bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical model of hypoxia and tumor signaling interplay reveals the importance of hypoxia and cell-to-cell variability in tumor growth inhibition
Authors: Chen Emile P. , Song Roy S. , Chen Xueer 
Published: October 2019

Abstract

Background
Human tumor is a complex tissue with multiple heterogeneous hypoxic regions and significant cell-to-cell variability. Due to the complexity of the disease, the explanation of why anticancer therapies fail cannot be attributed to intrinsic or acquired drug resistance alone. Furthermore, there are inconsistent reports of hypoxia-induced kinase activities in different cancer cell-lines, where increase, decreases, or no change has been observed. Thus, we asked, why are there widely contrasting results in kinase activity under hypoxia in different cancer cell-lines and how does hypoxia play a role in anti-cancer drug sensitivity?

Results
We took a modeling approach to address these questions by analyzing the model simulation to explain why hypoxia driven signals can have dissimilar impact on tumor growth and alter the efficacy of anti-cancer drugs. Repeated simulations with varying concentrations of biomolecules followed by decision tree analysis reveal that the highly differential effects among heterogeneous subpopulation of tumor cells could be governed by varying concentrations of just a few key biomolecules. These biomolecules include activated serine/threonine-specific protein kinases (pRAF), mitogen-activated protein kinase kinase (pMEK), protein kinase B (pAkt), or phosphoinositide-4,5-bisphosphate 3-kinase (pPI3K). Additionally, the ratio of activated extracellular signal-regulated kinases (pERK) or pAkt to its respective total was a key factor in determining the sensitivity of pERK or pAkt to hypoxia.

Conclusion
This work offers a mechanistic insight into how hypoxia can affect the efficacy of anti-cancer drug that targets tumor signaling and provides a framework to identify the types of tumor cells that are either sensitive or resistant to anti-cancer therapy.
Microbial biofilm correlates with an increased antibiotic tolerance and poor therapeutic outcome in infective endocarditis
Authors: Di Domenico Enea Gino , Rimoldi Sara Giordana , Cavallo Ilaria , D’Agosto Giovanna , Trento Elisabetta , Cagnoni Giovanni , Palazzin Alessandro , Pagani Cristina , Romeri Francesca , De Vecchi Elena , Schiavini Monica , Secchi Daniela , Antona Carlo , Rizzardini Giuliano , Dichirico Rita Barbara , Toma Luigi , Kovacs Daniela , Cardinali Giorgia , Gallo Maria Teresa , Gismondo Maria Rita , Ensoli Fabrizio 
Published: October 2019

Abstract

Background
Infective endocarditis (IE) is associated with high rates of mortality. Prolonged treatments with high-dose intravenous antibiotics often fail to eradicate the infection, frequently leading to high-risk surgical intervention. By providing a mechanism of antibiotic tolerance, which escapes conventional antibiotic susceptibility profiling, microbial biofilm represents a key diagnostic and therapeutic challenge for clinicians. This study aims at assessing a rapid biofilm identification assay and a targeted antimicrobial susceptibility profile of biofilm-growing bacteria in patients with IE, which were unresponsive to antibiotic therapy.

Results
Staphylococcus aureus was the most common isolate (50%), followed by Enterococcus faecalis (25%) and Streptococcus gallolyticus (25%). All microbial isolates were found to be capable of producing large, structured biofilms in vitro. As expected, antibiotic treatment either administered on the basis of antibiogram or chosen empirically among those considered first-line antibiotics for IE, including ceftriaxone, daptomycin, tigecycline and vancomycin, was not effective at eradicating biofilm-growing bacteria. Conversely, antimicrobial susceptibility profile of biofilm-growing bacteria indicated that teicoplanin, oxacillin and fusidic acid were most effective against S. aureus biofilm, while ampicillin was the most active against S. gallolyticus and E. faecalis biofilm, respectively.

