bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative frequency‐dependent growth underlies the stable coexistence of two cosmopolitan aquatic plants
Authors: Armitage David W. , Jones Stuart E.
Published: February 2019

Identifying and quantifying the mechanisms influencing species coexistence remains a major challenge for the study of community ecology. These mechanisms, which stem from species’ differential responses to competition and their environments, promote coexistence if they give each species a growth advantage when rare. Yet despite the widespread assumption that co‐occurring species stably coexist, there have been few empirical demonstrations in support of this claim. Likewise, coexistence is often assumed to result from interspecific differences in life‐history traits, but the relative contributions of these trait differences to coexistence are rarely quantified, particularly across environmental gradients. Using two widely co‐occurring and ecologically similar species of freshwater duckweed plants (Spirodela polyrhiza and Lemna minor), we tested hypotheses that interspecific differences in facultative dormancy behaviors, thermal reaction norms, and density‐dependent growth promote coexistence between these species, and that their relative influences on coexistence change as average temperatures and fluctuations around them vary. In competition experiments, we found strong evidence for negative frequency‐dependent growth across a range of both static and fluctuating temperatures, suggesting a critical role of fluctuation‐independent stabilization in coexistence. This negative frequency dependence could be explained by our observation that for both species, intraspecific competition was over 1.5 times stronger than interspecific competition, granting each species a low‐density growth advantage. Using an empirically parameterized competition model, we found that while coexistence was facilitated by environmental fluctuations, fluctuation‐independent stabilization via negative frequency dependence was crucial for coexistence. Conversely, the temporal storage effect, an important fluctuation‐dependent mechanism, was relatively weak in comparison. Contrary to expectations, differences in the species’ thermal reaction norms and dormancy behaviors did not significantly promote coexistence in fluctuating environments. Our results highlight how coexistence in two ubiquitous and ostensibly similar aquatic plants is not necessarily a product of their most obvious interspecific differences, and instead results from subtle niche differences causing negative frequency‐dependent growth, which acts consistently on both species across environmental gradients.
Magnetic digital microfluidics on a bioinspired surface for point‐of‐care diagnostics of infectious disease
Authors: Kanitthamniyom Pojchanun , Zhang Yi
Published: February 2019

Magnetic digital microfluidics uses magnetic force to manipulate droplets on a Teflon‐coated substrate through the added magnetic particles. To achieve a wide range of droplet manipulation, hydrophilic patterns, known as surface energy traps, are introduced onto the Teflon‐coated hydrophobic substrate. However, the Teflon‐coated substrate is difficult to modify because it is nonwettable, and existing techniques for patterning surface energy traps have many limitations. Inspired by the mussel adhesion mechanism, we use polydopamine, a bioinspired substance that adheres strongly to almost any materials, to pattern surface energy traps on the Teflon‐coated substrate with a great ease. We have optimized the polydopamine coating protocol and characterized the surface properties of the polydopamine surface energy traps. Droplet operations including particle extraction, liquid dispensing, liquid shaping, and cross‐platform transfer have been demonstrated on the polydopamine surface energy trap‐enabled magnetic digital microfluidic platform in both single‐plate and two‐plate configurations. Furthermore, the detection of hepatitis B surface antigen using ELISA has been demonstrated on the new magnetic dgitial microfluidic platform. This new bioinspired magnetic digital microfluidic platform is easy to fabricate and operate, showing a great potential for point‐of‐care applications.
Paleomedicine and the use of plant secondary compounds in the Paleolithic and Early Neolithic
Authors: Hardy Karen
Published: February 2019

Reconstructing plant use before domestication is challenging due to a lack of evidence. Yet, on the small number of sites with assemblages, the wide range of different plant species cannot be explained simply in terms of nutrition. Assemblages from the Lower Paleolithic to the Early Neolithic were examined to investigate the relative edible and medicinal properties of the plants. The assemblages contain a mixture of edible species, plants that are both edible and medicinal, and plants with only medicinal properties. The proportion of medicinal plants at all sites is well above the natural average and increases over time. Mechanisms for preventing intestinal parasitic infections are common among animals and together with chimpanzees’ preventative and curative self‐medication practices suggest an evolutionary context for this behavior. A broad‐spectrum approach to plant collection is likely to have been in place throughout the Paleolithic driven, in part, by the need for medicinal compounds.
WTI crude oil option implied VaR and CVaR: An empirical application
Authors: Barone‐Adesi Giovanni , Finta Marinela Adriana , Legnazzi Chiara , Sala Carlo
Published: February 2019

Using option market data we derive naturally forward‐looking, nonparametric and model‐free risk estimates, three desired characteristics hardly obtainable using historical returns. The option‐implied measures are only based on the first derivative of the option price with respect to the strike price, bypassing the difficult task of estimating the tail of the return distribution. We estimate and backtest the 1%, 2.5%, and 5% WTI crude oil futures option‐implied value at risk and conditional value at risk for the turbulent years 2011–2016 and for both tails of the distribution. Compared with risk estimations based on the filtered historical simulation methodology, our results show that the option‐implied risk metrics are valid alternatives to the statistically based historical models.
Detection and localization of chamber tombs in the environs of ancient Olympia, Peloponnese, Greece, based on a combination of archaeological survey and geophysical prospection
Authors: Obrocki Lea , Eder Birgitta , Gehrke Hans‐Joachim , Lang Franziska , Vött Andreas , Willershäuser Timo , Rusch Katharina , Wilken Dennis , Hatzi‐Spiliopoulou Georgia , Kolia Erofili‐Iris , Vikatou Olympia
Published: February 2019

