bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the pharmaceutical care provision to suspected COVID-19 patients in community pharmacies: a simulated patient study
Authors: Karout Samar , Khojah Hani M. J. , Itani Rania , Jaffal Fatima , El-Lakany Abdalla 
Published: April 2022

Abstract
Background
In the wake of COVID-19, community pharmacists (CP) were called upon to free up healthcare providers to treat more serious conditions and alleviate overcrowded healthcare centers. CPs were placed under tremendous pressure, where many patients primarily sought their health advice. This situation raised concerns about the preparedness of CPs in facing these challenges. Therefore, this study aimed to assess the appropriateness of pharmaceutical care provided by CPs to patients with suspected COVID-19 and to investigate their communication skills.

Methods
A simulated patient (SP) study was conducted among randomly selected community pharmacies in Beirut, Lebanon. Each pharmacy was visited by the SP who complained of fever and loss of smell sensation. Interactions between the attending pharmacist and the suspected COVID-19 patient were documented directly after each visit in a standardized data collection form.

Results
More than half of the CPs (56%) did not retrieve any relevant information to assess the patient’s condition. While pharmacists’ responses were limited to one to two recommendations, with the majority recommending the patient to perform the PCR test (90%). Inappropriate recommendations made by the CPs included mainly the confirmation that the patient had COVID-19 without prior testing (9%), and prescribing either an antimicrobial drug (5%) or dietary supplements (20%), claiming that the latter are essential to boost the patient’s immunity. As for the pharmacist-patient communication skills, the mean total score was 2.25 ± 0.79 (out of 4), displaying nonoptimal and ineffective communication.

Conclusion
An unsatisfactory and suboptimal provision of pharmaceutical care to a suspected COVID-19 case was evident. This may be a public health threat, particularly for developing countries that lack an efficient and unified healthcare system. The findings should alert health authorities to support and guide community pharmacists in assisting suspected COVID-19 patients.
Effectiveness of checklist-based box system intervention (CBBSI) versus routine care on improving utilization of antenatal care visits in Northwest Ethiopia: a cluster randomized controlled trial
Authors: Andargie Netsanet Belete , Debelew Gurmesa Tura 
Published: April 2022

Abstract
Background
In Ethiopia, the proportion of mothers who attend the fourth antenatal care visit is lower than the proportion who attend the first visit. Although the reasons for these dropouts were investigated, few studies introduced interventions to promote the fourth antenatal care visit. Hence, the aim of this study was to assess the effectiveness of checklist-based box system intervention on improving fourth antenatal care visit.

Method
This study employed a double-blind, parallel-group, two-arm cluster randomized controlled trial to compare the effectiveness of checklist-based box system intervention with the usual standard of care as a control arm. Study clusters are assigned to intervention and control arm in 1:1 allocation ratio using simple randomization technique. Pregnant mothers below 16 weeks of gestation were enrolled. Open data kit was used to collect data from the baseline and end-line surveys, and STATA version 15.0 was used to analyse the data. A difference-in-difference estimator was used to compare fourth antenatal care visit between the intervention and control groups across time. Mixed effect multi-level logistic regression was used to examine the relationship between the dependent and independent variables.

Result
Data were collected from 2224 mothers who belong to 15 intervention and 15 control clusters. The difference in difference estimation resulted in a significant difference (26.1, 95%CI: 18–34%, p < 0.0001) between the intervention and control groups. Similarly, as compared to controls, the fourth antenatal care visit was found significantly higher in the intervention clusters (432 (85.2%) Vs. 297 (53.7%), p < 0.0001)/(AOR:5.69, 95% CI:4.14–7.82). Mothers who were knowledgeable about the services given during antenatal care visits (AOR: 2.31, 95% CI:1.65–3.24) and mothers who had a high level of social support (AOR:1.47, 95% CI: 1.06–2.04) were more likely to attend the fourth antenatal care visit.

Conclusion
Implementation of checklist-based box system intervention resulted in a statistically significant effect in attendance of fourth antenatal care visit. Community-level variables were found to be more important in explaining variability in the fourth antenatal care visit. It is recommended that the intervention be implemented on a larger scale.

Trial registration
ClinicalTrials.gov, Retrospectively registered on 26/03/2019, with trial registration number-NCT03891030.
Hospital treatment costs associated with incident complications in patients with type 2 diabetes—real-world study based on electronic patient information systems
Authors: Sund Reijo , Peltonen Tuomas , Lehtimäki Aku-Ville , Martikainen Janne 
Published: April 2022

Abstract
Background
Type 2 diabetes (T2D) and its complications cause a significant public health and economic challenge. To enable the optimal resource allocation across different prevention and treatment policies for the management of T2D-related complications, detailed cost estimates related to the complications of T2D are needed. Therefore, the objective of the study was to provide reliable and sufficiently detailed real-world estimates of costs associated with different T2D complications in a Finnish university hospital setting.

