bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Mammary Tumor Virus, Human Papilloma Virus, and Epstein-Barr Virus Infection Are Associated With Sporadic Breast Cancer Metastasis
Authors: Al Hamad Mohammad , Matalka Ismail , Al Zoubi Mazhar Salim , Armogida Ivana , Khasawneh Rawan , Al-Husaini Maysa , Sughayer Maher , Jaradat Saied , Al-Nasser Amjad D , Mazzanti Chiara Maria
Published: November 2020

Background:

Viral cause of sporadic breast cancer (SBC) has been suggested based on the experimental murine model of mammary tumor caused by mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and human papillomavirus (HPV). While some studies have demonstrated the presence of viral sequences of MMTV, HPV, and EBV in breast cancer cells, others failed. These contradictions may be attributed to the geographical distribution of breast cancer incidence and/or technical variations. In the current study, we aimed to investigate the correlation of MMTV, HPV, and EBV infections with the development of breast cancer in Jordanian patients.

Methods:

One hundred SBC tissue samples were subjected to laser capture microdissection for the selection of tumor cells populations. Fluorescence polymerase chain reaction (PCR) was used to detect the presence of the MMTV env-like sequences. Real-time PCR was used for HPV and EBV detection, and EBV was further confirmed by chromogen in situ hybridization (CISH).

Results:

Mouse mammary tumor virus, HPV, and EBV were detected in SBC in 11%, 21%, and 23%, respectively. Only 3 of 52 (5.7%) positive cases demonstrated multiple virus infections. However, 49 of 52 (94%) of the positive cases revealed the presence of 1 type of viral sequences. Consequently, 52% of the studied breast cancer cases were infected with at least 1 type of the aforementioned viruses.

Conclusions:

The current cohort suggests that MMTV, HPV, and EBV have a potential role in the development of breast cancer and adding more reasons to proceed with the quest of a possible viral origin of breast cancer.
Alcohol lean burn in heavy duty engines: Achieving 25 bar IMEP with high efficiency in spark ignited operation
Authors: Mahendar Senthil Krishnan , Larsson Tara , Erlandsson Anders Christiansen
Published: November 2020

Knock is the most crucial limitation in attaining the peak load required at high efficiency in heavy duty (HD) spark ignition (SI) engines. Renewable fuels such as ethanol and methanol have high resistance to autoignition and can help overcome this limitation. To reduce knock and improve efficiency further, dilution can be used to add specific heat capacity and reduce combustion temperature. This work studied diluted combustion and knock characteristics of gasoline, ethanol, and methanol on a HD SI single cylinder engine for a wide load range. Ethanol and methanol displayed excellent knock resistance which allowed a peak gross IMEP of 25.1 and 26.8 bar respectively, compared to gasoline which only reached 8.3 bar at [Formula: see text]1.4 with a compression ratio of 13. Over 18% increase in gross IMEP was possible for gasoline and ethanol when increasing air excess ratio from 1 to 1.4. Methanol achieved the target gross IMEP at [Formula: see text]1 and required no spark retard at [Formula: see text]1.6. A peak indicated efficiency above 48% was recorded for ethanol and methanol at [Formula: see text]1.6 and gross IMEP of approximately 21 bar. At part loads, stable operation was possible until [Formula: see text]1.8 for all fuels. Increase in intake temperature showed a marginal improvement in stability but no increase in lean limit. The concept shows promise as diluted combustion of ethanol and methanol reduced knock and achieved diesel baseline load. With optimization, there is potential to improve efficiency further and possible cost savings compared to commercial diesel engines.
Numerical assessment of ozone addition potential in direct injection compression ignition engines
Authors: Giuffrida Vincent , Bardi Michele , Matrat Mickael , Robert Anthony , Pilla Guillaume
Published: November 2020

This paper aims at taking into account the chemistry of O3 in a 3D CFD simulation of compression ignition engine with Diesel type combustion for low load operating points. The methodology developed in this work includes 0D homogeneous reactors simulations, 3D RANS simulations and validation regarding experimental results. The 0D simulations were needed to take into account O3 reactions during the compression stroke because of the high reactivity of O3 with NO and dissociation at high temperature. The values found in these simulations were used as an input in the 3D model to match the correct O3 concentration at fuel injection timing. The 3D simulations were performed using CONVERGETM with a RANS approach. Simulations reproduce the compression/expansion stroke after the intake valve closure to focus on the impact of O3 on the fuel auto ignition. The comparison between numerical and experimental results demonstrates that the proposed methodology is able to capture correctly the impact of O3 addition on ignition delay and on heat release. Moreover, the analysis of the data enables to better understand the fundamental processes driving O3 impact in a CI engine. In particular, using 0D simulations, the plateau effect observed experimentally when increasing O3 concentration is attributed to O3 thermal decomposition and reaction with NO during the compression stroke. Also, 3D CFD results showed that O3 impact is observed mainly during LTHR phase and does not affect the topology and the propagation of the flame inside the combustion chamber.
Diabetes, metformin and glucose lowering therapies after myocardial infarction: Insights from the SWEDEHEART registry
Authors: Ritsinger Viveca , Lagerqvist Bo , Lundman Pia , Hagström Emil , Norhammar Anna
Published: November 2020

Objective:

To explore real-life use of glucose lowering drugs and prognosis after acute myocardial infarction (AMI) with a special focus on metformin.

