bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical application of electrical impedance technology in the detection of malignant neoplasms: a systematic review
Authors: Pathiraja Angela A. , Weerakkody Ruwan A. , von Roon Alexander C. , Ziprin Paul , Bayford Richard 
Published: June 2020

Abstract
Background
Electrical impedance technology has been well established for the last 20 years. Recently research has begun to emerge into its potential uses in the detection and diagnosis of pre-malignant and malignant conditions. The aim of this study was to systematically review the clinical application of electrical impedance technology in the detection of malignant neoplasms.

Methods
A search of Embase Classic, Embase and Medline databases was conducted from 1980 to 22/02/2018 to identify studies reporting on the use of bioimpedance technology in the detection of pre-malignant and malignant conditions. The ability to distinguish between tissue types was defined as the primary endpoint, and other points of interest were also reported.

Results
731 articles were identified, of which 51 reported sufficient data for analysis. These studies covered 16 different cancer subtypes in a total of 7035 patients. As the studies took various formats, a qualitative analysis of each cancer subtype’s data was undertaken. All the studies were able to show differences in electrical impedance and/or related metrics between malignant and normal tissue.

Conclusions
Electrical impedance technology provides a novel method for the detection of malignant tissue, with large studies of cervical, prostate, skin and breast cancers showing encouraging results. Whilst these studies provide promising insights into the potential of this technology as an adjunct in screening, diagnosis and intra-operative margin assessment, customised development as well as multi-centre clinical trials need to be conducted before it can be reliably employed in the clinical detection of malignant tissue.
NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice
Authors: Song Ao-Qi , Gao Bo , Fan Jun-Juan , Zhu Ya-Jing , Zhou Jun , Wang Yu-Ling , Xu Li-Zhong , Wu Wen-Ning 
Published: June 2020

Abstract
Background
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression.

Methods
Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion.

Results
Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus.

Conclusions
NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.
Habit formation in support of antiretroviral medication adherence in clinic-enrolled HIV-infected adults: a qualitative assessment using free-listing and unstructured interviewing in Kampala, Uganda
Authors: Jennings Mayo-Wilson Larissa , Devoto Bianca , Coleman Jessica , Mukasa Barbara , Shelton Angela , MacCarthy Sarah , Saya Uzaib , Chemusto Harriet , Linnemayr Sebastian 
Published: June 2020

Abstract
Background
Despite initial high motivation, individuals receiving antiretroviral therapy (ART) for several years may experience incomplete adherence over time, increasing their risk of HIV-related morbidity and mortality. Habits, defined as automatic and regular practices, do not rely on conscious effort, and may therefore support high long-term ART adherence.

Methods
This qualitative study contributes to the evidence on how clients with adherence problems remember and form habits to take ART medications. Free-listing and unstructured interviewing were used among 42 clinic-enrolled adults in Kampala, Uganda who were receiving ART and participating in a randomized clinical trial for treatment adherence (clinicaltrials.gov: NCT03494777). Data were coded and analyzed using inductive content analysis.

Results
Findings indicated that clients’ most routine habits (eating, bathing, sleeping) did not always occur at the same time or place, making it difficult to reliably link to pill-taking times. Efforts to improve ART habits included having a relative to ask about pill-taking, re-packaging medications, leaving medications in view, using alarms, carrying water, or linking pill-taking to radio/prayer schedules. Reported challenges were adhering to ART schedules during changing employment hours, social activities, and travel.

Conclusion
While habit-forming interventions have the potential to improve ART adherence, targeting treatment-mature clients’ existing routines may be crucial in this population.
Analysis of trace metal distribution in plants with lab-based microscopic X-ray fluorescence imaging
Authors: Mijovilovich Ana , Morina Filis , Bokhari Syed Nadeem , Wolff Timo , Küpper Hendrik 
Published: June 2020

Abstract
Background
Many metals are essential for plants and humans. Knowledge of metal distribution in plant tissues in vivo contributes to the understanding of physiological mechanisms of metal uptake, accumulation and sequestration. For those studies, X-rays are a non-destructive tool, especially suited to study metals in plants.

