bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dry‐season irrigation on leaf physiology and biomass allocation in tropical lianas and trees
Authors: Smith‐Martin Chris M. , Bastos Carolina L. , Lopez Omar R. , Powers Jennifer S. , Schnitzer Stefan A.
Published: July 2019

Lianas are more abundant in seasonal forests than in wetter forests and are thought to perform better than trees when light is abundant and water is limited. We tested the hypothesis that lianas perform better than trees during seasonal drought using a common garden experiment with 12 taxonomically diverse species (six liana and six tree species) in 12 replicated plots. We irrigated six of the plots during the dry season for four years, while the remaining six control plots received only ambient rainfall. In year 5, we measured stem diameters for all individuals and harvested above‐ and belowground biomass for a subset of individuals to quantify absolute growth and biomass allocation to roots, stems, and leaves, as well as total root length and maximum rooting depth. We also measured rate of photosynthesis, intrinsic water use efficiency (iWUE), pre‐dawn and midday water potential, and a set of functional and hydraulic traits. During the peak of the dry season, lianas in control plots had 54% higher predawn leaf water potentials (ΨPD), and 45% higher photosynthetic rates than trees in control plots. By contrast, during the peak of the wet season, these physiological differences between lianas and trees become less pronounced and, in some cases, even disappeared. Trees had higher specific leaf area (SLA) than lianas; however, no other functional trait differed between growth forms. Trees responded to the irrigation treatment with 15% larger diameters and 119% greater biomass than trees in control plots. Liana growth, however, did not respond to irrigation; liana diameter and biomass were similar in control and irrigation plots, suggesting that lianas were far less limited by soil moisture than were trees. Contrary to previous hypotheses, lianas did not have deeper roots than trees; however, lianas had longer roots per stem diameter than did trees. Our results support the hypothesis that lianas perform better and experience less physiological stress than trees during seasonal drought, suggesting clear differences between growth forms in response to altered rainfall regimes. Ultimately, better dry‐season performance may explain why liana abundance peaks in seasonal forests compared to trees, which peak in abundance in less seasonal, wetter forests.
Sex differences on peak oxygen uptake in heart failure
Authors: Palau Patricia , Domínguez Eloy , Núñez Julio
Published: July 2019

Women represent nearly half of the adult heart failure (HF) population and they remain underrepresented in HF studies. We aimed to evaluate the evidence about peak oxygen uptake (peak VO2) for clinical stratification in women with HF. This narrative review summarizes (i) the evidence endorsing the value of cardiopulmonary exercise testing for clinical stratification and phenotyping HF population; (ii) the determinants of a person's functional aerobic capacity to understand predicted values for patients with chronic HF; and (iii) sex differences on peak VO2 data in different forms of HF. Lastly, based on existing data in patients with HF, we provide a perspective on how to improve existing gaps about the utility of peak VO2 in clinical stratification in women. Peak VO2 provides prognosis information in patients with HF; however, its use has been limited for a reduced number of patients excluding women, elderly, and HF patients with preserved ejection fraction. Further studies will help to fill the wide gender gap about the utility of cardiopulmonary exercise testing in the risk assessment and management in women with HF.
Differences in blood pressure riser pattern in patients with acute heart failure with reduced mid‐range and preserved ejection fraction
Authors: Ueda Tomoya , Kawakami Rika , Nakada Yasuki , Nakano Tomoya , Nakagawa Hitoshi , Matsui Masaru , Nishida Taku , Onoue Kenji , Soeda Tsunenari , Okayama Satoshi , Watanabe Makoto , Okura Hiroyuki , Saito Yoshihiko
Published: July 2019

Aims

Heart failure (HF) is classified into three types according to left ventricular ejection fraction (EF). The effect of blood pressure (BP) on the pathogenesis of each type is assumed to be different. However, the association between the prognosis of each type of HF and abnormal BP variations assessed by ambulatory BP monitoring (ABPM), such as nocturnal hypertension and the riser pattern, remains unclear.

Methods and results

We studied 325 consecutive patients with decompensated HF who were acutely admitted to our hospital and underwent ABPM at discharge. During a mean follow‐up of 30.0 months, 52 cardiovascular and 112 all‐cause deaths occurred. The Cox proportional hazards model showed that the mean values of 24 h, awake, and sleep‐time systolic BP (SBP), and abnormal 24 h ABPM patterns, such as nocturnal hypertension and non‐dipper pattern, were not associated with either all‐cause or cardiovascular mortality in patients with HF with reduced EF (HFrEF), HF with mid‐range EF (HFmrEF), or HF with preserved EF (HFpEF), except for sleep‐time SBP in HFrEF. However, the riser pattern was a significant and independent predictor of all‐cause and cardiovascular deaths in patients with HFpEF (hazard ratio, 2.01; 95% confidence interval, 1.12–3.62; 0.0200; and hazard ratio, 2.48; 95% confidence interval, 1.08–5.90; 0.0332, respectively). Sleep‐time pulse rate was similarly decreased in both the riser and non‐riser groups.