Mycenaean chamber tombs are composed of air‐filled burial cavities and, therefore, can be detected by non‐invasive geophysical methods. In this study, an electrical resistivity tomography (ERT)‐based approach was used to detect graves at three different sites in the area surrounding ancient Olympia. We collected ERT data at the necropolis of Mageiras‐Kioupia, where a number of chamber tombs had already been located and partly excavated in order to ground‐truth the ERT response for chamber tombs in different states of preservation. Near the village of Epitalio, a preceding archaeological survey discovered remains of a one chamber tomb in mid‐slope position of a larger hill. There, we applied the ERT‐approach, calibrated at Mageiras‐Kioupia, to the tomb and detected ten more tomb candidates at this site. In addition to ERT, we carried out ground penetrating radar (GPR) studies at the Epitalio site. In general GPR, data are highly consistent with ERT results. We were thus able to localize an unknown, most probably Mycenaean cemetery where no systematic archaeological information previously existed. In the third area of investigation, the Dartisa plateau, no potential chamber tomb comparable to the ones excavated and measured at Mageiras‐Kioupia and Epitalio were identified.
Impact of American Joint Committee on Cancer Eighth Edition clinical stage and smoking history on oncologic outcomes in human papillomavirus‐associated oropharyngeal squamous cell carcinoma
Authors: Hawkins Peter G. , Mierzwa Michelle L. , Bellile Emily , Jackson William C. , Malloy Kelly M. , Chinn Steven B. , Spector Matthew E. , Shuman Andrew G. , Stucken Chaz L. , McLean Scott A. , Bradford Carol R. , Prince Mark E. , Carey Thomas E. , Worden Francis P. , Swiecicki Paul L. , Taylor Jeremy M. G. , Wolf Gregory T. , Eisbruch Avraham , Casper Keith A.
Published: February 2019

Background

The purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification.

Methods

Kaplan‐Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence‐free survival (LRFS), and distant recurrence‐free survival (DRFS). Concordance statistics (C‐indices) were used to compare discriminating ability.

Results

The OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C‐indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack‐year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2‐3.1; P < .01) but not LRFS or DRFS.

Conclusion

These results support implementation of the AJCC eighth edition for HPV‐associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification.
Transoral supraglottic laryngectomy using a next‐generation single‐port robotic surgical system
Authors: Orosco Ryan K. , Tam Kenric , Nakayama Meijin , Holsinger F. Christopher , Spriano Giuseppe
Published: February 2019

Background

To investigate the feasibility of transoral robotic surgery (TORS) supraglottic laryngectomy (SGL) using a next‐generation flexible surgical robot.

Methods

Preclinical human cadaver anatomic study of TORS SGL via en bloc resection.

Results

A single‐port robotic surgical system (da Vinci Sp, Intuitive Surgical, Inc., Sunnyvale, California) provided sufficient access, reach, and visualization to perform TORS SGL. Access and exposure were achieved with a standard laryngo‐pharyngoscope retractor. The remote center of the robotic system was located 10 cm from the maxillary alveolus. Three surgical instruments and one flexible camera could be deployed with minimal collision or restriction of arm movement.

Conclusions

Routine resection supraglottic cancers through TORS have been hindered by challenging exposure and visualization and limited instrument maneuverability deep within the laryngopharyngeal complex. This preclinical feasibility study demonstrates the technical feasibility for TORS SGL using a next‐generation flexible surgical robot.
Ex Vivo Hepatocyte Reprograming Promotes Homology‐Directed DNA Repair to Correct Metabolic Disease in Mice After Transplantation
Authors: VanLith Caitlin J. , Guthman Rebekah M. , Nicolas Clara T. , Allen Kari L. , Liu Yuanhang , Chilton Jennifer A. , Tritz Zachariah P. , Nyberg Scott L. , Kaiser Robert A. , Lillegard Joseph B. , Hickey Raymond D.
Published: February 2019

