bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pitfalls of Relating Weeds, Herbicide Use, and Crop Yield: Don't Fall Into the Trap! A Critical Review
Authors: Colbach Nathalie , Petit Sandrine , Chauvel Bruno , Deytieux Violaine , Lechenet Martin , Munier-Jolain Nicolas , Cordeau Stéphane
Published: December 2020

The growing recognition of the environmental and health issues associated to pesticide use requires to investigate how to manage weeds with less or no herbicides in arable farming while maintaining crop productivity. The questions of weed harmfulness, herbicide efficacy, the effects of herbicide use on crop yields, and the effect of reducing herbicides on crop production have been addressed over the years but results and interpretations often appear contradictory. In this paper, we critically analyze studies that have focused on the herbicide use, weeds and crop yield nexus. We identified many inconsistencies in the published results and demonstrate that these often stem from differences in the methodologies used and in the choice of the conceptual model that links the three items. Our main findings are: (1) although our review confirms that herbicide reduction increases weed infestation if not compensated by other cultural techniques, there are many shortcomings in the different methods used to assess the impact of weeds on crop production; (2) Reducing herbicide use rarely results in increased crop yield loss due to weeds if farmers compensate low herbicide use by other efficient cultural practices; (3) There is a need for comprehensive studies describing the effect of cropping systems on crop production that explicitly include weeds and disentangle the impact of herbicides from the effect of other practices on weeds and on crop production. We propose a framework that presents all the links and feed-backs that must be considered when analyzing the herbicide-weed-crop yield nexus. We then provide a number of methodological recommendations for future studies. We conclude that, since weeds are causing yield loss, reduced herbicide use and maintained crop productivity necessarily requires a redesign of cropping systems. These new systems should include both agronomic and biodiversity-based levers acting in concert to deliver sustainable weed management.
The Ocular Neural Crest: Specification, Migration, and Then What?
Authors: Williams Antionette L. , Bohnsack Brenda L.
Published: December 2020

During vertebrate embryonic development, a population of dorsal neural tube-derived stem cells, termed the neural crest (NC), undergo a series of morphogenetic changes and extensive migration to become a diverse array of cell types. Around the developing eye, this multipotent ocular NC cell population, called the periocular mesenchyme (POM), comprises migratory mesenchymal cells that eventually give rise to many of the elements in the anterior of the eye, such as the cornea, sclera, trabecular meshwork, and iris. Molecular cell biology and genetic analyses of congenital eye diseases have provided important information on the regulation of NC contributions to this area of the eye. Nevertheless, a complete understanding of the NC as a contributor to ocular development remains elusive. In addition, positional information during ocular NC migration and the molecular pathways that regulate end tissue differentiation have yet to be fully elucidated. Further, the clinical challenges of ocular diseases, such as Axenfeld-Rieger syndrome (ARS), Peters anomaly (PA) and primary congenital glaucoma (PCG), strongly suggest the need for better treatments. While several aspects of NC evolution have recently been reviewed, this discussion will consolidate the most recent current knowledge on the specification, migration, and contributions of the NC to ocular development, highlighting the anterior segment and the knowledge obtained from the clinical manifestations of its associated diseases. Ultimately, this knowledge can inform translational discoveries with potential for sorely needed regenerative therapies.
Does the Microbiome Affect the Outcome of Renal Transplantation?
Authors: Campbell Paul M. , Humphreys Gavin J. , Summers Angela M. , Konkel Joanne E. , Knight Christopher G. , Augustine Titus , McBain Andrew J.
Published: December 2020

The role of the human microbiome in health and disease is becoming increasingly apparent. Emerging evidence suggests that the microbiome is affected by solid organ transplantation. Kidney transplantation is the gold standard treatment for End-Stage Renal Disease (ESRD), the advanced stage of Chronic Kidney Disease (CKD). The question of how ESRD and transplantation affect the microbiome and vice versa includes how the microbiome is affected by increased concentrations of toxins such as urea and creatinine (which are elevated in ESRD), whether restoration of renal function following transplantation alters the composition of the microbiome, and the impact of lifelong administration of immunosuppressive drugs on the microbiome. Changes in microbiome composition and activity have been reported in ESRD and in therapeutic immunosuppression, but the effect on the outcome of transplantation is not well-understood. Here, we consider the current evidence that changes in kidney function and immunosuppression following transplantation influence the oral, gut, and urinary microbiomes in kidney transplant patients. The potential for changes in these microbiomes to lead to disease, systemic inflammation, or rejection of the organ itself is discussed, along with the possibility that restoration of kidney function might re-establish orthobiosis.
The Interaction Between Microorganisms, Metabolites, and Immune System in the Female Genital Tract Microenvironment
Authors: Li Huanrong , Zang Yuqin , Wang Chen , Li Huiyang , Fan Aiping , Han Cha , Xue Fengxia
Published: December 2020