Conclusions

The riser pattern of SBP was associated with an increased risk of adverse outcomes among patients with HFpEF but not HFrEF or HFmrEF.
Development of Nanostructured Lipid Carriers (NLCs) Using Pumpkin and Kenaf Seed Oils with Potential Photoprotective and Antioxidative Properties
Authors: Chu Chee Chin , Tan Chin Ping , Nyam Kar Lin
Published: July 2019

Both pumpkin and kenaf seed oil with carnauba wax (CW) and beeswax (BW) are used to develop nanostructured lipid carriers (NLCs) loaded with Uvinul T150 and Uvinul A Plus Granular for a UV protection formulation. The study aims to optimize the concentration and the type of seed oil in order to develop a stable NLC formulation with high entrapment efficiency, drug loading, antioxidant activities, and UV absorbing properties. The physical properties of the NLCs are analyzed based on the mean particle size, polydispersity index (PDI), long‐term storage stability, Fourier‐transform infrared spectroscopy (FT‐IR), and differential scanning calorimetry (DSC). They are also compared for their entrapment efficiency, drug loading, in vitro antioxidant activities, and in vitro UV absorbing properties. The optimized NLC consists of 10% lipid phase and 1% Uvinul T150 and Uvinul A Plus Granular, respectively. It has mean particle size of 238.20 ± 3.61 nm and remains physically stable on storage at both 25 ± 2 and 40 ± 2 °C. Spherical amorphous NLC structure with encapsulated UV filters is observed by transmission electron microscopy (TEM). Besides, it shows high entrapment efficiency (≥95%) for both Uvinul T150 and Uvinul A Plus Granular in addition to its antioxidant activities as indicated by both DPPH and ABTS radical scavenging activities. In addition, the formulation had high UV absorbing properties, showing its potential to be utilized in the formation of sunscreen prototype.

Practical Application: The preliminary study on pumpkin and kenaf seed oil shows bioactive potential with high antioxidant activities. The finding of kenaf seed oil‐NLC can be applied in the cosmetic industry to produce a wide variety of environmental‐friendly products with improved stability and beneficial properties. Also, the application of technology by forming NLCs can be used to develop lotions, creams, etc., with multifunctional properties. Besides, NLCs as carriers for UV filters is proven in the present study to exhibit high entrapment efficiency and drug loading properties. This is beneficial in developing advanced cosmetic prototypes that possess broad spectrum effectiveness with fewer side effects.

Nanostructure lipid carriers (NLCs)are applied to encapsulate UV filters with pumpkin and kenaf seed oils. Kenaf seed oil‐NLC (F7) is selected as the best formulation for UV filters encapsulation. With spherical amorphous NLC structure, it shows high entrapment efficiency for the UV filters and antioxidant activities. Results indicate that F7 with high UV absorbing properties remains physically stable upon 12 weeks of storage period.
Concurrent validity of a low‐cost and time‐efficient clinical sensory test battery to evaluate somatosensory dysfunction
Authors: Zhu Guan Cheng , Böttger Karina , Slater Helen , Cook Chad , Farrell Scott F. , Hailey Louise , Tampin Brigitte , Schmid Annina B.
Published: July 2019

Background

This study describes a low‐cost and time‐efficient clinical sensory test (CST) battery and evaluates its concurrent validity as a screening tool to detect somatosensory dysfunction as determined using quantitative sensory testing (QST).

Method

Three patient cohorts with carpal tunnel syndrome (CTS, n = 76), non‐specific neck and arm pain (NSNAP, n = 40) and lumbar radicular pain/radiculopathy (LR, n = 26) were included. The CST consisted of 13 tests, each corresponding to a QST parameter and evaluating a broad spectrum of sensory functions using thermal (coins, ice cube, hot test tube) and mechanical (cotton wool, von Frey hairs, tuning fork, toothpicks, thumb and eraser pressure) detection and pain thresholds testing both loss and gain of function. Agreement rate, statistical significance and strength of correlation (phi coefficient) between CST and QST parameters were calculated.

Results

Several CST parameters (cold, warm and mechanical detection thresholds as well as cold and pressure pain thresholds) were significantly correlated with QST, with a majority demonstrating >60% agreement rates and moderate to relatively strong correlations. However, agreement varied among cohorts. Gain of function parameters showed stronger agreement in the CTS and LR cohorts, whereas loss of function parameters had better agreement in the NSNAP cohort. Other CST parameters (16 mN von Frey tests, vibration detection, heat and mechanical pain thresholds, wind‐up ratio) did not significantly correlate with QST.

Conclusion

Some of the tests in the CST could help detect somatosensory dysfunction as determined with QST. Parts of the CST could therefore be used as a low‐cost screening tool in a clinical setting.

Significance

Quantitative sensory testing, albeit considered the gold standard to evaluate somatosensory dysfunction, requires expensive equipment, specialized examiner training and substantial time commitment which challenges its use in a clinical setting. Our study describes a CST as a low‐cost and time‐efficient alternative. Some of the CST tools (cold, warm, mechanical detection thresholds; pressure pain thresholds) significantly correlated with the respective QST parameters, suggesting that they may be useful in a clinical setting to detect sensory dysfunction.
Experimental investigation on engine performance, emission, and combustion characteristics of a DI CI engine using tyre pyrolysis oil and diesel blends doped with nanoparticles
Authors: Thangavelu S Kumaravel , Arthanarisamy Murugesan
Published: July 2019

This article investigates the utility of waste tyre oil as a potential source of partial replacement of diesel fuel. The experimental study of engine parameters such as performance, emissions, along with combustion characteristics of tyre oil blends with cerium oxide (CeO2) and without CeO2 nano additive in a four‐stroke single‐cylinder water‐cooled compression ignition engine was conducted without any engine adjustment. Tyre oil was blended with diesel fuel at the volumetric proportions of 5, 10, 15, and 20%. These experimental results reveal that B5 blend has increased Brake thermal efficiency compared to other blends and nearer to diesel fuel at full load. The emissions of Hydrocarbon (HC), smoke are lower than diesel fuel by 3, 3.22% for B5 blend of full load. If CeO2 nano additives are doped with tyre oil blends in such case the B5D85 + CeO2 100 ppm blends were increased in efficiency of 2.85% and emissions like HC, CO, Smoke are decreased by 3, 1.33, 7.7%, respectively compared to diesel. From the experimental results, B5D85 + CeO2 100 ppm fuel blend is the best fuel ratio for a CI engine for increased efficiency, reduced emission and better combustion. Hence, the tyre oil with CeO2 nano additives is a suitable alternative fuel for CI engine.
Exergetic, economic, and environmental analyses of combined cooling and power plants with parabolic solar collector
Authors: Javadi Mohammad Amin , Ahmadi Mohammad Hossein , Khalaji Mehdi
Published: July 2019