Ex vivo CRISPR/Cas9‐mediated gene editing in hepatocytes using homology‐directed repair (HDR) is a potential alternative curative therapy to organ transplantation for metabolic liver disease. However, a major limitation of this approach in quiescent adult primary hepatocytes is that nonhomologous end‐joining is the predominant DNA repair pathway for double‐strand breaks (DSBs). This study explored the hypothesis that ex vivo hepatocyte culture could reprogram hepatocytes to favor HDR after CRISPR/Cas9‐mediated DNA DSBs. Quantitative PCR (qPCR), RNA sequencing, and flow cytometry demonstrated that within 24 hours, primary mouse hepatocytes in ex vivo monolayer culture decreased metabolic functions and increased expression of genes related to mitosis progression and HDR. Despite the down‐regulation of hepatocyte function genes, hepatocytes cultured for up to 72 hours could robustly engraft in vivo. To assess functionality long‐term, primary hepatocytes from a mouse model of hereditary tyrosinemia type 1 bearing a single‐point mutation were transduced ex vivo with two adeno‐associated viral vectors to deliver the Cas9 nuclease, target guide RNAs, and a 1.2‐kb homology template. Adeno‐associated viral Cas9 induced robust cutting at the target locus, and, after delivery of the repair template, precise correction of the point mutation occurred by HDR. Edited hepatocytes were transplanted into recipient fumarylacetoacetate hydrolase knockout mice, resulting in engraftment, robust proliferation, and prevention of liver failure. Weight gain and biochemical assessment revealed normalization of metabolic function. Conclusion: The results of this study demonstrate the potential therapeutic effect of ex vivo hepatocyte‐directed gene editing after reprogramming to cure metabolic disease in a preclinical model of hereditary tyrosinemia type 1.
Predictors of in‐hospital mortality after ischemic stroke: A prospective, single‐center study
Authors: Kortazar‐Zubizarreta Izaro , Pinedo‐Brochado Ana , Azkune‐Calle Itxaso , Aguirre‐Larracoechea Urko , Gomez‐Beldarrain Marian , Garcia‐Monco Juan Carlos
Published: February 2019

Background and Aims

Stroke is the second leading cause of death around the globe. Studies examining the predictors of in‐hospital mortality and the impact of complications on early outcome of acute ischemic stroke are scant. The aim of this study was to identify predictors of in‐hospital mortality in patients with acute ischemic stroke.

Methods

This was a prospective, single‐center study of patients with acute ischemic stroke consecutively admitted to the Neurology Department of a general hospital during a 2‐year period (from January 1, 2010 to December 31, 2011). Prospective data from this single‐center study included variables related to sociodemographics, comorbidities, and medical complications, together with in‐hospital mortality. Since stroke mortality may impact differently by sex and is also influenced by hospital length of stay, we proceeded to stratify by these variables.

Results

Six‐hundred and seventy‐three patients were included. Overall, in‐hospital mortality rate was 7.13%. Stratifying by length of stay in‐hospital (< 7 days and ≥ 7 days), we observed that within the first week, overall mortality was related to a history of previous stroke, higher stroke severity, and to cardiovascular and respiratory complications. After 7 days, the main factor independently associated with overall in‐hospital mortality was stroke severity (National Institutes of Health Stroke Scale (NIHSS) ≥ 14, odds ratio (OR): 17.15; 95% CI, 3.06‐96.07).

Stratifying by sex, we observed that females had a worse outcome if there was a history of prior stroke (OR: 3.29; 95% CI, 1.19‐9.10), higher stroke severity (NIHSS ≥ 14, OR: 16.63; 95% CI, 4.66‐59.31), and cardiovascular complications (OR: 29.70; 95% CI, 5.70‐154.8). Among men, stroke severity (NIHSS ≥ 14, OR: 23.19; 95% CI, 5.69‐94.56), respiratory infections (OR: 3.84; 95% CI, 1.32‐11.20), and older age had significant negative impact.

Conclusions

Stroke severity and potentially modifiable complications (respiratory infections and cardiovascular complications) confer an increased risk of in‐hospital death in both women and men, particularly during the first week of admission.
Evaluation of basin storage–discharge sensitivity in Taiwan using low‐flow recession analysis
Authors: Yeh Hsin‐Fu , Huang Chia‐Chi
Published: February 2019

Sensitivity analysis of the hydrological behaviour of basins has mainly focused on the correlation between streamflow and climate, ignoring the uncertainty of future climate and not utilizing complex hydrological models. However, groundwater storage is affected by climatic change and human activities. The streamflow of many basins is primarily sourced from the natural discharge of aquifers in upstream regions. The correlation between streamflow and groundwater storage has not been thoroughly discussed. In this study, the storage–discharge sensitivity of 22 basins in Taiwan was investigated by means of daily streamflow and rainfall data obtained over more than 30 years. The relationship between storage and discharge variance was evaluated using low‐flow recession analysis and a water balance equation that ignores the influence of rainfall and evapotranspiration. Based on the obtained storage–discharge sensitivity, this study explored whether the water storage and discharge behaviour of the studied basins is susceptible to climate change or human activities and discusses the regional differences in storage–discharge sensitivity. The results showed that the average storage–discharge sensitivities were 0.056 and 0.162 mm−1 in the northern and southern regions of Taiwan, respectively. In the central and eastern regions, the values were both 0.020 mm−1. The storage–discharge sensitivity was very high in the southern region. The regional differences in storage–discharge sensitivity with similar climate conditions are primarily due to differences in aquifer properties. Based on the recession curve, other factors responsible for these differences include land utilization, land coverage, and rainfall patterns during dry and wet seasons. These factors lead to differences in groundwater recharge and thus to regional differences in storage–discharge sensitivity.
Impact of intertwin interval on short‐term neonatal outcomes of the second twin in dichorionic pregnancies with vaginal delivery
Authors: Benito Marta , De Bonrostro Carlos , Agustín Andrea , Roca Montserrat , Campillos Jose M. , Castán Sergio
Published: February 2019

Objective

To examine the effect of intertwin interval on umbilical cord pH and Apgar scores of the second twin after vaginal delivery.

