bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of endovascular repair of ascending aortic dissection
Authors: Zhang Lei , Li Zhenjiang , Li Shuangshuang , Zhao Zhiqing , Bao Junmin , Zhou Jian , Jing Zaiping
Published: October 2019

Background

Endovascular repair has been used in selected ascending aortic dissection patients judged unfit for direct open surgery. However, the selective criteria and the results of endovascular repair of ascending aortic dissection, and the potential risk factors of adverse events were still obscure. The aim of this study was to summarize the published data linking endovascular therapy for ascending aortic dissection.

Methods

Studies reporting endovascular repair of ascending aortic dissections were identified by searching PubMed and Embase databases in accordance with preferred reporting items for systematic reviews and meta‐analyses guidelines, and by reviewing the reference lists of retrieved articles. All available data were pooled and the subgroup analyses were conducted.

Results

A total of nine studies were identified according to the inclusion criteria. The overall technical success was 91.7%. The mean period of follow‐up was 34.7 months. The early mortality within 30 days and late mortality during the follow‐up were 10.3% and 19.0%, respectively. The incidence of endoleak was 14.3%. In the subgroup analysis, we found that female and oversizing >10% were risk factors of adverse events.

Conclusions

The pooled results suggested that endovascular repair of ascending aortic dissection was feasible, promising, and inspiring. The selection of endovascular therapy should be cautious based on preoperative evaluation. Application of different strategies for different ascending lesions should be considered. The dedicated endograft for ascending aorta is desperately needed before broader application of endovascular repair for ascending aortic pathologies can be achieved.
Acute pulmonary embolism unmasking underlying chronic thromboembolic pulmonary hypertension and iliac vein compression syndrome
Authors: Brener Michael I. , Green Philip , Parikh Sahil A. , Sethi Sanjum S.
Published: October 2019

We describe the case of a 72‐year‐old gentleman who was referred to our institution for management of cardiogenic shock from a massive pulmonary embolism. Right heart catheterization revealed a low cardiac index and markedly elevated pulmonary pressures, suggested long‐standing venous thromboembolic (VTE) disease that evolved into chronic thromboembolic pulmonary hypertension (CTEPH). The patient was cannulated to veno‐arterial extra‐corporeal membrane oxygenation and eventually treated with pulmonary embolectomy and thromboendarterectomy. Subsequently discovered inferior vena cava clot and left iliac deep vein thrombosis were treated with suction and mechanical thrombectomy. Intravascular ultrasound of the left lower extremity venous system identified iliac vein compression syndrome (IVCS) as the culprit of the patient's VTE and CTEPH. A left iliac stent was placed and the patient was discharged on Warfarin for anticoagulation. The case illustrates the rapidly expanding armamentarium for VTE treatment and proposes IVCS as a new, potentially underrecognized risk factor for CTEPH.
Spontaneous subgaleal hematoma in a patient with sickle cell disease: A case report and literature review
Authors: Foula Mohammed S. , Hassan Ali , AlQurashi Ahmed , Alsaihati Amna , Sharroufna Mohammed
Published: October 2019

Sickle cell disease (SCD) is a common hemoglobin disorder with variable clinical manifestations. Spontaneous subgaleal hematoma is rare, with sporadic cases reported in patients with SCD. Most cases resolve with conservative measures. Skull bone infarction should be considered a possible cause of severe acute headache in patients with SCD.
High‐Throughput Synthesis and Characterization of Aryl Silicones by Using the Piers–Rubinsztajn Reaction
Authors: Schneider Alyssa F. , Brook Michael A.
Published: October 2019

