bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the associations between transcript levels and fluxes in constraint-based models of metabolism
Authors: Sinha Neeraj , van Schothorst Evert M. , Hooiveld Guido J. E. J. , Keijer Jaap , Martins dos Santos Vitor A. P. , Suarez-Diez Maria 
Published: November 2021

Abstract
Background
Several computational methods have been developed that integrate transcriptomics data with genome-scale metabolic reconstructions to increase accuracy of inferences of intracellular metabolic flux distributions. Even though existing methods use transcript abundances as a proxy for enzyme activity, each method uses a different hypothesis and assumptions. Most methods implicitly assume a proportionality between transcript levels and flux through the corresponding function, although these proportionality constant(s) are often not explicitly mentioned nor discussed in any of the published methods. E-Flux is one such method and, in this algorithm, flux bounds are related to expression data, so that reactions associated with highly expressed genes are allowed to carry higher flux values.

Results
Here, we extended E-Flux and systematically evaluated the impact of an assumed proportionality constant on model predictions. We used data from published experiments with Escherichia coli and Saccharomyces cerevisiae and we compared the predictions of the algorithm to measured extracellular and intracellular fluxes.

Conclusion
We showed that detailed modelling using a proportionality constant can greatly impact the outcome of the analysis. This increases accuracy and allows for extraction of better physiological information.
Trophic niche shifts and phenotypic trait evolution are largely decoupled in Australasian parrots
Authors: García-Navas Vicente , Tobias Joseph A. , Schweizer Manuel , Wegmann Daniel , Schodde Richard , Norman Janette A. , Christidis Les 
Published: November 2021

AbstractBackgroundTrophic shifts from one dietary niche to another have played major roles in reshaping the evolutionary trajectories of a wide range of vertebrate groups, yet their consequences for morphological disparity and species diversity differ among groups.MethodsHere, we use phylogenetic comparative methods to examine whether the evolution of nectarivory and other trophic shifts have driven predictable evolutionary pathways in Australasian psittaculid parrots in terms of ecological traits such as body size, beak shape, and dispersal capacity.ResultsWe found no evidence for an ‘early-burst’ scenario of lineage or morphological diversification. The best-fitting models indicate that trait evolution in this group is characterized by abrupt phenotypic shifts (evolutionary jumps), with no sign of multiple phenotypic optima correlating with different trophic strategies. Thus, our results point to the existence of weak directional selection and suggest that lineages may be evolving randomly or slowly toward adaptive peaks they have not yet reached.ConclusionsThis study adds to a growing body of evidence indicating that the relationship between avian morphology and feeding ecology may be more complex than usually assumed and highlights the importance of adding more flexible models to the macroevolutionary toolbox.
Response of physiological parameters in Dionaea muscipula J. Ellis teratomas transformed with rolB oncogene
Authors: Makowski Wojciech , Królicka Aleksandra , Tokarz Barbara , Miernicka Karolina , Kołton Anna , Pięta Łukasz , Malek Kamilla , Ekiert Halina , Szopa Agnieszka , Tokarz Krzysztof Michał 
Published: November 2021

Abstract
Background
Plant transformation with rol oncogenes derived from wild strains of Rhizobium rhizogenes is a popular biotechnology tool. Transformation effects depend on the type of rol gene, expression level, and the number of gene copies incorporated into the plant’s genomic DNA. Although rol oncogenes are known as inducers of plant secondary metabolism, little is known about the physiological response of plants subjected to transformation.

Results
In this study, the physiological consequences of rolB oncogene incorporation into the DNA of Dionaea muscipula J. Ellis was evaluated at the level of primary and secondary metabolism. Examination of the teratoma (transformed shoots) cultures of two different clones (K and L) showed two different strategies for dealing with the presence of the rolB gene. Clone K showed an increased ratio of free fatty acids to lipids, superoxide dismutase activity, synthesis of the oxidised form of glutathione, and total pool of glutathione and carotenoids, in comparison to non-transformed plants (control). Clone L was characterised by increased accumulation of malondialdehyde, proline, activity of superoxide dismutase and catalase, total pool of glutathione, ratio of reduced form of glutathione to oxidised form, and accumulation of selected phenolic acids. Moreover, clone L had an enhanced ratio of total triglycerides to lipids and accumulated saccharose, fructose, glucose, and tyrosine.