The female reproductive tract microenvironment includes microorganisms, metabolites, and immune components, and the balance of the interactions among them plays an important role in maintaining female reproductive tract homeostasis and health. When any one of the reproductive tract microorganisms, metabolites, or immunity is out of balance, it will affect the other two, leading to the occurrence and development of diseases and the appearance of corresponding symptoms and signs, such as infertility, miscarriage, premature delivery, and gynecological tumors caused by infectious diseases of the reproductive tract. Nutrients in the female reproductive tract provide symbiotic and pathogenic microorganisms with a source of nutrients for their own reproduction and utilization. At the same time, this interaction with the host forms a variety of metabolites. Changes in metabolites in the host reproductive tract are related not only to the interaction between the host and microbiota under dysbiosis but also to changes in host immunity or the environment, all of which will participate in the pathogenesis of diseases and lead to disease-related phenotypes. Microorganisms and their metabolites can also interact with host immunity, activate host immunity, and change the host immune status and are closely related to persistent genital pathogen infections, aggravation of infectious diseases, severe pregnancy outcomes, and even gynecological cancers. Therefore, studying the interaction between microorganisms, metabolites, and immunity in the reproductive tract cannot only reveal the pathogenic mechanisms that lead to inflammation of the reproductive tract, adverse pregnancy outcomes and tumorigenesis but also provide a basis for further research on the diagnosis and treatment of targets.
The Discourse and Reality of Carbon Dioxide Removal: Toward the Responsible Use of Metaphors in Post-normal Times
Authors: Castree Noel
Published: December 2020

There's little doubt that a variety of CDR techniques will be employed worldwide in the decades and centuries to come. Together, these techniques will alter the character and functioning of the biosphere, hydrosphere, cryosphere, pedosphere, and atmosphere. More locally, they will have immediate impacts on people and place, within diverse national state contexts. However, for the moment CDR exists more in the realm of discourse than reality. Its future roll-out in many and varied forms will depend on a series of discussions in the governmental, commercial, and civic spheres. Metaphor will be quite central to these formative discussions. Metaphors serve to structure perceptions of unfamiliar phenomena by transferring meaning from a recognized “source” domain to a new “target” domain. They can be employed in more or less felicitous, more or less noticeable, more or less defensible ways. Metaphors help to govern future action by framing present-day understandings of a world to come. To govern metaphor itself may seem as foolhardy as attempting to sieve water or converse with rocks. Yet by rehearsing some old lessons about metaphor we stand some chance of responsibly steering its employment in unfolding debates about CDR techniques and their practical governance globally. This Perspective identifies some key elements of metaphor's use that will require attention in the different contexts where CDR techniques presently get (and will in future be) discussed meaningfully. Various experts involved in CDR development and deployment have an important, though not controlling, role to play in how it gets metaphorized. This matters in our age of populism, rhetoric, misinformation, and disinformation where the willful (mis)use of certain metaphors threatens to depoliticize, polarize, or simplify future debates about CDR. What is needed is “post-normal” discourse where high stakes decisions made in the context of epistemic uncertainty are informed by clear reasoning among disparate parties whose values diverge.
The Role of Artificial Intelligence in Cardiovascular Imaging: State of the Art Review
Authors: Seetharam Karthik , Brito Daniel , Farjo Peter D. , Sengupta Partho P.
Published: December 2020

In this current digital landscape, artificial intelligence (AI) has established itself as a powerful tool in the commercial industry and is an evolving technology in healthcare. Cutting-edge imaging modalities outputting multi-dimensional data are becoming increasingly complex. In this era of data explosion, the field of cardiovascular imaging is undergoing a paradigm shift toward machine learning (ML) driven platforms. These diverse algorithms can seamlessly analyze information and automate a range of tasks. In this review article, we explore the role of ML in the field of cardiovascular imaging.
Geological and Geophysical Factors Constraining the Occurrence of Earthquake Precursors in Geofluids: A Review and Reinterpretation
Authors: Martinelli Giovanni , Tamburello Giancarlo
Published: December 2020

In this paper, we update the previous compilations of observed earthquake precursors from the published scientific literature of the last decade. We collected the epicentral coordinates, magnitude, hypocentral depth of each earthquake and the distance from the observed precursor and its time lag. The locations are reported and compared with data concerning geological and geophysical parameters like global seismicity, volcanic locations, heat flow and tectonic regimes. Possible relations between geological and geophysical parameters and the occurrence of fluid-related earthquake precursors are considered and discussed. Some geological and geophysical conditions can be deemed responsible for the occurrence of fluid-related earthquake precursory phenomena. Geophysical models used to explain the occurrence of earthquake precursors are discussed with the purpose of contributing to engineering proper monitoring networks. Areas of the world potentially suitable for earthquake fluid-related precursor monitoring are suggested.
Deep Learning Based Proactive Multi-Objective Eco-Routing Strategies for Connected and Automated Vehicles
Authors: Alfaseeh Lama , Farooq Bilal
Published: December 2020

This study exploited the advancements in information and communication technology (ICT), connected and automated vehicles (CAVs), and sensing to develop proactive multi-objective eco-routing strategies for travel time and Greenhouse Gas (GHG) emissions reduction on urban road networks. For a robust application, several GHG costing approaches were examined. The predictive models for link level traffic and emission states were developed using the long short-term memory (LSTM) deep network with exogenous predictors. It was found that proactive routing strategies outperformed the reactive strategies regardless of the routing objective. Whether reactive or proactive, the multi-objective routing, with travel time and GHG minimization, outperformed the single objective routing strategies. Using a proactive multi-objective (travel time and GHG) routing strategy, we observed a reduction in average travel time (17%), average vehicle kilometer traveled (22%), total GHG (18%), and total nitrogen oxide (20%) when compared with the reactive single-objective (travel time).
(In)Essential Bordering: Canada, COVID, and Mobility
Authors: Macklin Audrey
Published: December 2020