Conclusions
This study indicates that biofilm-producing bacteria, from surgically treated IE, display a high tolerance to antibiotics, which is undetected by conventional antibiograms. The rapid identification and antimicrobial tolerance profiling of biofilm-growing bacteria in IE can provide key information for both antimicrobial therapy and prevention strategies.
Auxin regulates adventitious root formation in tomato cuttings
Authors: Guan Ling , Tayengwa Reuben , Cheng Zongming (Max) , Peer Wendy Ann , Murphy Angus S. , Zhao Mizhen 
Published: October 2019

Abstract

Background
Adventitious root (AR) formation is a critical developmental process in cutting propagation for the horticultural industry. While auxin has been shown to regulate this process, the exact mechanism and details preceding AR formation remain unclear. Even though AR and lateral root (LR) formation share common developmental processes, there are exist some differences that need to be closely examined at the cytological level. Tomato stem cuttings, which readily form adventitious roots, represent the perfect system to study the influence of auxin on AR formation and to compare AR and LR organogenesis.

Results
Here we show the progression by which AR form from founder cells in the basal pericycle cell layers in tomato stem cuttings. The first disordered clumps of cells assumed a dome shape that later differentiated into functional AR cell layers. Further growth resulted in emergence of mature AR through the epidermis following programmed cell death of epidermal cells. Auxin and ethylene levels increased in the basal stem cutting within 1 h. Tomato lines expressing the auxin response element DR5pro:YFP showed an increase in auxin distribution during the AR initiation phase, and was mainly concentrated in the meristematic cells of the developing AR. Treatment of stem cuttings with auxin, increased the number of AR primordia and the length of AR, while stem cuttings treated with the pre-emergent herbicide/auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) occasionally developed thick, agravitropic AR. Hormone profile analyses showed that auxin positively regulated AR formation, whereas perturbations to zeatin, salicylic acid, and abscisic acid homeostasis suggested minor roles during tomato stem rooting. The gene expression of specific auxin transporters increased during specific developmental phases of AR formation.

Conclusion
These data show that AR formation in tomato stems is a complex process. Upon perception of a wounding stimulus, expression of auxin transporter genes and accumulation of auxin at founder cell initiation sites in pericycle cell layers and later in the meristematic cells of the AR primordia were observed. A clear understanding and documentation of these events in tomato is critical to resolve AR formation in recalcitrant species like hardwoods and improve stem cutting propagation efficiency and effectiveness.
Comprehensive analysis of multiprotein bridging factor 1 family genes and SlMBF1c negatively regulate the resistance to Botrytis cinerea in tomato
Authors: Zhang Xu , Xu Zhixuan , Chen Lichen , Ren Zhonghai 
Published: October 2019

Abstract

Background
Multiprotein bridging factor 1 s (MBF1s) are members of the transcriptional co-activator family that have involved in plant growth, development and stress responses. However, little is known about the Solanum lycopersicum MBF1 (SlMBF1) gene family.

Results
In total, five SlMBF1 genes were identified based on the tomato reference genome, and these genes were mapped to five chromosomes. All of the SlMBF1 proteins were highly conserved, with a typical MBF1 domain and helix-turn-helix_3 domain. In addition, the promoter regions of the SlMBF1 genes have various stress and hormone responsive cis-regulatory elements. Encouragingly, the SlMBF1 genes were expressed with different expression profiles in different tissues and responded to various stress and hormone treatments. The biological function of SlMBF1c was further identified through its overexpression in tomato, and the transgenic tomato lines showed increased susceptibility to Botrytis cinerea (B. cinerea). Additionally, the expression patterns of salicylic acid (SA)-, jasmonic acid (JA)- and ethylene (ET)- mediated defense related genes were altered in the transgenic plants.

Conclusions
Our comprehensive analysis provides valuable information for clarifying the evolutionary relationship of the SlMBF1 members and their expression patterns in different tissues and under different stresses. The overexpression of SlMBF1c decreased the resistance of tomato to B. cinerea through enhancing the gene expression of the SA-mediated signaling pathway and depressing JA/ET-mediated signaling pathways. These results will facilitate future functional studies of the transcriptional co-activator family.
The intraoperative use of non-opioid adjuvant analgesic agents: a survey of anaesthetists in Australia and New Zealand
Authors: Thiruvenkatarajan Venkatesan , Wood Richard , Watts Richard , Currie John , Wahba Medhat , Van Wijk Roelof M. 
Published: October 2019

Abstract

Background
Opioids have long been the mainstay of drugs used for intra-operative analgesia. Due to their well-known short and long term side effects, the use of non-opioid analgesics has often been encouraged to decrease the dose of opioid required and minimise these side effects. The trends in using non-opioid adjuvants among Australian Anaesthetists have not been examined before. This study has attempted to determine the use of non-opioid analgesics as part of an opioid sparing practice among anaesthetists across Australia and New Zealand.