Methods:

Patients ( n = 70270) admitted for AMI 2012–2017 were stratified by diabetes status and glucose lowering treatment and followed for mortality and MACE+ (AMI, heart failure (HF), stroke, mortality) until end of 2017 (mean follow-up time 3.4 ± 1.4 years) through linkage with national registries and SWEDEHEART. Hazard ratios (HR) were calculated in adjusted Cox proportional hazard regression models.

Results:

Mean age was 68 ± 11 years and 70% were male. Of patients with diabetes ( n = 16356; 23%), a majority had at least one glucose lowering drug (81%) of whom 51% had metformin (24% monotherapy), 43% insulin and a minority any SGLT2i/GLP-1 RA (5%). Adjusted HR for patients with versus without diabetes was 1.31 (95% CI 1.27–1.36) for MACE+ and 1.48 (1.41–1.56) for mortality. Adjusted HR for MACE+ for diabetes patients on metformin was 0.92 (0.85–0.997), p = 0.042 compared to diet treated diabetes.

Conclusion:

Diabetes still implies a high complication risk after AMI. Metformin and insulin were the most common treatment used in almost half of the diabetes population. Furthermore, patients treated with metformin had a lower cardiovascular risk after AMI and needs to be confirmed in prospective controlled trials.
Repeat pattern segmentation of print fabric based on adaptive template matching
Authors: Xiang Zhong , Zhou Ding , Qian Miao , Ma Miao , Liu Yang , Wu Zhenyu , Hu Xudong
Published: November 2020

Patterned fabrics are generally constructed from the periodic repetition of a primitive pattern unit. Repeat pattern segmentation of printed fabrics has a very significant impact on the pattern retrieval and pattern defect detection. In this paper, we propose a new approach for repeat pattern segmentation by employing the adaptive template matching method. In contrast to the traditional method for template matching, the proposed algorithm first selects an adaptive size template image in the repeat pattern image based on the size of the original image and its local maximum edge density. Then it uses the sum of absolute differences as the matching features to identify the matched regions in the original image, and the minimum envelope border of the primitive pattern, typically as a parallelogram, can be determined from the results of the four adjacent matched templates. Finally, image traversal base on the obtained parallelogram is implemented over the original image using minimum information loss theory to produce a well-segmented primitive pattern with a complete edge structure. The results from the experiments conducted using an extensive database of real fabric images show that the proposed algorithm has the advantage of rotation invariance and scaling invariance and will not be affected when the background or foreground color is changed.
Shape adaptation of beams (1D) and plates (2D) to maximise eigenfrequencies
Authors: Andresen Simone , Lottes Laura M , Linnemann Selina K , Kienzler Reinhold
Published: November 2020

Finding the optimal structural design to avoid resonance has been a goal for decades. While recent applied methods often result in using additional active systems or higher mass, structural adaptation enables to shift eigenfrequencies without adding weight. The aim of this study is to investigate the influence of the structural adaptation of a beam and a plate on its eigenfrequency change, while varying the height of the structural pre-deformation according to its mode shapes. Besides the maximisation of single eigenfrequencies, also the simultaneous increase of multiple eigenfrequencies is analysed. It is possible to almost exclusively raise the frequency of the targeted [Formula: see text]-th mode shape ([Formula: see text] = 1–5) of a beam, while the increase of the [Formula: see text]-th plate mode shape frequency ([Formula: see text] = 1–4) simultaneously alters other eigenfrequencies. Both the eigenfrequencies and specific mode shape frequencies are able to be significantly increased. In conclusion, the investigated, easy applicable method allows a strong eigenfrequency raise of axially constrained 1D and 2D structures by performing only small structural deformations without adding additional weight.
Comparative analysis of cycloid pump based on CFD and fluid structure interactions
Authors: Yanhua Wang , Longlong Huang , Yong Liu , Jingsong Xu
Published: November 2020

At present, in the aspect of numerical simulation of cycloid pump, most studies focused on CFD (Computational Fluid Dynamics) in analyzing the pump performance under different service conditions (such as speed, temperature, etc.). The characteristics of the pump under FSI (Fluid Solid Interaction) have not been considered yet. By means of the dynamic mesh technique in the rotating domain, the fluid structure coupling interface is set up on a cycloidal pump model building in COMSOL. The simulation results obtained by applying CFD and FSI are improved by experimental verification. The results show that: (1) the average flow rate of FSI simulation is closer to the test results, and the mean values of CFD and FSI pressure are closer to the actual outlet boundary settings; (2) by comparing the velocity and pressure of rotation region of CFD and FSI at different temperatures, it is concluded that the pressure CFD calculated in the region is more than FSI, and the velocity CFD calculated is less than FSI; (3) by comparing the pressure distribution at some contact point of the fluid structure coupling interface, it is concluded that the fluctuation value of the pressure of CFD with time is greater than that of FSI. Through the comparison, it is found that the coupling has a great influence on the calculation results. The FSI analysis of the pump makes the analysis results more real and more conducive to the analysis of the flow field and rotor dynamics characteristics of the pump.
Communities as asset: Using positive communication to enhance the holistic well-being of South Africans
Authors: Polk Denise M , Pollino Madison A
Published: November 2020

