bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Microorganisms of Public Health Significance in Ready-to-Eat Foods Sold in Developing Countries: Systematic Review and Meta-Analysis
Authors: Mengistu Dechasa Adare , Tolera Sina Temesgen 
Published: November 2020

Background. The issue of microbial quality and safety of ready-to-eat foods has become a public health concern that needs to be addressed to protect the consumer’s health. Contamination of ready-to-eat foods by enteric pathogens such as Escherichia coli, Salmonella, and Staphylococcus aureus bacteria is associated with potential health risks and can cause foodborne outbreaks. Thus, the systematic review and meta-analysis aimed at determining the overall evidence on the prevalence of microorganisms of public health significance in ready-to-eat foods based on previous studies. Methods. The articles published from 2015 to 2020 were searched from multiple electronic databases such as PubMed, Google Scholar, MEDLINE, CINAHL, Science Direct, Web of Science, and the Directory of Open Access Journals. The JBI critical appraisal tool was applied to the included articles. To determine the heterogeneity among the included articles,

I

2

statistics were used while publication bias was evaluated using the visual funnel plot. A Forest plot using the random effect model for meta-analysis was used to estimate the pooled prevalence of E. coli, Salmonella, and S. aureus in ready to eat foods. Results. The pooled prevalence of E. coli, Salmonella, and S. aureus in ready to eat foods was 33.8% (95% CI: 19.9, 51.2;

Q

value
=
67.080

,

I

2

=
89.56
%

), 26.0% (95% CI: 13.8, 43.6%;

Q

value
=
83.67

,

I

2

=
91.63
%

), and 46.3% (95% CI: 24.8, 69.4%,

I

2

=
94.9
%

), respectively. Conclusion. The findings show that contamination of ready-to-eat foods with pathogenic microorganisms continues to be a public health risk. Thus, effective food hygiene and safety systems are necessary to protect the health of the consumers and the public as a whole.
International Consensus Definition of DNA Methylation Subgroups in Juvenile Myelomonocytic Leukemia
Authors: Schönung Maximilian , Meyer Julia , Nöllke Peter , Olshen Adam B. , Hartmann Mark , Murakami Norihiro , Wakamatsu Manabu , Okuno Yusuke , Plass Christoph , Loh Mignon L. , Niemeyer Charlotte M. , Muramatsu Hideki , Flotho Christian , Stieglitz Elliot , Lipka Daniel B. 
Published: November 2020

Abstract

Purpose:
Known clinical and genetic markers have limitations in predicting disease course and outcome in juvenile myelomonocytic leukemia (JMML). DNA methylation patterns in JMML have correlated with outcome across multiple studies, suggesting it as a biomarker to improve patient stratification. However, standardized approaches to classify JMML on the basis of DNA methylation patterns are lacking. We, therefore, sought to define an international consensus for DNA methylation subgroups in JMML and develop classification methods for clinical implementation.

Experimental Design:
Published DNA methylation data from 255 patients with JMML were used to develop and internally validate a classifier model. Accuracy across platforms (EPIC-arrays and MethylSeq) was tested using a technical validation cohort (32 patients). The suitability of both methods for single-patient classification was demonstrated using an independent cohort (47 patients).

Results:
Analysis of pooled, published data established three DNA methylation subgroups as a de facto standard. Unfavorable prognostic parameters (PTPN11 mutation, elevated fetal hemoglobin, and older age) were significantly enriched in the high methylation (HM) subgroup. A classifier was then developed that predicted subgroups with 98% accuracy across different technological platforms. Applying the classifier to an independent validation cohort confirmed an association of HM with secondary mutations, high relapse incidence, and inferior overall survival (OS), while the low methylation subgroup was associated with a favorable disease course. Multivariable analysis established DNA methylation subgroups as the only significant factor predicting OS.