Methods
A survey was distributed to 985 anaesthetists in Australia and New Zealand. The questions focused on frequency of use of different adjuvants and any reasons for not using individual agents. The agents surveyed were paracetamol, dexamethasone, non-steroidal anti-inflammatory agents (NSAIDs), tramadol, ketamine, anticonvulsants, intravenous lidocaine, systemic alpha 2 agonists, magnesium sulphate, and beta blockers. Descriptive statistics were used and data are expressed as a percentage of response for each drug.

Results
The response rate was 33.4%. Paracetamol was the most frequently used; with 72% of the respondents describing frequent usage (defined as usage above 70% of the time); followed by parecoxib (42% reported frequent usage) and dexamethasone (35% reported frequent usage). Other adjuvants were used much less commonly, with anaesthetists reporting their frequent usage at less than 10%. The majority of respondents suggested that they would never consider dexmedetomidine, magnesium, esmolol, pregabalin or gabapentin. Perceived disincentives for the use of analgesic adjuvants varied. The main concerns were side effects, lack of evidence for benefit, and anaesthetists’ experience. The latter two were the major factors for magnesium, dexmedetomidine and esmolol.

Conclusion
The uptake of tramadol, lidocaine and magnesium amongst respondents from anaesthetists in Australia and New Zealand was poor. Gabapentin, pregabalin, dexmedetomidine and esmolol use was relatively rare. Most anaesthetists need substantial evidence before introducing a non-opioid adjuvant into their routine practice. Future trials should focus on assessing the opioid sparing benefits and relative risk of using individual non-opioid adjuvants in the perioperative period for specific procedures and patient populations.
Risk of subsequent ventricular arrhythmia is higher in primary prevention patients with implantable cardioverter defibrillator than in secondary prevention patients
Authors: Zhou You , Zhao Shuang , Chen Keping , Hua Wei , Su Yangang , Chen Silin , Liang Zhaoguang , Xu Wei , Zhang Shu 
Published: October 2019

Abstract

Background
Because of previous ventricular arrhythmia (VA) episodes, patients with implantable cardioverter-defibrillator (ICD) for secondary prevention (SP) are generally considered to have a higher burden of VAs than primary prevention (PP) patients. However, when PP patients experienced VA, the difference in the prognosis of these two patient groups was unknown.

Methods
The clinical characteristics and follow-up data of 835 ICD patients (364 SP patients and 471 PP patients) with home monitoring feature were retrospectively analysed. The incidence rate and risk of subsequent VA and all-cause mortality were compared between PP patients after the first appropriate ICD therapy and SP patients.

Results
During a mean follow-up of 44.72 ± 20.87 months, 210 (44.59%) PP patients underwent appropriate ICD therapy. In the Kaplan-Meier survival analysis, the PP patients after appropriate ICD therapy were more prone to VA recurrence and all-cause mortality than SP patients (P<0.001 for both endpoints). The rate of appropriate ICD therapy and all-cause mortality in PP patients after the first appropriate ICD therapy was significantly higher than that in SP patients (for device therapy, 59.46 vs 20.64 patients per 100 patient-years; incidence rate ratio [IRR] 2.880, 95% confidence interval [CI]: 2.305–3.599; P<0.001; for all-cause mortality, 14.08 vs 5.40 deaths per 100 patient-years; IRR 2.607, 95% CI: 1.884–3.606; P<0.001). After propensity score matching for baseline characteristics, the risk of VA recurrence in PP patients with appropriate ICD therapy was still higher than that in SP patients (41.80 vs 19.10 patients per 100 patient-years; IRR 2.491, 95% CI: 1.889–3.287; P<0.001), but all-cause mortality rates were similar between the two groups (12.61 vs 9.33 deaths per 100 patient-years; IRR 1.352, 95% CI: 0.927–1.972; P = 0.117).

Conclusions
Once PP patients undergo appropriate ICD therapy, they will be more prone to VA recurrence and death than SP patients.
Minimally invasive drainage versus open surgical debridement in SAP/SMAP – a network meta-analysis
Authors: Zhang Kai , Zhu Xiaole , Hou Chaoqun , Shi Chenyuan , Miao Yi , Li Qiang 
Published: October 2019

Abstract

Background
The efficacy of some therapeutic methods (open surgical debridement (OSD), conservative treatment (CST) and minimally invasive drainage (MID)) for severe acute pancreatitis (SAP) and moderately severe acute pancreatitis (MSAP) has been widely evaluated. However, the results remained controversial. We performed this study to illuminate whether any difference in incidence exists on patients with SAP/MSAP treated with OSD and MID.