Young South Africans who live in contexts of poverty face many challenges and obstacles in their attempts to rise out of their circumstances. However, adding support in the form of well-being teams who take ownership of promoting well-being may facilitate resilience and serve an important supportive function. Four different well-being teams participated in a focus group interview. They consisted of teachers, learners, parents, and a mixed group. The theory of positive communication provided a framework to understand the themes that emerged. Therefore, in an effort to level the playing field for these young South Africans, the educational system should create more spaces that enable and facilitate learning and that promote positive communication.
MiR-30a-5p ameliorates LPS-induced inflammatory injury in human A549 cells and mice via targeting RUNX2
Authors: Li Pibao , Yao Yanfen , Ma Yuezhen , Chen Yanbin
Published: November 2020

In this study, we aim to investigate the role of miR-30a-5p in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) using LPS-induced A549 cells and mice. We found cell viability was significantly declined accompanied by cell apoptosis and cell cycle arrest at G0/G1 phase in LPS-treated A549 cells. MiR-30a-5p was down-regulated by LPS treatment and miR-30a-5p significantly protected A549 cells from LPS-induced injury by increasing cell viability, reducing cell apoptosis, promoting cell cycle progression, and inhibiting inflammatory reactions. Dual-luciferase activity demonstrated that RUNX2 was a direct target for miR-30a-5p and its expression was negatively and directly regulated by miR-30a-5p. Over-expression of RUNX2 weakened the inhibitory effect of miR-30a-5p on inflammatory injury. In vivo, over-expression of miR-30a-5p alleviated LPS-induced inflammatory responses and lung injury in LPS-administrated mice. Besides, miR-30a-5p repressed LPS-elevated phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK), IκBα degradation, and NF-κB p65 phosphorylation. In conclusion, miR-30a-5p ameliorates LPS-induced inflammatory injury in A549 cells and mice via targeting RUNX2 and related signaling pathways, thereby influencing the progression of ARDS.
Targeting neutrophil extracellular traps in severe acute pancreatitis treatment
Authors: Hu Jing , Kang Hongxin , Chen Huan , Yao Jiaqi , Yi Xiaolin , Tang Wenfu , Wan Meihua
Published: November 2020

Severe acute pancreatitis (SAP) is a critical abdominal disease associated with high death rates. A systemic inflammatory response promotes disease progression, resulting in multiple organ dysfunction. The functions of neutrophils in the pathology of SAP have been presumed traditionally to be activation of chemokine and cytokine cascades accompanying the inflammatory process. Recently, since their discovery, a new type of antimicrobial mechanism, neutrophil extracellular traps (NETs), and their role in SAP, has attracted widespread attention from the scientific community. Significantly different from phagocytosis and degranulation, NETs kill extracellular microorganisms by releasing DNA fibers decorated with granular proteins. In addition to their strong antimicrobial functions, NETs participate in the pathophysiological process of many noninfectious diseases. In SAP, NETs injure normal tissues under inflammatory stress, which is associated with the activation of inflammatory cells, to cause an inflammatory cascade, and SAP products also trigger NET formation. Thus, due to the interaction between NET generation and SAP, a treatment targeting NETs might become a key point in SAP therapy. In this review, we summarize the mechanism of NETs in protecting the host from pathogen invasion, the stimulus that triggers NET formation, organ injury associated with SAP involving NETs, methods to interrupt the harmful effects of NETs, and different therapeutic strategies to preserve the organ function of patients with SAP by targeting NETs.
The ethics and politics of migration research
Authors: Jacobsen Malene H , Gilmartin Mary
Published: November 2020

In this response, we caution against making ‘irregular migrants’ the object of investigation. Instead, we suggest that a focus on encounters, rather than on becoming, offers a more productive and ethical approach. By considering the relationality of affective and ethical encounters, we can identify not only how migrants become subject to particular state categories, but also how these encounters shape people’s ways of knowing the state and each other. This knowledge is situated, embodied, and—most importantly—offers the possibility for political action and change.
Disrupting the library: Digital scholarship and Big Data at the National Library of Scotland
Authors: Ames Sarah , Lewis Stuart
Published: November 2020