Conclusions
This study showed that plant transformation with the rolB oncogene derived from R. rhizogenes induces a pleiotropic effect in plant tissue after transformation. Examination of D. muscipula plant in the context of transformation with wild strains of R. rhizogenes can be a new source of knowledge about primary and secondary metabolites in transgenic organisms.
Circ_MUC16 attenuates the effects of Propofol to promote the aggressive behaviors of ovarian cancer by mediating the miR-1182/S100B signaling pathway
Authors: Yang Hao , Guo Yunrui , Zhang Yecai , Wang Decai , Zhang Guoyun , Hou Jiali , Yang Jianming 
Published: November 2021

Abstract
Background
Propofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs (ncRNAs). The objective of this study was to explore the role of circular RNA mucin 16 (circ_MUC16) in Propofol-mediated inhibition of ovarian cancer.

Methods
The expression of circ_MUC16, microRNA-1182 (miR-1182) and S100 calcium-binding protein B (S100B) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). The expression of S100B protein was checked by western blot. Cell proliferation was assessed by 3-(4, 5-di methyl thiazol-2-yl)-2, 5-di phenyl tetrazolium bromide (MTT) assay and colony formation assay. Glycolysis metabolism was assessed by glucose consumption, lactate production and ATP level. Cell migration and cell invasion were assessed by transwell assay. Cell migration was also assessed by wound healing assay. Animal study was conducted in nude mice to determine the role of circ_MUC16 in vivo. The relationship between miR-1182 and circ_MUC16 or S100B was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.

Results
Propofol inhibited ovarian cancer cell proliferation, glycolysis metabolism, migration and invasion, which were partly recovered by circ_MUC16 overexpression. Circ_MUC16 was downregulated in Propofol-treated ovarian cancer cells. Besides, circ_MUC16 knockdown enhanced the effects of Propofol to further inhibit tumor growth in vivo. MiR-1182 was a target of circ_MUC16, and circ_MUC16 knockdown-inhibited cell proliferation, glycolysis metabolism, migration and invasion were partly restored by miR-1182 inhibition. In addition, S100B was a target of miR-1182, and miR-1182-suppressed cell proliferation, glycolysis metabolism, migration and invasion were partly restored by S100B overexpression.

Conclusion
Circ_MUC16 overexpression alleviated the effects of Propofol to promote the aggressive behaviors of ovarian cancer by targeting the miR-1182/S100B network.
Left circumflex artery pericardia fistula combined with huge pseudoaneurysm: a rare case report
Authors: Shen Zhiyan , Xia Kun , Liu Xinfeng , Wang Rongpin 
Published: November 2021

Abstract
Background
Coronary artery fistula refers to an abnormal communication between a coronary artery and great vessel, a cardiac chamber or other structure. The left circumflex artery (LCX) pericardia fistula combined with huge pseudoaneurysm is extremely rare.

Case presentation
A 39-year-old young female was admitted into our hospital because of palpitation and shortness of breath. Coronary computed tomography angiography (CCTA) showed a huge pseudoaneurysm located in pericardium. Coronary angiography revealed the LCX pericardia fistula. Then surgical treatment was performed. She was in good condition without complications after surgery.

Conclusions
Coronary artery fistula combined with pseudoaneurysm can be caused by congenital factors. Early surgical treatment can relieve the patient's symptoms and prevent the occurrence of adverse cardiovascular events.
Development of a dynamic interactive web tool to enhance understanding of multi-state model analyses: MSMplus
Authors: Skourlis Nikolaos , Crowther Michael J. , Andersson Therese M-L. , Lambert Paul C. 
Published: November 2021

Abstract
Background
Multi-state models are used in complex disease pathways to describe a process where an individual moves from one state to the next, taking into account competing states during each transition. In a multi-state setting, there are various measures to be estimated that are of great epidemiological importance. However, increased complexity of the multi-state setting and predictions over time for individuals with different covariate patterns may lead to increased difficulty in communicating the estimated measures. The need for easy and meaningful communication of the analysis results motivated the development of a web tool to address these issues.