Results
We present microfluorescence imaging of trace elements in living plants using a customized benchtop X-ray fluorescence machine. The system was optimized by additional detector shielding to minimize stray counts, and by a custom-made measuring chamber to ensure sample integrity. Protocols of data recording and analysis were optimised to minimise artefacts. We show that Zn distribution maps of whole leaves in high resolution are easily attainable in the hyperaccumulator Noccaea caerulescens. The sensitivity of the method was further shown by analysis of micro- (Cu, Ni, Fe, Zn) and macronutrients (Ca, K) in non-hyperaccumulating crop plants (soybean roots and pepper leaves), which could be obtained in high resolution for scan areas of several millimetres. This allows to study trace metal distribution in shoots and roots with a wide overview of the object, and thus avoids making conclusions based on singular features of tiny spots. The custom-made measuring chamber with continuous humidity and air supply coupled to devices for imaging chlorophyll fluorescence kinetic measurements enabled direct correlation of element distribution with photosynthesis. Leaf samples remained vital even after 20 h of X-ray measurements. Subtle changes in some of photosynthetic parameters in response to the X-ray radiation are discussed.

Conclusions
We show that using an optimized benchtop machine, with protocols for measurement and quantification tailored for plant analyses, trace metal distribution can be investigated in a reliable manner in intact, living plant leaves and roots. Zinc distribution maps showed higher accumulation in the tips and the veins of young leaves compared to the mesophyll tissue, while in the older leaves the distribution was more homogeneous.
Implementation science in times of Covid-19
Authors: Wensing Michel , Sales Anne , Armstrong Rebecca , Wilson Paul 
Published: June 2020

AbstractThe emergence of SARS-CoV-2/Covid-19 affects all of us and is associated with rapid and massive changes in healthcare and societies. As a response, a range of interventions for patients and populations have been implemented in health and preventive settings, or need to be implemented in the short and long term. Implementation science offers a multidisciplinary perspective and systematic approach for the design, evaluation and analysis of programmes and policies to enhance implementation. The emergence of Covid-19 provides an urgent need to develop new perspectives and approaches in implementation science, such as the addition of innovative and rigorous approaches to the collection, use and analysis of ‘real-world’ data. Above all, we hope that implementation scientists will focus on what they can contribute to manage Covid-19 and its consequences for people, healthcare and society.
Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis
Authors: Trone Jane-Chloe , Vallard Alexis , Sotton Sandrine , Ben Mrad Majed , Jmour Omar , Magné Nicolas , Pommier Benjamin , Laporte Silvy , Ollier Edouard 
Published: June 2020

Abstract
Background
Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line.

Materials/Methods
We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors.

Results
2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose.

Conclusions
Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved.
Cx3cr1CreERT2-driven Atg7 deletion in adult mice induces intestinal adhesion
Authors: Lee Younghwan , Lee Ji-Won , Nam Hyeri , Yu Seong-Woon 
Published: June 2020

AbstractMicroglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a Gαi-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1CreERT2 mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes in microglia, since microglia are long-lived cells and outlive peripheral macrophages, which continuously turn over and lose their gene modification over time. ATG7 is an E1-like enzyme that plays an essential role in two ubiquitin-like reactions, ATG12-ATG5 conjugation and LC3-lipidation in autophagy. To study the role of ATG7 in adult microglia, we generated Cx3cr1CreERT2:Atg7fl/fl mice and deleted Atg7 at the age of 8 weeks, and found induction of intestinal adhesion. Since intestinal adhesion is caused by excessive inflammation, these results suggest that deletion of Atg7 in intestinal macrophages even for a short time results in inflammation that cannot be rescued by replenishment with wild-type intestinal macrophages. Our finding suggests that, depending on the roles of the gene, Cx3cr1-Cre-mediated gene deletion may yield unanticipated physiological outcomes outside the central nervous system, and careful necropsy is necessary to assure the microglia-specific roles of the target gene.
VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling
Authors: Sun Jinbo , Tang Qisheng , Gao Yongheng , Zhang Wei , Zhao Zhining , Yang Fan , Hu Xiangnan , Zhang Dan , Wang Yong , Zhang Huizhong , Song Bin , Zhang Bo , Wang He 
Published: June 2020

Abstract
Background
Although ongoing development of therapeutic strategies contributes to the improvements in clinical management, clear cell renal cell carcinoma (ccRCC) deaths originate mainly from radiochemoresistant and metastatic disease. Transcription factor SALL4 has been implicated in tumorigenesis and metastasis of multiple cancers. However, it is not known whether SALL4 is involved in the pathogenesis of ccRCC.