With a mass digitisation programme underway and the addition of non-print legal deposit and web archive collections, the National Library of Scotland is now both producing and collecting data at an unprecedented rate, with over 5PB of storage in the Library’s data centres. As well as the opportunities to support large scale analysis of the collections, this also presents new challenges around data management, storage, rights, formats, skills and access. Furthermore, by assuming the role of both creators and collectors, libraries face broader questions about the concepts of ‘collections' and ‘heritage', and the ethical implications of collecting practices. While the ‘collections as data’ movement has encouraged cultural heritage organisations to present collections in machine-readable formats, new services, processes and tools also need to be established to enable these emerging forms of research, and new modes of working need to be established to take into account an increasing need for transparency around the creation and presentation of digital collections. This commentary explores the National Library of Scotland's new digital scholarship service, the implications of this new activity and the obstacles that libraries encounter when navigating a world of Big Data.
Does the Homeownership Gap Between Rural–Urban Migrants and Urban–Urban Migrants in China Vary by Income?
Authors: Ming Juan , Liu Jiachun , Wang Zicheng
Published: November 2020

Rural–urban migrants in China often experience poor living conditions and are less likely to be homeowners than urban–urban migrants. This study aims to investigate whether the homeownership gap between rural–urban migrants and urban–urban migrants in China vary by income. We explore the homeownership gap between the two migrant groups using the National Migrants Population Dynamic Monitoring Survey in 2014. Our findings show that the homeownership gap between rural–urban migrants and urban–urban migrants vary by income, and this gap is larger for high-income groups than for low-income groups. The estimations also demonstrate that social security insurance may act as the transmission channel, indicating a stratification process.
Relationship-Centered Care in a Novel Dual-Visit Model COVID Nursery Follow-Up Clinic
Authors: Saslaw Minna , Glassman Melissa E , Keown M Kathleen , Orange Jordan , Stockwell Melissa S
Published: November 2020

The COVID Nursery Follow-Up Clinic at our academic medical center in New York City was established during the COVID-19 pandemic to provide care to infants born to SARS-CoV-2 positive mothers. We describe a novel dual-visit model utilizing telehealth and an in-person visit to provide timely, inclusive and relationship-centered care to the mother/infant couplet in a situation where the mother was unable to come to a traditional in-person visit, but the infant needed medically necessary in-person evaluation.
Regeneration of Corticospinal Axons into Neural Progenitor Cell Grafts After Spinal Cord Injury
Authors: Poplawski Gunnar HD , Tuszynski Mark H
Published: November 2020

Spinal cord injuries leave patients with lifelong paralysis. To date, there are no therapies that promote the critical step required for the recovery of voluntary motor function: corticospinal axon regeneration. Spinal cord-derived neural progenitor cell (NPC) grafts integrate into the injured host spinal cord, enable robust corticospinal axon regeneration, and restore forelimb function following spinal cord injury in rodents. Consequently, engineered stem cell differentiation and transplantation techniques harbor promising potential for the design and implementation of therapies promoting corticospinal axon regeneration. However, in order to optimize the outcome of clinical trials, it is critical to fully understand the cellular and molecular mechanisms underlying this regeneration. Our recent study highlights the unexpected intrinsic potential of corticospinal neurons to regenerate and allows us to investigate new hypotheses exploiting this newly discovered potential.
Label-free quantitative proteomic analysis of insect larval and metamorphic molts
Authors: Si Weiye , Wang Qingjie , Li Yu , Dong Dujuan
Published: November 2020

Background

Molting is an essential biological process occurring characteristic times throughout the life cycle of holometabolous insects. However, it is not clear how insects determine the direction of molting to remain status quo or to initiate metamorphosis. To explore the functional factors that determine the direction of molts, liquid chromatography-mass spectrometry was used to identify the molecules involved in larval and metamorphic molting, and the differentially expressed proteins (DEPs) were compared in the two processes.

Results

There were 321 and 1140 DEPs identified in larval and metamorphic molting process, respectively. Bioinformatics analyses show that the amino sugar pathway was up-regulated in both processes. The up-regulated protease contributed to the metamorphosis. In addition, several proteins with different expression patterns in larval-larval and larval-pupal transitions, including Endochitinase, GRIM-19 (Genes associated with retinoid-IFN-induced mortality-19), IDE (Insulin-degrading enzyme), Sorcin (Soluble resistance related calcium binding protein), OBP (Odorant-binding protein-2 precursor), TRAP1(Tumor necrosis factor receptor associated protein-1), etc., were further identified by parallel reaction monitoring, which may play diverse functions in larval-larval and larval-pupal transitions.

Conclusions

These results provide a proteomic insight into molecules involved in larval and metamorphic molts, and will likely improve the current understanding of determination of direction of molts.
Metabolic healthy obesity is associated with higher incidence of mild decrease estimate glomerular rate in rural northeast Chinese
Authors: Yu Shasha , Guo Xiaofan , Li Guang Xiao , Yang Hongmei , Zheng Liqiang , Sun Yingxian
Published: November 2020

Background

Metabolic healthy obesity (MHO), a phenotype of obesity, seems to be associated with a lower risk of cardiovascular disease. However, MHO has a close relationship with a higher incidence of metabolic syndrome and diabetes. This study aimed to investigate the prevalence of MHO at baseline, the changes in the obese metabolic phenotype at follow-up and the relationship of this phenotype with the incidence of mildly reduced estimated glomerular filtration rate (eGFR) in rural Northeast Chinese.

