bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of lymphocyte cell-specific protein-tyrosine kinase (LCK) as a driver for invasion and migration of oral cancer by tumor heterogeneity exploitation
Authors: Weiße Jonas , Rosemann Julia , Müller Lisa , Kappler Matthias , Eckert Alexander W. , Glaß Markus , Misiak Danny , Hüttelmaier Stefan , Ballhausen Wolfgang G. , Hatzfeld Mechthild , Haemmerle Monika , Gutschner Tony 
Published: June 2021

Abstract
Background
Cancer metastases are the main cause of lethality. The five-year survival rate for patients diagnosed with advanced stage oral cancer is 30%. Hence, the identification of novel therapeutic targets is an urgent need. However, tumors are comprised of a heterogeneous collection of cells with distinct genetic and molecular profiles that can differentially promote metastasis making therapy development a challenging task. Here, we leveraged intratumoral heterogeneity in order to identify drivers of cancer cell motility that might be druggable targets for anti-metastasis therapy.

Methods
We used 2D migration and 3D matrigel-based invasion assays to characterize the invasive heterogeneity among and within four human oral cancer cell lines in vitro. Subsequently, we applied mRNA-sequencing to map the transcriptomes of poorly and strongly invasive subclones as well as primary tumors and matched metastasis.

Results
We identified SAS cells as a highly invasive oral cancer cell line. Clonal analysis of SAS yielded a panel of 20 subclones with different invasive capacities. Integrative gene expression analysis identified the Lymphocyte cell-specific protein-tyrosine kinase (LCK) as a druggable target gene associated with cancer cell invasion and metastasis. Inhibition of LCK using A-770041 or dasatinib blocked invasion of highly aggressive SAS cells. Interestingly, reduction of LCK activity increased the formation of adherens junctions and induced cell differentiation.

Conclusion
Analysis of invasive heterogeneity led to the discovery of LCK as an important regulator of motility in oral cancer cells. Hence, small molecule mediated inhibition of LCK could be a promising anti-metastasis therapy option for oral cancer patients.
Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease
Authors: Sun Xiao-ying , Li Ling-jie , Dong Quan-Xiu , Zhu Jie , Huang Ya-ru , Hou Sheng-jie , Yu Xiao-lin , Liu Rui-tian 
Published: June 2021

Abstract
Background
Tau pathology is a hallmark of Alzheimer’s disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment.

Methods
The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1β and TNF-α in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1β and TNF-α, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA.

Results
We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition.

Conclusion
In combination with the previously reported therapeutic effects of rutin on Aβ pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and Aβ.
Long-term outcomes of cementless femoral stem revision with the Wagner cone prosthesis
Authors: Park Kyung-Soon , Jin Sheng-Yu , Lim Jun-Hyuk , Yoon Taek-Rim 
Published: June 2021

Abstract
Background
The procedure of femoral stem revision is challenging, and bone conservation with less stress shielding is a mandatory effort in these cases. Although there are several reports of stem revision with stems designed for primary total hip arthroplasty (THA), there is no report on stem revision with the Wagner cone prosthesis.

Methods
Between 1996 and 2008, 41 hips of 41 consecutive patients were subjected to femoral revision THA using the Wagner cone prosthesis. The mean age during revision surgery was 56.1 years, and the mean follow-up period was 14.8 years. The clinical results were evaluated, and the femoral component was assessed radiologically.

Results
The results showed that the average period from the first operation to revision THA was 8.0 years. Additionally, the mean Harris hip score improved from 52 points preoperatively to 83 points at the final follow-up. All stems showed bone integration in the radiological evaluation. A subsidence of more than 5 mm was observed in 3 out of 28 (10.7%) femoral stems. Two patients needed an acetabular revision for acetabular cup loosening during the follow-up period. Furthermore, one patient had recurrent dislocation and had to undergo revision surgery for soft tissue augmentation.

