bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Glycated Hemoglobin Is Associated With Liver Fibrosis, as Assessed by Elastography, in a Population‐Based Study of Mexican Americans
Authors: Watt Gordon P. , De La Cerda Isela , Pan Jen‐Jung , Fallon Michael B. , Beretta Laura , Loomba Rohit , Lee Miryoung , McCormick Joseph B. , Fisher‐Hoch Susan P.
Published: October 2020

Diabetes is associated with liver disease and risk of hepatocellular carcinoma. In this study, we evaluated the association between liver fibrosis measured by transient elastography and four glucose metabolism measures in the Cameron County Hispanic Cohort, a population‐based, randomly selected cohort of Mexican American Hispanics with high rates of diabetes and liver cancer. We measured liver fibrosis (a risk factor for hepatocellular carcinoma) in 774 well‐characterized cohort participants using transient elastography. We evaluated the association of liver fibrosis with glycated hemoglobin (HbA1c), fasting blood glucose, insulin, and insulin resistance using multivariable linear regression models. In multivariable models, log‐transformed HbA1c had the strongest association with liver fibrosis (β = 0.37, 95% confidence interval [CI] 0.04‐0.69, P = 0.038), after controlling for waist circumference, aspartate aminotransferase, alanine aminotransferase, liver fat, and other known confounders. The association was statistically significant among women (β = 0.33, 95% CI 0.10‐0.56, P = 0.009) and similar but nonsignificant among men (β = 0.41, 95% CI −0.17 to 0.98, P = 0.593). Waist circumference, platelet count, aspartate transaminase, and liver steatosis were each associated with liver stiffness. Conclusions: Elevated HbA1c is associated with liver fibrosis, a key risk factor for HCC, particularly among women. Our results indicate that Mexican Americans with uncontrolled HbA1c may benefit from routine screening by liver elastography to identify individuals at risk of liver disease progression.
What about reservoirs? Questioning anthropogenic and climatic interferences on water availability
Authors: Akbas Abdullah , Freer Jim , Ozdemir Hasan , Bates Paul D. , Turp M. Tufan
Published: October 2020

Water resources in semi‐arid regions like the Mediterranean Basin are highly vulnerable because of the high variability of weather systems. Additionally, climate change is altering the timing and pattern of water availability in a region where growing populations are placing extra demands on water supplies. Importantly, how reservoirs and dams have an influence on the amount of water resources available is poorly quantified. Therefore, we examine the impact of reservoirs on water resources together with the impact of climate change in a semi‐arid Mediterranean catchment. We simulated the Susurluk basin (23.779‐km2) using the Soil and Water Assessment Tool (SWAT) model. We generate results for with (RSV) and without reservoirs (WRSV) scenarios. We run simulations for current and future conditions using dynamically downscaled outputs of the MPI‐ESM‐MR general circulation model under two greenhouse gas relative concentration pathways (RCPs) in order to reveal the coupled effect of reservoir and climate impacts. Water resources were then converted to their usages – blue water (water in aquifers and rivers), green water storage (water in the soil) and green water flow (water losses by evaporation and transpiration). The results demonstrate that all water resources except green water flow are projected to decrease under all RCPs compared to the reference period, both long‐term and at seasonal scales. However, while water scarcity is expected in the future, reservoir storage is shown to be adequate to overcome this problem. Nevertheless, reservoirs reduce the availability of water, particularly in soil moisture stores, which increases the potential for drought by reducing streamflow. Furthermore, reservoirs cause water losses through evaporation from their open surfaces. We conclude that pressures to protect society from economic damage by building reservoirs have a strong impact on the fluxes of watersheds. This is additional to the effect of climate change on water resources.
Short tandem repeat profiling for the authentication of cancer stem‐like cells
Authors: Visconti Paola , Parodi Federica , Parodi Barbara , Casarino Lucia , Romano Paolo , Buccarelli Mariachiara , Pallini Roberto , D'Alessandris Quintino Giorgio , Montori Andrea , Pilozzi Emanuela , Ricci‐Vitiani Lucia
Published: October 2020

Colorectal and glioblastoma cancer stem‐like cells (CSCs) are essential for translational research. Cell line authentication by short tandem repeat (STR) profiling ensures reproducibility of results in oncology research. This technique enables to identify mislabeling or cross‐contamination of cell lines. In our study, we provide a reference dataset for a panel of colorectal and glioblastoma CSCs that allows authentication. Each cell line was entered into the cell Line Integrated Molecular Authentication database 2.1 to be compared to the STR profiles of 4485 tumor cell lines. This article also provides clinical data of patients from whom CSCs arose and data on the parent tumor stage and mutations. STR profiles and information of our CSCs are also available in the Cellosaurus database (ExPASy) as identified by unique research resource identifier codes.
Preterm birth, neonatal therapies and the risk of childhood cancer
Authors: Seppälä Laura K. , Vettenranta Kim , Leinonen Maarit K. , Tommiska Viena , Madanat‐Harjuoja Laura‐Maria
Published: October 2020