Methods
A cohort of T2D patients living in the catchment area of a university hospital during 2012 and 2016 was identified from the comprehensive national FinDM diabetes database for longitudinal assessment of T2D associated complication treatment costs. Data on patient-level events were extracted from the FinDM data and complemented with all accountable services and related detailed costing data gathered from the university hospital’s electronic patient information systems by using unique personal identity codes. Patients were screened for their first diagnoses of complications using the same national quality registry definitions as in the FinDM database. Multivariable gamma regression model with a log link function was applied to study the association between baseline factors and complication costs. In addition, an interactive online tool was developed to create predicted costs for complication costs with selected baseline factors.

Results
A total of 27 255 prevalent and incident patients with T2D were identified from the national FinDM register. Finally, a total of 16 148 complication episodes for 7 895 patients were included in the cost analyses. The mean estimated one-year hospital treatment costs of T2D-related complication varied from 6 184 to 24 507 euros per complication. Regression analyses showed that coexisting conditions are significantly associated with initial and recurrent complication costs.

Conclusions
The study shows updated Finnish cost estimates and their main cost drivers for T2D-related complications treated in the university hospital setting. The results of our study highlight the significance of guideline implementation, effective preventive treatments for T2D, as well as the importance of treatment adherence to avoid these costly complications.
Prevalence of porcine parvovirus 1 through 7 (PPV1-PPV7) and co-factor association with PCV2 and PRRSV in Korea
Authors: Kim Seung-Chai , Kim Jae-Hong , Kim Jae-Yeob , Park Gyeong-Seo , Jeong Chang-Gi , Kim Won-Il 
Published: April 2022

Abstract
Background
Classical porcine parvovirus (PPV1) and novel porcine parvoviruses designated porcine parvovirus 2 through 7 (PPV2-PPV7) are widespread in pig populations. The objective of this study was to investigate the prevalence rates of PPV1-PPV7 in Korea by detecting PPVs in serum, lung and fecal samples and to elucidate the association of PPVs with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory virus (PRRSV), major pathogens involved in porcine respiratory disease complex (PRDC). A total of 286 serum, 481 lung, and 281 fecal samples collected from 2018 to 2020 were analyzed.

Results
The results showed that PPVs are widespread in Korea; the highest detection rates were found in lung samples and ranged from 7.9% (PPV1) to 32.6% (PPV2). Regarding age groups, fattening pigs had the highest detection rates of PPVs, ranging from 6.4% (PPV1) to 36.5% (PPV6); this finding suggests the chronic nature of PPV infections and the continual circulation of these viruses. When compared with PCV2- and PRRSV-negative lung samples, PCV2-positive samples with or without PRRSV positivity had significantly higher detection levels of PPV1 and PPV6. In contrast, the prevalence of PPV2 and PPV7 was significantly higher in PRRSV-infected lung samples regardless of PCV2 detection. PPV5 was detected significantly more frequently in samples with both PCV2 and PRRSV positivity.

Conclusions
This study could offer a better understanding of the role of PPVs in PCV2 and/or PRRSV infection though further studies are needed to experimentally assess the impact of PPVs in coinfections.
Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure
Authors: Sforza Annalisa , Vigorelli Vera , Rurali Erica , Perrucci Gianluca Lorenzo , Gambini Elisa , Arici Martina , Metallo Alessia , Rinaldi Raffaella , Fiorina Paolo , Barbuti Andrea , Raucci Angela , Sacco Elena , Rocchetti Marcella , Pompilio Giulio , Genovese Stefano , Vinci Maria Cristina 
Published: April 2022

Abstract
Background
Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34+ hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34+ HSPC function.

Methods
In cord blood (CB)-derived CD34+ HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and Western Blot respectively. CD34+ HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34+ HSPC were evaluated.

Results
CD34+ HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation, CXCR4/SDF-1α axis activity and metabolic imbalance from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9–39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects.

