bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug metabolic activity is a critical cell-intrinsic determinant for selection of hepatocytes during long-term culture
Authors: Akiyama Saeko , Saku Noriaki , Miyata Shoko , Ite Kenta , Toyoda Masashi , Kimura Tohru , Kuroda Masahiko , Nakazawa Atsuko , Kasahara Mureo , Nonaka Hidenori , Kamiya Akihide , Kiyono Tohru , Kobayshi Tohru , Murakami Yasufumi , Umezawa Akihiro 
Published: March 2022

Abstract
Background
The liver plays an important role in various metabolic processes, including protein synthesis, lipid and drug metabolisms and detoxifications. Primary culture of hepatocytes is used for the understanding of liver physiology as well as for the drug development. Hepatocytes are, however, hardly expandable in vitro making it difficult to secure large numbers of cells from one donor. Alternatively, systems using animal models and hepatocellular carcinoma cells have been established, but interspecies differences, variation between human cell sources and limited hepatic functions are among the challenges faced when using these models. Therefore, there is still a need for a highly stable method to purify human hepatocytes with functional sufficiency. In this study, we aimed to establish an in vitro long-term culture system that enables stable proliferation and maintenance of human hepatocytes to ensure a constant supply.

Methods
We first established a growth culture system for hepatocytes derived from patients with drug-induced liver injury using fetal mouse fibroblasts and EMUKK-05 medium. We then evaluated the morphology, proliferative capacity, chromosome stability, gene and protein expression profiles, and drug metabolic capacity of hepatocytes in early, middle and late passages with and without puromycin. In addition, hepatic maturation in 3D culture was evaluated from morphological and functional aspects.

Results
In our culture system, the stable proliferation of human hepatocytes was achieved by co-culturing with mouse fetal fibroblasts, resulting in dedifferentiation into hepatic progenitor-like cells. We purified human hepatocytes by selection with cytocidal puromycin and cultured them for more than 60 population doublings over a span of more than 350 days. Hepatocytes with high expression of cytochrome P450 genes survived after exposure to cytocidal antibiotics because of enhanced drug-metabolizing activity.

Conclusions
These results show that this simple culture system with usage of the cytocidal antibiotics enables efficient hepatocyte proliferation and is an effective method for generating a stable supply of hepatocytes for drug discovery research at a significant cost reduction.
Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study
Authors: Zhang Shengyang , Xu Huihui , He Bangjian , Fan Mengqiang , Xiao Miaomiao , Zhang Jingjing , Chen Di , Tong Peijian , Mao Qiang 
Published: March 2022

Abstract
Background
The short-term safety and efficacy of stromal vascular fraction (SVF) in treating knee osteoarthritis (KOA) have been extensively studied but the mid-term and long-term prognoses remain unknown.

Methods
126 KOA patients were recruited and randomly assigned to SVF group and hyaluronic acid (HA) group (control group). The scores of visual analogue scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were assessed and compared between the two groups 1, 2, 3, and 5 years after treatment. The endpoint was defined as surgeries related to KOA or clinical scores exceeding the patient acceptable symptom state (PASS).

Results
The VAS and WOMAC scores in the SVF group were significantly better than those in the HA group during the 5-year follow-up after treatment. The average responsive time to SVF treatment (61.52 months) was significantly longer than HA treatment (30.37 months). The adjusted Cox proportional hazards model showed that bone marrow lesion (BML) severity, body mass index (BMI) and treatment were independent risk factors and that the use of SVF reduced the risk of clinical failure by 2.602 times. The cartilage volume was reduced in both the SVF and control groups at 5 years but reduced less in the SVF group.