The global migration of COVID-19 not only disrupted transborder movement. In many (if not most) states, statis, and closure became the default norm at and within borders. This, in turn, generated exceptions organized around an idea of “essential” entry. The category of “essential” was produced, revised, and represented through the interaction of pandemic-driven exigencies and nationally specific configurations of the legal, political, and economic forces in play. To understand how the admission into Canada of certain people was accepted as legally, economically and/or politically essential, one must take account of Canada's character as a settler society, its economic integration with the United States, and its growing dependence on migrant workers and international students to subsidize food production and higher education for nationals.
Distinguishing Sepsis From Infection by Neutrophil Dysfunction: A Promising Role of CXCR2 Surface Level
Authors: Seree-aphinan Chutima , Vichitkunakorn Polathep , Navakanitworakul Raphatphorn , Khwannimit Bodin
Published: December 2020

Sepsis is one of the well-established diseases with specific patterns of neutrophil dysfunctions. Previous studies demonstrated sepsis-related neutrophil dysfunctions in comparison with subjects without infection. Since sepsis and infection are recently recognized as distinctive processes, whether these neutrophil dysfunctions are associated with sepsis or infection are not known. Therefore, we longitudinally compared neutrophil functions, widely-cited as exhibiting sepsis-related changes, between patients with septic shock and infection. The surface level of cluster of differentiation 64 (CD64), C-C motif chemokine receptor 2 (CCR2), C-X-C motif chemokine receptor 2 (CXCR2); apoptosis; and NETosis were measured from peripheral blood neutrophils for seven consecutive days using flow cytometry. The between-group comparisons of neutrophil functions were made both on a day-by-day basis and as linear regression between time and measured neutrophil functions (sepsis status included as model predictors). Our study found that, among neutrophil functions studied, only CXCR2 surface level is associated with sepsis. At disease onset, CXCR2 level decrease, with a dose-response relationship with clinical severity. Its level reverts to resemble infected patients by the end of the week. The relationship between CD64 surface level, CCR2 surface level, NETosis, and sepsis are mediated through the effect of infection. Apoptosis activity between these groups are similar, hence, not sepsis-related.
Modeling MyD88 Deficiency In Vitro Provides New Insights in Its Function
Authors: Craig-Mueller Nils , Hammad Ruba , Elling Roland , Alzubi Jamal , Timm Barbara , Kolter Julia , Knelangen Nele , Bednarski Christien , Gläser Birgitta , Ammann Sandra , Ivics Zoltán , Fischer Judith , Speckmann Carsten , Schwarz Klaus , Lachmann Nico , Ehl Stephan , Moritz Thomas , Henneke Philipp , Cathomen Toni
Published: December 2020

Inherited defects in MyD88 and IRAK4, two regulators in Toll-like receptor (TLR) signaling, are clinically highly relevant, but still incompletely understood. MyD88- and IRAK4-deficient patients are exceedingly susceptible to a narrow spectrum of pathogens, with ∼50% lethality in the first years of life. To better understand the underlying molecular and cellular characteristics that determine disease progression, we aimed at modeling the cellular response to pathogens in vitro. To this end, we determined the immunophenotype of monocytes and macrophages derived from MyD88- and IRAK4-deficient patients. We recognized that macrophages derived from both patients were particularly poorly activated by streptococci, indicating that both signaling intermediates are essential for the immune response to facultative pathogens. To characterize this defect in more detail, we generated induced pluripotent stem cells (iPSCs) of fibroblasts derived from an MyD88-deficient patient. The underlying genetic defect was corrected using Sleeping Beauty transposon vectors encoding either the long (L) or the short (S) MYD88 isoform, respectively. Macrophages derived from these iPSC lines (iMacs) expressed typical macrophage markers, stably produced either MyD88 isoform, and showed robust phagocytic activity. Notably, iMacs expressing MyD88-L, but not MyD88-S, exhibited similar responses to external stimuli, including cytokine release patterns, as compared to genetically normal iMacs. Thus, the two MyD88 isoforms assume distinct functions in signaling. In conclusion, iPSC technology, in combination with efficient myeloid differentiation protocols, provides a valuable and inexhaustible source of macrophages, which can be used for disease modeling. Moreover, iPSC-derived macrophages may eventually aid in stabilizing MyD88-deficient patients during pyogenic infections.
Imprint of Climate Change on Pan-Arctic Marine Vegetation
Authors: Krause-Jensen Dorte , Archambault Philippe , Assis Jorge , Bartsch Inka , Bischof Kai , Filbee-Dexter Karen , Dunton Kenneth H. , Maximova Olga , Ragnarsdóttir Sunna Björk , Sejr Mikael K. , Simakova Uliana , Spiridonov Vassily , Wegeberg Susse , Winding Mie H. S. , Duarte Carlos M.
Published: December 2020

