bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Not at target’: prevalence and consequences of inadequate disease control in systemic lupus erythematosus—a multinational observational cohort study
Authors: Kandane-Rathnayake Rangi , Louthrenoo Worawit , Hoi Alberta , Luo Shue-Fen , Wu Yeong-Jian J. , Chen Yi-Hsing , Cho Jiacai , Lateef Aisha , Hamijoyo Laniyati , Navarra Sandra V. , Zamora Leonid , Sockalingam Sargunan , An Yuan , Li Zhanguo , Katsumata Yasuhiro , Harigai Masayoshi , Hao Yanjie , Zhang Zhuoli , Kikuchi Jun , Takeuchi Tsutomu , Basnayake B. M. D. B. , Chan Madelynn , Ng Kristine Pek Ling , Tugnet Nicola , Kumar Sunil , Oon Shereen , Goldblatt Fiona , O’Neill Sean , Gibson Kathryn A. , Ohkubo Naoaki , Tanaka Yoshiya , Bae Sang-Cheol , Lau Chak Sing , Nikpour Mandana , Golder Vera , Morand Eric F. ,   For the Asia-Pacific Lupus Collaboration
Published: March 2022

Background

The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes.

Methods

Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K ≥10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI).

Results

A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9]; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI] = 4.98 [2.07, 12.0], p<0.001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI] = 5.45 [2.75, 10.8], p<0.001) patients.

Conclusion

Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.
Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes
Authors: Seyres Denis , Cabassi Alessandra , Lambourne John J. , Burden Frances , Farrow Samantha , McKinney Harriet , Batista Joana , Kempster Carly , Pietzner Maik , Slingsby Oliver , Cao Thong Huy , Quinn Paulene A. , Stefanucci Luca , Sims Matthew C. , Rehnstrom Karola , Adams Claire L. , Frary Amy , Ergüener Bekir , Kreuzhuber Roman , Mocciaro Gabriele , D’Amore Simona , Koulman Albert , Grassi Luigi , Griffin Julian L. , Ng Leong Loke , Park Adrian , Savage David B. , Langenberg Claudia , Bock Christoph , Downes Kate , Wareham Nicholas J. , Allison Michael , Vacca Michele , Kirk Paul D. W. , Frontini Mattia
Published: March 2022

Background

This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature.

Methods/results

We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention.

Conclusions

We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.
Liver infarctions as the first manifestation of antiphospholipid antibody syndrome in pregnancy: a case report
Authors: Meloni Claudia , Schreiber Cornelia , Studt Jan-Dirk , Kamm Simone , Di Chiara Manuela , Herren Thomas
Published: March 2022

Background

The differential diagnosis of abdominal pain in pregnant women is broad. Liver diseases as the origin of abdominal pain in pregnancy are rare, and severe forms occur in less than 0.1% of pregnancies. Some disorders, such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and preeclampsia, are unique to pregnancy, while others, such as antiphospholipid antibody syndrome, may manifest in pregnancy but have consequences beyond the current pregnancy. All of them require prompt identification and treatment.

Case presentation

A 27-year-old Caucasian woman who was 15+1 weeks pregnant reported to the emergency department twice due to stabbing right-upper-quadrant abdominal pain. Initial laboratory testing revealed mild leukocytosis and slightly elevated liver enzymes. On second presentation, the patient was febrile and had an increased C-reactive protein concentration. Over the course of the next days, nonhemolytic anemia and thrombocytopenia emerged with elevated liver enzymes. Coagulation studies also revealed a prolongation of activated partial thromboplastin time. Magnetic resonance imaging showed nonspecific alterations in the right liver lobe, possibly corresponding to infection or infarction. A hepatic viral infection was ruled out. At that time, the most likely diagnosis was cholangitis with liver abscess formation, and antibiotic therapy was started. Further worsening of the anemia and thrombocytopenia, development of proteinuria, together with a miscarriage on the fourth day of hospitalization resulted in the tentative diagnosis of (triple-positive) antiphospholipid antibody syndrome, which was confirmed 12 weeks after the initial investigation. Treatment consisted of prompt anticoagulation with heparin and later on with a vitamin K antagonist as well as high-dose glucocorticoid therapy. There was no need for intravenous immunoglobulin therapy or plasma exchange, although we suspected a catastrophic form of antiphospholipid antibody syndrome due to infarctions of the liver, placenta, and possibly kidneys (proteinuria). The outcome was favorable.