Methods
Eligible articles were collected base of a comprehensive review of PUBMED, EMBASE, COCHRANE, CKNI and WANGFANG for published randomized controlled trials. Two steps of meta-analysis were performed, routine pair-wise meta-analysis and network meta-analysis.

Results
Thirteen studies were included in this study. Participants were classed as 5 groups, CST, early MID (EMID), late MID (LMID), early OSD (EOSD) and late OSD (LOSD). And MID contains endoscopic drainage (ESD), percutaneous catheter drainage (PCD) and minimally invasive surgery (MIS). Compared with CST, MID could decrease both mortality and multiple organ dysfunction syndrome (MODS) rate but OSD couldn’t. Both EMID and MID can significantly decrease the mortality and MODS rate compared to CST. PCD might be most likely to have a benefit compared to CST.

Conclusion
Existing evidence for the use of MID in SAP/MSAP is reliable and it can be used as early treatment. OSD, if necessary, should be avoided or delayed as long as possible.
A four-stage process for intervention description and guide development of a practice-based intervention: refining the Namaste Care intervention implementation specification for people with advanced dementia prior to a feasibility cluster randomised trial
Authors: Walshe Catherine , Kinley Julie , Patel Shakil , Goodman Claire , Bunn Frances , Lynch Jennifer , Scott David , Lund Anne Davidson , Stacpoole Min , Preston Nancy , Froggatt Katherine 
Published: October 2019

AbstractBackgroundSome interventions are developed from practice, and implemented before evidence of effect is determined, or the intervention is fully specified. An example is Namaste Care, a multi-component intervention for people with advanced dementia, delivered in care home, community, hospital and hospice settings. This paper describes the development of an intervention description, guide and training package to support implementation of Namaste Care within the context of a feasibility trial. This allows fidelity to be determined within the trial, and for intervention users to understand how similar their implementation is to that which was studied.MethodsA four-stage approach: a) Collating existing intervention materials and drawing from programme theory developed from a realist review to draft an intervention description. b) Exploring readability, comprehensibility and utility with staff who had not experienced Namaste Care. c) Using modified nominal group techniques with those with Namaste Care experience to refine and prioritise the intervention implementation materials. d) Final refinement with a patient and public involvement panel.ResultsEighteen nursing care home staff, one carer, one volunteer and five members of our public involvement panel were involved across the study steps. A 16-page A4 booklet was designed, with flow charts, graphics and colour coded information to ease navigation through the document. This was supplemented by infographics, and a training package. The guide describes the boundaries of the intervention and how to implement it, whilst retaining the flexible spirit of the Namaste Care intervention.ConclusionsThere is little attention paid to how best to specify complex interventions that have already been organically implemented in practice. This four-stage process may have utility for context specific adaptation or description of existing, but untested, interventions. A robust, agreed, intervention and implementation description should enable a high-quality future trial. If an effect is determined, flexible practice implementation should be enabled through having a clear, evidence-based guide.
Characteristics of residual lymph nodes after six months of antituberculous therapy in HIV-negative individuals with cervical tuberculous lymphadenitis
Authors: Seok Hyeri , Jeon Ji Hoon , Oh Kyung Ho , Choi Hee Kyoung , Choi Won Suk , Lee Young Hen , Seo Hyung Suk , Kwon Soon Young , Park Dae Won 
Published: October 2019

Abstract

Background
The therapeutic response of cervical tuberculous lymphadenitis (CTBL) may be delayed or paradoxical, with the frequent development of residual lymph nodes (LNs) during and after antituberculous treatment. We investigated the incidence of residual LNs and the clinical, radiological, microbiological, and pathologic responses of patients with CTBL after 6 months of antituberculous therapy.

Methods
The medical records of HIV-negative adult patients with CTBL diagnosed between July 2009 and December 2017 were analyzed. After 6 months of first-line antituberculous treatment, computed tomography (CT) scans were conducted to evaluate for residual LNs. Fine-needle aspiration biopsy (FNAB) was carried out if a patient presented with residual LNs > 10 mm in diameter with central necrosis, peripheral rim enhancement, or perinodal inflammation on CT scan.