Methods

A retrospective study of twin deliveries at a university hospital in Spain between August 2012 and September 2017. Inclusion criteria were vaginal delivery of both twins at 32 gestational weeks or more. Exclusion criteria were monochorionic pregnancies and indication for cesarean delivery. The sample was dichotomized by intertwin interval (<10 and ≥10 minutes). Neonatal outcomes including Apgar scores and umbilical cord pH were evaluated.

Results

Overall, 323 twin deliveries were included. Intertwin interval was less than 10 minutes in 277 (85.6%) cases, and 10 minutes or longer in 46 (14.2%). There were no differences in maternal or obstetric characteristics between the groups. Incidence of instrumental delivery (P<0.001) and internal podalic version (P<0.001) for the second twin was higher in the longer interval group. A longer interval was associated with higher frequencies of 1‐minute Apgar score below 4 (P=0.009), 5‐minute Apgar score below 7 (P<0.001), and umbilical cord pH below 7.15 (P<0.001).

Conclusion

Second twins with an intertwin interval of 10 minutes or longer are more likely to have poorer Apgar scores and arterial blood pH below 7.15.
Evaluating Reform of Australia's Water Policy Framework
Authors: Tan Poh‐Ling
Published: February 2019

In the past two decades Australia has shifted from an administrative grants regime for allocating water to a statutory planning regime that shares water between consumptive and environmental use. This was to address problems of overuse of water primarily in the Murray‐Darling Basin. A suite of measures were introduced including institutional reform to set out the roles and responsibilities of those involved in the water industry; commitment to provide cost‐based pricing; trading to allow for transfer of water from low‐value crops to high value uses and water for the environment. The National Water Initiative, 2004 (NWI) is the current blueprint for reform. An independent statutory authority has audited national water reforms finding that measures have been successful in areas such as the introduction of tradable water entitlements. Environmental benefits will take many more years to be gauged, while the effects of climate change have not been consistently reflected in decision‐making. A developmental paradigm continues to dominate policy development for Northern Australia.
Use of affinity allows anti‐inflammatory and anti‐microbial dual release that matches suture wound resolution
Authors: Haley Rebecca M. , Qian Victoria R. , Learn Greg D. , von Recum Horst A.
Published: February 2019

Surgical sutures are vulnerable to bacterial infections and biofilm formation. At the suture site, pain and undesirable, excess inflammation are additionally detrimental to wound healing. The development of a polymerized cyclodextrin (pCD) coated surgical suture introduces the capability to locally deliver both anti‐inflammatory and anti‐microbial drugs throughout the phases of acute and chronic healing. Local delivery allows for the improvement of wound healing while reducing related systemic side effects and drug resistance. Through testing, it has been shown that the fabrication of our pCD coating minimally affects the suture's mechanical properties. In vitro studies show measurable and consistent drug delivery for nearly 5 weeks. The therapeutic level of this delivery is sufficient to show inhibition of bacterial growth for 4 weeks, and free‐radical scavenging (an in vitro anti‐inflammatory activity approximation) for 2 weeks. With this pCD coating technique, we maintain clinical performance standards while also introducing a long‐term dual delivery system relevant to the wound healing timeframe. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
Biomechanical characterization of a novel collagen‐hyaluronan infused 3D‐printed polymeric device for partial meniscus replacement
Authors: Ghodbane Salim A. , Patel Jay M. , Brzezinski Andrzej , Lu Tyler M. , Gatt Charles J. , Dunn Michael G.
Published: February 2019

The menisci transmit load by increasing the contact area and decreasing peak contact stresses on the articular surfaces. Meniscal lesions are among the most common orthopedic injuries, and resulting meniscectomies are associated with adverse polycaprolactone contact mechanics changes and, ultimately, an increased likelihood of osteoarthritis. Meniscus scaffolds were fabricated by 3D‐printing a network of circumferential and radial filaments of resorbable polymer (poly(desaminotyrosyl‐tyrosine dodecyl ester dodecanoate)) and infused with collagen‐hyaluronan. The scaffold demonstrated an instantaneous compressive modulus (1.66 ± 0.44 MPa) comparable to native meniscus (1.52 ± 0.59 MPa). The scaffold aggregate modulus (1.33 ± 0.51 MPa) was within 2% of the native value (1.31 ± 0.36 MPa). In tension, the scaffold displayed a comparable stiffness to native tissue (127.6–97.1 N/mm) and an ultimate load of 33% of the native value. Suture pull‐out load of scaffolds (83.1 ± 10.0 N) was within 10% of native values (91.5 ± 15.4 N). Contact stress analysis demonstrated the scaffold reduced peak contact stress by 60–67% and increased contact area by 38%, relative to partial meniscectomy. This is the first meniscal scaffold to match both the axial compressive properties and the circumferential tensile stiffness of the native meniscus. The improvement of joint contact mechanics, relative to partial meniscectomy alone, motivates further investigation using a large animal model. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2457–2465, 2019.
A proposal for sectorial organizing and quality standards in therapeutic apheresis: The therapeutic apheresis unit (TAU) standards
Authors: Pierelli Luca , Iaconianni Vincenzo , Vacca Michele
Published: February 2019