Due to the necessity of achieving the energy systems with improved efficiency, combined power plants are developing in recent decades. Moreover, employing renewable energy sources in the power generation and heating/cooling purposes is an attractive idea to obtain more environmentally benign energy systems. In the current study, a combined cooling and power (CCP) plant is analyzed based on exergy and economic concepts. Afterward, by adding lithium‐bromide refrigeration cycle and parabolic solar collectors, the plant is investigated. The exergy efficiency, carbon dioxide emission, and cost of generated electricity are evaluated on the basis of SPECO model. The results of the study show that thermal and exergy efficiencies of the CCP plant with the solar collector depend on various parameters and can be affected significantly. The efficiency of the plant after applying lithium‐bromide refrigeration cycle and the solar collector increased from 50.33 to 51.73%, while the exergy efficiency enhanced from 47.48 to 48.22%. In addition, it was concluded that adding the collector and absorption chiller leads to 1.5% reduction in environmental pollutants.
Geomorphic and hydrological controls on groundwater dolocrete formation in the semi‐arid Hamersley Basin, northwest Australia
Authors: Mather Caroline C. , Nash David J. , Dogramaci Shawan , Grierson Pauline F. , Skrzypek Grzegorz
Published: July 2019

Groundwater dolocretes may exert an important geomorphic control on landscape evolution within sub‐humid to arid regions. However, the geomorphic and hydrogeological settings of dolocrete remain poorly described. The hydrochemical conditions of dolomite precipitation in groundwater environments are also not well known. Classic models of dolocrete formation explain dolomite precipitation from highly evolved groundwaters at the terminus of major drainage but do not explain dolocrete distributed in regionally elevated landscapes, upgradient of major drainage. This study investigated the mineralogy, micromorphology and stable carbon and oxygen isotope compositions of three dolocrete profiles within a regionally elevated sub‐basin of the Hamersley Ranges in the Pilbara region of northwest Australia. We sought to establish the environmental and hydrochemical conditions and present a model for dolocrete formation. We found that dolocrete formed within zones of emerging groundwater under saline‐evaporitic conditions within internally draining sub‐basins, most likely during the Late Miocene and Pliocene. Saline‐evaporitic conditions were indicated by: (i) the mineralogy, dominated by dolomite, palygorskite and smectite; (ii) desiccation features and the presence of phreatic and vadose cements, indicative of a shallow fluctuating water table, and; (iii) dolomite δ18O values (median = –5.88 ‰). Dolomite precipitation was promoted by evaporation and carbon dioxide degassing from shallow magnesium (Mg)‐rich groundwater. These factors appear to have been the major drivers of dolocrete development without a requirement for significant down‐dip hydrochemical modification. Primary dolomite precipitation was possible due to the presence of microbial extracellular polymeric substances (EPS). EPS provided negatively charged nucleation sites, which bound Mg2+, overcoming kinetic effects. High microbial activity within groundwater systems suggest these processes may be important for dolocrete formation worldwide and that groundwater dolocretes may be more pervasive in landscapes than currently recognized. © 2019 John Wiley & Sons, Ltd. © 2019 John Wiley & Sons, Ltd.
Options pricing and short‐selling in the underlying: Evidence from India
Authors: Dixit Alok ,   Vipul , Singh Shivam
Published: July 2019

This study provides new insights into certain recent developments in derivatives trading in India. Specifically, it examines the implications of introduction of short‐selling for pricing efficiency of the Nifty 50 index derivative contracts of National Stock Exchange of India. The empirical results suggest that the introduction of short‐selling, supported by a well‐functioning security lending and borrowing market, has significantly reduced the overpricing of Nifty 50 index put options. Moreover, the introduction of this short‐selling mechanism has lessened the underpricing of Nifty 50 index futures.
A dimension‐invariant cascade model for VIX futures
Authors: Wang Zhiguang , Dupoyet Brice
Published: July 2019

We propose a new stochastic volatility model by allowing for a cascading structure of volatility components. The model, under a minor assumption, allows us to add as many components as desired with no additional parameters, effectively defeating the curse of dimensionality often encountered in traditional models. We derive a semi‐closed‐form solution to the VIX futures price, and find that our six‐factor model with only six parameters can closely fit spot VIX and VIX futures prices from 2004 to 2015 and produce out‐of‐sample pricing errors of magnitudes similar to those of in‐sample errors.
Role of a Contactin multi‐molecular complex secreted by oligodendrocytes in nodal protein clustering in the CNS
Authors: Dubessy Anne‐Laure , Mazuir Elisa , Rappeneau Quentin , Ou Sokounthie , Abi Ghanem Charly , Piquand Kevin , Aigrot Marie‐Stéphane , Thétiot Melina , Desmazières Anne , Chan Eric , Fitzgibbon Matt , Fleming Mark , Krauss Raul , Zalc Bernard , Ranscht Barbara , Lubetzki Catherine , Sol‐Foulon Nathalie
Published: July 2019