Methods

The Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to calculate eGFR. A total of 4903 participants aged ≥35 years with eGFR > 90 ml/min/1.73 m2 at baseline were enrolled and successfully followed. All participants completed the questionnaires, anthropometric measurements, and blood tests during baseline and follow-up. Mild renal dysfunction was defined as mildly reduced eGFR between 60 and 90 ml/min/1.73 m2.

Results

The prevalence of MHO was 20.0% at baseline (19.0% for women and 21.1% for men), which was secondary to metabolic abnormal obesity (MAO) (24.4, 27.2% for women and 21.5% for men). A total of 38.4% of women and 38.9% of men experienced phenotypic changes during follow-up. The cumulative incidence of mildly reduced eGFR in the MHO group was 20.1% (17.7% for women and 22.3% for men), which was also secondary to the incidence in the MAO group (20.8, 18.6% for women and 23.5% for men). After adjusting for age, current smoking, current drinking, chronic diseases, LDL-C, ALT, and AST, MHO was associated with a higher incidence of mildly reduced eGFR among women [OR (95% CI) =1.6 (1.2, 2.3)] and men [OR (95% CI) =1.6(1.2, 2.1)], whereas MAO was related to a higher incidence of mildly reduced eGFR among men only [OR (95% CI) =1.7 (1.3, 2.3)].

Conclusion

MHO was associated with a higher incidence of mildly reduced eGFR in both sexes; however, there was a specific relationship between MAO and mildly reduced eGFR in men only. Therefore, it is necessary to monitor kidney function among participants with both MHO and MAO.
Haploidentical related donor compared to HLA-identical donor transplantation for chemosensitive Hodgkin lymphoma patients
Authors: Castagna Luca , Busca Alessandro , Bramanti Stefania , Raiola Anna Maria , Malagola Michele , Ciceri Fabio , Arcese William , Vallisa Daniele , Patriarca Francesca , Specchia Giorgina , Raimondi Roberto , Devillier Raynier , Furst Sabine , Giordano Laura , Sarina Barbara , Mariotti Jacopo , Olivieri Attilio , Bouabdallah Reda , Carlo-Stella Carmelo , Rambaldi Alessandro , Santoro Armando , Corradini Paolo , Bacigalupo Andrea , Bonifazi Francesca , Blaise Didier
Published: November 2020

Background

Allogeneic stem cell transplantation from haploidentical donor using an unmanipulated graft and post-transplantation cyclophosphamide (PT-Cy) is growing. Haploidentical transplantation with PT-Cy showed a major activity in Hodgkin lymphoma (HL), reducing the relapse incidence. The most important predictive factor of survival and toxicity was disease status before transplantation, which was better in patients with well controlled disease.

Methods

We included 198 HL in complete (CR) or partial remission (PR) before transplantation. Sixty-five patients were transplanted from haploidentical donor and 133 from a HLA identical donor (both sibling and unrelated donors). Survival analysis was defined according to the EBMT criteria. Survival curves were generated by using Kaplan-Meier method and differences between groups were compared by the log rank test or by the log rank test for trend when appropriated.

Results

The PFS, OS, and RI were significantly better in patients in CR compared to PR (55% vs 29% p = 0.001, 74% vs 55% p = 0.03, 27% vs 55% p <  0.001, respectively). The 2-year PFS was significantly better for HAPLO than HLA-id (63% vs 37%, p = 0.03), without difference in OS. The 1-year NRM was not different. The 2-year relapse incidence (RI) was lower in the HAPLO group (24% vs 44%, p = 0.008). Patients in CR receiving haplo HSCT showed higher 2-year PFS and lower 2-year RI than those allografted with HLA-id donor (75% vs 47%, p <  0.001 and 11% vs 34%, p < 0.001, respectively). In multivariate analysis, donor type and disease status before transplantation were independent predictors of PFS as well as they predict the risk of relapse. Disease status at transplantation and age were independently associated to OS.

Conclusions

Nonetheless this is a retrospective study, limiting the wide applicability of results, data from this analysis suggest that HLA mismatch can induce a strong graft versus lymphoma effect leading to an enhanced PFS.
Correction to: Neighborhood’s locality, road types, and residents’ multimorbidity: evidence from China’s middle-aged and older adults
Authors: Yu Xuexin , Zhang Wei
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Patient-reported outcome after patient-specific unicondylar knee arthroplasty for unicompartmental knee osteoarthritis
Authors: Freigang Viola , Rupp Markus , Pfeifer Christian , Worlicek Michael , Radke Stefan , Deckelmann Stephan , Alt Volker , Baumann Florian
Published: November 2020

Background

Unicondylar knee arthroplasty was introduced in the late 1960s and remains a topic of controversial discussion. Patient-specific instruments and patient-specific implants are not yet the standard of care. The question remains whether this time-consuming and costly technique can be beneficial for the patient. The aim of this study was to evaluate whether a custom-made unicondylar knee arthroplasty leads to improved patient-reported outcome.