Conclusions
We achieved favorable clinical and radiological long-term outcomes in femoral stem revision using the Wagner cone prosthesis. This cementless femoral stem could be an option for femoral stem revision in cases with relatively good bone stock.
The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis
Authors: Ma Jimin , Lu Hanli , Chen Xinxing , Wang Dasai , Wang Qiang 
Published: June 2021

Abstract
Objective
The present meta-analysis was conducted to evaluate the efficacy and safety of the application of tranexamic acid (TXA) in patients undergoing high tibial osteotomy (HTO).

Methods
PubMed (MEDLINE), EMBASE, and Cochrane Library were systematically searched for relevant literature from inception until 1 February 2021. A combined searching strategy of subject words and random words was adopted. After testing for potential publication bias and/or heterogeneity, we aggregated variables by using the random-effect model. The primary comparison outcome measures were total blood loss, hemoglobin decrease, drain output, wound complications, thrombotic events, and blood transfusion rate of the TXA group versus control. The meta-analysis was performed using the RevMan 5.3 software.

Results
A total of 5 studies were included involving 532 patients. The results showed that there were significant differences in the two groups concerning total blood loss (95% confidence interval [CI] − 332.74 to − 146.46, P < 0.00001), hemoglobin decrease on postoperative day (POD) 1, 2, and 5 (POD 1 95% CI − 1.34 to − 0.63, P < 0.00001; POD 2 95% CI − 1.07 to − 0.68, P < 0.00001; POD 5 95% CI − 1.46 to − 0.84, P < 0.00001), drain output (POD total 95% CI − 195.86 to − 69.41, P < 0.00001) and wound complications (RR = 0.34, 95% CI 0.12 to 0.97, P = 0.04). Nonsignificant differences were found in the incidence of thromboembolic events (RR = 0.46, 95% CI 0.09 to 2.41, P = 0.36) and blood transfusion rate (RR = 0.25, 95% CI 0.03 to 2.27, P = 0.22).

Conclusions
This meta-analysis of the available evidence demonstrated that TXA could reduce total blood loss, hemoglobin decrease, drain output, and wound complications without increasing the incidence of thromboembolic events in patients undergoing HTO. But there is no obvious evidence that TXA could reduce blood transfusion rates. Further studies, including more large-scale and well-designed randomized controlled trials, are warranted to assess the efficacy and safety issues of routine TXA use in HTO patients.
Factors contributing to emotional distress in Sierra Leone: a socio-ecological analysis
Authors: Horn Rebecca , Arakelyan Stella , Wurie Haja , Ager Alastair 
Published: June 2021

Abstract
Background
There is increasing global evidence that mental health is strongly determined by social, economic and environmental factors, and that strategic action in these areas has considerable potential for improving mental health and preventing and alleviating mental disorders. Prevention and promotion activities in mental health must address the needs prioritised by local actors. The aim of this study was to identify stressors with the potential to influence emotional wellbeing and distress within the general population of Sierra Leone, in order to contribute to an inter-sectoral public mental health approach to improving mental health within the country.

Methodology
Respondents were a convenience sample of 153 respondents (60 women, 93 men) from five districts of Sierra Leone. Using freelisting methodology, respondents were asked to respond to the open question ‘What kind of problems do women/men have in your community?’. Data analysis involved consolidation of elicited problems into a single list. These were then organised thematically using an adaptation of the socio-ecological model, facilitating exploration of the interactions between problems at individual, family, community and societal levels

Results
Overall, respondents located problems predominantly at community and societal levels. Although few respondents identified individual-level issues, they frequently described how problems at other levels contributed to physical health difficulties and emotional distress. Women identified significantly more problems at the family level than men, particularly related to relationships with an intimate partner. Men identified significantly more problems at the societal level than women, primarily related to lack of infrastructure. Men and women were equally focused on problems related to poverty and lack of income generating opportunities.