Conclusions
Up to 5 years after SVF treatment, acceptable clinical state was present for approximately 60% of patients. BML severity and BMI were independent predictors of the prognosis.
Trial Registry: This study was retrospectively registered at Chinses Clinical Trial Registry with identifier ChiCTR2100052818 and was approved by ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, number 2013-X-063.
An inertial s-iteration process for a common fixed point of a family of quasi-Bregman nonexpansive mappings
Authors: Ali Bashir , Adam Aisha A. 
Published: March 2022

AbstractIn this paper, an inertial S-iteration iterative process for approximating a common fixed point of a finite family of quasi-Bregman nonexpansive mappings is introduced and studied in a reflexive Banach space. A strong convergence theorem is proved. Some applications of the theorem are presented. The results presented here improve, extend, and generalize some recent results in the literature.
Mutual insurance in the entrepreneurial landscape
Authors: Logvinova Irina L. , Rubin Yury B. , Lednev Mikhail V. , Mozhzhukhin Daniel P. 
Published: March 2022

AbstractIn this article, the authors introduce mutual insurance as a constructive component of the modern entrepreneurial landscape aimed at the protection of the wealth-related interests of the participants of the mutual insurance company (mutual insurance society, friendly society, etc.). Analyzing mutual insurance, the authors display it from the standpoint of entrepreneurship and assume that such companies (MICs) are among the insurance market actors. The specific feature of MICs is that they form the community of their members-policyholders. As far as members of each organization of this kind are its co-owners, they carry out some critical entrepreneurial activity functions. The object of this research is represented by the insurance market of the Russian Federation, through the prism of which the degree of development of MICs was demonstrated, and the barriers to its infrastructure growth were determined.
The embarking of COVID-19 and the perishable products’ value chain in Ethiopia
Authors: Ababulgu Nasir , Abajobir Nugusa , Wana Hika 
Published: March 2022

AbstractThe aim of this paper is analyzing the impact of COVID-19 on the perishable products’ value chain in Ethiopia. As a methodology, both data sources and types: primary and secondary, qualitative and quantitative, were used to achieve the objective of the study under consideration. The primary data sources used in this work is mainly phone survey, expert opinions and judgments based on real situation observation, and that of secondary data were collected through review of materials published on lessons learned from previous pandemics by different reputable sources. Therefore, this work is based on systematically reviewing and retrieving secondary sources through Google search, library plus harvesting and word type searching. The findings of the study revealed that the COVID-19 pandemic cut the full functioning of the value and supply chain of perishable products due to social distance restrictions imposed by the government, fear of the disease, cutoff transportation and even lock-down of market centers. This led to price changes, gross domestic product loss, the start-up of agro-industrial parks was delayed, reduced export and more women become out of work due to their high participation in perishable products’ value chain. To mention, Ethiopia has lost about $25 million—almost 10% of annual revenue—just over $10 million within the horticultural sector and around 50,000 workers lose their jobs—mostly female labourers. Based on the results, the authors forwarded the collective engagement of the concerned bodies to reduce the negative impacts of COVID-19 on perishable products by using the possible mechanism.
Epidemiological and genetic characteristics of vancomycin-resistant Enterococcus faecium isolates in a University Children's Hospital in Germany: 2019 to 2020
Authors: Trautmannsberger Ilona , Kolberg Laura , Meyer-Buehn Melanie , Huebner Johannes , Werner Guido , Weber Robert , Heselich Valerie , Schroepf Sebastian , Muench Hans-Georg , von Both Ulrich 
Published: March 2022

Abstract
Background
Vancomycin-resistant Enterococcus faecium (VREfm) strains are one of the most important pathogens causing nosocomial infections in Germany. Due to limited treatment options and an increased risk for acquisition in immunocompromised children, surveillance to monitor occurrence of VREfm in paediatric clinical facilities is of critical importance. Following an unusual accumulation of VREfm positive patients between April 2019 and August 2020 at Dr. von Hauner Children’s Hospital in Munich, Germany, our study aimed to identify dynamics and routes of transmission, and analyse the affected population in view of previously described host risk factors for VREfm colonisation or infection.

Methods
The hospital database was used to collect epidemiological and clinical data of VREfm cases. Descriptive statistical analyses were conducted to outline patient characteristics and depict possible differences between VREfm-colonised and -infected children. An outbreak investigation determining genetic relatedness among VREfm isolates was performed by core genome multilocus sequence typing (cgMLST). To examine potential transmission pathways, results of genome analysis were compared with epidemiological and clinical data of VREfm positive patients.