The fast and reliable propagation of action potentials along myelinated fibers relies on the clustering of voltage‐gated sodium channels at nodes of Ranvier. Axo‐glial communication is required for assembly of nodal proteins in the central nervous system, yet the underlying mechanisms remain poorly understood. Oligodendrocytes are known to support node of Ranvier assembly through paranodal junction formation. In addition, the formation of early nodal protein clusters (or prenodes) along axons prior to myelination has been reported, and can be induced by oligodendrocyte conditioned medium (OCM). Our recent work on cultured hippocampal neurons showed that OCM‐induced prenodes are associated with an increased conduction velocity (Freeman et al., 2015). We here unravel the nature of the oligodendroglial secreted factors. Mass spectrometry analysis of OCM identified several candidate proteins (i.e., Contactin‐1, ChL1, NrCAM, Noelin2, RPTP/Phosphacan, and Tenascin‐R). We show that Contactin‐1 combined with RPTP/Phosphacan or Tenascin‐R induces clusters of nodal proteins along hippocampal GABAergic axons. Furthermore, Contactin‐1‐immunodepleted OCM or OCM from Cntn1‐null mice display significantly reduced clustering activity, that is restored by addition of soluble Contactin‐1. Altogether, our results identify Contactin‐1 secreted by oligodendrocytes as a novel factor that may influence early steps of nodal sodium channel cluster formation along specific axon populations.
Characterization of a long noncoding RNA Pcdh17it as a novel marker for immature premyelinating oligodendrocytes
Authors: Kasuga Yusuke , Fudge Alexander D. , Zhang Yumeng , Li Huiliang
Published: July 2019

Oligodendrocyte precursors (OPs) proliferate and differentiate into oligodendrocytes (OLs) during postnatal development and into adulthood in the central nervous system (CNS). Following the initiation of differentiation, OPs give rise to immature, premyelinating OLs, which undergo further differentiation and mature into myelin‐forming OLs. We identified an immature OL‐specific long noncoding RNA, named Pcdh17it. Through co‐localization analysis and morphological characterization of OLs, we found that Pcdh17it is a specific marker for newly born immature OLs in the developing and adult forebrain of mice, and we used this new marker to analyze OL generation over the lifespan of mice. Pcdh17it is an effective tool for monitoring newly born OLs in adult brain, allowing detailed study of the dynamics of OP differentiation into OLs in the normal and pathological CNS.
The Mutational Features of Aristolochic Acid–Induced Mouse and Human Liver Cancers
Authors: Lu Zhao‐Ning , Luo Qing , Zhao Li‐Nan , Shi Yi , Wang Na , Wang Lan , Han Ze‐Guang
Published: July 2019

Background and Aims

Aristolochic acid (AA) exposure has been statistically associated with human liver cancers. However, direct evidence of AA exposure–induced liver cancer is absent. This study aims to establish a direct causal relationship between AA exposure and liver cancers based on a mouse model and then explores the AA‐mediated genomic alterations that could be implicated in human cancers with AA‐associated mutational signature.

Approach and Results

We subjected mice, including phosphatase and tensin homolog (Pten)‐deficient ones, to aristolochic acid I (AAI) alone or a combination of AAI and CCl4. Significantly, AAI exposure induced mouse liver cancers, including hepatocellular carcinoma (HCC) and combined HCC and intrahepatic cholangiocarcinoma, in a dose‐dependent manner. Moreover, AAI exposure also enhanced tumorigenesis in these CCl4‐treated or Pten‐deficient mice. AAI led to DNA damage and AAI‐DNA adduct that could initiate liver cancers through characteristic adenine‐to‐thymine transversions, as indicated by comprehensive genomic analysis, which revealed recurrent mutations in Harvey rat sarcoma virus oncogene. Interestingly, an AA‐associated mutational signature was mainly implicated in human liver cancers, especially from China. Moreover, we detected the AAI‐DNA adduct in 25.8% (16/62) of paratumor liver tissues from randomly selected Chinese patients with HCC. Furthermore, based on phylogenetic analysis, the characteristic mutations were found in the initiating malignant clones in the AA‐implicated mouse and human liver cancers where the mutations of tumor protein p53 and Janus kinase 1 were prone to be significantly enriched in the AA‐affected human tumors.

Conclusions

This study provides evidence for AA‐induced liver cancer with the featured mutational processes during malignant clonal evolution, laying a solid foundation for the prevention and diagnosis of AA‐associated human cancers, especially liver cancers.
Peribiliary Gland Niche Participates in Biliary Tree Regeneration in Mouse and in Human Primary Sclerosing Cholangitis
Authors: Carpino Guido , Nevi Lorenzo , Overi Diletta , Cardinale Vincenzo , Lu Wei‐Yu , Di Matteo Sabina , Safarikia Samira , Berloco Pasquale Bartolomeo , Venere Rosanna , Onori Paolo , Franchitto Antonio , Forbes Stuart J. , Alvaro Domenico , Gaudio Eugenio
Published: July 2019

Background and Aims

Mechanisms underlying the repair of extrahepatic biliary tree (EHBT) after injury have been scarcely explored. The aims of this study were to evaluate, by using a lineage tracing approach, the contribution of peribiliary gland (PBG) niche in the regeneration of EHBT after damage and to evaluate, in vivo and in vitro, the signaling pathways involved.