Conclusions:
This study provides an international consensus definition for DNA methylation subgroups in JMML. We developed and validated methods which will facilitate the design of risk-stratified clinical trials in JMML.
The MEK/ERK Network as a Therapeutic Target in Human Cancer
Authors: Barbosa Renee , Acevedo Lucila A. , Marmorstein Ronen 
Published: November 2020

Abstract

The RAS–RAF–MEK–ERK pathway is the most well-studied of the MAPK cascades and is critical for cell proliferation, differentiation, and survival. Abnormalities in regulation resulting from mutations in components of this pathway, particularly in upstream proteins, RAS and RAF, are responsible for a significant fraction of human cancers and nearly all cutaneous melanomas. Activation of receptor tyrosine kinases by growth factors and various extracellular signals leads to the sequential activation of RAS, RAF, MEK, and finally ERK, which activates numerous transcription factors and facilitates oncogenesis in the case of aberrant pathway activation. While extensive studies have worked to elucidate the activation mechanisms and structural components of upstream MAPK components, comparatively less attention has been directed toward the kinases, MEK and ERK, due to the infrequency of oncogenic-activating mutations in these kinases. However, acquired drug resistance has become a major issue in the treatment of RAS- and RAF-mutated cancers. Targeting the terminal kinases in the MAPK cascade has shown promise for overcoming many of these resistance mechanisms and improving treatment options for patients with MAPK-aberrant cancers. Here, we will describe the role of MEK and ERK in MAPK signaling and summarize the current understanding of their interaction and activation mechanisms. We will also discuss existing approaches for targeting MEK and ERK, and the benefits of alternative strategies. Areas requiring further exploration will be highlighted to guide future research endeavors and aid in the development of alternative therapeutic strategies to combat surmounting drug resistance in treating MAPK-mediated cancers.

Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/19/3/361/F1.large.jpg.
Progesterone Receptor Is a Haploinsufficient Tumor-Suppressor Gene in Cervical Cancer
Authors: Park Yuri , Baik Seunghan , Ho Charles , Lin Chin-Yo , Chung Sang-Hyuk 
Published: November 2020

Abstract

Tumor-suppressor genes (TSG) are often deleted or transcriptionally suppressed in cancer. PGR codes for progesterone receptor (PR), a transcription factor whose function depends on its ligand. Although PR expression is often undetectable in cervical cancer, its relevance to the endocrine-related etiology of this prevalent gynecological disease remains unclear. In this study, we show that the deletion of one Pgr allele in cervical epithelium promoted spontaneous cervical cancer in human papilloma viral oncogene-expressing transgenic mice as efficiently as the ablation of both Pgr alleles. We also show that tumors arising in the transgenic mice with one or both Pgr alleles did not express PR or expressed at the reduced levels compared with the normal epithelium. PR status correlated with estrogen receptor α (ERα) status in the mouse model and the Cancer Genome Atlas (TCGA) dataset. TCGA data analyses revealed that PGR expression significantly decreased in cervical cancer and that the biallelic deletion of PGR was rare. Furthermore, low PGR expression was associated with poor prognosis in young patients with cervical cancer. These discoveries point to PGR as a haploinsufficient TSG in the uterine cervix. They also raise the possibility that the restoration of PGR expression may improve the survival rate.

Implications:
The decreased expression of PR may increase the risk of cervical cancer in human papillomavirus–infected women.

Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/19/1/42/F1.large.jpg.
Hitting Gliomas When They Are Down: Exploiting IDH-Mutant Metabolic Vulnerabilities
Authors: Pirozzi Christopher J. , Yan Hai 
Published: November 2020

Abstract

Summary:
Tumors mutated in IDH1 tend to have lower levels of the essential substrate NAD+. In this issue of Cancer Discovery, Nagashima and colleagues exploit this metabolic sensitivity by devising a combinatorial therapy that both further reduces the pools as well as sequesters the remaining substrate in PAR chains, sensitizing the cells to temozolomide and PARG inhibition.
See related article by Nagashima et al., p. 1672.
An Expanded Tool Kit for Modeling the Oncogenic Functions of KRAS
Authors: Kostyrko Kaja , Sweet-Cordero E. Alejandro 
Published: November 2020