Conclusion
We provided the first evidence that CD34+ HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients.
Towards an understanding of oleate hydratases and their application in industrial processes
Authors: Prem Sophia , Helmer Carl P. O. , Dimos Nicole , Himpich Stephanie , Brück Thomas , Garbe Daniel , Loll Bernhard 
Published: April 2022

AbstractFatty acid hydratases are unique to microorganisms. Their native function is the oxidation of unsaturated C–C bonds to enable detoxification of environmental toxins. Within this enzyme family, the oleate hydratases (Ohys), which catalyze the hydroxylation of oleic acid to 10-(R)-hydroxy stearic acid (10-HSA) have recently gained particular industrial interest. 10-HSA is considered to be a replacement for 12-(R)-hydroxy stearic acid (12-HSA), which has a broad application in the chemical and pharmaceutical industry. As 12-HSA is obtained through an energy consuming synthesis process, the biotechnological route for sustainable 10-HSA production is of significant industrial interest. All Ohys identified to date have a non-redox active FAD bound in their active site. Ohys can be divided in several subfamilies, that differ in their oligomerization state and the decoration with amino acids in their active sites. The latter observation indicates a different reaction mechanism across those subfamilies. Despite intensive biotechnological, biochemical and structural investigations, surprising little is known about substrate binding and the reaction mechanism of this enzyme family. This review, summarizes our current understanding of Ohys with a focus on sustainable biotransformation.
One-pot biosynthesis of 7β-hydroxyandrost-4-ene-3,17-dione from phytosterols by cofactor regeneration system in engineered mycolicibacterium neoaurum
Authors: Zhao Yun-Qiu , Liu Yong-Jun , Ji Wei-Ting , Liu Kun , Gao Bei , Tao Xin-Yi , Zhao Ming , Wang Feng-Qing , Wei Dong-Zhi 
Published: April 2022

Abstract
Background
7β-hydroxylated steroids (7β-OHSt) possess significant activities in anti-inflammatory and neuroprotection, and some of them have been widely used in clinics. However, the production of 7β-OHSt is still a challenge due to the lack of cheap 7β-hydroxy precursor and the difficulty in regio- and stereo-selectively hydroxylation at the inert C7 site of steroids in industry. The conversion of phytosterols by Mycolicibacterium species to the commercial precursor, androst-4-ene-3,17-dione (AD), is one of the basic ways to produce different steroids. This study presents a way to produce a basic 7β-hydroxy precursor, 7β-hydroxyandrost-4-ene-3,17-dione (7β-OH-AD) in Mycolicibacterium, for 7β-OHSt synthesis.

Results
A mutant of P450-BM3, mP450-BM3, was mutated and engineered into an AD producing strain for the efficient production of 7β-OH-AD. The enzyme activity of mP450-BM3 was then increased by 1.38 times through protein engineering and the yield of 7β-OH-AD was increased from 34.24 mg L− 1 to 66.25 mg L− 1. To further enhance the performance of 7β-OH-AD producing strain, the regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) for the activity of mP450-BM3-0 was optimized by introducing an NAD kinase (NADK) and a glucose-6-phosphate dehydrogenase (G6PDH). Finally, the engineered strain could produce 164.52 mg L− 1 7β-OH-AD in the cofactor recycling and regeneration system.

Conclusions
This was the first report on the one-pot biosynthesis of 7β-OH-AD from the conversion of cheap phytosterols by an engineered microorganism, and the yield was significantly increased through the mutation of mP450-BM3 combined with overexpression of NADK and G6PDH. The present strategy may be developed as a basic industrial pathway for the commercial production of high value products from cheap raw materials.
Comparison of household socioeconomic status classification methods and effects on risk estimation: lessons from a natural experimental study, Kisumu, Western Kenya
Authors: Were Vincent , Foley Louise , Turner-Moss Eleanor , Mogo Ebele , Wadende Pamela , Musuva Rosemary , Obonyo Charles 
Published: April 2022

Abstract
Introduction
Low household socioeconomic status is associated with unhealthy behaviours including poor diet and adverse health outcomes. Different methods leading to variations in SES classification has the potential to generate spurious research findings or misinform policy. In low and middle-income countries, there are additional complexities in defining household SES, a need for fieldwork to be conducted efficiently, and a dearth of information on how classification could impact estimation of disease risk.

Methods
Using cross-sectional data from 200 households in Kisumu County, Western Kenya, we compared three approaches of classifying households into low, middle, or high SES: fieldworkers (FWs), Community Health Volunteers (CHVs), and a Multiple Correspondence Analysis econometric model (MCA). We estimated the sensitivity, specificity, inter-rater reliability and misclassification of the three methods using MCA as a comparator. We applied an unadjusted generalized linear model to determine prevalence ratios to assess the association of household SES status with a self-reported diagnosis of diabetes or hypertension for one household member.