The Arctic climate is changing rapidly. The warming and resultant longer open water periods suggest a potential for expansion of marine vegetation along the vast Arctic coastline. We compiled and reviewed the scattered time series on Arctic marine vegetation and explored trends for macroalgae and eelgrass (Zostera marina). We identified a total of 38 sites, distributed between Arctic coastal regions in Alaska, Canada, Greenland, Iceland, Norway/Svalbard, and Russia, having time series extending into the 21st Century. The majority of these exhibited increase in abundance, productivity or species richness, and/or expansion of geographical distribution limits, several time series showed no significant trend. Only four time series displayed a negative trend, largely due to urchin grazing or increased turbidity. Overall, the observations support with medium confidence (i.e., 5–8 in 10 chance of being correct, adopting the IPCC confidence scale) the prediction that macrophytes are expanding in the Arctic. Species distribution modeling was challenged by limited observations and lack of information on substrate, but suggested a current (2000–2017) potential pan-Arctic brown macroalgal distribution area of 655,111 km2(140,433 km2intertidal, 514,679 km2subtidal), representing an increase of about 45% for subtidal- and 8% for intertidal macroalgae since 1940–1950, and associated polar migration rates averaging 18–23 km decade–1. Adjusting the potential macroalgal distribution area by the fraction of shores represented by cliffs halves the estimate (340,658 km2). Warming and reduced sea ice cover along the Arctic coastlines are expected to stimulate further expansion of marine vegetation from boreal latitudes. The changes likely affect the functioning of coastal Arctic ecosystems because of the vegetation’s roles as habitat, and for carbon and nutrient cycling and storage. We encourage a pan-Arctic science- and management agenda to incorporate marine vegetation into a coherent understanding of Arctic changes by quantifying distribution and status beyond the scattered studies now available to develop sustainable management strategies for these important ecosystems.
Effect of Early vs. Delayed or No Intubation on Clinical Outcomes of Patients With COVID-19: An Observational Study
Authors: Siempos Ilias I. , Xourgia Eleni , Ntaidou Theodora K. , Zervakis Dimitris , Magira Eleni E. , Kotanidou Anastasia , Routsi Christina , Zakynthinos Spyros G.
Published: December 2020

Background: Optimal timing of initiation of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 is unknown. Thanks to early flattening of the epidemiological curve, ventilator demand in Greece was kept lower than supply throughout the pandemic, allowing for unbiased comparison of the outcomes of patients undergoing early intubation vs. delayed or no intubation.

Methods: We conducted an observational study including all adult patients with laboratory-confirmed COVID-19 consecutively admitted in Evangelismos Hospital, Athens, Greece between March 11, 2020 and April 15, 2020. Patients subsequently admitted in the intensive care unit (ICU) were categorized into the “early intubation” vs. the “delayed or no intubation” group. The “delayed or no intubation” group included patients receiving non-rebreather mask for equal to or more than 24 h or high-flow nasal oxygen for any period of time or non-invasive mechanical ventilation for any period of time in an attempt to avoid intubation. The remaining intubated patients comprised the “early intubation” group.

Results: During the study period, a total of 101 patients (37% female, median age 65 years) were admitted in the hospital. Fifty-nine patients (58% of the entire cohort) were exclusively hospitalized in general wards with a mortality of 3% and median length of stay of 7 days. Forty-two patients (19% female, median age 65 years) were admitted in the ICU; all with acute hypoxemic respiratory failure. Of those admitted in the ICU, 62% had at least one comorbidity and 14% were never intubated. Early intubation was not associated with higher ICU-mortality (21 vs. 33%), fewer ventilator-free days (3 vs. 2 days) or fewer ICU-free days than delayed or no intubation.

Conclusions: A strategy of early intubation was not associated with worse clinical outcomes compared to delayed or no intubation. Given that early intubation may presumably reduce virus aerosolization, these results may justify further research with a randomized controlled trial.
Imaging Mass Cytometric Analysis of Postmortem Tissues Reveals Dysregulated Immune Cell and Cytokine Responses in Multiple Organs of COVID-19 Patients
Authors: Wang Chong , Xu Jiqian , Wang Shaoyuan , Pan Shangwen , Zhang Jiancheng , Han Yang , Huang Muhan , Wu Di , Yang Qingyu , Yang Xiaobo , Yang Yang , Shu Ting , Zou Xiaojing , Li Ruiting , Luo Yufeng , Yao Runqing , Wang Yaxin , Qiu Yang , Wang Yu , Zhang Ding-Yu , Yao Qun , Yan Yongpan , Zhou Xi , Shang You
Published: December 2020

SARS-coronavirus-2–induced immune dysregulation and inflammatory responses are involved in the pathogenesis of coronavirus disease-2019 (COVID-19). However, very little is known about immune cell and cytokine alterations in specific organs of COVID-19 patients. Here, we evaluated immune cells and cytokines in postmortem tissues, i.e., lungs, intestine, liver, kidneys, and spleen of three patients with COVID-19. Imaging mass cytometry revealed monocyte, macrophage, and dendritic cell (DC) infiltration in the lung, intestine, kidney, and liver tissues. Moreover, in patients with COVID-19, natural killer T cells infiltrated the liver, lungs, and intestine, whereas B cells infiltrated the kidneys, lungs, and intestine. CD11b+ macrophages and CD11c+ DCs also infiltrated the lungs and intestine, a phenomenon that was accompanied by overproduction of the immunosuppressive cytokine interleukin (IL)-10. However, CD11b+ macrophages and CD11c+ DCs in the lungs or intestine of COVID-19 patients did not express human leukocyte antigen DR isotype. In contrast, tumor necrosis factor (TNF)-α expression was higher in the lungs, intestine, liver, and kidneys, but not in the spleen, of all COVID-19 patients (compared to levels in controls). Collectively, these findings suggested that IL-10 and TNF-α as immunosuppressive and pro-inflammatory agents, respectively,—might be prognostic and could serve as therapeutic targets for COVID-19.
MogR Is a Ubiquitous Transcriptional Repressor Affecting Motility, Biofilm Formation and Virulence in Bacillus thuringiensis
Authors: Smith Veronika , Josefsen Malin , Lindbäck Toril , Hegna Ida K. , Finke Sarah , Tourasse Nicolas J. , Nielsen-LeRoux Christina , Økstad Ole Andreas , Fagerlund Annette
Published: December 2020