Therapeutic apheresis (TA) includes a wide range of therapeutic procedures based on the separation of blood components and the collection of cells with therapeutic activity or the removal of unwanted plasma or cellular components involved in the etiology of various hematologic, renal, neurological, and medical diseases. The complexity of these interventions requires an organizing model to assure a proper clinical environment, technology, quality requirements, and personnel as well as an active system for outcome monitoring for safety and efficacy. Finally, a structured organizing model may favor the efficiency of the TA unit and economic affordability. Here, we describe the more relevant characteristics of a model of TA standards, named TA unit (TAU) standards, that may help to establish a quality program in units working in the field of TA (shown as supplementary material and available at http://www.ifeit.org/pdf/TAU_Standards_3.0.pdf.
Knockdown of Sal‐like 4 expression by siRNA induces apoptosis in colorectal cancer
Authors: Hesari AmirReza , Rajab Shadi , Rezaei Marzieh , Basam Maryam , Golmohamadi Sara , Ghasemi Faezeh
Published: February 2019

Colorectal cancer (CRC) is known as the third most common malignancies among men and women and is also the second leading cause of cancer‐related deaths worldwide. It has been indicated that a variety of risk factors are involved in the pathogenesis of CRC. Spalt‐like transcription factor 4 (SALL4) is known as a transcription factor that plays an important role in the proliferation of cancerous cells. In this study, using a specific sequence of small interfering RNA (siRNA) against the sequence of SALL4, its activity is investigated in the CRC cell line (sw742). The CRC cells (sw742) were cultured and then, using a specific anti‐SALL4 siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and Bcl‐2 gene were measured using the real‐time polymerase chain reaction method. Cell death was evaluated by propidium iodide staining and fluorescence‐activated cell sorting analysis. Our results indicated that the specific concentration of siRNA of the SALL4 gene was 62.5 nmole. Gene expression of SALL4 and Bcl‐2 results showed that expression of Bcl‐2 gene in the siRNA group was significantly reduced. In conclusion, our finding indicated that it could be used as a therapeutic and diagnostic biomarker in the treatment of patients with CRC.
Effects of SRSF1 on subnuclear localization of topoisomerase I
Authors: Girstun Agnieszka , Ishikawa Takao , Staron Krzysztof
Published: February 2019

Subnuclear localization of topoisomerase I (top I) is determined by its DNA relaxation activity and a net of its interactions with in majority unidentified nucleolar and nucleoplasmic elements. Here, we recognized SR protein SRSF1 (Serine/arginine‐rich splicing factor 1, previously known as SF2/ASF) as a new element of the net. In HeLa cells, overexpression of SRSF1 recruited top I to the nucleoplasm whereas its silencing concentrated it in the nucleolus. Effect of SRSF1 was independent of top I relaxation activity and was the best pronounced for the mutant inactive in relaxation reaction. In HCT116 cells where top I was not released from the nucleolus upon halting relaxation activity, it was also not relocated by elevated level of SRSF1. Out of remaining SR proteins, SRSF5, SRSF7, and SRSF9 did not influence the localization of top I in HeLa cells whereas overexpression of SRSF2, SRSF3, SRSF6, and partly SRSF4 concentrated top I in the nucleolus, most possibly due to the reduction of the SRSF1 accessibility. Specific effect of SRSF1 was exerted because of its distinct RS domain. Silencing of SRSF1 compensated the deletion of the top I N‐terminal region, individually responsible for nucleoplasmic localization of the mutant, and restored the wild‐type phenotype of deletion mutant localization. SRSF1 was essential for the camptothecin‐induced clearance from the nucleolus. These results suggest a possible role of SRSF1 in establishing partition of top I between the nucleolus and the nucleoplasm in some cell types with distinct combinations of SR proteins levels.
Natural compounds with DPP‐4 inhibitory effects: Implications for the treatment of diabetes
Authors: Yaribeygi Habib , Atkin Stephen L. , Sahebkar Amirhossein
Published: February 2019

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are antidiabetes agents that decrease blood glucose by preventing the degradation of endogenous glucagon‐like peptide‐1. The first DPP‐4 was sitagliptin followed by several other agents in the class introduced to manage diabetes. Recent studies have suggested that naturally occurring compounds can exert an antidiabetes effect through DPP‐4 inhibition. Such compounds may have a place in the treatment of diabetes within the diet; however, while DPP‐4 inhibition alone is not associated with hypoglycemia, in combinations with other medication hypoglycemia can result, therefore, it is critical to know what herbal or food‐based compounds may have these activities in the management of diabetes patients. In this review, we have outlined the compounds that have DPP‐4 inhibition that may have utility in the treatment of diabetes.
Occult hepatitis C virus infection in patients with beta‐thalassemia major: Is it a neglected and unexplained phenomenon?
Authors: Ayadi Ahmad , Nafari Amir Hossein , Irani Shiva , Mohebbi Elham , Mohebbi Fahimeh , Sakhaee Fatemeh , Vaziri Farzam , Siadat Seyed Davar , Fateh Abolfazl
Published: February 2019

Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Beta‐thalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity. A total of 181 BTM patients with HCV negative markers were selected. HCV RNA was tested in PBMCs using nested polymerase chain reaction assay. The positive samples were then genotyped via restriction fragment‐length polymorphism (RFLP) and 5′‐untranslated region sequencing. Six (3.3%) out of 181 BTM patients had viral HCV genomes in PBMC samples. Three (50.0%), two (33.3%), and one (16.7%) out of these six patients were infected with HCV‐1b, HCV‐1a, and HCV‐3a, respectively. OCI positivity was significantly associated with the serum level of uric acid (P = 0.045) and ABO blood group (P = 0.032). Also, OCI patients had unfavorable IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ∆G/∆G genotypes. In conclusion, we indicated the low frequency of OCI in BTM patients. Nevertheless, more attention is warranted considering the importance of this infection. Also, further studies are necessary to determine the actual prevalence of OCI among BTM patients in Iran.
Psychometric properties of the self‐sufficiency matrix among homeless and vulnerably housed individuals and families
Authors: Cummings Camilla , Brown Molly
Published: February 2019

Homeless service systems have been implementing assessment tools to inform service provision for individuals and families. Although a variety of assessments are available, their psychometric evidence base is limited. The self‐sufficiency matrix (SSM) is one assessment that demonstrates promising reliability and validity. However, the SSM's factor structure has been inconsistent across studies. This study explored the factor structure of the SSM, using exploratory factor analysis and confirmatory factor analysis in a sample of individuals (N = 427) and families (
N = 428) at risk of or experiencing homelessness. Data were derived from a midwestern city's Homeless Management Information System and included all participants from the Homelessness Prevention and Rapid Re‐Housing Program. Results suggest the SSM is multidimensional and the factor structure differs across individuals and families. Additionally, the SSM demonstrates measurement invariance across racial and gender groups. Further development and testing of the SSM is necessary to better serve individuals experiencing homelessness.
Retracted: Tetramethylpyrazine partially relieves hypoxia‐caused damage of cardiomyocytes H9c2 by downregulation of miR‐449a
Authors: Zhang Xuesong , Dong Huawei , Liu Yong , Han Junxia , Tang Shouyi , Si Jingna
Published: February 2019

Inadequate oxygen supply is probably one of the most important pathophysiological mechanisms of cardiomyocyte damage in ischemic heart disease. Tetramethylpyrazine (TMP, also known as ligustrazine) is the main active ingredient isolated from the rhizome of Ligusticum chuanxiong Hort. A previous study reported that the TMP could exert cardioprotective activity. This study aimed to explore the molecular mechanism of the protective effects of TMP on cardiomyocyte damage caused by hypoxia. The viability and apoptosis of cardiomyocytes H9c2 were detected using cell counting kit‐8 assay and annexin V‐FITC/PI staining, respectively. Quantitative reverse transcription polymerase chain reaction was conducted to measure the expression level of microRNA‐449a (miR‐449a). Cell transfection was performed to upregulate the expression level of miR‐449a or downregulate the expression level of sirtuin 1 (Sirt1). The protein expression levels of Sirt1 and key factors involved in cell apoptosis and phosphatidylinositol 3‐kinase/protein kinase 3 (PI3K/AKT) pathway were evaluated using western blot analysis. We found that the hypoxia incubation inhibited H9c2 viability, induced cell apoptosis, and inactivated the PI3K/AKT pathway. TMP treatment partially relieved the hypoxia‐caused H9c2 cell viability loss and apoptosis, as well as reversed the hypoxia‐caused inactivation of the PI3K/AKT pathway. Moreover, TMP partially alleviated the upregulation of miR‐449a in H9c2 cells caused by hypoxia. Overexpression of miR‐449a weakened the effects of TMP on hypoxia‐treated H9c2 cells. Furthermore, Sirt1 was a target gene of miR‐449a. Knockdown of Sirt1 also weakened the effects of TMP on hypoxia‐treated H9c2 cells. In conclusion, TMP partially relieved hypoxia‐caused cardiomyocytes H9c2 viability loss and apoptosis at least through downregulating miR‐499a, upregulating Sirt1, and then activating the PI3K/AKT pathway.
Mechanism of bioactive polysaccharide from Lachnum sp. acts synergistically with 5‐fluorouracil against human hepatocellular carcinoma
Authors: Zong Shuai , Li Jinglei , Yang Liu , Huang Qianli , Hou Guohua , Ye Ziyang , Ye Ming
Published: February 2019