Methods

This retrospective study evaluates the patient-reported outcome after custom-made unicondylar knee arthroplasty (CM-UKA, ConforMIS™ iUni® G2, ConforMIS Inc., Billerica, MA, USA). We evaluated 29 patients (31 knees) at an average of 2.4 years (range 1.2–3.6 years) after operation for unicondylar osteoarthritis of the knee. The target zone for the postoperative leg axis was a slight under-correction of 0–2° varus. Follow-up evaluation included the Forgotten Joint Score (FJS), the Knee Society Score (KSS), a Visual Analogue Scale (VAS) and a radiographic evaluation including a long-leg radiograph. Primary outcome measure was patient satisfaction based on the Forgotten Joint Score.

Results

We found an excellent postoperative health-related quality of life with a mean FJS of 76.8 (SD 17.9) indicating a low level of joint awareness after CM-UKA. The mean preoperative KSS was 66.0 (SD 13.71) and 59.4 (17.9) for the KSS function score. The increase was 22.8 points for the KSS knee score (p < 0.0001) and 34.8 points for the KSS function score (p < 0.0001). The VAS for pain decreased from a mean of 5.4 (SD 1.8) to 1.1 (SD 1.2) (p < 0.0001). The malalignment rate with a postoperative deviation of more than 2° in the leg axis was 29%. There was no evidence of component loosening after a mean follow-up of 2.4 years.

Conclusions

Custom-made unicondylar knee arthroplasty (CM-UKA) can provide improved clinical and functional outcomes for patients with isolated knee osteoarthritis of the medial compartment. We found excellent results regarding patient satisfaction and a low malalignment rate for CM-UKA. Further studies are needed to investigate long-term survivorship of the implant.

Level of evidence

Level IV.

Trial registration

Trial Registration number:Z-2014-0389-10Regensburg Clinical Studies Center (REGCSC) 09/07/2014.
Quantitative DCE-MRI: an efficient diagnostic technique for evaluating early micro-environment permeability changes in ankylosing spondylitis
Authors: Yang Hui , Jiang Ling , Li Jiang , Zheng Xiuzhu , Yao Qianqian , Li Changqin , Zhu Jianzhong , Qin Jian
Published: November 2020

Background

In the management of early inflammatory joint of ankylosing spondylitis (AS), there is a need for reliable noninvasive quantitative monitoring biomarker to closely assess status of synovitis progression. Cognizant to this,studies geared on improving techniques for quantitative evaluation of micro-environment permeability of the joint space are necessary. Such improved techniques may provide tissue perfusion as important biological parameters and can further help in understanding the origin of early changes associated with AS. The purpose of this study was to prospectively evaluate the diagnostic performance and determine longitudinal relationships of early micro-environment active in the joint space of the sacroiliac joint (SIJ) with a rat model by using quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Methods

Thirty wistar male rats were randomly assigned to the model (n = 15) or control (n = 15) group. All rats underwent DCE-MRI of SIJ region at fixed time points (12, 17 and 22 weeks),between September 2018 and October 2019. Differences in permeability parameters between the two groups at the same time point were compared by using an independent samples t test. Spearman correlations of DCE-MRI parameters with different time points in model group were analyzed. All statistical analyses were performed with software.

Results

At 12 weeks,the Ktrans,Kep and Ve values in the model group were slightly lower than those in control group,but all the differences were not statistically significant (p > 0.05). Compared with control group,the transfer constant (Ktrans) values increased significantly at 17 weeks and 22 weeks in model group,while the rate constant (Kep) and volume of extravascular extracellular space (Ve) significantly increased only at 22 weeks(p < 0.05). The Ktrans,Kep and Ve were positively correlated with increasing time points (r = 0.946, P<0.01 for Ktrans; r = 0.945, P<0.01 for Kep; and r = 0.832, P<0.01 for Ve).

Conclusion

Quantitative DCE-MRI parameters are valuable for evaluating the early longitudinal relationship of micro-environment permeability changes in the joint space of SIJ.
Differences in growth-economics of fast vs. slow growing grass species in response to temperature and nitrogen limitation individually, and in combination
Authors: Colesie Claudia , Stangl Zsofia Reka , Hurry Vaughan
Published: November 2020

Background

Fast growing invasive alien species are highly efficient with little investment in their tissues. They often outcompete slower growing species with severe consequences for diversity and community composition. The plant economics trait-based approach provides a theoretical framework, allowing the classification of plants with different performance characteristics. However, in multifaceted background, this approach needs testing. The evaluation and prediction of plant performance outcomes in ecologically relevant settings is among the most pressing topics to understand and predict ecosystem functioning, especially in a quickly changing environment. Temperature and nutrient availability are major components of the global environmental change and this study examines the response of growth economic traits, photosynthesis and respiration to such changes for an invasive fast-growing (Bromus hordaceus) and a slow-growing perennial (Bromus erectus) grass species.