Flagellar motility is considered an important virulence factor in different pathogenic bacteria. In Listeria monocytogenes the transcriptional repressor MogR regulates motility in a temperature-dependent manner, directly repressing flagellar- and chemotaxis genes. The only other bacteria known to carry a mogR homolog are members of the Bacillus cereus group, which includes motile species such as B. cereus and Bacillus thuringiensis as well as the non-motile species Bacillus anthracis, Bacillus mycoides and Bacillus pseudomycoides. Furthermore, the main motility locus in B. cereus group bacteria, carrying the genes for flagellar synthesis, appears to be more closely related to L. monocytogenes than to Bacillus subtilis, which belongs to a separate phylogenetic group of Bacilli and does not carry a mogR ortholog. Here, we show that in B. thuringiensis, MogR overexpression results in non-motile cells devoid of flagella. Global gene expression profiling showed that 110 genes were differentially regulated by MogR overexpression, including flagellar motility genes, but also genes associated with virulence, stress response and biofilm lifestyle. Accordingly, phenotypic assays showed that MogR also affects cytotoxicity and biofilm formation in B. thuringiensis. Overexpression of a MogR variant mutated in two amino acids within the putative DNA binding domain restored phenotypes to those of an empty vector control. In accordance, introduction of these mutations resulted in complete loss in MogR binding to its candidate flagellar locus target site in vitro. In contrast to L. monocytogenes, MogR appears to be regulated in a growth-phase dependent and temperature-independent manner in B. thuringiensis 407. Interestingly, mogR was found to be conserved also in non-motile B. cereus group species such as B. mycoides and B. pseudomycoides, which both carry major gene deletions in the flagellar motility locus and where in B. pseudomycoides mogR is the only gene retained. Furthermore, mogR is expressed in non-motile B. anthracis. Altogether this provides indications of an expanded set of functions for MogR in B. cereus group species, beyond motility regulation. In conclusion, MogR constitutes a novel B. thuringiensis pleiotropic transcriptional regulator, acting as a repressor of motility genes, and affecting the expression of a variety of additional genes involved in biofilm formation and virulence.
PolB1 Is Sufficient for DNA Replication and Repair Under Normal Growth Conditions in the Extremely Thermophilic Crenarchaeon Sulfolobus acidocaldarius
Authors: Miyabayashi Hiroka , Jain Rupal , Suzuki Shoji , Grogan Dennis W. , Kurosawa Norio
Published: December 2020

The thermophilic crenarchaeonSulfolobus acidocaldariushas four DNA polymerases (DNAPs): PolB1, PolB2, PolB3, and Dbh (PolY). Previousin vitrostudies suggested that PolB1 is the main replicative DNAP ofSulfolobaleswhereas PolB2 and Y-family polymerases Dpo4 (Saccharolobus solfataricus) or Dbh are involved in DNA repair and translesion DNA synthesis. On the other hand, there are various opinions about the role of PolB3, which remains to be clearly resolved. In order to examine the roles of the DNAPs ofS. acidocaldariusthroughin vivoexperiments, we constructedpolB2,polB3, anddbhdeletion strains and characterized their phenotypes. Efforts to construct apolB1deletion strain were not successful; in contrast, it was possible to isolate triple gene-deletion strains lackingpolB2,polB3, anddbh. The growth of these strains was nearly the same as that of the parent strains under normal growth conditions. ThepolB2,polB3, anddbhsingle-deletion strains were sensitive to some types of DNA-damaging treatments, but exhibited normal sensitivity to UV irradiation and several other damaging treatments. Overall, the genotype which exhibited the greatest sensitivity to the DNA-damaging treatments we tested was the ΔpolB2ΔpolB3combination, providing the first evidence of overlapping function for these two DNAPsin vivo. The results of our study strongly suggest that PolB1 is responsible for the DNA replication of both the leading and lagging strands and is sufficient to complete the repair of most DNA damage under normal growth conditions inS. acidocaldarius.
Revisiting Bap Multidomain Protein: More Than Sticking Bacteria Together
Authors: Valle Jaione , Fang Xianyang , Lasa Iñigo
Published: December 2020

One of the major components of the staphylococcal biofilm is surface proteins that assemble as scaffold components of the biofilm matrix. Among the different surface proteins able to contribute to biofilm formation, this review is dedicated to the Biofilm Associated Protein (Bap). Bap is part of the accessory genome of Staphylococcus aureus but orthologs of Bap in other staphylococcal species belong to the core genome. When present, Bap promotes adhesion to abiotic surfaces and induces strong intercellular adhesion by self-assembling into amyloid like aggregates in response to the levels of calcium and the pH in the environment. During infection, Bap enhances the adhesion to epithelial cells where it binds directly to the host receptor Gp96 and inhibits the entry of the bacteria into the cells. To perform such diverse range of functions, Bap comprises several domains, and some of them include several motifs associated to distinct functions. Based on the knowledge accumulated with the Bap protein of S. aureus, this review aims to summarize the current knowledge of the structure and properties of each domain of Bap and their contribution to Bap functionality.
Does Diet Have a Role in the Treatment of Alzheimer's Disease?
Authors: Thelen Mitchell , Brown-Borg Holly M.
Published: December 2020