Results
MSMplus is a publicly available web tool, developed via the Shiny R package, with the aim of enhancing the understanding of multi-state model analyses results. The results from any multi-state model analysis are uploaded to the application in a pre-specified format. Through a variety of user-tailored interactive graphs, the application contributes to an improvement in communication, reporting and interpretation of multi-state analysis results as well as comparison between different approaches. The predicted measures that can be supported by MSMplus include, among others, the transition probabilities, the transition intensity rates, the length of stay in each state, the probability of ever visiting a state and user defined measures. Representation of differences, ratios and confidence intervals of the aforementioned measures are also supported. MSMplus is a useful tool that enhances communication and understanding of multi-state model analyses results.

Conclusions
Further use and development of web tools should be encouraged in the future as a means to communicate scientific research.
Does pre-notification increase questionnaire response rates: a randomised controlled trial nested within a systematic review
Authors: Woolf Benjamin , Edwards Phil 
Published: November 2021

Abstract
Background
Missing outcome data can lead to bias in the results of systematic reviews. One way to address missing outcome data is by requesting the data from the trial authors, but non-response is common. One way to potentially improve response rates is by sending study participants advance communication. During the update of a systematic review examining the effect of pre-notification on response rates, study authors needed to be contacted for further information. This study was nested within the systematic review by randomising authors to receive a notification of the upcoming request for information. The objective was to test if pre-notification increased response rates.

Methods
The participants were study authors included in the systematic review, whose studies were at unclear risk of bias. The intervention was a pre-notification of the request for further information, sent 1 day before the request. The outcome was defined as the proportion of authors who responded to the request for information. Authors were randomised by simple randomisation. Thirty three authors were randomised to the pre-notification arm, and 42 were randomised to the control arm. Authors were blinded to the possibility of an alternative condition.

Results
All authors randomised were analysed. 14/33 (42.4%) authors in the pre-notification arm had returned responses to the questionnaire, and 18/42 (42.9%) in the control arm. There was no evidence of a difference between these groups (absolute difference = − 0.5, 95% CI (− 23.4 to 22.5%), p = 1). We received no complaints about receiving the pre-notification.

Conclusions
This study’s results do not support the hypothesis that pre-notification increases response from study authors being contacted for a request for more information. However, the study has a low power, and the results may not generalise to other contexts, methods of administering a pre-notification, or study populations.

Trial registration
Registration and protocol:
This trial is not registered with any trial registry. However, the protocol was posted in advance on the Open Science Framework website and is available on the Open Science Framework website: DOI: 10.17605/OSF.IO/MSV2W or https://osf.io/msv2w/
Exploring the impact of ineligibility on individuals expressing interest in a trial aimed at improving daily functioning regarding perceptions of self, research and likelihood of future participation
Authors: Dwyer Christopher P. , McAneney Helen , Rogers Fionnuala M. , Joyce Robert , Hynes Sinéad M. 
Published: November 2021

AbstractBackgroundEligibility guidelines in research trials are necessary to minimise confounds and reduce bias in the interpretation of potential treatment effects. There is limited extant research investigating how being deemed ineligible for such trials might impact patients’ perceptions of themselves and of research. Better understanding of the impact of patient ineligibility could enhance design and implementation of future research studies.MethodsEight semi-structured telephone interviews were conducted to explore the impact of ineligibility on self-perceptions; perceptions regarding the nature of research; and the likelihood of expressing interest in future research. Data were collected and analysed thematically through inductive, interpretive phenomenological analysis (IPA).ResultsFive themes emerged regarding the experience of being deemed ineligible: (1) Being deemed ineligible is emotion and reaction evoking; (2) ‘Doing your bit’: Helping others and increasing the value of research; (3) Communication of ineligibility; (4) Appreciation for those who express interest; and (5) Subsequent perceptions and attitudes towards research.ConclusionsThe results suggest that being deemed ineligible can elicit negative emotional outcomes but is not likely to change perceptions of or attitudes towards research, possibly due to a desire to help similar others. Ineligibility can impact future participation in some cases, thus reducing the recruitment pool for subsequent research studies. Recommendations are provided to help minimise this risk. Advising of ineligibility in a personal way is recommended: with enhanced clarity regarding the reasoning behind the decision; providing opportunities to ask questions; and ensuring that appreciation for the patient’s time and interest are communicated.
Epidemiology and infection control of carbapenem resistant Acinetobacter baumannii and Klebsiella pneumoniae at a German university hospital: a retrospective study of 5 years (2015–2019)
Authors: Chhatwal Patrick , Ebadi Ella , Schwab Frank , Ziesing Stefan , Vonberg Ralf-Peter , Simon Nicolas , Gerbel Svetlana , Schlüter Dirk , Bange Franz-Christoph , Baier Claas 
Published: November 2021