Our aim was to study the impact of preterm birth and neonatal therapies on the risk of childhood cancer using a nationwide, registry‐based, case‐control design. Combining population‐based data from Finnish Medical Birth Registry (MBR) and Finnish Cancer Registry, we identified a total of 2029 patients diagnosed with cancer under the age of 20 years and 10 103 age‐ and sex‐matched controls over the years 1996 to 2014. Information on the prenatal and perinatal conditions was obtained from the MBR. Gestational age was categorized into early (<32) and late preterm (32‐36) and term (≥37 weeks). Cancer risk among the preterm compared to term neonates was evaluated using conditional logistic regression. We identified 141 cancers among the preterm (20.8% of 678) vs 1888 cancers in the term children (16.5% of 11 454). The risk of any cancer was increased for the preterm (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06‐1.57), especially for the early preterm (OR 1.84, 95% CI 1.16‐2.92). The risk of acute myeloid leukemia (AML; OR 2.33, 95% CI 1.25‐4.37), retinoblastoma (OR 3.21, 95% CI 1.22‐8.41) and germ cell tumors (OR 5.89, 95% CI 2.29‐15.18) was increased among the preterm compared to term. Germ cell tumors were diagnosed at a significantly younger age among the preterm. Neonatal therapies, for example, mechanical ventilation, were associated with an increased risk of childhood cancer independent of gestational age. Preterm, especially early preterm birth, is associated with an increased risk of childhood cancer, especially germ cell tumors and AML. Respiratory distress requiring neonatal intervention also appears to be associated with an increased risk.
FIGO/ICM guidelines for preventing Rhesus disease: A call to action
Authors: Visser Gerard H. A. , Thommesen Trude , Di Renzo Gian Carlo , Nassar Anwar H. , Spitalnik Steven L. ,   FIGO Committee for Safe Motherhood, Newborn Health
Published: October 2020

The introduction of anti‐Rh(D) immunoglobulin more than 50 years ago has resulted in only a 50% decrease in Rhesus disease globally owing to a low uptake of this prophylactic approach. The International Federation of Gynecology and Obstetrics, International Confederation of Midwives, and Worldwide Initiative for Rhesus Disease Eradication have reviewed current evidence regarding the utility of anti‐Rh(D) immunoglobulin. Taking into account the effectiveness anti‐Rh(D), the new guidelines propose adjusting the dose for different indications and prioritizing its administration by indication.
In vitro effects of photobiomodulation therapy on 50B11 sensory neurons: evaluation of cell metabolism, oxidative stress, mitochondrial membrane potential (MMP), and capsaicin‐induced calcium flow
Authors: Zupin Luisa , Barbi Egidio , Sagredini Raffaella , Ottaviani Giulia , Crovella Sergio , Celsi Fulvio
Published: October 2020

The analgesic properties of photobiomodulation therapy (PBMT) have been raising increasing interest in the clinical community due to the positive effects observed on patients, nevertheless the mechanistic basis of its action on peripheral sensory neurons remains still elusive. In this study, the effect of near‐infrared (NIR) PBMT at 800 and 970 nm of wavelength was investigated on the 50B11 immortalized nociceptive sensory neuronal cell line by evaluating capsaicin‐induced calcium flow and different markers correlated to mitochondria, that is, ATP, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP). Calcium peak stimulated by capsaicin, the ligand of TRPV1 channel, was decreased in neurons pre‐irradiated with the combination of the two wavelengths. Furthermore, delivering the 800 and 970 nm separately an increment of ATP, as well as MMP hyperpolarization were detected; notably, the 800 nm wavelength also increased ROS and O2− levels. Our findings, obtained on an in vitro model of nociception, show the positive effect of PBMT on two potential photo‐targets of NIR light, namely the TRPV1 channel and the mitochondria.
Microscopic phase reconstruction of cervical exfoliated cell under partially coherent illumination
Authors: Lu Xingyuan , Wang Zhuoyi , Zhang Suxia , Konijnenberg A. P. , Ouyang Yiqin , Zhao Chengliang , Cai Yangjian
Published: October 2020

Basic coherent diffraction imaging methods strongly rely on having a highly coherent illumination in order to reconstruct the phase accurately. However, regardless of considering the turbulent transport medium, the instability of the system or the generation mechanism of the light source, partially coherent illumination is more common in real case. In this paper, we proposed an efficient microscopic phase imaging method to study normal and abnormal cervical exfoliated cells. By applying three phase modulations in a single point of the sample's transmitted field, the phase can be retrieved with correspoding three intensities under partially coherent illumination. Compared with intensity map, we can efficiently and clearly judge the proportion of high density shrinking abnormal cells from the phase distributions, which provides a confident analysis and evaluation basis for early medical diagnosis of cervical cancer. This study also has potential applications in noninvasive optical imaging of dynamic biological tissues.
How the COVID‐19 pandemic has changed our lives: A study of psychological correlates across 59 countries
Authors: Alzueta Elisabet , Perrin Paul , Baker Fiona C. , Caffarra Sendy , Ramos‐Usuga Daniela , Yuksel Dilara , Arango‐Lasprilla Juan Carlos
Published: October 2020

Objective

This study examined the impact of the COVID‐19 pandemic and subsequent social restrictions or quarantines on the mental health of the global adult population.

Method

A sample of 6,882 individuals (Mage = 42.30; 78.8% female) from 59 countries completed an online survey asking about several pandemic‐related changes in life and psychological status.