The aging process causes many changes to the brain and is a major risk factor for the development of neurodegenerative diseases such as Alzheimer's Disease (AD). Despite an already vast amount of research on AD, a greater understanding of the disease's pathology and therapeutic options are desperately needed. One important distinction that is also in need of further study is the ability to distinguish changes to the brain observed in early stages of AD vs. changes that occur with normal aging. Current FDA-approved therapeutic options for AD patients have proven to be ineffective and indicate the need for alternative therapies. Aging interventions including alterations in diet (such as caloric restriction, fasting, or methionine restriction) have been shown to be effective in mediating increased health and lifespan in mice and other model organisms. Because aging is the greatest risk factor for the development of neurodegenerative diseases, certain dietary interventions should be explored as they have the potential to act as a future treatment option for AD patients.
Large-Scale Desynchronization During Interictal Epileptic Discharges Recorded With Intracranial EEG
Authors: Bou Assi Elie , Zerouali Younes , Robert Manon , Lesage Frederic , Pouliot Philippe , Nguyen Dang K.
Published: December 2020

It is increasingly recognized that deep understanding of epileptic seizures requires both localizing and characterizing the functional network of the region where they are initiated, i. e., the epileptic focus. Previous investigations of the epileptogenic focus' functional connectivity have yielded contrasting results, reporting both pathological increases and decreases during resting periods and seizures. In this study, we shifted paradigm to investigate the time course of connectivity in relation to interictal epileptiform discharges. We recruited 35 epileptic patients undergoing intracranial EEG (iEEG) investigation as part of their presurgical evaluation. For each patient, 50 interictal epileptic discharges (IEDs) were marked and iEEG signals were epoched around those markers. Signals were narrow-band filtered and time resolved phase-locking values were computed to track the dynamics of functional connectivity during IEDs. Results show that IEDs are associated with a transient decrease in global functional connectivity, time-locked to the peak of the discharge and specific to the high range of the gamma frequency band. Disruption of the long-range connectivity between the epileptic focus and other brain areas might be an important process for the generation of epileptic activity. Transient desynchronization could be a potential biomarker of the epileptogenic focus since 1) the functional connectivity involving the focus decreases significantly more than the connectivity outside the focus and 2) patients with good surgical outcome appear to have a significantly more disconnected focus than patients with bad outcomes.
Neural Correlates of Cognitive Dysfunctions in Cervical Spondylotic Myelopathy Patients: A Resting-State fMRI Study
Authors: Zhao Rui , Su Qian , Chen Zhao , Sun Haoran , Liang Meng , Xue Yuan
Published: December 2020

Cervical spondylotic myelopathy (CSM) is a common disease of the elderly that is characterized by gait instability, sensorimotor deficits, etc. Recurrent symptoms including memory loss, poor attention, etc. have also been reported in recent studies. However, these have been rarely investigated in CSM patients. To investigate the cognitive deficits and their correlation with brain functional alterations, we conducted resting-state fMRI (rs-fMRI) signal variability. This is a novel indicator in the neuroimaging field for assessing the regional neural activity in CSM patients. Further, to explore the network changes in patients, functional connectivity (FC) and graph theory analyses were performed. Compared with the controls, the signal variabilities were significantly lower in the widespread brain regions especially at the default mode network (DMN), visual network, and somatosensory network. The altered inferior parietal lobule signal variability positively correlated with the cognitive function level. Moreover, the FC and the global efficiency of DMN increased in patients with CSM and positively correlated with the cognitive function level. According to the study results, (1) the cervical spondylotic myelopathy patients exhibited regional neural impairments, which correlated with the severity of cognitive deficits in the DMN brain regions, and (2) the increased FC and global efficiency of DMN can compensate for the regional impairment.
Image Patch-Based Net Water Uptake and Radiomics Models Predict Malignant Cerebral Edema After Ischemic Stroke
Authors: Fu Bowen , Qi Shouliang , Tao Lin , Xu Haibin , Kang Yan , Yao Yudong , Yang Benqiang , Duan Yang , Chen Huisheng
Published: December 2020