Abstract
Background
Carbapenem resistant (CR) Klebsiella pneumoniae (Kp) and Acinetobacter baumannii (Ab) are emerging multidrug resistant bacteria with very limited treatment options in case of infection. Both are well-known causes of nosocomial infections and outbreaks in healthcare facilities.

Methods
A retrospective study was conducted to investigate the epidemiology of inpatients with CR Kp and CR Ab in a 1500-bed German university hospital from 2015 to 2019. We present our infection control concept including a weekly microbiologic screening for patients who shared the ward with a CR Kp or CR Ab index patient.

Results
Within 5 years, 141 CR Kp and 60 CR Ab cases were hospitalized corresponding to 118 unique patients (74 patients with CR Kp, 39 patients with CR Ab and 5 patients with both CR Ab and CR Kp). The mean incidence was 0.045 (CR Kp) and 0.019 (CR Ab) per 100 inpatient cases, respectively. Nosocomial acquisition occurred in 53 cases (37.6%) of the CR Kp group and in 12 cases (20.0%) of the CR Ab group. Clinical infection occurred in 24 cases (17.0%) of the CR Kp group and in 21 cases (35.0%) of the CR Ab group. 14 cases (9.9%) of the CR Kp group and 29 cases (48.3%) of the CR Ab group had a history of a hospital stay abroad within 12 months prior to admission to our hospital. The weekly microbiologic screening revealed 4 CR Kp cases caused by nosocomial transmission that would have been missed without repetitive screening.

Conclusions
CR Kp and CR Ab cases occurred infrequently. A history of a hospital stay abroad, particularly in the CR Ab group, warrants pre-emptive infection control measures. The weekly microbiologic screening needs further evaluation in terms of its efficiency.
Intravenous cyclophosphamide induces remission in children with difficult to treat steroid resistant nephrotic syndrome from minimal change disease
Authors: Haddad Maha , Kale Arundhati , Butani Lavjay 
Published: November 2021

Abstract
Background
Steroid resistant nephrotic syndrome (SRNS), while uncommon in children, is associated with significant morbidity. Calcineurin inhibitors (CNIs) remain the first line recommended therapy for children with non-genetic forms of SRNS, but some children fail to respond to them. Intravenous (IV) cyclophosphamide (CTX) has been shown to be effective in Asian-Indian children with difficult to treat SRNS (SRNS-DTT). Our study evaluated the outcome of IV CTX treatment in North American children with SRNS-DTT.

Methods
Retrospective review of the medical records of children with SRNS-DTT treated with IV CTX from January 2000 to July 2019 at our center. Data abstracted included demographics, histopathology on renal biopsy, prior and concomitant use of other immunosuppressive agents and serial clinical/laboratory data. Primary outcome measure was attainment of complete remission (CR).

Results
Eight children with SRNS-DTT received monthly doses (median 6; range 4–6) of IV CTX. Four (50%) went into CR, 1 achieved partial remission and 3 did not respond. Three of the 4 responders had minimal change disease (MCD). Excluding the 1 child who responded after the 4th infusion, the median time to CR was 6.5 (range 0.5–8) months after completion of IV CTX infusions. Three remain in CR at a median of 8.5 years (range: 3.7–10.5 years) after completion of CTX; one child relapsed and became steroid-dependent. No infections or life-threatening complications related to IV CTX were observed.