Results

Of these participants, 25.4% and 19.5% reported moderate‐to‐severe depression (DASS‐21) and anxiety symptoms (GAD‐7), respectively. Demographic characteristics (e.g. higher‐income country), COVID‐19 exposure (e.g., having had unconfirmed COVID‐19 symptoms), government‐imposed quarantine level, and COVID‐19‐based life changes (e.g., having a hard time transitioning to working from home; increase in verbal arguments or conflict with other adult in home) explained 17.9% of the variance in depression and 21.5% in anxiety symptoms.

Conclusions

In addition to posing a high risk to physical health, the COVID‐19 pandemic has robustly affected global mental health, so it is essential to ensure that mental health services reach individuals showing pandemic‐related depression and anxiety symptoms.
Effects of Continuous Albuterol Inhalation on Serum Metabolome in Healthy Subjects: More Than Just Lactic Acid
Authors: Nowadly Craig D. , Liao Shu‐Yi , Rose John S.
Published: October 2020

Treatment with β2‐agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2‐agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty‐four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1‐hour, and 2‐hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (P = .02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P = .02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that β2‐receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.
System‐level analyses of keystone genes required for mammalian tooth development
Authors: Hallikas Outi , Das Roy Rishi , Christensen Mona M. , Renvoisé Elodie , Sulic Ana‐Marija , Jernvall Jukka
Published: October 2020

When a null mutation of a gene causes a complete developmental arrest, the gene is typically considered essential for life. Yet, in most cases, null mutations have more subtle effects on the phenotype. Here we used the phenotypic severity of mutations as a tool to examine system‐level dynamics of gene expression. We classify genes required for the normal development of the mouse molar into different categories that range from essential to subtle modification of the phenotype. Collectively, we call these the developmental keystone genes. Transcriptome profiling using microarray and RNAseq analyses of patterning stage mouse molars show highly elevated expression levels for genes essential for the progression of tooth development, a result reminiscent of essential genes in single‐cell organisms. Elevated expression levels of progression genes were also detected in developing rat molars, suggesting evolutionary conservation of this system‐level dynamics. Single‐cell RNAseq analyses of developing mouse molars reveal that even though the size of the expression domain, measured in the number of cells, is the main driver of organ‐level expression, progression genes show high cell‐level transcript abundances. Progression genes are also upregulated within their pathways, which themselves are highly expressed. In contrast, a high proportion of the genes required for normal tooth patterning are secreted ligands that are expressed in fewer cells than their receptors and intracellular components. Overall, even though expression patterns of individual genes can be highly different, conserved system‐level principles of gene expression can be detected using phenotypically defined gene categories.
Toughness and spanning trees in K4‐minor‐free graphs
Authors: Ellingham M. N. , Shan Songling , Ye Dong , Zha Xiaoya
Published: October 2020

For an integer , a ‐tree is a tree with maximum degree at most . More generally, if is an integer‐valued function on vertices, an ‐tree is a tree in which each vertex has degree at most . Let denote the number of components of a graph . We show that if is a connected ‐minor‐free graph and
then has a spanning ‐tree. Consequently, if is a ‐tough ‐minor‐free graph, then has a spanning ‐tree. These results are stronger than results for general graphs due to Win (for ‐trees) and Ellingham, Nam, and Voss (for ‐trees). The ‐minor‐free graphs form a subclass of planar graphs, and are identical to graphs of treewidth at most 2, and also to graphs whose blocks are series‐parallel. We provide examples to show that the inequality above cannot be relaxed by adding 1 to the right‐hand side, and also to show that our result does not hold for general planar graphs. Our proof uses a technique where we incorporate toughness‐related information into weights associated with vertices and cutsets.
Edge‐decomposing graphs into coprime forests
Authors: Klimošová Tereza , Thomassé Stéphan
Published: October 2020

The Barát‐Thomassen conjecture, recently proved in Bensmail et al. (2017), asserts that for every tree , there is a constant such that every ‐edge‐connected graph with number of edges (size) divisible by the size of admits an edge partition into copies of (a ‐decomposition). In this paper, we investigate in which case the connectivity requirement can be dropped to a minimum degree condition. For instance, it was shown in Bensmail et al. (2019) that when is a path with edges, there is a constant such that every 24‐edge‐connected graph with size divisible by and minimum degree has a ‐decomposition. We show in this paper that when is a coprime forest (the sizes of its components being a coprime set of integers), any graph with sufficiently large minimum degree has an ‐decomposition provided that the size of divides the size of (no connectivity is required). A natural conjecture asked in Bensmail et al. (2019) asserts that for a fixed tree , any graph of size divisible by the size of with sufficiently high minimum degree has a ‐decomposition, provided that is sufficiently highly connected in terms of the maximal degree of . The case of maximum degree 2 is answered by paths. We provide a counterexample to this conjecture in the case of maximum degree 3.
Proton MR Spectroscopy in Assessing the Biochemical Milieu of Human Testes
Authors: Tsili Athina C. , Astrakas Loukas , Sofikitis Nikolaos , Argyropoulou Maria I.
Published: October 2020

Proton magnetic resonance spectroscopy (MRS), considered a connection between metabolism and anatomic and functional information provided by standard MRI, gives information on various tissue metabolites and their pathologic changes. Recently, proton MRS has been added as an adjunct tool to the multiparametric protocol of scrotal MRI, providing a new insight into the extremely complex biochemical milieu of normal and abnormal testes. This article reviews proton MR spectra of normal testes, showing age and bilateralism dependence. Disturbances of various metabolic pathways in testes of infertile men resulting in alterations of metabolite peaks are discussed. Preliminary data on proton MR spectra of testicular mass lesions are presented.

