, the advanced ADS modeling was conducted via mass and heat recovery among beds, condensers, and evaporators. In addition to the amount of desalinated water, the time history chart of the equipment applied in the process with and without the thermal and mass recovery is also illustrated. Finally, under such operating conditions, the specific daily water production (SDWP) advanced ADS is 153% higher than conventional ADS.
Fate and persistence of antibiotic-resistant bacteria and genes through a multi-barrier treatment facility for direct potable reuse
Authors: Wallmann Lina , Krampe Jörg , Lahnsteiner Josef , Radu Elena , van Rensburg Pierre , Slipko Katarzyna , Wögerbauer Markus , Kreuzinger Norbert 
Published: January 2021

Abstract
Given the availability of technological solutions and guidelines for safe drinking water, direct potable reuse of reclaimed water has become a promising option to overcome severe lack of potable water in arid regions. However, the growing awareness of the presence of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARG) in corresponding raw wastes has led to new safety concerns. This study investigated the fate of ARB and intracellular and extracellular ARG after each treatment step of an advanced water treatment facility in Windhoek, Namibia. The New Goreangab Water Reclamation Plant (NGWRP) produces drinking water from domestic secondary wastewater treatment plant effluent and directly provides for roughly a quarter of Windhoek's potable water demand. Procedures to study resistance determinants were based on both molecular biology and culture-based microbiological methods. TaqMan real-time PCR was employed to detect and quantify intracellular resistance genes sul1, ermB, vanA, nptII and nptIII as well as extracellular resistance gene sul1. The NGWRP reduced the amount of both culturable bacterial indicators as well as the resistance genes to levels below the limit of detection in the final product. The main ozonation and the ultrafiltration had the highest removal efficiencies on both resistance determinants.
Spread das debêntures brasileiras: Uma aplicação da Modelagem de Equações Estruturais sob os direcionadores de covenants brasileiros
Authors: Alves Confessor Kliver Lamarthine , Dos Santos Josete Florencio 
Published: January 2021

Este artigo identificou quais são os constructos formados a partir dos direcionadores de covenants que exercem efeito sob o Spread das debêntures emitidas por empresas brasileiras listadas na Brasil, Bolsa e Balcão, no período de 2010 a 2018, sob a hipótese de que os covenants possuem conteúdo informacional e podem influenciar a valorização das debêntures. A amostra é composta por 225 emissões primárias de debêntures de empresas brasileiras. Os direcionadores de covenants foram identificados a partir dos formulários de referência das empresas e as demais variáveis desse estudo foram obtidas por meio da consulta aos endereços eletrônicos das empresas emissoras de debêntures, no Sistema Nacional de Debêntures (SND) e na base de dados do Economatica®. Para o spread das debêntures, tomou-se como base quatro perspectivas de mensuração, uma medida padrão, denominada por Spread_G e outras três medidas conforme os indexadores: DI, DI + % e IPCA + %, denominadas, respectivamente, por Spread_DI, Spread_DIMAIS e Spread_IPCAMAIS. Os dados foram analisados pela modelagem de equações estruturais e os resultados sugerem que duas dimensões são relevantes: Desempenho Financeiro, Situação Patrimonial e de Endividamento (DFSPE) para o spread_DIMAIS; e Comprometimento da Dívida (CD) para o spread_DIMAIS e spread_DI e são medidas que influenciam o spread das debêntures e também na função de reduzir o conflito de agência. Portanto, investidores e demais interessados na avaliação das debêntures devem considerar estas medidas durante o processo de avaliação do risco e retorno.
High-dose Vitamin D Supplementation on Type 1 Diabetes Mellitus Patients: Is there an Improvement in Glycemic Control?
Authors: de Melo Franciane Trindade Cunha , Felício Karem Mileo , de Queiroz Natércia Neves Marques , de Rider Brito Hana Andrade , Neto João Felício Abrahão , Janaú Luísa Corrêa , de Souza Neto Norberto Jorge Kzan , Silva Ana Luíza Aires , de Lemos Manuela Nascimento , de Oliveira Maria Clara Neres Iunes , de Alcântara Angélica Leite , de Moraes Lorena Vilhena , de Souza Ícaro José Araújo , Said Nivin Mazen , da Silva Wanderson Maia , de Lemos Gabriela Nascimento , dos Santos Márcia Costa , De Souza D Albuquerque Silva Lilian , Motta Ana Regina Bastos , de Figueiredo Priscila Boaventura Barbosa , de Souza Ana Carolina Contente Braga , Piani Pedro Paulo Freire , Felício João Soares 
Published: January 2021

Background:
Some authors evaluated the effect of VD on hyperglycemia in T1DM, but the results remain
controversial. This study aims to analyze the effects of high-dose VD supplementation on T1DM patients’ glycemic
levels, maintaining stable doses of insulin.