Approach and Results

Bile duct injury was induced by the administration of 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) diet for 14 days to Krt19CreTdTomatoLSL mice. Human biliary tree stem/progenitor cells (BTSC) within PBGs were isolated from EHBT obtained from liver donors. Hepatic duct samples (n = 10) were obtained from patients affected by primary sclerosing cholangitis (PSC). Samples were analyzed by histology, immunohistochemistry, western blotting, and polymerase chain reaction. DDC administration causes hyperplasia of PBGs and periductal fibrosis in EHBT. A PBG cell population (Cytokeratin19‐/SOX9+) is involved in the renewal of surface epithelium in injured EHBT. The Wnt signaling pathway triggers human BTSC proliferation in vitro and influences PBG hyperplasia in vivo in the DDC‐mediated mouse biliary injury model. The Notch signaling pathway activation induces BTSC differentiation in vitro toward mature cholangiocytes and is associated with PBG activation in the DDC model. In human PSC, inflammatory and stromal cells trigger PBG activation through the up‐regulation of the Wnt and Notch signaling pathways.

Conclusions

We demonstrated the involvement of PBG cells in regenerating the injured biliary epithelium and identified the signaling pathways driving BTSC activation. These results could have relevant implications on the pathophysiology and treatment of cholangiopathies.
LncRNA LINP1 regulates acute myeloid leukemia progression via HNF4α/AMPK/WNT5A signaling pathway
Authors: Shi Jie , Dai Rongqin , Chen Yuqing , Guo Honggang , Han Yinyin , Zhang Yin
Published: July 2019

LncRNAs play critical roles in various pathophysiological and biological processes, such as protein translation, RNA splicing, and epigenetic modification. Indeed, abundant evidences demonstrated that lncRNA act as competing endogenous RNAs (ceRNAs) to participate in tumorigenesis. However, little is known about the underlying function of lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1) in pediatric and adolescent acute myeloid leukemia (AML). The expression of LINP1 was examined in AML patient samples by qRT‐PCR. Cell proliferation was examined by CCK‐8 and Edu assays. β‐Galactosidase senescence assay, mGlucose uptake assay, lactate production assay, and Gene Ontology (GO) analysis were performed for functional analysis. We found that LINP1 was significantly overexpressed in AML patients at diagnosis, whereas downregulated after complete remission (CR). Furthermore, knockdown of LINP1 expression remarkably suppressed glucose uptake and AML cell maintenance. Mechanistically, LINP1 was found to inhibit the glucose metabolism by suppressing the expression of HNF4a. Both LINP1 and HNF4a knockdown reduced the expression levels of AMPK phosphorylation and WNT5A, indicating for the first time that LINP1 strengthened the HNF4a‐AMPK/WNT5A signaling pathway involved in cell glucose metabolism modulation and AML cell survival. Taken together, our results indicated that LINP1 promotes the malignant phenotype of AML cells and stimulates glucose metabolism, which can be regarded as a potential prognostic marker and therapeutic target for AML.
Minimal residual disease (MRD) in non‐Hodgkin lymphomas: Interlaboratory reproducibility on marrow samples with very low levels of disease within the FIL (Fondazione Italiana Linfomi) MRD Network
Authors: Della Starza Irene , Cavalli Marzia , De Novi Lucia Anna , Genuardi Elisa , Mantoan Barbara , Drandi Daniela , Barbero Daniela , Ciabatti Elena , Grassi Susanna , Gazzola Anna , Mannu Claudia , Agostinelli Claudio , Piccaluga Pier Paolo , Bomben Riccardo , Degan Massimo , Gattei Valter , Guarini Anna , Foà Robin , Galimberti Sara , Ladetto Marco , Ferrero Simone , Del Giudice Ilaria ,   on behalf of the Fondazione Italiana Linfomi (FIL) MRD Network
Published: July 2019

In 2009, the four laboratories of the Fondazione Italiana Linfomi (FIL) minimal residual disease (MRD) Network started a collaborative effort to harmonize and standardize their methodologies at the national level, performing quality control (QC) rounds for follicular lymphoma (FL) and mantle cell lymphoma (MCL) MRD assessment. In 16 QC rounds between 2010 and 2017, the four laboratories received 208 bone marrow (BM) samples (126 FL; 82 MCL); 187 were analyzed, according to the EuroMRD Consortium guidelines, by both nested (NEST) polymerase chain reaction (PCR) and real‐time quantitative (RQ) PCR for BCL2/IGH MBR or IGHV rearrangements. Here, we aimed at analyzing the samples that challenged the interlaboratory reproducibility and data interpretation. Overall, 156/187 BM samples (83%) were concordantly classified as NEST+/RQ+ or NEST−/RQ− by all the four laboratories. The remaining 31 samples (17%) resulted alternatively positive and negative in the interlaboratory evaluations, independently of the method and the type of rearrangement, and were defined “borderline” (brd) samples: 12 proved NEST brd/RQ brd, 7 NEST−/RQ brd, 10 NEST brd/RQ positive not quantifiable (PNQ), and 2 NEST brd/RQ−. Results did not change even increasing the number of replicates/sample. In 6/31 brd samples, droplet digital PCR (ddPCR) was tested and showed no interlaboratory discordance. Despite the high interlaboratory reproducibility in the MRD analysis obtained and maintained by the QC round strategy, samples with the lowest MRD levels can still represent a challenge: 17% (31/187) of our samples showed discordant results in interlaboratory assessments, with 6.4% (12/187) remained brd even applying the two methods. Thus, although representing a minority, brd samples are still problematic, especially when a clinically oriented interpretation of MRD results is required. Alternative, novel methods such as ddPCR and next‐generation sequencing have the potential to overcome the current limitations.
Human papillomavirus genotypes in women with invasive cervical cancer with and without human immunodeficiency virus infection in Botswana
Authors: Tawe Leabaneng , MacDuffie Emily , Narasimhamurthy Mohan , Wang Qiao , Gaseitsiwe Simani , Moyo Sikhulile , Kasvosve Ishmael , Shin Sanghyuk S. , Zetola Nicola M. , Paganotti Giacomo M. , Grover Surbhi
Published: July 2019