The antimetabolite 5‐fluorouracil (5‐FU) is a widely used antitumor agent, however the overall response rate to 5‐FU as a single agent is usually limited. Herein, how Lachnum expolysaccharide (LEP‐2a), a type of active polysaccharide isolated from
Lachnum sp., acted synergistically with 5‐FU on HepG2 cells was investigated. It was found that LEP‐2a notably enhanced 5‐FU sensitivity in HepG2 cells in a synergistic manner. After combination treatment of 5‐FU and LEP‐2a, Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathway were inactivated. In addition, combination treatment induced generation of reactive oxygen species, decreased the levels of intracellular antioxidant enzymes and triggered mitochondrial apoptosis pathway. Furthermore, 5‐FU combined with LEP‐2a also resulted in p53 activation and NF‐κB inhibition, and cell cycle arrest in the S phase as well as cell metastasis stagnation. Interestingly, LEP‐2a treatment also blocked the DNA damage repair procedure. These findings demonstrate that LEP‐2a enhanced 5‐FU sensitivity and combination of 5‐FU and LEP‐2a exerts synergistic antitumor efficiency through multiple approaches.
Strategies to inhibit arsenic trioxide‐induced cardiotoxicity in acute promyelocytic leukemia
Authors: Haybar Habib , Shahrabi Saeid , Rezaeeyan Hadi , Jodat Hosein , Saki Najmaldin
Published: February 2019

Objective

Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO‐induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity.

Methods

The key search terms were “arsenic trioxide,” “acute promyelocytic leukemia,” “cardiotoxicity,” “molecular pathway,” and “biomarker.”

Results

Studies have indicated the involvement of several molecular pathways in ATO‐induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity.

Conclusion

Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO‐induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.
8‐chloro‐adenosine activity in FLT3‐ITD acute myeloid leukemia
Authors: Buettner Ralf , Nguyen Le Xuan Truong , Kumar Bijender , Morales Corey , Liu Chao , Chen Lisa S. , Pemovska Tea , Synold Timothy W. , Palmer Joycelynne , Thompson Ryan , Li Ling , Hoang Dinh Hoa , Zhang Bin , Ghoda Lucy , Kowolik Claudia , Kontro Mika , Leitch Calum , Wennerberg Krister , Yu Xiaochun , Chen Ching‐Cheng , Horne David , Gandhi Varsha , Pullarkat Vinod , Marcucci Guido , Rosen Steven T.
Published: February 2019

Nucleoside analogs represent the backbone of several distinct chemotherapy regimens for acute myeloid leukemia (AML) and combination with tyrosine kinase inhibitors has improved survival of AML patients, including those harboring the poor‐risk FLT3‐ITD mutation. Although these compounds are effective in killing proliferating blasts, they lack activity against quiescent leukemia stem cells (LSCs), which contributes to initial treatment refractoriness or subsequent disease relapse. The reagent 8‐chloro‐adenosine (8‐Cl‐Ado) is a ribose‐containing, RNA‐directed nucleoside analog that is incorporated into newly transcribed RNA rather than in DNA, causing inhibition of RNA transcription. In this report, we demonstrate antileukemic activities of 8‐Cl‐Ado in vitro and in vivo and provide mechanistic insight into the mode of action of 8‐Cl‐Ado in AML. 8‐Cl‐Ado markedly induced apoptosis in LSC, with negligible effects on normal stem cells. 8‐Cl‐Ado was particularly effective against AML cell lines and primary AML blast cells harboring the FLT3‐ITD mutation. FLT3‐ITD is associated with high expression of miR‐155. Furthermore, we demonstrate that 8‐Cl‐Ado inhibits miR‐155 expression levels accompanied by induction of DNA‐damage and suppression of cell proliferation, through regulation of miR‐155/ErbB3 binding protein 1(Ebp1)/p53/PCNA signaling. Finally, we determined that combined treatment of NSG mice engrafted with FLT3‐ITD
+ MV4−11 AML cells with 8‐Cl‐Ado and the FLT3 inhibitor AC220 (quizartinib) synergistically enhanced survival, compared with that of mice treated with the individual drugs, suggesting a potentially effective approach for FLT3‐ITD AML patients.
Use of stem cells as carriers of oncolytic viruses for cancer treatment
Authors: Zendedel Elham , Atkin Stephen L. , Sahebkar Amirhossein
Published: February 2019

Therapeutic application of stem cells and oncolytic viruses in cancer treatment has rapidly increased in the last decade. Oncolytic viruses are considered as a new class of anticancer agents because of their ability to selectively infect and destroy cancer cells. Furthermore, regarding the specific migratory capacity of stem cells, they can be used as carriers or vectors targeting metastatic cancer. Promising results have been reported regarding the use of stem cells and oncolytic viruses as a therapeutic approach for the treatment of metastatic cancer. The present review aimed to determine the approaches involved in the use of the tumor‐homing capacity of stem cells for cancer treatment.
The roles of signaling pathways in liver repair and regeneration
Authors: Valizadeh Amir , Majidinia Maryam , Samadi‐Kafil Hossein , Yousefi Mehdi , Yousefi Bahman
Published: February 2019

The liver has remarkable regeneration potency that restores liver mass and sustains body hemostasis. Liver regeneration through signaling pathways following resection or moderate damages are well studied. Various cell signaling, growth factors, cytokines, receptors, and cell types implicated in liver regeneration undergo controlled hypertrophy and proliferation. Some aspects of liver regeneration have been discovered and many investigations have been carried out to identify its mechanisms. However, for optimizing liver regeneration more should be understood about mechanisms that control the growth of hepatocytes and other liver cell types in adults. The current paper deals with the possible applicability of liver regeneration signaling pathways as a target for therapeutic approaches and preventing various liver damages. Furthermore, the latest findings of spectrum‐specific signaling pathway mechanisms that underlie liver regeneration are briefly described.
Criss‐cross heart with double‐outlet right ventricle, subpulmonary ventricular septal defect, and bicuspid pulmonary valve
Authors: Ren Sihua , Ma Chunyan , Li Songbai
Published: February 2019