Results

The fully controlled growth chamber experiment simulated temperature—and changes in nitrogen availability individually and in combination. We therefore provide maximum control and monitoring of growth responses allowing general growth trait response patterns to be tested. Under optimal nitrogen availability the slow growing B. erectus was better able to handle the lower temperatures (7 °C) whilst both species had problems at higher temperatures (30 °C). Stresses produced by a combination of heat and nutrient availability were identified to be less limiting for the slow growing species but the combination of chilling with low nutrient availability was most detrimental to both species.

Conclusions

For the fast-growing invader B. hordeaceus a reduction of nitrogen availability in combination with a temperature increase, leads to limited growth performance in comparison to the slow-growing perennial species B.erectus and this may explain why nutrient-rich habitats often experience more invasion than resource-poor habitats.
Diversity of entomopathogenic fungi associated with Mediterranean fruit fly (Ceratitis capitata (Diptera: Tephritidae)) in Moroccan Argan forests and nearby area: impact of soil factors on their distribution
Authors: Hallouti Ayoub , Ait Hamza Mohamed , Zahidi Abdelaziz , Ait Hammou Rachid , Bouharroud Rachid , Ait Ben Aoumar Abdellah , Boubaker Hassan
Published: November 2020

Background

Studying the ecology of biocontrol-agents is a prerequisite to effectively control medfly (Ceratitis capitata(Diptera: Tephritidae)) with entomopathogenic fungi. In this context, factors affecting the occurrence and distribution of medfly-associated entomopathogenic-fungi were studied. Soil samples (22) were collected from natural and cultivated areas of Souss-region Morocco.

Results

A total of 260 fungal isolates belonging to 22 species and 10 genera were obtained by using medfly pupae as bait. Medfly-associated fungi were detected in all studied soils and pupae infection percentages ranged from 3.33% to 48%. Two genera,FusariumandBeauveriawere the most frequent with 83 isolates (32%) and 50 isolates (19.23%) respectively. Pathogenicity test of isolated species against medfly pupae showed high mortality rates up to 91% for some strains. Principal component analysis (PCA) demonstrated a strong influence of origin, physical, and chemical properties of soil on the abundance of these fungi. In general, medfly-associated fungi were more abundant in soils with moderate pH (7.5 to 8) having high sand and organic content. High relative humidity negatively influenced the abundance of these fungi. Both factors directly affected the fungal infection percentages in pupae. The response of fungi to these parameters varied among species. According to principal component analysis (PCA), the soils of argan fields and forests were more suitable for the development of medfly-associated fungi than citrus orchards.

Conclusions

These results guide identifying suitable soils for the effective application of entomopathogenic fungi as biological control agents. In summary, isolated indigenous strains seem to be a promising option to controlC. capitata.
Physicians’ clinical prediction of survival in head and neck cancer patients in the palliative phase
Authors: Hoesseini Arta , Offerman Marinella P. J. , van de Wall-Neecke Bojou J. , Sewnaik Aniel , Wieringa Marjan H. , Baatenburg de Jong Robert J.
Published: November 2020

Background

The prognosis of patients with incurable head and neck cancer (HNC) is a relevant topic. The mean survival of these patients is 5 months but may vary from weeks to more than 3 years. Discussing the prognosis early in the disease trajectory enables patients to make well-considered end-of-life choices, and contributes to a better quality of life and death. However, physicians often are reluctant to discuss prognosis, partly because of the concern to be inaccurate. This study investigated the accuracy of physicians’ clinical prediction of survival of palliative HNC patients.

Methods

This study was part of a prospective cohort study in a tertiary cancer center. Patients with incurable HNC diagnosed between 2008 and 2011 (n = 191), and their treating physician were included. Analyses were conducted between July 2018 and February 2019. Patients’ survival was clinically predicted by their physician ≤3 weeks after disclosure of the palliative diagnosis. The clinical prediction of survival in weeks (CPS) was based on physicians’ clinical assessment of the patient during the outpatient visits. More than 25% difference between the actual survival (AS) and the CPS was regarded as a prediction error. In addition, when the difference between the AS and CPS was 2 weeks or less, this was always considered as correct.

Results

In 59% (n = 112) of cases survival was overestimated. These patients lived shorter than predicted by their physician (median AS 6 weeks, median CPS 20 weeks). In 18% (n = 35) of the cases survival was correctly predicted. The remaining 23% was underestimated (median AS 35 weeks, median CPS 20 weeks). Besides the differences in AS and CPS, no other significant differences were found between the three groups. There was worse accuracy when predicting survival closer to death: out of the 66 patients who survived 6 weeks or shorter, survival was correctly predicted in only eight (12%).