Conclusion
Poverty and inability to earn an income underpinned many of the problems described at individual, family and community level. Actions to address livelihoods, together with improving infrastructure and addressing gender norms which are harmful to both men and women, are likely key to improving the wellbeing of the Sierra Leone population.
Development of a rapid and sensitive immunochromatographic strip based on EuNPs-ES fluorescent probe for the detection of early Trichinella spiralis-specific IgG antibody in pigs
Authors: Wang Xinyu , Tang Bin , Zhao Ying , Ding Jing , Wang Nan , Liu Yan , Dong Zijian , Sun Xiangdong , Xu Quangang , Liu Mingyuan , Liu Xiaolei 
Published: June 2021

AbstractTrichinellosis, which is caused by nematodes of the genusTrichinella, is one of the most important zoonotic parasite diseases in the world. A rapid and sensitive immunochromatographic strip (ICS) based on Eu (III) nanoparticles (EuNPs) was developed for the detection ofTrichinella spiralis(T. spiralis) infection in pigs.T. spiralismuscle larvae excretory secretory or preadult worm excretory secretory (ML-ES or PAW-ES) antigens were conjugated with EuNPs probes to captureT. spiralis-specific antibodies in pig sera, after which the complex bound to mouse anti-pig IgG deposited on the test line (T-line), producing a fluorescent signal. In the pigs infected with 100, 1000 and 10 000 ML, seroconversion was first detectable for the EuNPs-ML-ES ICS at 30, 25 and 21 days post-infection (dpi) and for the EuNPs-PAW-ES ICS at 25, 21 and 17 dpi. These results show that EuNPs-PAW-ES ICS detects anti-TrichinellaIgG in pigs 4–5 days earlier that test using ML-ES antigens. Our ICS have no cross reaction with other parasite infection sera. Furthermore, the detection process could be completed in 10 min. This study indicated that our ICS can be used for the detection of the circulating antibodies in earlyT. spiralisinfection and provide a novel method for on-site detection ofT. spiralisinfection in pigs.
New fragmented electro-active biofilm (FAB) reactor to increase anode surface area and performance of microbial fuel cell
Authors: Atnafu Tesfalem , Leta Seyoum 
Published: June 2021

Abstract
Background
Microbial fuel cell (MFC) technology is a promising sustainable future energy source with a renewable and abundant substrate. MFC critical drawbacks are anode surface area limitations and electrochemical loss. Recent studies recommend thick anode biofilm growth due to the synergetic effect between microbial communities. Engineering the anode surface area is the prospect of MFC. In this study, a microbial electrode jacket dish (MEJ-dish) was invented, first time to the authors’ knowledge, to support MFC anode biofilm growth. The MFC reactor with MEJ-dish was hypothesized to develop a variable biofilm thickens. This reactor is called a fragmented electro-active biofilm-microbial fuel cell (FAB-MFC). It was optimized for pH and MEJ-dish types and tested at a bench-scale.

Results
Fragmented (thick and thin) anode biofilms were observed in FAB-MFC but not in MFC. During the first five days and pH 7.5, maximum voltage (0.87 V) was recorded in MFC than FAB-MFC; however, when the age of the reactor increases, all the FAB-MFC gains momentum. It depends on the MEJ-dish type that determines the junction nature between the anode and MEJ-dish. At alkaline pH 8.5, the FAB-MFC generates a lower voltage relative to MFC. On the contrary, the COD removal was improved regardless of pH variation (6.5–8.5) and MEJ-dish type. The bench-scale studies support the optimization findings. Overall, the FAB improves the Coulombic efficiency by 7.4–9.6 % relative to MFC. It might be recommendable to use both FAB and non-FAB in a single MFC reactor to address the contradictory effect of increasing COD removal associated with the lower voltage at higher pH.

Conclusions
This study showed the overall voltage generated was significantly higher in FAB-MFC than MFC within limited pH (6.5–7.5); relatively, COD removal was enhanced within a broader pH range (6.5–8.5). It supports the conclusion that FAB anode biofilms were vital for COD removal, and there might be a mutualism even though not participated in voltage generation. FAB could provide a new flexible technique to manage the anode surface area and biofilm thickness by adjusting the MEJ-dish size. Future studies may need to consider the number, size, and conductor MEJ-dish per electrode.
Mass spectrometry imaging of L-[ring-13C6]-labeled phenylalanine and tyrosine kinetics in non-small cell lung carcinoma
Authors: Cao Jianhua , Balluff Benjamin , Arts Martijn , Dubois Ludwig J. , van Loon Luc J. C. , Hackeng Tilman M. , van Eijk Hans M. H. , Eijkel Gert , Heij Lara R. , Soons Zita , Olde Damink Steven W. M. , Heeren Ron M. A. 
Published: June 2021