Abstract

Summary:
Zafra and colleagues developed new mouse models to study the role of specific KRAS mutations in pancreatic, lung, and colon cancer pathogenesis. Their studies clearly describe the distinct ability of these mutations to drive pathogenesis in a tissue-specific fashion.
See related article by Zafra et al., p. 1654.
Free Asparagine or Die: Cancer Cells Require Proteasomal Protein Breakdown to Survive Asparagine Depletion
Authors: Davidsen Kristian , Sullivan Lucas B. 
Published: November 2020

Abstract

Summary:
The chemotherapeutic enzyme asparaginase depletes systemic asparagine to kill cancers; however, its efficacy thus far is limited to a subset of leukemias. Hinze and colleagues identify that inhibiting proteasomal release of asparagine can sensitize colorectal cancers to asparagine depletion, providing a potential avenue to repurpose asparaginase for treatment of solid tumors.
See related article by Hinze et al., p. 1690.
DISENGAGE Registry
Authors: Pellicano Mariano , Ciccarelli Giovanni , Xaplanteris Panagiotis , Di Gioia Giuseppe , Milkas Anastasios , Colaiori Iginio , Heyse Alex , Van Durme Frederik , Vanderheyden Marc , Bartunek Jozef , De Bruyne Bernard , Barbato Emanuele 
Published: November 2020

Background:
During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making.

Methods:

In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFR
eng
] and disengaged [FFR
dis
]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFR
eng
–FFR
dis
was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFR
eng
–FFR
dis
could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFR
eng
–FFR
dis
related to the stenosis location, that is, proximal and middle versus distal coronary segments.

Results:

Overall, FFR significantly changed after GC disengagement: FFR
eng
0.84±0.08 versus FFR
dis
0.80±0.09,
P
<0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFR
eng
–FFR
dis
, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03;
P
=0.042).

Conclusions:
GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.
Feasibility of Transcatheter Aortic Valve Replacement in Prior Aortic Root Surgery
Authors: Brener Michael I. , Yamabe Tsuyoshi , Leb Jay , Khalique Omar K. , Takayama Hiroo , George Isaac 
Published: November 2020

Background:
Aortic root replacement (ARR) introduces several anatomic complexities relevant to valve-in-valve (VIV)–transcatheter aortic valve replacement (TAVR) that may (1) increase the risk of coronary obstruction, (2) necessitate transcatheter valve overexpansion to accommodate large annuli, and (3) require alternative vascular access to navigate aortic kinking. Therefore, we aimed to quantify the feasibility of VIV-TAVR in patients who underwent aortic root surgery.

Methods:
Postoperative computed tomography scans were reviewed for consecutive patients who underwent ARR between 2005 and 2019 to obtain measurements relevant for VIV-TAVR planning. Virtual transcatheter valve to coronary ostia distance was measured to assess the risk of coronary obstruction. Root morphologies were classified into 1 of 4 groups based on aortic graft type, aortic diameter at the sinotubular junction, sinus height, estimated transcatheter heart valve height, and diameter. VIV-TAVR was projected to be complex in patients with an aortic kink, extremely large annulus, or heightened risk of coronary obstruction.

Results:

Among 848 patients who underwent ARR during the 15-year study period, qualifying contrast-enhanced scans post-ARR were performed in 81 patients. Complex VIV-TAVR was anticipated in 50.6% of subjects. Patients with abnormal root anatomy experienced increased odds of complex VIV-TAVR relative to patients with normal root physiology (ie, sinotubular junction diameter>transcatheter heart valve diameter, sinus height>transcatheter heart valve height) or those who received straight tube grafts (odds ratio, 4.53 [95% CI, 1.02–20.1],
P
=0.046). The odds of complex VIV-TAVR were also higher among patients who underwent aortic valve replacement–ARR with a stentless bioprosthesis (stentless versus stented, odds ratio, 4.63 [95% CI, 1.40–15.3],
P
=0.012; stentless versus valve-sparing ARR, odds ratio, 3.78 [95% CI, 1.14–12.5],
P
=0.029).