Malignant cerebral edema (MCE) after an ischemic stroke results in a poor outcome or death. Early prediction of MCE helps to identify subjects that could benefit from a surgical decompressive craniectomy. Net water uptake (NWU) in an ischemic lesion is a predictor of MCE; however, CT perfusion and lesion segmentation are required. This paper proposes a new Image Patch-based Net Water Uptake (IP-NWU) procedure that only uses non-enhanced admission CT and does not need lesion segmentation. IP-NWU is calculated by comparing the density of ischemic and contralateral normal patches selected from the middle cerebral artery (MCA) area using standard reference images. We also compared IP-NWU with the Segmented Region-based NWU (SR-NWU) procedure in which segmented ischemic regions from follow-up CT images are overlaid onto admission images. Furthermore, IP-NWU and its combination with imaging features are used to construct predictive models of MCE with a radiomics approach. In total, 116 patients with an MCA infarction (39 with MCE and 77 without MCE) were included in the study. IP-NWU was significantly higher for patients with MCE than those without MCE (p < 0.05). IP-NWU can predict MCE with an AUC of 0.86. There was no significant difference between IP-NWU and SR-NWU, nor between their predictive efficacy for MCE. The inter-reader and interoperation agreement of IP-NWU was exceptional according to the Intraclass Correlation Coefficient (ICC) analysis (inter-reader: ICC = 0.92; interoperation: ICC = 0.95). By combining IP-NWU with imaging features through a random forest classifier, the radiomics model achieved the highest AUC (0.96). In summary, IP-NWU and radiomics models that combine IP-NWU with imaging features can precisely predict MCE using only admission non-enhanced CT images scanned within 24 h from onset.
Early Nutrition and Risk of Type 1 Diabetes: The Role of Gut Microbiota
Authors: Verduci Elvira , Mameli Chiara , Amatruda Matilde , Petitti Agnese , Vizzuso Sara , El Assadi Farah , Zuccotti Gianvincenzo , Alabduljabbar Shaikha , Terranegra Annalisa
Published: December 2020

Type 1 diabetes (T1D) appears most frequently in childhood, with an alarming increasing incidence in the last decades. Although the genetic predisposition is a major risk factor, it cannot solely explain the complex etiology of T1D which is still not fully understood. In this paper, we reviewed the most recent findings on the role of early nutrition and the involvement of the gut microbiota in the etiopathogenesis of T1D. The main conclusions that are withdrawn from the current literature regarding alleviating the risk of developing T1D through nutrition are the encouragement of long-term breast-feeding for at least the first 6 months of life and the avoidance of early complementary foods and gluten introduction (before 4 months of age) as well as cow milk introduction before 12 months of life. These detrimental feeding habits create a gut microbiota dysbiotic state that can contribute to the onset of T1D in infancy. Finally, we discussed the possibility to introduce probiotics, prebiotics and post-biotics in the prevention of T1D.
Reciprocal Induction of MDM2 and MYCN in Neural and Neuroendocrine Cancers
Authors: Tran Hung N. , Singh Hardeep P. , Guo Wenxuan , Cambier Linda , Riggan Luke , Shackleford Gregory M. , Thornton Matthew E. , Grubbs Brendan H. , Erdreich-Epstein Anat , Qi Dong-Lai , Cobrinik David
Published: December 2020

MYC family oncoproteins MYC, MYCN, and MYCL are deregulated in diverse cancers and via diverse mechanisms. Recent studies established a novel form of MYCN regulation in MYCN-overexpressing retinoblastoma and neuroblastoma cells in which the MDM2 oncoprotein promotes MYCN translation and MYCN-dependent proliferation via a p53-independent mechanism. However, it is unclear if MDM2 also promotes expression of other MYC family members and has similar effects in other cancers. Conversely, MYCN has been shown to induce MDM2 expression in neuroblastoma cells, yet it is unclear if MYC shares this ability, if MYC family proteins upregulate MDM2 in other malignancies, and if this regulation occurs during tumorigenesis as well as in cancer cell lines. Here, we report that intrinsically high MDM2 expression is required for high-level expression of MYCN, but not for expression of MYC, in retinoblastoma, neuroblastoma, small cell lung cancer, and medulloblastoma cells. Conversely, ectopic overexpression of MYC as well as MYCN induced high-level MDM2 expression and gave rise to rapidly proliferating and MDM2-dependent cone-precursor-derived masses in a cultured retinoblastoma genesis model. These findings reveal a highly specific collaboration between the MDM2 and MYCN oncoproteins and demonstrate the origin of their oncogenic positive feedback circuit within a normal neuronal tissue.
Relevance of STK11 Mutations Regarding Immune Cell Infiltration, Drug Sensitivity, and Cellular Processes in Lung Adenocarcinoma
Authors: Li Zhenqing , Ding Bo , Xu Jianxun , Mao Kai , Zhang Pengfei , Xue Qun
Published: December 2020

Serine/threonine kinase 11 (STK11) is one member of the serine/threonine kinase family, which is involved in regulating cell polarity, apoptosis, and DNA damage repair. In lung adenocarcinoma (LUAD), it can play as one tumor suppressor and always be mutated. In this study, we aimed to assess the relevance of STK11 mutations in LUAD, in which we also studied the correlation among immune cell infiltration, drug sensitivity, and cellular processes. By performing the bioinformatics analysis of the Cancer Genome Atlas (TCGA) about LUAD patients, we found that the mutation efficiency of STK11 mutations is about 19%. Additionally, the differentially expressed gene analysis showed that there were 746 differentially expressed genes (DEGs) between LUAD patients with and without STK11 mutations. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis showed that the DEGs were enriched in various tumorigenesis signaling pathways and metabolic processes. Among these DEGs, the top ranking 21 genes were found that they were more frequently mutated in the STK11 mutation group than in the wild-type group (p-value<0.01). Finally, the LUAD patients with STK11 mutations suffered the worse immune cell infiltration levels than the LUAD patients with wild-type. The STK11 gene copy number was correlated with immune cell infiltration. Aiming to develop the therapeutic drugs, we performed Genomics of Drug Sensitivity in Cancer (GDSC) data to identify the potential therapeutic candidate and the results showed that Nutlin-3a(-) may be a sensitive drug for LUAD cases harboring STK11 mutations. The specific genes and pathways shown to be associated with LUAD cases involving STK11 mutations may serve as targets for individualized LUAD treatment.
Concordance Between Watson for Oncology and Multidisciplinary Teams in Colorectal Cancer: Prognostic Implications and Predicting Concordance
Authors: Mao Chenchen , Yang Xinxin , Zhu Ce , Xu Jingxuan , Yu Yaojun , Shen Xian , Huang Yingpeng
Published: December 2020