Results
Compared with MCA, FWs successfully classified 21.7% (95%CI = 14.4%-31.4%) of low SES households, 32.8% (95%CI = 23.2–44.3) of middle SES households, and no high SES households. CHVs successfully classified 22.5% (95%CI = 14.5%-33.1%) of low SES households, 32.8% (95%CI = 23.2%-44.3%) of middle SES households, and no high SES households. The level of agreement in SES classification was similar between FWs and CHVs but poor compared to MCA, particularly for high SES. None of the three methods differed in estimating the risk of hypertension or diabetes.

Conclusions
FW and CHV assessments are community-driven methods for SES classification. Compared to MCA, these approaches appeared biased towards low or middle SES households and not sensitive to high household SES. The three methods did not differ in risk estimation for diabetes and hypertension. A mix of approaches and further evaluation to refine SES classification methodology is recommended.
The number of cycles of adjuvant chemotherapy in stage III and high-risk stage II rectal cancer: a nomogram and recursive partitioning analysis
Authors: Chen Wei-Wei , Wang Wen-Ling , Dong Hong-Min , Wang Gang , Li Xiao-Kai , Li Guo-Dong , Chen Wang-Hua , Chen Juan , Bai Sai-Xi 
Published: April 2022

Abstract
Objective
The prognostic role of the number of cycles of adjuvant chemotherapy (ACT) after total mesorectal excision in stage III and high-risk stage II rectal cancer is unknown. As a result of this, our study was designed to assess the effect of the number of cycles of ACT on the prediction of cancer-specific survival.

Methods
Four hundred patients that were diagnosed as stage III and high-risk stage II rectal cancer from January 2012 to January 2018 and who had received total mesorectal excision were enrolled in this study. A nomogram incorporating the number of cycles of ACT was also developed in this study. For internal validation, the bootstrap method was used and the consistency index was used to evaluate the accuracy of the model. The patients were stratified into risk groups according to their tumor characteristics by recursive partitioning analysis.

Results
We found that the risk of death was decreased by 26% (HR = 0.74, 95% CI: 0.61–0.89, P = 0.0016) with each increasing ACT cycle. The N stage, positive lymph node ratio (PLNR), carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, and the number of cycles of ACT were chosen and entered into the nomogram model. Recursive partitioning analysis-based risk stratification revealed a significant difference in the prognosis in rectal cancer patients with high-risk, intermediate-risk, and low-risk (3-year cancer-specific survival: 0.246 vs. 0.795 vs. 0.968, P < 0.0001). Seven or more cycles of ACT yielded better survival in patients with PLNR ≥ 0.28 but not in patients with PLNR < 0.28.

Conclusion
In conclusion, the nomogram prognosis model based on the number of cycles of ACT predicted individual prognosis in rectal cancer patients who had undergone total mesorectal excision. These findings further showed that in patients with PLNR ≥ 0.28, no fewer than 7 cycles of ACT are needed to significantly reduce the patient’s risk of death.
β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?
Authors: Diane Abdoulaye , Al-Shukri Noora Ali , Bin Abdul Mu-u-min Razik , Al-Siddiqi Heba H. 
Published: April 2022

AbstractDiabetes mellitus (DM), currently affecting 463 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from the loss or dysfunction of pancreatic β-cells with the former preponderating in type 1 diabetes (T1DM) and the latter in type 2 diabetes (T2DM). Because impaired insulin secretion due to dysfunction or loss of pancreatic β-cells underlies different types of diabetes, research has focused its effort towards the generation of pancreatic β-cells from human pluripotent stem cell (hPSC) as a potential source of cells to compensate for insulin deficiency. However, many protocols developed to differentiate hPSCs into insulin-expressing β-cells in vitro have generated hPSC-derived β-cells with either immature phenotype such as impaired glucose-stimulated insulin secretion (GSIS) or a weaker response to GSIS than cadaveric islets. In pancreatic β-cells, mitochondria play a central role in coupling glucose metabolism to insulin exocytosis, thereby ensuring refined control of GSIS. Defects in β-cell mitochondrial metabolism and function impair this metabolic coupling. In the present review, we highlight the role of mitochondria in metabolism secretion coupling in the β-cells and summarize the evidence accumulated for the implication of mitochondria in β-cell dysfunction in DM and consequently, how targeting mitochondria function might be a new and interesting strategy to further perfect the differentiation protocol for generation of mature and functional hPSC-derived β-cells with GSIS profile similar to human cadaveric islets for drug screening or potentially for cell therapy.
Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer
Authors: Li Tong , Cao Huiyuan , Wu Sa , Zhong Peimin , Ding Jie , Wang Jing , Wang Fangfang , He Zhiwei , Huang Guo-Liang 
Published: April 2022

AbstractBackgroundStudies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2).MethodsImmunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184.ResultsHigh expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC.ConclusionOur results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.