Conclusion

We report a 27-year-old pregnant woman whose abdominal pain was caused by liver infarctions as the first manifestation of catastrophic antiphospholipid antibody syndrome. The antiphospholipid antibody syndrome was possibly secondary to hitherto clinically silent systemic lupus erythematosus since the antinuclear antibodies were increased later on. Hydroxychloroquine therapy was initiated to prevent antiphospholipid antibody syndrome recurrence in a future pregnancy.
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

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

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

In 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

In 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

The 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

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

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

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

Supercritical 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

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

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

We 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.
Efficacy and safety testing of a COVID-19 era emergency ventilator in a healthy rabbit lung model
Authors: White Luke A. , Maxey Benjamin S. , Solitro Giovanni F. , Takei Hidehiro , Conrad Steven A. , Alexander J. Steven
Published: March 2022

Background

The COVID-19 pandemic revealed a substantial and unmet need for low-cost, easily accessible mechanical ventilation strategies for use in medical resource-challenged areas. Internationally, several groups developed non-conventional COVID-19 era emergency ventilator strategies as a stopgap measure when conventional ventilators were unavailable. Here, we compared our FALCON emergency ventilator in a rabbit model and compared its safety and functionality to conventional mechanical ventilation.

Methods

New Zealand white rabbits (n = 5) received mechanical ventilation from both the FALCON and a conventional mechanical ventilator (Engström Carestation™) for 1 h each. Airflow and pressure, blood O2 saturation, end tidal CO2, and arterial blood gas measurements were measured. Additionally, gross and histological lung samples were compared to spontaneously breathing rabbits (n = 3) to assess signs of ventilator induced lung injury.

Results

All rabbits were successfully ventilated with the FALCON. At identical ventilator settings, tidal volumes, pressures, and respiratory rates were similar between both ventilators, but the inspiratory to expiratory ratio was lower using the FALCON. End tidal CO2 was significantly higher on the FALCON, and arterial blood gas measurements demonstrated lower arterial partial pressure of O2 at 30 min and higher arterial partial pressure of CO2 at 30 and 60 min using the FALCON. However, when ventilated at higher respiratory rates, we observed a stepwise decrease in end tidal CO2. Poincaré plot analysis demonstrated small but significant increases in short-term and long-term variation of peak inspiratory pressure generation from the FALCON. Wet to dry lung weight and lung injury scoring between the mechanically ventilated and spontaneously breathing rabbits were similar.

Conclusions

Although conventional ventilators are always preferable outside of emergency use, the FALCON ventilator safely and effectively ventilated healthy rabbits without lung injury. Emergency ventilation using accessible and inexpensive strategies like the FALCON may be useful for communities with low access to medical resources and as a backup form of emergency ventilation.
Microbial community composition, dynamics, and biogeochemistry during the start-up of a partial nitritation-anammox pathway in an upflow reactor
Authors: Ribeiro Hugo , Wijaya I. Made W. , Soares-Santos Verónica , Soedjono Eddy Setiadi , Slamet Agus , Teixeira Catarina , Bordalo Adriano A.
Published: March 2022

The dynamics of the microbial community and functional taxa related to nitrogen (N) removal biogeochemical processes can be important to the development of new cost-effective processes in wastewater treatment. This work consisted of the start-up of an upflow reactor for N-removal by partial nitritation/anammox pathway, working at ambient temperature, during 397 d. After an adaptation to the reactor operational conditions, a stable total N-removal (52% efficiency) was linked to ammonium deletion. High-throughput sequencing of 16S rRNA gene amplicons analysis revealed a relative abundance of about 1% of anammox genus Candidatus Brocadia after 397 d. Nitrosomonas, a nitrifying bacterium also increased the relative abundance, together with the accretion of relative numbers of Denitratisoma and Thiobacillus, recognized as heterotrophic and chemolithoautotrophic denitrifying bacteria, respectively. These findings provide a better understanding of the N-removal by key microbial groups that may be useful to optimize future field application of systems working at ambient temperature.
Agreement and accuracy of radiographic assessment using a decision aid for medial Oxford partial knee replacement: multicentre study
Authors: Hiranaka Takafumi , Furuhashi Ryosuke , Takashiba Kenichiro , Kodama Takao , Michishita Kazuhiko , Inui Hiroshi , Togashi Eita
Published: March 2022

Background

Indication for mobile-bearing partial knee replacement (PKR) is made on the basis of a radiological decision aid. This study aimed to reveal the inter-rater reproducibility and accuracy of the decision aid when used by experienced surgeons.