Background

Watson for Oncology (WFO) is a cognitive computing system that provides clinical decision support. This study examined the concordance between the treatment recommendations for colorectal cancer (CRC) proposed by WFO and those recommended by the multidisciplinary teams (MDTs), and evaluated the influence of concordance on the prognosis.

Methods

We retrospectively collected 175 patients with colorectal cancer who received treatment recommended by MDTs at a hospital in China, and evaluated them using WFO. Concordance between the two recommendations was analyzed. The overall survival was analyzed between concordant and non-concordant groups. Logistic regression analyses were performed and a concordance-predicting model was developed.

Results

Concordance between WFO’ and MDTs’ recommendations occurred in 66.9% (117/175) of cases. The overall survival (OS) was significantly better in concordant group and non-concordance was found to be an independent prognostic factor [hazard ratio (HR)=2.784 (95% CI 1.264–6.315)]. Logistic regression analyses determined that tumor type [odds ratio (OR)= 2.195 for left colon cancer and OR=2.502 for rectum cancer], and TNM stage (OR=0.545 for stage II, OR=0.187 for stage III, OR=0.127 for stage IV) were independently related with concordance, which were used to develop a concordance-predictive-nomogram.

Conclusions

Treatment recommendations for patients with colorectal cancer determined by WFO and MDTs were mostly concordant. However, the survival was better among concordant patients and non-concordance was found to be an independent prognostic factor. This study presents a nomogram that can be conveniently used for predicting individualized concordance. However, our findings should be prospectively validated in multi-center trials.
Histological Characteristics and Early-Stage Diagnosis Are Associated With Better Survival in Young Patients With Epithelial Ovarian Cancer: A Retrospective Analysis Based on Surveillance Epidemiology and End Results Database
Authors: Huang Yue , Ming Xiu , Li Bingjie , Li Zhengyu
Published: December 2020

Purpose

To analyze the potential prognostic factors of epithelial ovarian cancer (EOC) in women aged under 35 compared to those aged 60–79.

Methods

Cases were retrospectively obtained from SEER database. Clinical characteristics, such as race, histological type, AJCC stage, laterality of tumors, CA125 results, and surgical strategies, were analyzed in < 35 years group and 60–79 years group. Kaplan-Meier survival curves were used to evaluate overall survival (OS) and cause-specific survival (CSS). Cox proportional hazard model was used to identify the predictors for CSS.

Results

Sixteen thousand eight hundred forty-seven EOC patients diagnosed in 2004–2015 were identified from SEER database, with 1,015 aged under 35 and 15,833 aged 60–79. In < 35 years group, mucinous (32.2%) was the most common histological type, followed by high-grade serous (26.6%) and endometrioid (18.3%), while in 60–79 years group, high-grade serous (68.3%) represented the leading histological type. Most young women were diagnosed at stage I (57.7%), while most old women were diagnosed at stage (48.1%). Both 5-year OS and 5-year CSS were higher in < 35 years group (5-year OS: 76.00% vs 40.18%, p < 0.001; 5-year CSS: 83.56% vs 55.18%, p < 0.001). The multivariate analysis identified histological type and stage as prognostic factors for CSS in both groups. Endometrioid represented a positive predictor for CSS, while carcinosarcoma and malignant Brenner were related to a worse CSS. (< 35 years group: carcinosarcoma vs endometrioid: HR 5.630, p=0.024; malignant Brenner vs endometrioid: HR 4.005, p < 0.001; 60–79 years group: carcinosarcoma vs endometrioid: HR 3.606, p < 0.001; malignant Brenner vs endometrioid: HR 2.291, p < 0.001). Tumors laterality, CA125 levels, surgery and lymphadenectomy failed to be associated with the CSS in < 35 years group, while found to be independent risk factors in 60–79 years group.

Conclusion

EOC women aged under 35 had a better survival outcome over EOC women aged 60–79, owing to high proportion of endometrioid and mucinous types in histology, as well as early-stage diagnosis. Identification of histological types and gene profiles should be underscored in young EOC patients.
Analyzing the Motion of Symmetric Tops Without Recurring to Analytical Mechanics
Authors: Lázár Zsolt I. , Jakovác Antal , Hantz Péter
Published: December 2020

Characterizing the dynamics of heavy symmetric tops is essential in several fields of theoretical and applied physics. Accordingly, a series of approaches have been developed to describe their motion. In this paper, we present a derivation based on elementary geometric considerations carried out in the laboratory frame. Our framework enabled the simple derivation of the equation of motion for small nutations. The introduced formalism is also employed to determine the alteration of the dynamics of heavy, symmetric, spinning tops in a rotating force field, that is compared to the precession characteristics of a quantum magnetic dipole in rotating magnetic field.