Level of Evidence

5.

Technical Efficacy Stage

5.
Leucine‐rich alpha‐2 glycoprotein (LRG): A novel acute phase protein expressed in Stage 3 Grade C periodontitis before and after periodontal therapy
Authors: Keles Yucel Zeynep Pinar , Balli Umut
Published: October 2020

Background

Leucine‐rich alpha‐2 glycoprotein (LRG) is a novel acute phase protein involved in inflammation‐associated diseases and that considered to be induced by multiple proinflammatory cytokines. This study aimed to investigate gingival crevicular fluid (GCF) and serum levels of LRG, interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α in patients with Stage 3 periodontitis before and after non‐surgical periodontal treatment.

Methods

Twenty‐five Stage 3 periodontitis and twenty‐five periodontally healthy individuals were enrolled in the study. Clinical periodontal measurements were recorded; periodontitis patients received non‐surgical periodontal treatment, and GCF and serum samples were obtained at baseline and at 6 weeks after treatment. LRG, IL‐6 and TNF‐α were determined by ELISA.

Results

GCF and serum LRG, IL‐6 and TNF‐α were significantly higher in periodontitis group than healthy controls (P < .001). A significant decrease in GCF and serum LRG, IL‐6 and TNF‐α was detected after periodontal treatment compared with baseline values of periodontitis patients (P < .001).

Conclusion

Our findings revealed that LRG expression was increased in Stage 3 periodontitis both locally and systemically, and non‐surgical periodontal therapy was effective in reducing LRG levels in GCF and serum of these patients.
Porphyromonas gingivalis infection alters Nrf2‐phase II enzymes and nitric oxide in primary human aortic endothelial cells
Authors: Sampath Chethan , Okoro Emmanuel U. , Gipson Michael J. , Chukkapalli Sasanka S. , Farmer‐Dixon Cherae M. , Gangula Pandu R.
Published: October 2020

Background

Periodontal disease (PD) is known to be associated with endothelial dysfunction in patients with coronary artery and/or cardiovascular disease. In our study, we sought to explore the virulence of P. gingivalis (Pg) affecting glycogen synthase kinase 3 beta (GSK‐3β)/nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/tetrahydrobiopterin (BH4)/ nitric oxide synthase (NOS) expression in primary human aortic endothelial cells (pHAECs).

Methods

pHAECs were infected for 48 hours with Pg in vitro using the Human oxygen‐Bacteria anaerobic coculture technique. Cell viability was determined, and target gene expression changes were evaluated by quantitative real‐time polymerase chain reaction at the end of each incubation period.

Results

Pg impaired pHAEC viability 24 hours post‐infection. Pg infection reduced mRNA expression levels of endothelial NOS (eNOS), Nrf2, and Phase II enzymes (heme oxygenase‐1, catalase, superoxide dismutase‐1) in a time‐dependent manner. Significant (P <0.05) increase in the inflammatory markers (interleukin [IL]‐1β, IL‐6, and tumor necrosis factor‐α) were observed in the medium as well as in the infected cells. Interestingly, inducible NOS mRNA levels showed a significant (P <0.05) increase at 12 hours and 24 hours and were reduced at later time points. BH4 (cofactor of eNOS) biosynthesis enzyme dihydrofolate reductase (DHFR, salvage pathway) mRNA levels showed a significant (P <0.05) decrease, while mRNA levels of GSK‐3β were elevated.

Conclusions

These results suggest that periodontal bacterial infection may cause significant changes in the endothelial GSK‐3β/BH4/eNOS/Nrf2 pathways, which may lead to impaired vascular relaxation. Greater understanding of the factors that adversely affect endothelial cell function could contribute to the development of new therapeutic compounds to treat PD‐induced vascular diseases.
Impact of adjunctive procedures on recombinant human fibroblast growth factor‐2–mediated periodontal regeneration therapy: A retrospective study
Authors: Nakayama Yohei , Matsuda Hideo , Itoh Shoichi , Iwai Yasunobu , Takai Hideki , Mezawa Masaru , Yoshino Shoichi , Ogata Yorimasa
Published: October 2020

Background

Human fibroblast growth factor‐2 (rhFGF‐2) therapy has been used for periodontal tissue regeneration. However, few studies have reported their adjunctive procedures based on strategy of tissue engineering. The aim of this retrospective study is to assess the adjunctive effects of modified papilla preservation technique (mPPT) and combination with autogenous bone grafts (AG) on the rhFGF‐2 therapy.

Methods

Total of 44 sites underwent rhFGF‐2 therapies and the evaluations in the survey periods. The primary outcome was set to the radiographic bone fill by radiographic examinations at 6 and 12 months after surgeries. We analyzed the correlation between influencing factors and the primary outcome, and differences of therapeutic effect by combination therapy with mPPT and that with AG.