Patients and methods

Anonymised radiographic image sets (anteroposterior, lateral, varus/valgus stress in 20° knee flexion, and skyline views) from 20 consecutive patients who underwent knee replacement were assessed by 12 experienced surgeons. Agreements of each section and accuracy were compared by intra-operative inspection of the status of the anterior cruciate ligament (ACL) and medial and lateral cartilage according to the protocol of Radiographic Assessment for Medial Oxford PKR. Fleiss’ kappa (κ) values were used as a statistical measure.

Results

Full-thickness medial cartilage had the best agreement between the surgeons (κ = 94.7%) and best accuracy (94.2%). Although functioning ACL (90.8%), intact cartilage (91.7%) and full-thickness lateral cartilage defects (86.1%) were accurately diagnosed, diagnoses of deficient ACL (up to 42.5%) and partial-thickness lateral cartilage defects (11.7%) were poor; they were sometimes misdiagnosed as being intact. Moreover, agreement of lateral and valgus stress radiographs regarding intact MCL function, as well as the overall decision, was considered to be inadequate (κ = 0.47, 0.58 and 0.51, respectively).

Conclusions

Although the radiological aid is useful for selection of patients who are likely to be suitable for PKR, surgeons should still carefully assess the lateral weight-bearing area for partial-thickness loss and deficiency of the ACL because they were sometimes overlooked by surgeons using radiographs. MRI will be helpful to improve the accuracy of determination of Oxford PKR indication.
Association of CDKN2A/B gene polymorphisms (rs10811661 and rs2383208) with type 2 diabetes mellitus in a sample of Iraqi population
Authors: Fadheel Hussein K. , Kaftan Ahmed N. , Naser Farah H. , Hussain Majid K. , Algenabi Abdul Hussein A. , Mohammad Hamza J. , Al-Kashwan Thekra A.
Published: March 2022

Background

Type 2 diabetes mellitus (T2DM) is chronic metabolic disorder manifested by increased blood glucose (hyperglycemia) due to pancreatic β-cell dysfunction and/or decreased sensitivity of peripheral tissue to insulin. T2DM is a multifactorial disease that may results from interaction of environmental and genetic factors.

Methods

A case–control study consisting of 400 T2DM patients in addition to 400 as control. Phenotyping as well as anthropometric data included body mass index BMI, fasting plasma glucose (FPG), serum total cholesterol, serum triglyceride, VLDL, LDL, HDL insulin levels and Homeostatic Model Assessment for Insulin Resistance HOMA-IR were estimated for the two groups. PCR–RFLP was used to carry out genotyping of CDKN2A/B gene (rs10811661 T>C and rs2383208 A>G) SNPs.

Results

For rs10811661 SNP the genotype and allele frequencies of CDKN2A/B gene for T2DM and control subjects showed that the co-dominant model in patients with the homozygous (TT) was found to be significantly (OR 2.51, 95% CI 1.47–4.24, P 0.004) higher than those in control group. In contrast, the heterozygous genotype (TC) did not reveal this significance (OR 1.14, 95% CI 0.77–2.62, P = 0.13), ANOVA test for mean comparison of biochemical markers under the co-dominant model of rs10811661 SNP genotype in CDKN2A/B gene, revealed a significant difference for insulin (P < 0.0001) and HOMA-IR (P < 0.0001) in T2DM group as compared to control one; However (rs2383208) SNP did not show any significant association with T2DM and with the measured biochemical marker at any model.