Results
VREfm acquisition was documented in a total of 33 children (< 18 years). Seven VREfm-colonised patients (21.2%), especially those with a haemato-oncological disease (4/7; p = 0.011), showed signs of clinical infection. cgMLST analysis revealed seven distinct clusters, demonstrating a possible connection within each clonal lineage. Additional eight singletons were identified. Comparison with epidemiological and clinical data provided strong evidence for a link between several VREfm positive patients within the hospital.

Conclusions
A nosocomial spread—at least in part—was the most likely reason for the unusual accumulation of VREfm cases. The study highlights that there is a constant need to increase efforts in hygiene measures, infection control and antibiotic stewardship to combat VREfm transmission events within German paediatric hospitals. Continuous monitoring of adherence to respective policies might reduce the occurrence of clustered cases and prevent future outbreaks.
Factors associated with post-operative delirium in hip fracture patients: what should we care
Authors: Kong Dequn , Luo Weihua , Zhu Zhijun , Sun Sixin , Zhu Jian 
Published: March 2022

Abstract
Background
The postoperative delirium is a common yet serious complication in elderly patients with hip fracture. We aimed to evaluate the potential risk factors of delirium in patients with hip fracture, to provide reliable evidence to the clinical management of hip fracture.

Methods
This study was a retrospective design. Elderly patients who underwent hip fracture surgery in our hospital from June 1, 2019 to December 30, 2020 were selected. The characteristics and treatment data of delirium and no delirium patients were collected and compared. Multivariate logistic regression analysis was performed to analyze the influencing factors affecting postoperative delirium in elderly patients with hip fracture.

Results
A total of 245 patients with hip fracture were included, the incidence of postoperative delirium in patients with hip fracture was 13.06%. There were significant differences in the age, BMI, history of delirium, estimated blood loss and duration of surgery (all p  < 0.05). There were significant differences in the albumin and TSH between delirium and no delirium group (all p < 0.05), Logistics analyses indicated that age ≥ 75 years (OR 3.112, 95% CI 1.527–5.742), BMI ≥ 24 kg/m2 (OR 2.127, 95% CI 1.144–3.598), history of delirium (OR 1.754, 95% CI 1.173–2.347), estimated blood loss ≥ 400 mL (OR 1.698, 95% CI 1.427–1.946), duration of surgery ≥ 120 min (OR 2.138, 95% CI 1.126–3.085), preoperative albumin ≤ 40 g/L (OR 1.845, 95% CI 1.102–2.835) and TSH ≤ 2 mU/L (OR 2.226, 95% CI 1.329–4.011) were the independent risk factors of postoperative delirium in patients with hip fracture(all p < 0.05).

Conclusions
Postoperative delirium is very common in elderly patients with hip fracture, and it is associated with many risk factors, clinical preventions targeted on those risk factors are needed to reduce the postoperative delirium.
TIP, TORQUE & ROTATIONS: How accurately do digital superimposition software packages quantify tooth movement?
Authors: Adel Samar M. , Vaid Nikhilesh R. , El-Harouni Nadia , Kassem Hassan , Zaher Abbas R. 
Published: March 2022

Abstract
Background
To investigate the accuracy of three different 3D digital model registration software for tip, torque and rotation measurements, with reference to a 3D digital virtual setup. Twenty maxillary and mandibular pre-treatment scans of patients undergoing clear aligner therapy were used. Digital setups were generated from pre-treatment scans using a tooth movement software. Both the pretreatment digital scans (T1) and digital setups (T2) were converted to STL files to be exported to the 3 studied software that employed: (1) Semiautomatic best fit registration (S-BF), (2) Interactive surface-based registration (I-SB), and (3) Automatic best fit registration (A-BF) respectively. Changes in tip, torque and rotation were calculated for all the registered pairs.