Results

After surgeries, probing depth (PD), clinical attachment level (CAL) and bone defects significantly improved. The improvements of radiographic bone fill were significantly positive correlated with a number of bone walls, combination with mPPT, and AG at 6 months after surgeries, and with combination with mPPT and AG at 12 months after surgeries. The significant differences of improvements of radiographic bone fill were demonstrated between combination with or without mPPT at 12 months after surgeries, and with or without AG at 6 and 12 months after surgeries. Moreover, the multiple linear regression analysis for the radiographic bone fill indicated the significant regression coefficient with conducts of mPPT.

Conclusions

mPPT and AG had powerfully adjunctive effects on rhFGF‐2 therapy. Further studies are needed in order to verify by randomized clinical trials.
Posttraumatic Stress Disorder and Conduct Problems: The Role of Self‐Control Demands
Authors: Simons Raluca M. , Walters Kyle J. , Keith Jessica A. , Simons Jeffrey S.
Published: October 2020

We tested within‐ and between‐person effects of posttraumatic stress disorder (PTSD) symptoms on conduct problems and alcohol intoxication via self‐control demands using multilevel structural equation modeling in a longitudinal burst‐design study of 251 U.S. veterans who participated in the recent wars in Iraq and Afghanistan. We theorized that experiencing PTSD symptoms engenders efforts to regulate mood, control thoughts, and inhibit or control behavior that is taxing to the individual (i.e., it places demands on self‐control) and hypothesized that this process results in subsequent deficits in regulatory control that manifest in heightened intoxication and conduct problems associated with PTSD. At the within‐person level, daytime PTSD symptoms, IRR = 1.09, and self‐control demands, IRR = 1.12, exhibited within‐person associations with nighttime conduct problems over and above nighttime intoxication. Consistent with our hypothesis, daytime increases in self‐control demands mediated the associations between daytime PTSD symptoms and subsequent nighttime conduct problems. The indirect effect between daytime PTSD symptoms and nighttime intoxication via self‐control demands was nonsignificant. At the between‐person level, self‐control demands mediated the associations between PTSD symptoms and conduct problems; however, the expected between‐person associations with intoxication were nonsignificant. Drinking behavior is related to but cannot fully account for various difficulties in psychosocial functioning associated with PTSD. The present results suggest that dysregulated behavior may, ironically, stem from individuals’ concerted efforts to control and manage overwhelming symptoms. Self‐control demands may be a common factor that accounts for a broad range of functional impairments associated with PTSD.
Mobile fosfomycin resistance genes in Enterobacteriaceae—An increasing threat
Authors: Zurfluh Katrin , Treier Andrea , Schmitt Kira , Stephan Roger
Published: October 2020

Antimicrobial resistance is one of the major threats to the health and welfare of both humans and animals. The shortage of new antimicrobial agents has led to the re‐evaluation of old antibiotics such as fosfomycin as a potential regimen for treating multidrug‐resistant bacteria especially extended‐spectrum‐beta‐lactamase‐ and carbapenemase‐producing Enterobacteriaceae. Fosfomycin is a broad‐spectrum bactericidal antibiotic that inhibits the initial step of the cell wall biosynthesis. Fosfomycin resistance can occur due to mutation in the drug uptake system or by the acquisition of fosfomycin‐modifying enzymes. In this review, we focus on mobile fosfomycin‐resistant genes encoding glutathione‐S‐transferase which are mainly responsible for fosfomycin resistance in Enterobacteriaceae, that is, fosA and its subtypes, fosC2, and the recently described fosL1‐L2. We summarized the proposed origins of the different resistance determinants and highlighted the different plasmid types which are attributed to the dissemination of fosfomycin‐modifying enzymes. Thereby, IncF and IncN plasmids play a predominant role. The detection of mobile fosfomycin‐resistant genes in Enterobacteriaceae has increased in recent years. Similar to the situation in (East) Asia, the most frequently detected fosfomycin‐resistant gene in Europe is fosA3. Mobile fosfomycin‐resistant genes have been detected in isolates of human, animal, food, and environmental origin which leads to a growing concern regarding the risk of spread of such bacteria, especially Escherichia coli and Salmonella, at the human–animal–environment interface.
Biologically active indolizidine alkaloids
Authors: Zhang Junmin , Morris‐Natschke Susan L. , Ma Di , Shang Xiao‐Fei , Yang Chen‐Jie , Liu Ying‐Qian , Lee Kuo‐Hsiung
Published: October 2020

Indolizidine alkaloids are chemical constituents isolated from various marine and terrestrial plants and animals, including but not limited to trees, fungi, ants, and frogs, with a myriad of important biological activities. In this review, we discuss the biological activity and pharmacological effects of indolizidine alkaloids and offer new avenues toward the discovery of new and better drugs based on these naturally occurring compounds.
Upregulation of miR‐9 and miR‐193b over human Th17 cell differentiation
Authors: Shirani Fahimeh , Baghi Masoud , Rostamian Delavar Mahsa , Shoaraye Nejati Alireza , Eshaghiyan Amir , Nasr‐Esfahani Mohammad Hossein , Peymani Maryam , Ghaedi Kamran
Published: October 2020

Background

Th17 cells are a newly discovered subset of CD4+ T cells known as key participants in various immune responses and inflammatory conditions including autoimmune diseases. Mi(cro)RNAs are a family of non‐coding RNAs that regulate numerous critical immune functions. Immuno‐miRNAs modulate cell biological processes in T cells, such as differentiation and function of Th17 cells. The aim of the present study is to investigate the expression of miR‐9‐5p, miR‐193b‐3p, and autoimmunity‐related genes during human Th17 cells differentiation.