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer‐related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real‐time PCR assay. Overall, 88 (69.8%) women were HIV‐infected. Fifty‐seven (64.8%) of the HIV‐infected women had a baseline CD4+ count ≥350 cells/μl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV‐infected patients was significantly younger than that of HIV‐uninfected patients (p < 0.001). HPV DNA was detected in all of 126 (100%) of tissues analyzed in our study. The HPV genotypes identified included the HPV‐16 (75.4%), HPV‐18 (28.6%) and other high‐risk (hr) HPV genotypes (16.7%). HIV infection was positively associated with the presence of the HPV‐16 genotype (p = 0.036), but not with HPV‐18 or with other high‐risk (hr)‐HPV genotypes. Thirty‐three percent of the patients had multiple hr‐HPV genotypes, with higher rates in HIV‐infected women. These results highlight the importance and potential impact of large‐scale HPV vaccination programs covering HPV‐16 and HPV‐18 genotypes in countries like Botswana with high burden of HIV infection.
Potent antileukemic activity of curaxin CBL0137 against MLL‐rearranged leukemia
Authors: Somers Klaartje , Kosciolek Angelika , Bongers Angelika , El‐Ayoubi Ali , Karsa Mawar , Mayoh Chelsea , Wadham Carol , Middlemiss Shiloh , Neznanov Nickolay , Kees Ursula R. , Lock Richard B. , Gudkov Andrei , Sutton Rosemary , Gurova Katerina , Haber Michelle , Norris Murray D. , Henderson Michelle J.
Published: July 2019

Around 10% of acute leukemias harbor a rearrangement of the MLL/KMT2A gene, and the presence of this translocation results in a highly aggressive, therapy‐resistant leukemia subtype with survival rates below 50%. There is a high unmet need to identify safer and more potent therapies for MLL‐rearranged (MLL‐r) leukemia that can be combined with established chemotherapeutics to decrease treatment‐related toxicities. The curaxin, CBL0137, has demonstrated nongenotoxic anticancer and chemopotentiating effects in a number of preclinical cancer models and is currently in adult Phase I clinical trials for solid tumors and hematological malignancies. The aim of our study was to investigate whether CBL0137 has potential as a therapeutic and chemopotentiating compound in MLL‐r leukemia through a comprehensive analysis of its efficacy in preclinical models of the disease. CBL0137 decreased the viability of a panel of MLL‐r leukemia cell lines (n = 12) and xenograft cells derived from patients with MLL‐r acute lymphoblastic leukemia (ALL, n = 3) in vitro with submicromolar IC50s. The small molecule drug was well‐tolerated in vivo and significantly reduced leukemia burden in a subcutaneous MV4;11 MLL‐r acute myeloid leukemia model and in patient‐derived xenograft models of MLL‐r ALL (n = 5). The in vivo efficacy of standard of care drugs used in remission induction for pediatric ALL was also potentiated by CBL0137. CBL0137 exerted its anticancer effect by trapping Facilitator of Chromatin Transcription (FACT) into chromatin, activating the p53 pathway and inducing an Interferon response. Our findings support further preclinical evaluation of CBL0137 as a new approach for the treatment of MLL‐r leukemia.
Recent research progresses in ether‐ and ester‐based electrolytes for sodium‐ion batteries
Authors: Lin Zeheng , Xia Qingbing , Wang Wanlin , Li Weishan , Chou Shulei
Published: July 2019

Owing to the natural abundance and low cost of sodium resources, sodium‐ion batteries (SIBs) have drawn considerable attention for state‐of‐the‐art power storage devices over the last few years. To enable advanced SIBs with a brighter future, great effort has been made, not only through optimizing the electrode materials, but also with rationally designing various electrolyte systems. Among the available electrolyte systems, organic electrolytes, especially those based on esters as well as ethers, are the most promising ones for practical application in the foreseeable future, due to their numerous inherent advantages. This review is concerned with the recent research progresses on organic electrolytes for SIBs, focusing on ether‐based and ester‐based ones.
Detecting nucleic acid fragments in serum using a magnetically modulated sandwich assay
Authors: Margulis Michael , Ashri Saar , Cohen Meir , Danielli Amos
Published: July 2019

We present a novel assay for rapid and highly sensitive detection of specific nucleic acid fragments in human serum. In a magnetic modulation biosensing (MMB) system, magnetic beads and fluorescently labeled probes are attached to the target analyte and form a “sandwich” complex. An alternating external magnetic field gradient condenses the magnetic beads (and hence the target molecules with the fluorescently labeled probes) to the detection volume and sets them in a periodic motion, in and out of a laser beam. A synchronous detection enables the removal of background signal from the oscillating target signal without complicated sample preparation. The high sensitivity of the MMB system, combined with the specificity of a sandwich hybridization assay, enables detection of DNA fragments without enzymatic signal amplification. Here, we demonstrate the sensitivity of the assay by directly detecting the EML4‐ALK oncogenic translocation sequence spiked in human serum. The calculated limit of detection is 1.4 pM, which is approximately 150 times better than a conventional plate reader. In general, the MMB‐assisted SHA can be implemented in many other applications for which enzymatic amplification, such as PCR, is not applicable and where rapid detection of specific nucleic acid targets is required.
Physiological model using diffuse reflectance spectroscopy for nonmelanoma skin cancer diagnosis
Authors: Zhang Yao , Moy Austin J. , Feng Xu , Nguyen Hieu T. M. , Reichenberg Jason S. , Markey Mia K. , Tunnell James W.
Published: July 2019