Criss‐cross heart (CCH) is an extremely rare complex congenital heart malformation. It accounts for less than 0.1% of congenital heart diseases. Here, we describe a unique case of CCH with double‐outlet right ventricle, huge subpulmonary ventricular septal defect, bicuspid pulmonary valve, and right‐hand aortic arch. The anatomic features were observed with echocardiography, and the diagnosis was confirmed at surgery. Many variations of CCH have been described. The present case expands the spectrum of this entity and may provide new insight into this complex anatomy.
A novel approach to offering additional genomic findings—A protocol to test a two‐step approach in the healthcare system
Authors: Martyn Melissa , Kanga‐Parabia Anaita , Lynch Elly , James Paul A. , Macciocca Ivan , Trainer Alison H. , Halliday Jane , Keogh Louise , Wale Janney , Winship Ingrid , Bogwitz Michael , Valente Giulia , Walsh Maie , Downie Lilian , Amor David , Wallis Mathew , Cunningham Fiona , Burgess Matthew , Brown Natasha J. , Jarmolowicz Anna , Lunke Sebastian , Goranitis Ilias ,   Melbourne Genomics Health Alliance, Gaff Clara L.
Published: February 2019

Internationally, the practice of offering additional findings (AFs) when undertaking a clinically indicated genomic test differs. In the USA, the recommendation is to include analysis for AFs alongside diagnostic analysis, unless a patient opts‐out, whereas European and Canadian guidelines recommend opt‐in models. These guidelines all consider the offer of AFs as an activity concurrent with the offer of diagnostic testing. This paper describes a novel two‐step model for managing AFs within the healthcare system in Victoria, Australia and presents the study protocol for its evaluation. Adults who have received results of diagnostic whole exome sequencing undertaken within the healthcare system are invited to attend a genetic counseling appointment to consider reanalysis of their stored genomic data for AFs. The evaluation protocol addresses uptake, decision‐making, understanding, counseling challenges, and explores preferences for future models of care. Recruitment commenced in November 2017 and will cease when 200 participants have been approached. When the study is concluded, the evaluation results will contribute to the evidence base guiding approaches to counseling and models of care for AFs.
Evaluation of polyol‐made Gd3+‐substituted Co0.6Zn0.4Fe2O4 nanoparticles as high magnetization MRI negative contrast agents
Authors: Mnasri Walid , Bentahar Lotfi , Nowak Sophie , Sandre Olivier , Boissière Michel , Ammar Souad
Published: February 2019

The structural, microstructural, and magnetic properties of ~5‐nm‐sized Co0.6Zn0.4Fe2 − xGdxO4 nanoparticles were investigated in order to evaluate their capability to enhance the magnetic resonance imaging contrast as high magnetization agents. A focus was made on the solubility of Gd3+ cations within the spinel lattice. By coupling X‐ray diffraction to X‐ray fluorescence spectroscopy, we demonstrated that only a limited fraction of Gd3+ can substitute Fe3+ ions into the whole crystal structure and does not exceed 6 at.‐%. At this concentration, the room temperature (27°C) saturation magnetizations of the prepared superparamagnetic nanocrystals were found to be close to 80 emu g−1. Coating these nanoparticles with hydrophilic dopamine ligands leads to the formation of ~50‐nm‐sized clusters in water. As a consequence, relatively high r2/r1 ratios of transverse to longitudinal proton relaxivities and high r2 values were measured in the resulting colloids at physiological temperature (37°C) for an applied magnetic field of 1.41 T: 33 and 188 mM−1 sec−1, respectively, for the richest system in gadolinium. Moreover, after incubation with healthy human model cells (fibroblasts) at doses as high as 10 μg mL−1, they induce neither cellular death nor acute cellular damage making the engineered probes particularly valuable for negative magnetic resonance imaging contrasting.
Unraveling the host's immune response to infection: Seeing is believing
Authors: Scott Brittney N V , Sarkar Tina , Kratofil Rachel M , Kubes Paul , Thanabalasuriar Ajitha
Published: February 2019

It has long been appreciated that understanding the interactions between the host and the pathogens that make us sick is critical for the prevention and treatment of disease. As antibiotics become increasingly ineffective, targeting the host and specific bacterial evasion mechanisms are becoming novel therapeutic approaches. The technology used to understand host-pathogen interactions has dramatically advanced over the last century. We have moved away from using simple in vitro assays focused on single-cell events to technologies that allow us to observe complex multicellular interactions in real time in live animals. Specifically, intravital microscopy (IVM) has improved our understanding of infection, from viral to bacterial to parasitic, and how the host immune system responds to these infections. Yet, at the same time it has allowed us to appreciate just how complex these interactions are and that current experimental models still have a number of limitations. In this review, we will discuss the advances in vivo IVM has brought to the study of host-pathogen interactions, focusing primarily on bacterial infections and innate immunity.