Conclusion

Physicians tend to overestimate the survival of palliative HNC patients. This optimism can result in suboptimal use of palliative and end-of-life care. The future development of a prognostic model that provides more accurate estimates, could help physicians with personalized prognostic counseling.
Validation and cultural adaptation of the Integrated Palliative care Outcome Scale (IPOS) for the Portuguese population
Authors: Antunes Bárbara , Ferreira Pedro Lopes
Published: November 2020

Background

To culturally adapt and validate the Integrated Palliative care Outcome Scale to European Portuguese.

Methods

Multi-centred observational study with 2 assessment points. Data were collected in nine centres using consecutive sampling. All patients were screened for eligibility. Inclusion criteria: ≥18 years, mentally fit to give consent, diagnosed with an incurable, potentially life-threatening illness, read, write and understand Portuguese. Translation and back translation with independent native speakers blind to the original measure created a Portuguese version, which was culturally adapted using cognitive interviews. For psychometric testing, the COSMIN checklist was followed. Reliability and content validity were assessed for patient and staff versions. Construct and criterion validity were tested for patient version.

Results

1703 individuals were screened between July 1st 2015 and February 2016, 135 (7.9%) were included. Mean age was 66.8 years (SD 12.7), 58 (43%) were female. Most patients (109; 80.7%) had a cancer diagnosis. Cronbach’s alpha showed good internal consistency, 0.657 for patient, 0.705 for staff versions. Intraclass correlation coefficient testing reproducibility revealed very good reliability, 0.794–0.950 for patient and 0.456–0.925 for staff versions. There was good content validity and significant results for construct validity. Physical symptoms were better detected by females. IPOS could discriminate: practical issues in different places of care, based on cancer diagnosis, physical and emotional symptoms based on life expectancy both for patient and professional dimensions, physical and emotional symptoms based on phase of illness, for professional dimensions, and physical symptoms from the patients’ viewpoint.

Conclusions

The Portuguese IPOS is a reliable and valid measure.
Deconvolution of cellular subsets in human tissue based on targeted DNA methylation analysis at individual CpG sites
Authors: Schmidt Marco , Maié Tiago , Dahl Edgar , Costa Ivan G. , Wagner Wolfgang
Published: November 2020

Background

The complex composition of different cell types within a tissue can be estimated by deconvolution of bulk gene expression profiles or with various single-cell sequencing approaches. Alternatively, DNA methylation (DNAm) profiles have been used to establish an atlas for multiple human tissues and cell types. DNAm is particularly suitable for deconvolution of cell types because each CG dinucleotide (CpG site) has only two states per DNA strand—methylated or non-methylated—and these epigenetic modifications are very consistent during cellular differentiation. So far, deconvolution of DNAm profiles implies complex signatures of many CpGs that are often measured by genome-wide analysis with Illumina BeadChip microarrays. In this study, we investigated if the characterization of cell types in tissue is also feasible with individual cell type-specific CpG sites, which can be addressed by targeted analysis, such as pyrosequencing.

Results

We compiled and curated 579 Illumina 450k BeadChip DNAm profiles of 14 different non-malignant human cell types. A training and validation strategy was applied to identify and test for cell type-specific CpGs. We initially focused on estimating the relative amount of fibroblasts using two CpGs that were either hypermethylated or hypomethylated in fibroblasts. The combination of these two DNAm levels into a “FibroScore” correlated with the state of fibrosis and was associated with overall survival in various types of cancer. Furthermore, we identified hypomethylated CpGs for leukocytes, endothelial cells, epithelial cells, hepatocytes, glia, neurons, fibroblasts, and induced pluripotent stem cells. The accuracy of this eight CpG signature was tested in additional BeadChip datasets of defined cell mixtures and the results were comparable to previously published signatures based on several thousand CpGs. Finally, we established and validated pyrosequencing assays for the relevant CpGs that can be utilized for classification and deconvolution of cell types.

Conclusion

This proof of concept study demonstrates that DNAm analysis at individual CpGs reflects the cellular composition of cellular mixtures and different tissues. Targeted analysis of these genomic regions facilitates robust methods for application in basic research and clinical settings.
Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study
Authors: Richardson Kathryn , Loke Yoon K. , Fox Chris , Maidment Ian , Howard Robert , Steel Nicholas , Arthur Antony , Boyd Penelope J. , Aldus Clare , Ballard Clive , Savva George M.
Published: November 2020

Background

Sleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia.

Methods

We used data from 27,090 patients diagnosed with dementia between January 2000 and March 2016 from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines. We defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to ≥ 7.5 mg zopiclone or > 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates.

Results

The mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women. Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67 (1.13–2.46), 1.96 (1.16–3.31), 1.33 (1.06–1.66), and 1.88 (1.14–3.10), respectively. We observed similar associations when compared to non-sedative-users with proximal GP consultation. Minimal or inconsistent excess risks were observed at ≤ 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism. We observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR [95% confidence interval] of 0.73 [0.64–0.83]).

Conclusions

Higher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed.

Trial registration

ENCePP e-register of studies,EUPAS18006