Abstract
Background
Metabolic reprogramming is a common phenomenon in tumorigenesis and tumor progression. Amino acids are important mediators in cancer metabolism, and their kinetics in tumor tissue are far from being understood completely. Mass spectrometry imaging is capable to spatiotemporally trace important endogenous metabolites in biological tissue specimens. In this research, we studied L-[ring-13C6]-labeled phenylalanine and tyrosine kinetics in a human non-small cell lung carcinoma (NSCLC) xenografted mouse model using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI).

Methods
We investigated the L-[ring-13C6]-Phenylalanine (13C6-Phe) and L-[ring-13C6]-Tyrosine (13C6-Tyr) kinetics at 10 min (n = 4), 30 min (n = 3), and 60 min (n = 4) after tracer injection and sham-treated group (n = 3) at 10 min in mouse-xenograft lung tumor tissues by MALDI-FTICR-MSI.

Results
The dynamic changes in the spatial distributions of 19 out of 20 standard amino acids are observed in the tumor tissue. The highest abundance of 13C6-Phe was detected in tumor tissue at 10 min after tracer injection and decreased progressively over time. The overall enrichment of 13C6-Tyr showed a delayed temporal trend compared to 13C6-Phe in tumor caused by the Phe-to-Tyr conversion process. Specifically, 13C6-Phe and 13C6-Tyr showed higher abundances in viable tumor regions compared to non-viable regions.

Conclusions
We demonstrated the spatiotemporal intra-tumoral distribution of the essential aromatic amino acid 13C6-Phe and its de-novo synthesized metabolite 13C6-Tyr by MALDI-FTICR-MSI. Our results explore for the first time local phenylalanine metabolism in the context of cancer tissue morphology. This opens a new way to understand amino acid metabolism within the tumor and its microenvironment.
A cross-sectional survey on community pharmacists readiness to fight COVID-19 in a developing country: knowledge, attitude, and practice in Lebanon
Authors: Zeenny Rony M. , Dimassi Ahmad , Sacre Hala , El Khoury Ghada , Hajj Aline , Farah Rita , Hajj Hind , Lahoud Nathalie , Akel Marwan , Hallit Souheil , Salameh Pascale 
Published: June 2021

Abstract
Background
Lebanon, a developing Middle Eastern country, was hit by the COVID-19 pandemic that occurred amid a severe national economic crisis. Community pharmacists are responsible for dispensing appropriate medications and products in addition to counseling, informing and educating the public, and promoting disease prevention and infection control.

Objective
This study aimed to assess community pharmacists' knowledge, attitude, and practice towards the COVID-19 pandemic and evaluate behavior changes and safety measures.

Methods
An anonymous and standardized online questionnaire in English was disseminated via social media platforms to Lebanese community pharmacists. The questionnaire consisted of 95 items designed as Likert-scales and multiple-choice questions divided into four different sections: socio-demographic characteristics, knowledge-based, attitude-based, and pharmacy practice questions. Descriptive statistical analysis was used to summarize the demographic characteristics, and indices were created for knowledge, attitude, and practice by computing the correct answers for each section.

Results
A total of 310 questionnaires were completed. Around 61% have expressed their fear of getting infected with COVID-19 due to occupational exposure. The respondents were able to answer 80–90% of the knowledge-based questions of the survey. A more careful/anxious attitude, but not knowledge, was associated with overall better practice (p = 0.03). Also, respondents stated that they are dispensing protective equipment items such as masks (87%), gloves (60%), and sanitizers (77%) in small quantities due to limited availability.