Conclusions:
ARR patients with atypical root morphologies or those who underwent valve replacement with stentless bioprostheses may be at high risk for complex VIV-TAVR. Prospective evaluation is required to assess the impact of these conclusions on procedural feasibility.
Live Imaging of Intracranial Lymphatics in the Zebrafish
Authors: Castranova Daniel , Samasa Bakary , Venero Galanternik Marina , Jung Hyun Min , Pham Van N. , Weinstein Brant M. 
Published: November 2020

Rationale:
The recent discovery of meningeal lymphatics in mammals is reshaping our understanding of fluid homeostasis and cellular waste management in the brain, but visualization and experimental analysis of these vessels is challenging in mammals. Although the optical clarity and experimental advantages of zebrafish have made this an essential model organism for studying lymphatic development, the existence of meningeal lymphatics has not yet been reported in this species.

Objective:
Examine the intracranial space of larval, juvenile, and adult zebrafish to determine whether and where intracranial lymphatic vessels are present.

Methods and Results:
Using high-resolution optical imaging of the meninges in living animals, we show that zebrafish possess a meningeal lymphatic network comparable to that found in mammals. We confirm that this network is separate from the blood vascular network and that it drains interstitial fluid from the brain. We document the developmental origins and growth of these vessels into a distinct network separated from the external lymphatics. Finally, we show that these vessels contain immune cells and perform live imaging of immune cell trafficking and transmigration in meningeal lymphatics.

Conclusions:
This discovery establishes the zebrafish as a important new model for experimental analysis of meningeal lymphatic development and opens up new avenues for probing meningeal lymphatic function in health and disease.
Observations of Stably Stratified Flow through a Microscale Gap
Authors: Vassallo Daniel , Krishnamurthy Raghavendra , Menke Robert , Fernando Harindra J. S. 
Published: November 2020

Abstract
This paper reports the findings of a comprehensive field investigation on flow through a mountain gap subject to a range of stably stratified environmental conditions. This study was embedded within the Perdigão field campaign, which was conducted in a region of parallel double-ridge topography with ridge-normal wind climatology. One of the ridges has a well-defined gap (col) at the top, and an array of in situ and remote sensors, including a novel triple Doppler lidar system, was deployed around it. The experimental design was mostly guided by previous numerical and theoretical studies conducted with an idealized configuration where a flow (with characteristic velocity U
0 and buoyancy frequency N) approaches normal to a mountain of height h with a gap at its crest, for which the governing parameters are the dimensionless mountain height G = Nh/U
0 and various gap aspect ratios. Modified forms of G were proposed to account for real-world atmospheric variability, and the results are discussed in terms of a gap-averaged value G

c
. The nature of gap flow was highly dependent on G

c
, wherein a nearly neutral flow regime (G

c
< 1), a transitional mountain wave regime [G

c
~ O(1)], and a gap-jetting regime [G

c
> O(1)] were identified. The measurements were in broad agreement with previous numerical and theoretical studies on a single ridge with a gap or double-ridge topography, although details vary. This is the first-ever detailed field study reported on microscale [O(100) m] gap flows, and it provides useful data and insights for future theoretical and numerical studies.
Statewide Seasonal Variations of Infections Within the Intensive Care Unit Among the Trauma Population
Authors: Clark Jason M. , Durrani Hamza , Hagan Josh D. , Watson Carrie , Richards Winston T. , Taylor Dana , Ang Darwin N. 
Published: November 2020