Conclusions
IV CXT can induce long term remission in North-American children with MCD who have SRNS-DTT.
The risk of lymph node metastasis in gastric cancer conforming to indications of endoscopic resection and pylorus-preserving gastrectomy: a single-center retrospective study
Authors: Yanzhang Wu , Guanghua Li , Zhihao Zhou , Zhixiong Wang , Zhao Wang 
Published: November 2021

Abstract
Background
Lymph node metastasis (LNM) status is an important prognostic factor that strongly influences the treatment decision of early gastric cancer (EGC). This study aimed to evaluate the pattern and clinical significance of LNM in EGC.

Methods
A total of 354 patients with carcinoma in situ (n = 42), EGC (n = 312) who underwent radical gastrectomy were enrolled. Their clinicopathological features, pathological reports, and prognostic data were collected and analyzed.

Results
The incidence of LNM in all patients was 18.36% (65/354). The rates of D1 and D2 station metastases were 12.10% (43/354) and 6.21% (22/354), respectively. The rates of LNM in absolute indication of endoscopic resection and expanded indication were 3.27% (2/61) and 28.55% (4/14), respectively. Skip LNM was observed in 3.67% (13/354) of patients. For those with middle-third tumor, the metastasis rate of the No. 5 lymph node was 3.05% (5/164). The independent risk factors for LNM were tumors measuring > 30 mm, poorly differentiated tumors, and lymphovascular invasion (all P < 0.05; area under the curve, 0.783). The 5-year disease-free survival rates of patients with and without LNM were 96.26 and 79.17%, respectively (P = 0.011). Tumors measuring > 20 mm and LNM were independent predictive factors for poor survival outcome in all patients.

Conclusions
Patients with EGC conforming to expanded indications have a relatively high risk of LNM and may not be suitable for endoscopic submucosal dissection. Pylorus-preserving gastrectomy for patients with middle-third EGC remains controversial due to the high metastasis rate of the No. 5 lymph node.
Temporality of clinical factors associated with pancreatic cancer: a case-control study using linked electronic health records
Authors: Dayem Ullah Abu Z. M. , Stasinos Konstantinos , Chelala Claude , Kocher Hemant M. 
Published: November 2021

Abstract
Background
Pancreatic cancer risk is poorly quantified in relation to the temporal presentation of medical comorbidities and lifestyle. This study aimed to examine this aspect, with possible influence of demographics.

Methods
We conducted a retrospective case-control study on the ethnically-diverse population of East London, UK, using linked electronic health records. We evaluated the independent and two-way interaction effects of 19 clinico-demographic factors in patients with pancreatic cancer (N = 965), compared with non-malignant pancreatic conditions (N = 3963) or hernia (control; N = 4355), reported between April 1, 2008 and March 6, 2020. Risks were quantified by odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models.

Results
We observed increased odds of pancreatic cancer incidence associated with recent-onset diabetes occurring within 6 months to 3 years before cancer diagnosis (OR 1.95, 95% CI 1.25-3.03), long-standing diabetes for over 3 years (OR 1.74, 95% CI 1.32-2.29), recent smoking (OR 1.81, 95% CI 1.36-2.4) and drinking (OR 1.76, 95% CI 1.31-2.35), as compared to controls but not non-malignant pancreatic conditions. Pancreatic cancer odds was highest for chronic pancreatic disease patients (recent-onset: OR 4.76, 95% CI 2.19-10.3, long-standing: OR 5.1, 95% CI 2.18-11.9), amplified by comorbidities or harmful lifestyle. Concomitant diagnosis of diabetes, upper gastrointestinal or chronic pancreatic conditions followed by a pancreatic cancer diagnosis within 6 months were common, particularly in South Asians. Long-standing cardiovascular, respiratory and hepatobiliary conditions were associated with lower odds of pancreatic cancer.

Conclusions
Several factors are, independently or via effect modifications, associated with higher incidence of pancreatic cancer, but some established risk factors demonstrate similar magnitude of risk measures of developing non-malignant pancreatic conditions. The findings may inform refined risk-stratification strategies and better surveillance for high-risk individuals, and also provide a means for systematic identification of target population for prospective cohort-based early detection research initiatives.