Methods

Human naïve CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) by magnetic cell sorting system (MACS) and their purity was checked by flow‐cytometric analysis. Naïve CD4+ T cells were cultured under Th17‐polarizing condition for 6 days. IL‐ 17 secretion was determined by means of enzyme‐linked immunosorbent assay (ELISA). Next, the expression levels of miRNAs and putative targets genes were assessed by qRT‐PCR at different time points of differentiation.

Results

Our result showed dramatic downregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes during human Th17 differentiation. Polarization also had a significant inducible effect on the expression of miR‐9 and miR‐193b over differentiation of human Th17 cells. According to our results, miR‐9‐5p and miR‐193b‐3p may contribute to Th17 differentiation probably by inhibiting the expression of negative regulators of Th17 differentiation.

Conclusion

This study confirmed deregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes in Th17 differentiation process and introduced miR‐9 and miR‐193b as Th17 cell‐associated miRNAs, making them good candidates for further investigations.
A k‐space‐to‐image reconstruction network for MRI using recurrent neural network
Authors: Oh Changheun , Kim Dongchan , Chung Jun‐Young , Han Yeji , Park HyunWook
Published: October 2020

Purpose

Reconstructing the images from undersampled k‐space data are an ill‐posed inverse problem. As a solution to this problem, we propose a method to reconstruct magnetic resonance (MR) images directly from k‐space data using a recurrent neural network.

Methods

A novel neural network architecture named “ETER‐net” is developed as a unified solution to reconstruct MR images from undersampled k‐space data, where two bi‐RNNs and convolutional neural network (CNN) are utilized to perform domain transformation and de‐aliasing. To demonstrate the practicality of the proposed method, we conducted model optimization, cross‐validation, and network pruning using in‐house data from a 3T MRI scanner and public dataset called “FastMRI.”

Results

The experimental results showed that the proposed method could be utilized for accurate image reconstruction from undersampled k‐space data. The size of the proposed model was optimized and cross‐validation was performed to show the robustness of the proposed method. For in‐house dataset (R = 4), the proposed method provided nMSE = 1.09% and SSIM = 0.938. For “FastMRI” dataset, the proposed method provided nMSE = 1.05 % and SSIM = 0.931 for R = 4, and nMSE = 3.12 % and SSIM = 0.884 for R = 8. The performance of the pruned model trained the loss function including with L2 regularization was consistent for a pruning ratio of up to 70%.

Conclusions

The proposed method is an end‐to‐end MR image reconstruction method based on recurrent neural networks. It performs direct mapping of the input k‐space data and the reconstructed images, operating as a unified solution that is applicable to various scanning trajectories.
Breast tumor segmentation in 3D automatic breast ultrasound using Mask scoring R‐CNN
Authors: Lei Yang , He Xiuxiu , Yao Jincao , Wang Tonghe , Wang Lijing , Li Wei , Curran Walter J. , Liu Tian , Xu Dong , Yang Xiaofeng
Published: October 2020

Purpose

Automatic breast ultrasound (ABUS) imaging has become an essential tool in breast cancer diagnosis since it provides complementary information to other imaging modalities. Lesion segmentation on ABUS is a prerequisite step of breast cancer computer‐aided diagnosis (CAD). This work aims to develop a deep learning‐based method for breast tumor segmentation using three‐dimensional (3D) ABUS automatically.

Methods

For breast tumor segmentation in ABUS, we developed a Mask scoring region‐based convolutional neural network (R‐CNN) that consists of five subnetworks, that is, a backbone, a regional proposal network, a region convolutional neural network head, a mask head, and a mask score head. A network block building direct correlation between mask quality and region class was integrated into a Mask scoring R‐CNN based framework for the segmentation of new ABUS images with ambiguous regions of interest (ROIs). For segmentation accuracy evaluation, we retrospectively investigated 70 patients with breast tumor confirmed with needle biopsy and manually delineated on ABUS, of which 40 were used for fivefold cross‐validation and 30 were used for hold‐out test. The comparison between the automatic breast tumor segmentations and the manual contours was quantified by I) six metrics including Dice similarity coefficient (DSC), Jaccard index, 95% Hausdorff distance (HD95), mean surface distance (MSD), residual mean square distance (RMSD), and center of mass distance (CMD); II) Pearson correlation analysis and Bland–Altman analysis.

Results

The mean (median) DSC was 85% ± 10.4% (89.4%) and 82.1% ± 14.5% (85.6%) for cross‐validation and hold‐out test, respectively. The corresponding HD95, MSD, RMSD, and CMD of the two tests was 1.646 ± 1.191 and 1.665 ± 1.129 mm, 0.489 ± 0.406 and 0.475 ± 0.371 mm, 0.755 ± 0.755 and 0.751 ± 0.508 mm, and 0.672 ± 0.612 and 0.665 ± 0.729 mm. The mean volumetric difference (mean and ± 1.96 standard deviation) was 0.47 cc ([−0.77, 1.71)) for the cross‐validation and 0.23 cc ([−0.23 0.69]) for hold‐out test, respectively.