Background Infections within intensive care unit (ICU) are a persistent problem among the critically ill. Viral pneumonias have already been established as having a season variations. We attempt to evaluate the seasonal variations of pneumonia among the traumatically injured and the critically ill. Materials and Methods A retrospective cohort study among traumatized patients admitted from 1997 to 2017 to an ICU within the state of Florida was performed who were diagnosed with pneumonia. A multivariate regression analysis was performed to adjust for confounders. Time periods were divided into seasons: summer, winter, spring, and fall. A subset analysis of geriatric patients (>65 years) was also performed. Results A total of 869 553 patients were identified. The most common viral infection was influenza with adenovirus the least. The most common bacterial pneumonia was Staphylococcus aureus with Bordetella pertussis the least. Pneumonias had a seasonal variation. Compared to summer, winter had a higher likelihood of pneumonia overall (Adjusted Odds Ratio (AOR)1.13). This was seen in the spring (AOR 1.04) but not in fall (AOR 1.00). Viral infections were more pronounced (AOR 3.79) in all other seasons, while bacterial showed increased likelihood during winter (AOR 1.05). In geriatrics, pneumonia was again more likely in the winter (AOR 1.22) with both viral and bacterial infections being more pronounced during winter (AOR 4.79, AOR 1.09). Discussion Pneumonias are seen more frequently within the ICU during the winter for the traumatized patient. This held true with the critically ill geriatric population as well. This effect was observed in both viral and bacterial pneumonias.
Facial Nerve Paralysis Following Endovascular Embolization: A Case Report and Review of the Literature
Authors: Feng Austin Y. , Jin Michael C. , Wong Sandy , Pepper Jon-Paul , Jackler Robert , Vaisbuch Yona 
Published: November 2020

Objective: We report a case of facial nerve paralysis post-endovascular embolization of a sigmoid sinus dural arterio-venous fistula from initial presentation to current management and discuss the merits of observation versus decompression through a systematic review of relevant literature. Patient: 61 F with right facial palsy. Intervention: Following a single intravenous dexamethasone injection with oral steroids over 2 months, patient was observed with no additional treatment other than Botox chemodenervation and facial rehabilitation. Outcome and Results: The patient initially presented with complete right facial palsy (HB 6/6). Post-op CT imaging indicated Onyx (ev3, Irvine, California, USA) particles present at the geniculate segment of the facial nerve. Observation was chosen over surgical intervention. At the most current follow up of 8 months, facial function has improved substantially (HB 2/6). Conclusion: Facial palsy is a serious, though rare, complication of transarterial endovascular embolization. With our case report and literature review, we highlight not only how conservative observation is the recommended treatment, but also that facial nerve recovery should be expected to reach near complete recovery, but not sooner than in 3 months.
Impact of Exchange Rate Changes on the Trade Balance of India: An Asymmetric Nonlinear Cointegration Approach
Authors: Bhat Sajad Ahmad , Bhat Javed Ahmad 
Published: November 2020

Applying an asymmetric model, the study reported no evidence of J-curve phenomenon in case of India. In the short-run currency appreciation deteriorates the trade balance and currency depreciation improves it. In the long-run, again the similar response is observed, however, only the impact of currency depreciation is statistically significant. Increase in domestic demand deteriorates the trade balance by a greater magnitude than improvement is observed due to the decline in domestic demand conditions. Finally, foreign demand hike improves the trade balance relatively by a higher magnitude; however, the impact of a foreign demand decline is statistically insignificant. JEL Codes: F4, F41, F42
Local public innovation: an analysis of its perceived impacts on public performance
Authors: Queyroi Yoann , Carassus David , Maurel Christophe , Favoreu Christophe , Marin Pierre 
Published: November 2020

This article explores public innovations implemented by local authorities, which consider them as a key means of improving their performance in response to a restrictive context. The authors thus propose to grasp the impacts of these innovations in terms of perceived performance from a global and multidimensional point of view. Based on a quantitative study conducted among French local authorities, this research first presents the results obtained from a theoretical point of view, providing insight into the multiple impacts of implementing innovations within the public sector. Then, at the managerial level, the study identifies specific impacts for each type of public innovation, the aim being to structure the innovation portfolio of public organisations. Points for practitioners An increasing number of innovations are being introduced in the public sector. However, the impact of these innovations on public performance is often not assessed. That is why by focusing our research on French local authorities, we guide managers both in analysing this influence by distinguishing several types of innovation and performance, and in building a portfolio of innovations in line with the internal resources of their local authority, as well as the public service provided in response to the needs of the territory.