Diffuse reflectance spectroscopy (DRS) is a noninvasive, fast, and low‐cost technology with potential to assist cancer diagnosis. The goal of this study was to test the capability of our physiological model, a computational Monte Carlo lookup table inverse model, for nonmelanoma skin cancer diagnosis. We applied this model on a clinical DRS dataset to extract scattering parameters, blood volume fraction, oxygen saturation and vessel radius. We found that the model was able to capture physiological information relevant to skin cancer. We used the extracted parameters to classify (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]) vs actinic keratosis (AK) and (BCC, SCC, AK) vs normal. The area under the receiver operating characteristic curve achieved by the classifiers trained on the parameters extracted using the physiological model is comparable to that of classifiers trained on features extracted via Principal Component Analysis. Our findings suggest that DRS can reveal physiologic characteristics of skin and this physiologic model offers greater flexibility for diagnosing skin cancer than a pure statistical analysis. Physiological parameters extracted from diffuse reflectance spectra data for nonmelanoma skin cancer diagnosis.
Aligned fibrous decellularized cell derived matrices for mesenchymal stem cell amplification
Authors: Ventre Maurizio , Coppola Valerio , Natale Carlo F. , Netti Paolo A.
Published: July 2019

Biochemical and biophysical stimuli of stem cell niches finely regulate the self‐renewal/differentiation equilibrium. Replicating this in vitro is technically challenging, making the control of stem cell functions difficult. Cell derived matrices capture certain aspect of niches that influence fate decisions. Here, aligned fibrous matrices synthesized by MC3T3 cells were produced and the role of matrix orientation and stiffness on the maintenance of stem cell characteristics and adipo‐ or osteo‐genic differentiation of murine mesenchymal stem cells (mMSCs) was investigated. Decellularized matrices promoted mMSC proliferation. Fibrillar alignment and matrix stiffness work in concert in defining cell fate. Soft matrices preserve stemness, whereas stiff ones, in presence of biochemical supplements, promptly induce differentiation. Matrix alignment impacts the homogeneity of the cell population, that is, soft aligned matrices ameliorate the spontaneous adipogenic differentiation, whereas stiff aligned matrices reduce cross‐differentiation. We infer that mechanical signaling is a dominant factor in mMSC fate decision and the matrix alignment contributes to produce a more homogeneous environment, which results in a uniform response of cells to biophysical environment. Matrix thus produced can be obtained in vitro in a facile and consistent manner and can be used for homogeneous stem cell amplification or for mechanotransduction‐related studies.
Integrin α7 high expression correlates with deteriorative tumor features and worse overall survival, and its knockdown inhibits cell proliferation and invasion but increases apoptosis in breast cancer
Authors: Bai Xiaorong , Gao Chen , Zhang Lifeng , Yang Suisheng
Published: July 2019

Background

This study aimed to investigate the correlation of integrin α7 (ITGA7) expression with clinical/pathological characteristics and overall survival (OS), and its knockdown on inhibiting cell activities in breast cancer.

Methods

A total of 191 breast cancer patients underwent surgery were retrospectively reviewed, and ITGA7 expression in tumor tissues was determined by immunofluorescence and real‐time quantitative polymerase chain reaction. Patients’ clinical/pathological data were recorded, and OS was calculated. In vitro, control shRNA and ITGA7 shRNA plasmids were transfected into MCF7 cells to evaluate the influence of ITGA7 knockdown on cell proliferation, apoptosis, and invasion.

Results

Ninety‐two (48.2%) patients presented with ITGA7 high expression, and 99 patients (51.8%) presented with ITGA7 low expression. ITGA7 expression was positively correlated with T stage, tumor‐node metastasis (TNM) stage, and pathological grade. Kaplan‐Meier curves showed that ITGA7 high expression was associated with shorter OS, and multivariate Cox's proportional hazards regression displayed that ITGA7 high expression was an independent predictive factor for poor OS. Moreover, in vitro experiments disclosed that cell proliferation (by Cell Counting Kit‐8 assay) and cell invasion (by Matrigel invasion assay) were reduced, while cell apoptosis rate (by Annexin V/propidium iodide assay) was enhanced by ITGA7 knockdown in MCF‐7 cells.

Conclusion

Integrin α7 high expression correlates with increased T stage, TNM stage, and pathological grade as well as worse OS, and its knockdown enhances cell apoptosis but inhibits cell proliferation and invasion in breast cancer.
Co‐sensitization and cross‐reactivity of Blomia tropicalis with two Dermatophagoides species in Guangzhou, China
Authors: Liu Xiaoqing , Zheng Peiyan , Zheng Song Guo , Zhai Yingying , Zhao Xiaoming , Chen Yin , Cai Chuanxu , Wu Zehong , Huang Zhifeng , Zou Xiangwei , Liao Chenxi , Sun Baoqing
Published: July 2019

Background

Contradictory results have been reported previously in the analyses of cross‐reactivity among Blomia tropicalis (Blo t), Dermatophagoides pteronyssinus (Der p), and Dermatophagoides farinae (Der f). This study aims to investigate the characteristics of co‐sensitization and the IgE cross‐reactivity among them and attempts to identify whether patients are sensitized to Blo t due to cross‐reaction or true sensitization.