Conclusion

We developed a novel Mask scoring R‐CNN approach for the automated segmentation of the breast tumor in ABUS images and demonstrated its accuracy for breast tumor segmentation. Our learning‐based method can potentially assist the clinical CAD of breast cancer using 3D ABUS imaging.
Acute ischemic stroke induces magnetic resonance susceptibility signs dominated by endothelial nitric oxide synthase activation
Authors: Chen Chiao‐Chi V. , Chang Chen , Lin Ming‐Fang , Huang Guo‐Shu , Chan Wing P.
Published: October 2020

Purpose

Acute ischemic stroke induces deoxyhemoglobin accumulation around the ischemic region while activating endothelial nitric oxide synthase (eNOS) coupling and the subsequent release of nitric oxide (NO). Because deoxyhemoglobin is a natural NO spin trap, its interplay with NO could be prominent during acute stroke. Its interaction with NO has been shown to induce overt paramagnetic signals in vitro; our goal was to investigate whether this interplay can be detected using MRI.

Methods

To verify the in vivo image effects using the deoxyhemoglobin‐NO interaction during acute stroke, eNOS states were manipulated in an animal model of acute ischemia, and the susceptibility signals, cerebral perfusion, and infarction were assessed noninvasively via MR susceptibility weighted imaging (SWI).

Results

Occlusion of the right middle cerebral artery increased eNOS coupling and susceptibility signals in the ischemic cortex while abolishing regional cerebral blood flow. Pharmacological eNOS blockage led to weakened susceptibility signals in the ischemic cortex as well as worsened tissue survival. Consistently, abolishment of eNOS coupling through genetic editing reduced the regional susceptibility signals in the ischemic cortex, causing large infarcts.

Conclusion

Upregulation of eNOS during acute ischemia sustains tissue viability through the interaction between NO and deoxyhemoglobin. This interplay can be traced in vivo using SWI and can be considered a sensitive marker revealing the delicate oxygenation status of the ischemic tissue, therefore, guiding the management of acute stroke in clinical settings.
Unsupervised learning for magnetization transfer contrast MR fingerprinting: Application to CEST and nuclear Overhauser enhancement imaging
Authors: Kang Beomgu , Kim Byungjai , Schär Michael , Park HyunWook , Heo Hye‐Young
Published: October 2020

Purpose

To develop a fast, quantitative 3D magnetization transfer contrast (MTC) framework based on an unsupervised learning scheme, which will provide baseline reference signals for CEST and nuclear Overhauser enhancement imaging.

Methods

Pseudo‐randomized RF saturation parameters and relaxation delay times were applied in an MR fingerprinting framework to generate transient‐state signal evolutions for different MTC parameters. Prospectively compressed sensing–accelerated (four‐fold) MR fingerprinting images were acquired from 6 healthy volunteers at 3 T. A convolutional neural network framework in an unsupervised fashion was designed to solve an inverse problem of a two‐pool MTC Bloch equation, and was compared with a conventional Bloch equation–based fitting approach. The MTC images synthesized by the convolutional neural network architecture were used for amide proton transfer and nuclear Overhauser enhancement imaging as a reference baseline image.

Results

The fully unsupervised learning scheme incorporated with the two‐pool exchange model learned a set of unique features that can describe the MTC–MR fingerprinting input, and allowed only small amounts of unlabeled data for training. The MTC parameter values estimated by the unsupervised learning method were in excellent agreement with values estimated by the conventional Bloch fitting approach, but dramatically reduced computation time by ~1000‐fold.

Conclusion

Given the considerable time efficiency compared to conventional Bloch fitting, unsupervised learning‐based MTC–MR fingerprinting could be a powerful tool for quantitative MTC and CEST/nuclear Overhauser enhancement imaging.
Root‐finding absorbing boundary condition for anisotropic scalar waves in infinite media
Authors: Lee Jin Ho
Published: October 2020

A root‐finding absorbing boundary condition (RFABC) for scalar‐wave propagation problems in infinite anisotropic media was developed. Although the phase velocity and the group velocity in isotropic media have the same sign, the sign of the latter can differ from that of the former in anisotropic media. Therefore, a RFABC for anisotropic scalar waves consistent with the group velocity of the considered media is developed, as the velocity is closely related to the direction of energy propagation. The developed boundary condition is shown to satisfy a criterion for an “enough accurate” boundary condition. The well‐posedness of the boundary condition is proven at the continuous level. Its finite‐element formulation, which ensures well‐posedness at a discrete level, is derived, after which it is demonstrated that accurate and stable solutions to the problem of antiplane shear‐wave propagation in an anisotropic elastic waveguide, an example of anisotropic scalar‐wave propagation, can be obtained using the proposed numerical approach.
ACanis lupusinspired upgraded Harris hawks optimizer for nonlinear, constrained, continuous, and discrete engineering design problem
Authors: Nandi Ayani , Kamboj Vikram Kumar
Published: October 2020