Conclusions

CDKN2A/B gene rs10811661 SNP was implicated in T2DM pathogenesis in this sample of Iraqi population also it affects insulin level in those patients, whereas the rs2383208 SNP did not impact the disease.
A softened membrane model for single-box multi-cell composite box-girders with corrugated steel webs under pure torsion
Authors: Shen Kongjian , Wan Shui , Zhu Yingbo , Lyu Debao , Wu Zhiqiang
Published: March 2022

To analyze the nonlinear torsional behavior of single-box multi-cell prestressed concrete (PC) or reinforced concrete (RC) composite box-girders with corrugated steel webs (BGCSWs), a new theoretical model called unified softened membrane model for torsion (USMMT) is proposed in this study. It is developed from the softened membrane model for torsion which was formerly proposed for the torsional analysis of single-box single-cell PC/RC composite BGCSWs. This proposed model incorporates the different contributions of inner and outer corrugated steel webs (CSWs) in the multi-cell BGCSW to the torsional capacity by introducing a rational relationship of shear strains between inner CSWs and outer CSWs. The satisfactory accuracy of the proposed model is obtained when comparing with the experimental and the finite element analysis results, including the torque-twist curves and the smeared shear strains in concrete slabs and CSWs in the full-range torsional analysis. The comparison indicates that the proposed model is capable of predicting the overall torsional behavior of single-box multi-cell BGCSWs.
A Data-Driven Approach to Predicting 5-Aminolevulinic Acid–Induced Fluorescence and World Health Organization Grade in Newly Diagnosed Diffuse Gliomas
Authors: Müther Michael , Jaber Mohammed , Johnson Timothy D. , Orringer Daniel A. , Stummer Walter
Published: March 2022

BACKGROUND:

A growing body of evidence has revealed the potential utility of 5-aminolevulinic acid (5-ALA) as a surgical adjunct in selected lower-grade gliomas. However, a reliable means of identifying which lower-grade gliomas will fluoresce has not been established.

OBJECTIVE:

To identify clinical and radiological factors predictive of intraoperative fluorescence in intermediate-grade gliomas. In addition, given that higher-grade gliomas are more likely to fluoresce than lower-grade gliomas, we also sought to develop a means of predicting glioma grade.

METHODS:

We investigated a cohort of patients with grade II and grade III gliomas who received 5-ALA before resection at a single institution. Using a logistic regression-based model, we evaluated 14 clinical and molecular variables considered plausible determinants of fluorescence. We then distilled the most predictive features to develop a model for predicting both fluorescence and tumor grade. We also explored the relationship between intraoperative fluorescence and diagnostic molecular markers.

RESULTS:

One hundered seventy-nine subjects were eligible for inclusion. Our logistic regression classifier accurately predicted intraoperative fluorescence in our cohort with 91.9% accuracy and revealed enhancement as the singular variable in determining intraoperative fluorescence. There was a direct relationship between enhancement on MRI and the likelihood of observed fluorescence. Observed fluorescence correlated with MIB-1 index but not with isocitrate dehydrogenase (IDH) status, 1p19q codeletion, or methylguanine DNA methyltransferase promoter methylation.

CONCLUSION:

We demonstrate a strong correlation between enhancement on preoperative MRI and the likelihood of visible fluorescence during surgery in patients with intermediate-grade glioma. Our analysis provides a robust method for predicting 5-ALA–induced fluorescence in patients with grade II and grade III gliomas.
Role of visceral fat areas defined by thoracic CT in acute pulmonary embolism
Authors: Meyer Hans-Jonas , Benkert Franz , Bailis Nikolaos , Lerche Marianne , Surov Alexey
Published: March 2022

Objective:

Visceral adipose tissue (VAT) has been established as an important parameter of body composition. It can be assessed by imaging modalities like computed tomography (CT). The purpose of the present study was to analyse the prognostic role of VAT derived from thoracic CT in patients with acute pulmonary embolism (PE).

Methods:

The clinical database of our center was retrospectively screened for patients with acute PE between 2014 and 2017. Overall, 184 patients were included into the analysis. VAT was assessed on axial slices of the thoracic CT at the level of the first lumbar vertebra. Clinical scores, serological parameters, need for intubation, ICU admission and 30 days mortality were assessed.

Results:

Using the previously reported threshold of 100 cm² for visceral obesity definition 136 (73.9%), patients were considered as visceral obese. There was a moderate correlation between VAT and BMI (r = 0.56, p < 0.0001). There was also a moderate correlation between VAT and body height (r = 0.41, p =< 0.0001). Of all investigated clinical scores relating to acute PE, only the GENEVA score correlated weakly with VAT (r = 0.15, p = 0.04). There were significant correlations between VAT and creatinine (r = 0.38, p < 0.0001) and Glomerular filtration rate (r = −0.21, p = 0.005). No associations were identified for VAT and mortality or visceral obesity and mortality.

Conclusion:

VAT was not associated with mortality in patients with acute pulmonary embolism.