Methods

Specific IgE (sIgE) in the sera from 1497 allergenic patients was determined by ImmunoCAP. Cross‐reactivity was analyzed and determined by sIgE inhibition with 21 sera samples.

Results

Around 85.50% of patients were sensitized to Der p, 85.37% of patients were sensitized to Der f, and 71.54% of patients were sensitized to Blo t. Further, 70.14% of patients were co‐sensitized to Blo t, Der p, and Der f, and only seven patients were sensitized solely to Blo t. With increasing sIgE levels for Blo t, the positive rates of severe‐level (class 5‐6) co‐sensitization to Der p or Der f significantly increased. Blo t was moderately associated with Der p and Der f, with correlation coefficients of 0.6998 and 0.6782, respectively. Der p and Der f inhibited IgE binding to Blo t more strongly than Blo t inhibited IgE binding to Der p or Der f in the patient groups CBlo t < CDer p and CBlo t < CDer f.

Conclusions

This study has established valuable information about the co‐sensitization and cross‐reactivity of Blo t with two Dermatophagoides species (Der p and Der f) and helps to provide adequate diagnosis and treatment of the mite‐allergic patients.
Association between subclinical hypothyroidism and metabolic disorders: A retrospective chart review study in an emerging university hospital
Authors: Aldossari Khaled , Al‐Ghamdi Sameer , Al‐Zahrani Jamaan , Al Jammah Anwar , Alanazi Bader , Al‐Briek Abdulilah , Alanazi Mohammad
Published: July 2019

Background

Subclinical hypothyroidism is defined as an increase in serum levels of Thyroid Stimulating Hormone (TSH) above the normal range, without alteration of total T4 concentrations that is reported to have association with various metabolic conditions. The study aimed to investigate any association between subclinical hypothyroidism and metabolic disorders in Al Kharj city.

Methods

This is a cross‐sectional study that included review of patients’ charts from prince Sattam bin Abdul‐Aziz University, Al Kharj, Saudi Arabia, from August 1 to November 30, 2016. Data were analyzed with SPSS version 21. Descriptive statistics were obtained as frequencies. Pearson chi‐square analysis was used to assess any differences between disease status and study variables. P‐value < 0.05 was considered significant.

Results

The mean age was 30.65 ± 13.3 with a female predominance. The average BMI was 29.5 ± 7.71; 46 (11.5%) had hypertension, 52 (46.8%) had diabetes, 173 (44%) had anemia, and 192 (56%) had vitamin D deficiency. Due to increased TSH levels, male gender had higher prevalence of subclinical hypothyroidism with P‐value < 0.001 and 0.011, respectively.

Conclusion

Subclinical hypothyroidism is a significant topic worldwide whose prevalence is rising. In this study, we could not find any significant association between subclinical hypothyroidism and metabolic disorder. Further longitudinal studies with large sample size are needed to study this association.
Recent advancements in the study of breast cancer exosomes as mediators of intratumoral communication
Authors: Groza Monica , Zimta Alina–Andreea , Irimie Alexandru , Achimas‐Cadariu Patriciu , Cenariu Diana , Stanta Giorgio , Berindan‐Neagoe Ioana
Published: July 2019

Breast cancer is a heterogeneous disease, with a morbidity rate of 27.8% and a mortality rate of 15% among women population worldwide. Understanding how this cancer develops and the mechanisms behind tumor progression and chemoresistance is of utmost importance. Exosomes mediate communication in a population of heterogeneous tumoral cells. They have a cargo composed of oncogenes and oncomiRs which change the transcriptomic scenario of their targeted cells and activate numerous tumor‐promoting signaling pathways. Exosomes secreted by breast cancer cells lead to enhanced cell proliferation, replicative immortality, angiogenesis, invasion, migration, and chemoresistance. Studying exosomes from this perspective offers more in depth understanding of breast malignancy and may aid in the future development of early diagnostic, prognostic and therapeutic options. We present the latest findings in this area and offer practical solutions which may further stimulate the much‐needed research of exosome in breast cancer.
Sequential treatment with bicarbonate and low‐temperature to potentiate both biomass and lipid productivity in Nannochloropsis oceanica
Authors: Yuan Wasiqi , Ma Yuhan , Wei Wei , Liu Wanjun , Ding Yu , Balamurugan Srinivasan
Published: July 2019

BACKGROUND

Microalgal lipid overproduction has been achieved greatly by stress treatments, which drastically impede cellular biomass and overall productivity, hence providing the impetus to develop a viable strategy to uncouple lipid enhancement from stress associated growth impairment.

RESULTS

We designed a sequential strategy in Nannochloropsis oceanica, to enhance cellular biomass and carbon sink by providing optimized bicarbonate source during the growth phase, followed by low‐temperature treatment to harness the increased cellular biomass and carbon precursors for lipid hyperaccumulation. Provision of bicarbonate (1.0 g/L) remarkably promoted cellular physiological properties, which in turn enhanced cellular biomass and photosynthetic carbon sink. Subsequent low‐temperature treatment (16 °C) significantly redirected the carbon flux towards lipogenesis and significantly altered fatty acid composition. The designed strategy resulted in significant enhancement of lipid productivity by 2.9‐fold than that of control cells and resulted in lipid accumulation up to 57% of dry cell weight without impeding cellular biomass. Interestingly, the sequential treatment altered fatty acid profile, particularly a 8.8‐fold increase in the content of eicosapentaenoic acid with health significance.

CONCLUSION

Our study exemplifies the feasible strategy to potentiate microalgal biomass, and also to circumvent stress associated growth impairment and consequent algal lipid productivity. © 2019 Society of Chemical Industry