Recently established Harris hawks optimization (HHO) has natural behavior for finding an optimum solution in global search space without getting trapped in previous convergence. However, the exploitation phase of the current Harris hawks optimizer algorithm is poor. In the present research, an improved version of the HHO algorithm, which combines Harris hawks optimizer withCanis lupusinspire grey wolf optimizer (GWO) and named as hHHO‐GWO algorithm, has been proposed to find the solution of various optimization problems such as nonlinear, nonconvex, and highly constrained engineering design problem. In the proposed research, the phase of exploration and exploitation of the existing HHO algorithm has been further improved using GWO algorithm and its performance has been tested for various benchmarks problems including CEC2005 (unimodal, multimodal, and fixed dimensions functions), multimodal functions with variable dimensions, and CEC‐BC‐2017 test functions. Further, the developed hybrid optimizer has been tested for 11 different engineering design and optimization problems and experimental results of hHHO‐GWO have been compared with other optimizer.
Emergence of gram‐negative organisms as the cause of infections in patients with sickle cell disease
Authors: Khalife Sara , Hanna‐Wakim Rima , Ahmad Rasha , Haidar Rachid , Makhoul Peter G. , Khoury Nabil , Dbaibo Ghassan , Abboud Miguel R.
Published: October 2020

Background

Patients with sickle cell disease are at higher risk of infections with encapsulated bacteria due to immature immune responses and functional asplenia. We aimed to study our patient population for the emergence of gram‐negative organisms other than Salmonella as the cause of osteomyelitis and document a vast decrease in Streptococcus pneumoniae bacteremia rates.

Methods

We conducted a retrospective chart review of 158 patients with sickle cell disease registered at our hospital. Over a period of 13 years, every patient presenting to the emergency department (ED) with fever had their medical record reviewed for blood cultures, wound cultures, and magnetic resonance imaging results for osteomyelitis.

Results

The number of patients presenting to the ED with fever was 105, with 581 febrile episodes and 893 blood cultures. Among those, no culture grew Streptococcus pneumoniae, 14 grew coagulase‐negative staphylococci (1.5%), one grew Salmonella enterica Paratyphi B, and three grew Salmonella enterica group C (in the same patient). The total number of osteomyelitis episodes in patients with sickle cell disease presenting with fever and documented by imaging was nine (1.5%). In patients with osteomyelitis, organisms were isolated in four patients (44%), including Enterobacter cloacae, Bacteroides, Pseudomonas aeruginosa, and Salmonella enterica group C.

Conclusions

Immunization against Streptococcus pneumoniae and the use of prophylactic penicillin has virtually eliminated pneumococcal bacteremia among our patients. We observed the emergence of gram‐negative organisms other than Salmonella as the cause of osteomyelitis in patients with sickle cell disease.
Personalized prenatal genomic testing: Couples' experience with choice regarding uncertain and adult‐onset findings from chromosomal‐microarray‐analysis
Authors: Millo Talya , Douiev Liza , Popper Dov , Shkedi‐Rafid Shiri
Published: October 2020

Background

Chromosomal‐microarray‐analysis (CMA) can identify variants of uncertain clinical significance, susceptibility‐loci for neurodevelopmental conditions, and risk for adult‐onset conditions. We explored choices made by couples undergoing prenatal CMA, their understanding of these findings, reasons for and against receiving them, and whether they believe parents or professionals should decide which are disclosed.

Methods

Semi‐structured interviews were conducted with women (n = 27) or their partners (n = 15) during the week following prenatal CMA testing and analyzed using grounded theory.

Results

Over half the interviewees (55%) recalled at least two of the three types of CMA results they chose whether to receive. Sixty‐four percent found the choice simple, whereas 36% found it difficult. All participants could clearly explain their choices, which were based on the perceived actionability and psychological impact of the information. Sixty percent viewed their choice favorably, whereas ~21% would have preferred clinicians to decide for them. More women than men, and more decisive than indecisive participants supported parental choice.

Conclusion

Overall, expectant parents can make informed choices about which uncertain findings about their fetuses they wish to receive, and value the opportunity to tailor results to their values and wishes. Arguments presented provide the basis for a decision‐aid tool for expecting parents.
Discovery of novel benzofuran scaffold as 4‐hydroxyphenylpyruvate dioxygenase inhibitors
Authors: Huang Hao , Zhang Jian‐qiu , Liu Jian‐min , Wang Man‐man , Shu Lei , Yan Yi‐le , Zhan Xiao‐hang , Wang Ping , Huan Xue‐ting , Zhang Da‐yong
Published: October 2020

BACKGROUND

4‐Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. This study sheds new light on the differences in molecular scaffold from commercialized HPPD inhibitors.

RESULTS

The compounds A1‐A18 and B1‐B27 were synthesized for in vitro and greenhouse experiments. The greenhouse experiment data indicated that compounds B14 and B18 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. In vitro testing indicated that the compounds were HPPD inhibitors. Moreover, molecular simulation results show that the compounds B14, B18, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on crop selectivity results, compounds B14 and B18 were selected for maize studies (injury≤10%), indicating its potential for weed control in maize fields.

CONCLUSION

These results showed that the pyrazole‐benzofuran structure could be used as possible lead compounds for the development of HPPD inhibitors. © 2020 Society of Chemical Industry