Methods
Analyses of clinical specimen and publicly available datasets were performed to determine the expression level and clinical significance of SALL4 in ccRCC. The influence of SALL4 expression on ccRCC tumor growth, metastasis and vascularity was evaluated through a series of in vitro and in vivo experiments. Western blotting, immunofluorescence staining and integrative database analysis were carried out to investigate the underlying mechanism for SALL4-mediated oncogenic activities in ccRCC.

Results
SALL4 expression was increased in ccRCC and positively correlated with tumor progression and poor prognosis. SALL4 could promote ccRCC cell proliferation, colony formation, cell cycle progression, migration, invasion and tumorigenicity and inhibit cell senescence. Further investigation revealed a widespread association of SALL4 with individual gene transcription and the involvement of SALL4 in endothelium development and vasculogenesis. In the context of ccRCC, SALL4 promoted tumor vascularization by recruiting endothelial cells. In addition, we found that SALL4 could exert its tumor-promoting effect via modulating Akt/GSK-3β axis and VEGFA expression. VHL mutation and DNA hypomethylation may be involved in the upregulation of SALL4 in ccRCC.

Conclusions
Overall, our results provide evidence that upregulated SALL4 can function as a crucial regulator of tumor pathogenesis and progression in ccRCC, thus offering potential therapeutic strategies for future treatment.
Expect delays: poor connections between rural and urban health systems challenge multidisciplinary care for rural Americans with diabetic foot ulcers
Authors: Sutherland Bryn L. , Pecanac Kristen , Bartels Christie M. , Brennan Meghan B. 
Published: June 2020

AbstractBackgroundRural Americans with diabetic foot ulcers (DFUs) face a 50% increased risk of major amputation compared to their urban counterparts. We sought to identify health system barriers contributing to this disparity.MethodsWe interviewed 44 participants involved in the care of rural patients with DFUs: 6 rural primary care providers (PCPs), 12 rural specialists, 12 urban specialists, 9 support staff, and 5 patients/caregivers. Directed content analysis was performed guided by a conceptual model describing how PCPs and specialists collaborate to care for shared patients.ResultsRural PCPs reported lack of training in wound care and quickly referred patients with DFUs to local podiatrists or wound care providers. Timely referrals to, and subsequent collaborations with, rural specialists were facilitated by professional connections. However, these connections often were lacking between rural providers and urban specialists, whose skills were needed to optimally treat patients with high acuity ulcers. Urban referrals, particularly to vascular surgery or infectious disease, were stymied by 1) time‐consuming processes, 2) negative provider interactions, and 3) multiple, disconnected electronic health record systems. Such barriers ultimately detracted from rural PCPs' ability to focus on medical management, as well as urban specialists' ability to appropriately triage referrals due to lacking information. Subsequent collaboration between providers also suffered as a result.ConclusionsPoor connections across rural and urban healthcare systems was described as the primary health system barrier driving the rural disparity in major amputations. Future interventions focusing on mitigating this barrier could reduce the rural disparity in major amputations.
First metatarsophalangeal joint range of motion is associated with lower limb kinematics in individuals with first metatarsophalangeal joint osteoarthritis
Authors: Allan Jamie J. , McClelland Jodie A. , Munteanu Shannon E. , Buldt Andrew K. , Landorf Karl B. , Roddy Edward , Auhl Maria , Menz Hylton B. 
Published: June 2020