Conclusion
Our findings revealed an adequate level of knowledge and good practice towards COVID-19 among Lebanese community pharmacists. Their fears of contracting the virus and compromising the safety of those around them are justified. However, their supply of protective equipment is limited.
Towards planning of osteotomy around the knee with quantitative inclusion of the adduction moment: a biomechanical approach
Authors: Biehl Margit , Damm Philipp , Trepczynski Adam , Preiss Stefan , Salzmann Gian Max 
Published: June 2021

Abstract
Purpose
Despite practised for decades, the planning of osteotomy around the knee, commonly using the Mikulicz-Line, is only empirically based, clinical outcome inconsistent and the target angle still controversial. A better target than the angle of frontal-plane static leg alignment might be the external frontal-plane lever arm (EFL) of the knee adduction moment. Hypothetically assessable from frontal-plane-radiograph skeleton dimensions, it might depend on the leg-alignment angle, the hip-centre-to-hip-centre distance, the femur- and tibia-length.

Methods
The target EFL to achieve a medial compartment force ratio of 50% during level-walking was identified by relating in-vivo-measurement data of knee-internal loads from nine subjects with instrumented prostheses to the same subjects’ EFLs computed from frontal-plane skeleton dimensions. Adduction moments derived from these calculated EFLs were compared to the subjects’ adduction moments measured during gait analysis.

Results
Highly significant relationships (0.88 ≤ R2 ≤ 0.90) were found for both the peak adduction moment measured during gait analysis and the medial compartment force ratio measured in vivo to EFL calculated from frontal-plane skeleton dimensions. Both correlations exceed the respective correlations with the leg alignment angle, EFL even predicts the adduction moment’s first peak. The guideline EFL for planning osteotomy was identified to 0.349 times the epicondyle distance, hence deducing formulas for individualized target angles and Mikulicz-Line positions based on full-leg radiograph skeleton dimensions. Applied to realistic skeleton geometries, widespread results explain the inconsistency regarding correction recommendations, whereas results for average geometries exactly meet the most-consented “Fujisawa-Point”.

Conclusion
Osteotomy outcome might be improved by planning re-alignment based on the provided formulas exploiting full-leg-radiograph skeleton dimensions.
Automated Self-Administered 24-H Dietary Assessment Tool (ASA24) recalls for parent proxy-reporting of children’s intake (> 4 years of age): a feasibility study
Authors: Sharpe Isobel , Kirkpatrick Sharon I. , Smith Brendan T. , Keown-Stoneman Charles D. G. , Omand Jessica , Vanderhout Shelley , Maguire Jonathon L. , Birken Catherine S. , Anderson Laura N. ,   on behalf of the TARGet Kids! collaboration
Published: June 2021

Abstract

Background
Robust measurement of dietary intake in population studies of children is critical to better understand the diet–health nexus. It is unknown whether parent proxy-report of children’s dietary intake through online 24-h recalls is feasible in large cohort studies.

Objectives
The primary objective of this study was to describe the feasibility of the Automated Self-Administered 24-h Dietary Assessment Tool (ASA24) to measure parent proxy-reported child dietary intake. A secondary objective was to compare intake estimates with those from national surveillance.

Methods
Parents of children aged 4–15 years participating in the TARGet Kids! research network in Toronto, Canada were invited by email to complete an online ASA24-Canada-2016 recall for their child, with a subsample prompted to complete a second recall about 2 weeks later. Descriptive statistics were reported for ASA24 completion characteristics and intake of several nutrients. Comparisons were made to the 2015 Canadian Community Health Survey (CCHS) 24-h recall data.

Results
A total of 163 parents completed the first recall, and 46 completed the second, reflecting response rates of 35% and 59%, respectively. Seven (4%) first recalls and one (2%) second recall were excluded for ineligibility, missing data, or inadvertent parental self-report. The median number of foods reported on the first recall was 18.0 (interquartile range (IQR) 6.0) and median time to complete was 29.5 min (IQR 17.0). Nutrient intakes for energy, total fat, protein, carbohydrates, fiber, sodium, total sugars, and added sugars were similar across the two recalls and the CCHS.

Conclusions
The ASA24 was found to be feasible for parent proxy-reporting of children’s intake and to yield intake estimates comparable to those from national surveillance, but strategies are needed to increase response rate and support completion to enhance generalizability.