Results
The change in tooth position was compared between the calculated tooth movement using each of the registration software packages versus the actual generated tooth movement from the digital setups. Continuous data was expressed as mean and standard deviation. Intra Class Correlation Coefficient for agreement between digital simulation and each software was used. Intra and Inter-examiner reliabilities were also assessed using Intra Class Correlation Coefficient. Significance of the obtained results was expressed at p ≤ 0.01. Semiautomatic best fit registration software showed excellent agreement (> 0.90) for all tooth movements, except for good agreement for torque (0.808). Interactive surface-based registration software showed moderate agreement for all measurements (0.50 and < 0.75), except for good agreement for rotation (0.783). Automatic best fit registration software demonstrated excellent agreement (> 0.90) for rotation, good agreement for tip (0.890) and moderate agreement for torque (0.740).

Conclusions
Overall, semiautomatic best fit registration software consistently showed excellent agreement in superimpositions compared to other software types. Automatic best fit registration software consistently demonstrated better agreement for mandibular superimpositions, compared to others. Accuracy of digital model superimpositions for tooth movements studied in superimposition studies, can be attributed to the algorithm employed for quantification.
Sc-CO2 extraction of fish and fish by-products in the production of fish oil and enzyme
Authors: Jamalluddin Nur Anati , Ismail Normah , Mutalib Siti Roha Ab. , Sikin Adi Md 
Published: March 2022

AbstractSupercritical carbon dioxide (Sc-CO2) is an alternative tool to extract lipid for the production of fish oil and enzyme from fish by-products (FBPs). In the application of Sc-CO2, this review covers sample preparation, lipid extraction operation, and characterization of fish oil and enzyme as final products. Generally, the fish samples with moisture content less than 20% and particle size less than 5 mm are considered before lipid extraction with Sc-CO2. Sc-CO2 parameters, such as pressure (P), temperature (T), extraction time (text), and flow rate (F), for simultaneous recovery of fish oil, protein, and enzyme were found to be less severe (P: 10.3–25 MPa; T: 25–45 °C, text: 20–150 min; F: 3–50 g/min) than the extraction of fish oil alone (P: 10–40 Mpa; T: 35–80 °C; text: 30–360 min; F: 1–3000 g/min). The enzyme from the Sc-CO2 defatted sample showed higher activity up to 45 U/mg due to lower denaturation of protein as compared to the organic solvent treated sample albeit both samples having similar pH (6–10) and temperature stability (20–60 °C). Overall, mild extraction of lipid from FBPs using Sc-CO2 is effective for the production of enzymes suitable in various industrial applications. Also, fish oil as a result of extraction can be produced as a health product with high polyunsaturated fatty acids (PUFAs) and low contamination of heavy metals.
Effect of the COVID-19 pandemic on contraceptive prescribing in general practice: a retrospective analysis of English prescribing data between 2019 and 2020
Authors: Walker Susan H. 
Published: March 2022

Abstract
Objectives
This paper looks at how contraceptive prescribing by General Practices in England was affected by the COVID-19pandemic and lockdown. It compares English prescribing data in April – June 2019, the year before COVID19, and April–June 2020, the first three months of ‘lockdown’.

Design & Setting
This paper is based on retrospective analysis of the English Prescribing Dataset which reports monthly on prescribed items from English General Practices. Data on all forms of prescribed contraceptive methods were extracted using BNF codes, and total quantities tabulated by method. To reach the total number of months of contraception provided, total quantities were divided or multiplied according the frequency with which the method is taken per month or the numbers of months of contraception provided.

Results
Prescription of the combined oral contraceptive pill reduced by 22% during the period of lockdown compared to the same three months in 2019. Prescriptions of Progestogen-Only pills remained stable. Prescription of long-acting methods reduced, with the greatest reductions in implants (76% reduction from pre-lockdown levels), intra-uterine systems (79% reduction from pre-lockdown levels) and intrauterine devices (76% reduction from pre-lockdown levels).