AbstractBackgroundOsteoarthritis of the first metatarsophalangeal joint (1st MTP joint OA) is a common and disabling condition that results in pain and limited joint range of motion. There is inconsistent evidence regarding the relationship between clinical measurement of 1st MTP joint maximum dorsiflexion and dynamic function of the joint during level walking. Therefore, the aim of this study was to examine the association between passive non‐weightbearing (NWB) 1st MTP joint maximum dorsiflexion and sagittal plane kinematics in individuals with radiographically confirmed 1st MTP joint OA.MethodsForty‐eight individuals with radiographically confirmed 1st MTP joint OA (24 males and 24 females; mean age 57.8 years, standard deviation 10.5) underwent clinical measurement of passive NWB 1st MTP joint maximum dorsiflexion and gait analysis during level walking using a 10‐camera infrared Vicon motion analysis system. Sagittal plane kinematics of the 1st MTP, ankle, knee, and hip joints were calculated. Associations between passive NWB 1st MTP joint maximum dorsiflexion and kinematic variables were explored using Pearson's r correlation coefficients.ResultsPassive NWB 1st MTP joint maximum dorsiflexion was significantly associated with maximum 1st MTPJ dorsiflexion (r = 0.486, p < 0.001), ankle joint maximum plantarflexion (r = 0.383, p = 0.007), and ankle joint excursion (r = 0.399, p = 0.005) during gait. There were no significant associations between passive NWB 1st MTP joint maximum dorsiflexion and sagittal plane kinematics of the knee or hip joints.ConclusionsThese findings suggest that clinical measurement of 1st MTP joint maximum dorsiflexion provides useful insights into the dynamic function of the foot and ankle during the propulsive phase of gait in this population.
Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping
Authors: Zhao Quanyi , Dacre Michael , Nguyen Trieu , Pjanic Milos , Liu Boxiang , Iyer Dharini , Cheng Paul , Wirka Robert , Kim Juyong Brian , Fraser Hunter B. , Quertermous Thomas 
Published: June 2020

Abstract
Background
To investigate the epigenetic and transcriptional mechanisms of coronary artery disease (CAD) risk, as well as the functional regulation of chromatin structure and function, we create a catalog of genetic variants associated with three stages of transcriptional cis-regulation in primary human coronary artery vascular smooth muscle cells (HCASMCs).

Results
We use a pooling approach with HCASMC lines to map regulatory variants that mediate binding of the CAD-associated transcription factor TCF21 with ChIPseq studies (bQTLs), variants that regulate chromatin accessibility with ATACseq studies (caQTLs), and chromosomal looping with Hi-C methods (clQTLs). We examine the overlap of these QTLs and their relationship to smooth muscle-specific genes and transcription factors. Further, we use multiple analyses to show that these QTLs are highly associated with CAD GWAS loci and correlate to lead SNPs where they show allelic effects. By utilizing genome editing, we verify that identified functional variants can regulate both chromatin accessibility and chromosomal looping, providing new insights into functional mechanisms regulating chromatin state and chromosomal structure. Finally, we directly link the disease-associated TGFB1-SMAD3 pathway to the CAD-associated FN1 gene through a response QTL that modulates both chromatin accessibility and chromosomal looping.

Conclusions
Together, these studies represent the most thorough mapping of multiple QTL types in a highly disease-relevant primary cultured cell type and provide novel insights into their functional overlap and mechanisms that underlie these genomic features and their relationship to disease risk.
A microbubble-sparged yeast propagation–fermentation process for bioethanol production
Authors: Raghavendran Vijayendran , Webb Joseph P. , Cartron Michaël L. , Springthorpe Vicki , Larson Tony R. , Hines Michael , Mohammed Hamza , Zimmerman William B. , Poole Robert K. , Green Jeffrey 
Published: June 2020

AbstractBackgroundIndustrial biotechnology will play an increasing role in creating a more sustainable global economy. For conventional aerobic bioprocesses supplying O2can account for 15% of total production costs. Microbubbles (MBs) are micron-sized bubbles that are widely used in industry and medical imaging. Using a fluidic oscillator to generate energy-efficient MBs has the potential to decrease the costs associated with aeration. However, little is understood about the effect of MBs on microbial physiology. To address this gap, a laboratory-scale MB-basedSaccharomyces cerevisiaeEthanol Red propagation–fermentation bioethanol process was developed and analysed.ResultsAeration with MBs increased O2transfer to the propagation cultures. Titres and yields of bioethanol in subsequent anaerobic fermentations were comparable for MB-propagated and conventional, regular bubble (RB)-propagated yeast. However, transcript profiling showed significant changes in gene expression in the MB-propagated yeast compared to those propagated using RB. These changes included up-regulation of genes required for ergosterol biosynthesis. Ergosterol contributes to ethanol tolerance, and so the performance of MB-propagated yeast in fed-batch fermentations sparged with 1% O2as either RBs or MBs were tested. The MB-sparged yeast retained higher levels of ergosteryl esters during the fermentation phase, but this did not result in enhanced viability or ethanol production compared to ungassed or RB-sparged fermentations.ConclusionsThe performance of yeast propagated using energy-efficient MB technology in bioethanol fermentations is comparable to that of those propagated conventionally. This should underpin the future development of MB-based commercial yeast propagation.