Advances in knowledge:

Visceral obesity is frequent in patients with acute pulmonary embolism but it is not associated with mortality.
Η παραγωγή ταινιών από τα παιδιά με τη μέθοδο του project με βάση το θεωρητικό πλαίσιο της Κριτικής Παιδαγωγικής
Authors: Χατζηθεοδωρίδου Μαρία
Published: March 2022

Η παρούσα διατριβή αφορά μία παρέμβαση που ξεκίνησε με τα παιδιά της Στ΄ τάξης που είχε η ερευνήτρια το σχολικό έτος 2011-2012 σε ένα σχολείο της Ανατολικής Θεσσαλονίκης, αποσκοπώντας στον κριτικό γραμματισμό στα μέσα διαμέσου τόσο της θέασης και ανάλυσης ταινιών, αλλά κύρια της παραγωγής ταινιών από τα ίδια. Από τα παιδιά αυτά καταδείχτηκε μία βασική ομάδα που συνέχισαν την παρέμβαση μέχρι και τον Ιούνιο του 2017 που ολοκληρώθηκε. Σε σύντομο χρονικό διάστημα, προστέθηκαν στη βασική ομάδα και άλλα τρία παιδιά. Σκοπός της διατριβής ήταν η διερεύνηση της ενδεχόμενης αλλαγής της στάσης των συμμετεχόντων, όπως και της δράσης και της κοινωνικής τους παρέμβασης. Η παρέμβαση διενεργήθηκε με τη μέθοδο του project με βάση το θεωρητικό πλαίσιο της Κριτικής Παιδαγωγικής, ενώ και ο Κριτικός Γραμματισμός στα Μέσα βασίζεται στο ίδιο θεωρητικό πλαίσιο. Ο ρόλος της ερευνήτριας στην ομάδα ήταν συμμετέχουσα ως παρατηρήτρια. Τη δεύτερη χρονιά 2012-2013, προστέθηκε στην ομάδα ως συνεργάτιδα της ερευνήτριας, μία συνάδελφος εκπαιδευτικός, η οποία λειτουργούσε και ως δεύτερη συμμετέχουσα ως παρατηρήτρια. Παράλληλα, μία τρίτη εκπαιδευτικός και θεατρολόγος, λειτουργούσε επίσης ως συνεργάτιδα όταν κατά τη διάρκεια της παρέμβασης γίνονταν θεατρικές δράσεις, κάνοντας τα διαγράμματα σχεδιασμού των δράσεων με βάση το θέατρο του καταπιεσμένου του Boal, καθώς στην έρευνα χρησιμοποιούνταν σε μεγάλο βαθμό τέτοιες δράσεις. Από την έρευνα καταδείχτηκε ότι τα παιδιά στο τέλος της παρέμβασης ανέπτυξαν σε σημαντικό βαθμό κριτική αυτονομία και κριτική συνειδητοποίηση, ενώ αλλαγές εντοπίστηκαν και στις στάσεις τους, στη δράση τους και στην κοινωνική τους παρέμβαση.
Socio-spatial transformation of neighbourhoods around rail transit stations: an experience from Tehran, Iran
Authors: Forouhar Amir , Zamani Bahador , Rafieian Mojtaba
Published: March 2022

While increasing evidence suggests that rail infrastructure plays a structuring role in shaping and transforming cities and regions over time, empirical studies on the simultaneous development of rail infrastructure and socio-spatial transformation of surrounding neighbourhoods, especially at a local scale, are scarce. The main aim of the article is to evaluate the transformation of neighbourhoods around rail transit stations, as well as provide a possible explanation of how neighbourhoods can be differently affected by the presence of rail stations. Based on a longitudinal dataset (2006–16) and using a Difference-in-Differences (DID) model and Multivariate Analysis of Variance (MANOVA), a comparative analysis of the Tehran Metro Rail System (TMRS) is conducted between high-income neighbourhoods and low-income neighbourhoods of the city. The results yield that the northern, high-income neighbourhoods and the southern, low-income neighbourhoods of Tehran have been transformed heterogeneously in terms of socio-demographic factors, land-use conditions and renewal processes. The findings also indicate that the mixed estimated transformation of neighbourhoods around TMRS’s stations could be explained by the contextual factors of the northern and southern study settings in Tehran, including land-use characteristics and socio-economic factors.