Methods:
Prospective, 12-week clinical trial including 67 T1DM patients, who were supplemented with high doses of
cholecalciferol according to participants' VD value. Patients with VD levels below 30 ng/mL received 10,000 IU/day;
those with levels between 30-60 ng/mL received 4,000 IU/day. Patients who had not achieved 25(OH)D levels > 30 ng/ml
or presented insulin dose variation during the study were not analyzed.

Results:
Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement
in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a posthoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13
(28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was
observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively) and a regression model demonstrated that 25(OH)D was
independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final
levels (Unstandardized B coefficient = −0.033 (CI 95%: −0.064 to −0.002), r² = 0.1, p <0.05).

Conclusion:
Our data suggests that VD is not widely recommended for glycemic control. Nevertheless, specific patients
might benefit from this approach.
Management of Advanced Staged Ovarian Cancer in a National Cancer Center: Comparison of the Efficacy of Primary Debulking Surgery Versus Neoadjuvant Chemotherapy
Authors: Kovačević Nina , Škof Erik , Cilenšek Ines , Merlo Sebastjan 
Published: January 2021

Background:
In most cases, ovarian cancer is diagnosed at an advanced stage. The aim
of this study was to determine if Primary Debulking Surgery (PDS) for women with advanced
epithelial ovarian cancer is an equivalent treatment approach to neoadjuvant chemotherapy
(NACT).

Methods:
A retrospective analysis of 214 women with stage FIGO IIIC and IV ovarian cancer
was performed at the Institute of Oncology Ljubljana, Slovenia. Women were divided into two
groups based on their primary treatment. The first group was the NACT group (184 women) and the
second the PDS group (30 women). The selection of the women for PDS or NACT was based on
the expertise of the gynecological-oncological surgeon and the image exam results. We used the
Kaplan-Meier method for calculating Overall Survival (OS) and Progression-Free Survival (PFS).
The statistical analysis was performed with IBM SPSS.

Results:
The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI
20.6-29.5) and 46 months (95% CI 32.9-62.1), respectively. The PFS in the NACT group was 8
months (95% CI 6.4-9.5) and 18 months (95% CI 12.5-23.4) in the PDS group. For women treated
with PDS the 5-year survival rate was 36.7% and 20.1% in the NACT group.

Conclusion:
In this study, the best survival results were observed in women treated with PDS,
followed by adjuvant chemotherapy. If a woman is not suitable for surgery, NACT doubles the
chance of a complete gross resection. Despite higher rates of complete gross resection after NACT,
women treated with PDS (complete gross resection or optimal surgery) had higher OS.
A Gas Chromatography Flame Ionization Detector Method for Rapid Simultaneous Separation and Determination of Six Active Ingredients of Anticold Drug
Authors: Dong Yuming , Yang Fatang , Duan Xiaoyun , Wang Zhen 
Published: January 2021