Results
Residual LNs were detected in 35 of 157 patients who underwent follow-up CT scans and were more commonly observed in younger patients who completed the treatment (mean years ± standard deviation [SD]: 33 ± 13 vs. 44 ± 16, p < 0.001). The recurrence rate was approximately 5%, which was not significantly different in both groups. Among the 15 patients who underwent FNAB, 3 (30%) presented with granuloma, and 2 of 15 and 10 of 14 patients had positive AFB and TB PCR results, respectively. The TB culture results of 15 patients were negative.

Conclusions
Residual LNs may still be observed after 6 months of antituberculous treatment. Although the radiologic and pathologic findings after treatment are still indicative of TB, not all residual LNs indicate recurrence or treatment failure. A six-month therapy may be sufficient for cervical tuberculous lymphadenitis.
MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not related to risk of cancer
Authors: Zhang Li-Feng , Zhu Li-Jie , Zhang Wei , Yuan Wei , Song Ning-Hong , Zuo Li , Mi Yuan-Yuan , Wang Zeng-Jun , Zhang Wei 
Published: October 2019

Abstract

Background
Several studies have focused on the relationship between MMP-8 variants and cancer risk, but they have been unsuccessful in drawing reliable conclusions.

Methods
We employed odds ratio (OR) together with 95% confidence interval (CI) to assess the correlation between MMP-8 C-799 T, Lys460Thr, and Lys87Glu polymorphisms and cancer risk. We further employed in silico tools to evaluate the effect of MMP-8 expression on cancer susceptibility and overall survival time.

Results
A total of 8140 patients with malignant carcinoma and 10,529 healthy individuals (control) were enrolled. Overall, the analysis showed that the relationship between three MMP-8 variants and cancer susceptibility was not significant (allelic contrast, C-799 T: OR = 0.98, 95% CI = 0.92–1.04, Pheterogeneity = 0.068; Lys460Thr: OR = 0.94, 95% CI = 0.67–1.32, Pheterogeneity = 0.905; Lys87Glu: OR = 1.05, 95% CI = 0.93–1.18, Pheterogeneity = 0.968). Similar results were observed in subgroup analysis by ethnicity, cancer type, and source of control. In silico analysis indicated that MMP-8 expression was elevated in bladder cancer tissue compared to that in the control. However, both the higher and lower MMP-8 expression groups did not show an impact on the overall survival time of the patients.

Conclusions
MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not participant with the susceptibility of cancer.
Experiences regarding nutrition and exercise among women during early postpartum: a qualitative grounded theory study
Authors: Murray-Davis Beth , Grenier Lindsay , Atkinson Stephanie A. , Mottola Michelle F. , Wahoush Olive , Thabane Lehana , Xie Feng , Vickers-Manzin Jennifer , Moore Caroline , Hutton Eileen K. 
Published: October 2019

Abstract

Background
Excess gestational weight gain has long- and short-term implications for women and children, and postpartum weight retention is associated with an increased risk of long-term obesity. Despite the existence of dietary and exercise guidelines, many women struggle to return to pre-pregnancy weight. Experiences of women in tackling postpartum weight loss are poorly understood. We undertook this study to explore experiences related to nutrition, exercise and weight in the postpartum in women in Ontario, Canada.

Methods
This was a nested qualitative study within The Be Healthy in Pregnancy Study, a randomized controlled trial. Women randomized to the control group were invited to participate. Semi-structured focus groups were conducted at 4–6 months postpartum. Focus groups were audio recorded, transcribed verbatim, coded and analyzed thematically using a constructivist grounded theory approach.

Results
Women experienced a complex relationship with their body image, due to unrealistic expectations related to their postpartum body. Participants identified barriers and enablers to healthy habits during pregnancy and postpartum. Gestational weight gain guidelines were regarded as unhelpful and unrealistic. A lack of guidance and information about weight management, healthy eating, and exercise in the postpartum period was highlighted.

Conclusion
Strategies for weight management that target the unique characteristics of the postpartum period have been neglected in research and in patient counselling. Postpartum women may begin preparing for their next pregnancy and support during this period could improve their health for subsequent pregnancies.

Trial registration
NCT01689961 registered September 21, 2012.