Conclusions
The disruption of face-to-face contraceptive consultations in General Practice during a COVID-19 ‘lockdown’ has resulted in a reduction in oestrogen –containing methods compared to progestogen-only methods, which require less face-to-face monitoring.
Implant and intrauterine contraceptive device prescription reduced by three quarters over the first three months of lockdown, which has the potential to result in a rise in unintended pregnancies.
Identification of chemical components from essential oils and aqueous extracts of some medicinal plants and their nematicidal effects on Meloidogyne incognita
Authors: Ardakani A. S. , Hosseininejad S. A. 
Published: March 2022

Abstract
Background
Essential oils from aerial parts of Achillea wilhelmsii, Tanacetum polycephalum and Teucrium polium were isolated by using Clevenger-type apparatus and tested at different concentrations for their nematicidal activity against the second stage juvenile (J2) of Meloidogyne incognita in vitro condition. The chemical components of the essential oils and seed extracts of each plant (0.2 g) were extracted with maceration with methanol/acetic acid mixture (85:15, v/v). Analysis was done by Gas Chromatography, GC-Mass Spectrometry) and HPLC. Identified chemical components were tested after this on J2 of M. incognitain. Nuclear magnetic resonance spectroscopy was done to investigate the properties of organic molecules by drawing their spectrum using Broker AVANCE AQS-300 MHz.

Results
Significant difference was achieved on nematicidal activity of essential oils based on the plant species and oil concentrations. GC and GC–MS led to identification of 41, 39 and 45 major compounds from T. polium, T. polycephalum and A. wilhelmsii oils, respectively. A number of 10 components with different ranges of percentage were recorded in all of the tested plants oils. Use of HPLC resulted in identification of 4, 3 and 2 chemical compounds in the extracts of A. wilhelmsii, T. polycephalum and T. polium, respectively. The nematicidal activity of commercial polyphenols at the concentration of 1100 ppm showed 58.3, 48.9, 28.2 and 26.8 percentages J2 mortalities by catechin, coumarin, gallic acid and chlorogenic, respectively. Nematotoxicity test of commercial terpenoids showed the highest J2 mortalities (more than 80%), in concentrations of 100 and 200 ppm limonene, β-pinene and α-pinene. However, it was less than 30% of J2 mortality caused by terpinen-4-ol, α-terpineol and linalool.

Conclusions
Compounds such as Limonene, β-pinene and α-pinene were detected in all of the tested plants, A. wilhelmsii, T. polycephalum and T. polium, having an effective nematicidal action versus terpinen-4-ol, α-terpineol and linalool.
The association between pharmaceutical innovation and both premature mortality and hospital utilization in Switzerland, 1996–2019
Authors: Lichtenberg Frank R. 
Published: March 2022

AbstractWe analyze the association that pharmaceutical innovation had with premature mortality from all diseases in Switzerland during the period 1996–2018, and its association with hospital utilization for all diseases in Switzerland during the period 2002–2019. The analysis is performed by investigating whether the diseases that experienced more pharmaceutical innovation had larger subsequent declines in premature mortality and hospitalization. Pharmaceutical innovation is measured by the growth in the number of drugs used to treat a disease ever registered in Switzerland. Utilization of a chemical substance reaches a peak 9–12 years after it was first launched, and then declines. Our estimates indicate that the number of years of potential life lost before ages 85, 75, and 65 is significantly inversely related to the number of chemical substances ever registered 6–9, 3–9, and 0–9 years earlier, respectively. The new chemical substances that were registered during the period 1990–2011 are associated with reductions in the number of years of potential life lost before ages 85, 75, and 65 in 2018 of 257 thousand, 163 thousand, and 102 thousand, respectively. The number of hospital days is significantly inversely related to the number of chemical substances ever registered 8–10 years earlier. The new chemical substances that were registered during the period 1994–2010 are associated with reductions in the number of hospital days in 2019 of 2.07 million. Average length of inpatient hospital stays is significantly inversely related to the number of chemical substances ever registered 2–10 years earlier. The new chemical substances that were registered during the period 1999–2015 are associated with reductions in the average length of stays in 2019 of 0.4 days. Under the assumption that pharmaceutical innovation is exogenous with respect to premature mortality and hospitalization, and that it is uncorrelated with other potential determinants of health outcomes, if we ignore the reduction in hospital utilization associated with previous pharmaceutical innovation, a rough estimate of the cost per life-year before age 85 gained in 2018 is € 14,310. However, about 85% of the 2018 expenditure on drugs registered during the period 1990–2011 may have been offset by the reduction in expenditure on inpatient curative and rehabilitative care. The net cost per life-year before age 85 gained in 2018 may therefore have been € 2201.