Aims:To establish a rapid and simultaneous determination of multiple effective ingredients in anti-cold drugs.Background:Anti-cold drugs are stock medicines at home, and most anti-cold formulations are compound preparations. Although the active ingredients of compound preparations have significant effects on the treatment of colds, the excessive dosage or long-term use can produce a series of adverse reactions, including dependence, liver and kidney function damage, digestive system reaction, blood system damage. Now, there are many mature methods for analyzing the active ingredients of anti-cold drugs. However, these methods may have shortcomings, such as a long analysis time or a small number of analysis components.Objective:Establish a gas chromatography-flame ionization detector method for the simultaneous determination of six active ingredients, including acetaminophen, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, chlorpheniramine maleate, diphenhydramine hydrochloride, and caffeine in anti-cold drugs.Method:After the standard was accurately weighed, dissolved in ethanol, filtered by 0.22 μm membrane and ultrasonically degassed, the gas chromatograph was used for detection. After the actual sample was removed from the coating, ground and crushed, accurately weighed, dissolved in ethanol, filtered by 0.22 μm membrane and ultrasonically degassed, the gas chromatograph was used for detection.Result:The six components can be completely separated within 7.0min. This method has good sensitivity, precision, accuracy and recovery rate. Under the optimum testing conditions, the limit of detection was 0.360-2.50μg/mL, the limit of quantification was 1.20-8.30μg/mL. The calibration curves showed good linearity (R2≥0.9932) over the investigated concentration range between 1.20 and 400μg/mL. The recoveries were 89.2% to 109.2%. The RSD of intra-day precision was less than 1.0%. The RSD of inter-day precision was less than 3.2%. The established method was used to determine the ingredients of three anti-cold drugs on the market, and the results showed that the method can accurately determine the ingredients.Conclusion:The method can quickly and simultaneously determine multiple active ingredients in anti-cold medicines. Compared with the published methods in literature, the proposed method has the advantages of fast, the number of analysis components wide application range, convenience, low cost, etc. It provides a reference method for quality control of active ingredients of anti-cold drugs.
Efficacy and Cardiovascular Safety of Metformin
Authors: Rajgopal Ranjith K. , Kochhar Rupinder S. 
Published: January 2021

Abstract::
Metformin has been the cornerstone of the medical management of type 2 diabetes mellitus
(T2DM) for over 6 decades now since its first-ever discovery. Although there were initial concerns
about its efficacy and safety, increasing evidence over the years proved it to be very effective
and safe. It has stood the test of time, proving to be much safer than other drugs in the same class
and garnering robust evidence in cardiovascular safety. In patients with T2DM, metformin lowers
mean glycated hemoglobin (HbA1c) levels by 1.1–1.2% as monotherapy, by 0.6–0.83% as an add-
on therapy to insulin, and by 0.9- 0.95% as add-on therapy to other oral agents. Recently its use
has also been explored for unlicensed indications other than diabetes, including but not limited to
obesity, polycystic ovarian syndrome (PCOS), and type 1 diabetes. Metformin is also currently under
investigation for its role as a cancer adjuvant therapy. We aim to provide a comprehensive review
of the available evidence for the safety and efficacy of metformin.
Repurposing Chloroquine Analogs as an Adjuvant Cancer Therapy
Authors: Fong Winnie , To Kenneth K.W. 
Published: January 2021

Background:
Drug repurposing is emerging as an attractive strategy with lower attrition
rate, lower cost and shorter timeframe than traditional drug discovery methods. Chloroquine (CQ)
and its analogs are old drugs originally indicated for malaria treatment. Serendipitous discovery in
early years revealed its anti-inflammatory properties, thus allowing its repositioned use in autoimmune
diseases. Recent evidence also suggested its potential therapeutic use for anticancer therapy.

Objective:
This article reviews the molecular mechanisms, clinical evaluation and recent patents of CQ analogs in cancer
therapy.

Methods:
Literature and patent searches were conducted using PubMed database and Google Patent/
USPTO Patent Search database, respectively. The keywords including “chloroquine”, “hydroxychloroquine”,
“chloroquine analogs”, “chloroquine derivatives”, “repurposing”, “autophagy”, and
“cancer” were used.

Results:
CQ analogs have been reported to elicit their anticancer effects by modulating autophagy,
inducing apoptosis, eliminating cancer stem cells, normalizing tumor vasculature and modulating
antitumor immunity. As documented by recent patents and clinical trials, CQ analogs have been repurposed
as an adjuvant therapy and combined with other anticancer agents for synergistic enhancement
of treatment efficacy. However, most clinical trials on CQ only demonstrated modest improvement
in anti-cancer efficacy.

Conclusion:
Given that CQ loses its anticancer activity in acidic and hypoxic environment within
a tumor, novel CQ analogs and/or their formulations are under active investigation to improve their
physicochemical properties and biological activity. On the other hand, identification of new biomarkers
for better patient selection has been advocated in future trials in order to realize the repurposing
of CQ analogs for cancer treatment in a personalized manner.