Arylsilicones are widely exploited for their thermal and optical properties. The creation of phenylsilicone elastomers with specific physical properties is typically done by a “one‐off” formulation and test process. Herein, it is demonstrated that high‐throughput synthesis methods can be used to rapidly prepare a series of arylsilicone elastomers and then the relative impact of different aryl groups on their physical properties is assessed. Aromatic groups were incorporated into polydimethylsiloxane (PDMS) elastomers by exploiting the relative reactivity of different functional groups in the Piers–Rubinsztajn reaction. To analyze trends in the silicone mechanical properties as a function of increasing aryl concentration—structure/property relationships—libraries of elastomers were both quickly synthesized and characterized by using high‐throughput suites starting from low viscosity silicone oils/monomers in 96‐well plates. Liquid handling parameters were optimized to effectively work with the silicones. Incorporating aryl instead of alkyl crosslinkers into the PDMS backbone increased the silicone elastomer modulus by approximately 50 % (at a crosslink density of 6 %); elastomers prepared with an aromatic crosslinker with three contact points led to much higher moduli compared with those with one contact point at the same crosslink density. When located at precise rather than random points on the silicone chains, diphenylsilicones had lower moduli than analogous monophenylsilicones.
A Light‐Activated Acyl Carrier Protein “Trap” for Intermediate Capture in Type II Iterative Polyketide Biocatalysis
Authors: Kilgour Samantha L. , Kilgour David P. A. , Prasongpholchai Panward , O'Connor Peter B. , Tosin Manuela
Published: October 2019

A discrete acyl carrier protein (ACP) bearing a photolabile nonhydrolysable carba(dethia) malonyl pantetheine cofactor was chemoenzymatically prepared and utilised for the trapping of biosynthetic polyketide intermediates following light activation. From the in vitro assembly of the polyketides SEK4 and SEK4b, by the type II actinorhodin “minimal” polyketide synthase (PKS), a range of putative ACP‐bound diketides, tetraketides, pentaketides and hexaketides were identified and characterised by FT‐ICR‐MS, providing direct insights on active site accessibility and substrate processing for this enzyme class.
Syntheses, Structures, and Spectroscopic Properties of 1,10‐Phenanthroline‐Based Macrocycles Threaded by PtC8Pt, PtC12Pt, and PtC16Pt Axles: Metal‐Capped Rotaxanes as Insulated Molecular Wires
Authors: Amini Hashem , Baranová Zuzana , Weisbach Nancy , Gauthier Sébastien , Bhuvanesh Nattamai , Reibenspies Joseph H. , Gladysz John A.
Published: October 2019

The platinum polyynyl complexes trans‐(C6F5)(p‐tol3P)2Pt(C≡C)n/2H undergo oxidative homocoupling (O2, CuCl/TMEDA) to diplatinum polyynediyl complexes trans, trans‐(C6F5)(p‐tol3P)2Pt(C≡C)nPt(Pp‐tol3)2(C6F5) (n=4, 2; 6, 5; 8, 8; 92–97 %) as reported previously. When related reactions are conducted in the presence of CuI adducts of the 1,10‐phenanthroline‐based macrocycles 2,9‐(1,10‐phenanthrolinediyl)(p‐C6H4O(CH2)6O)2(1,3‐C6H4) (10, 33‐membered) or 2,9‐(1,10‐phenanthrolinediyl)(p‐C6H4O(CH2)6O)2(2,7‐naphthalenediyl) (11, 35‐membered), excess K2CO3, and I2 (oxidant), rotaxanes are isolated that feature a Pt(C≡C)nPt axle that has been threaded through the macrocycle (2⋅10, 9 %; 5⋅10, 41 %; 5⋅11, 28 %; 8⋅10, 12 %; 8⋅11, 9 %). Their crystal structures are determined and analyzed in detail, particularly with respect to geometric perturbations and the degree of steric sp carbon chain insulation. NMR spectra show a number of shielding effects. UV/Vis spectra do not indicate significant electronic interactions between the Pt(C≡C)nPt axles and macrocycles, although cyclic voltammetry data suggest rapid reactions following oxidation.
Synthesis and characterization of visible light driven N—Fe‐codoped TiO2/SiO2 for simultaneous photoremoval of Cr (VI) and azo dyes in a novel fixed bed continuous flow photoreactor
Authors: Ghanbari Sina , Givianrad Mohammad Hadi , Aberoomand Azar Parviz
Published: October 2019

N─Fe‐codoped TiO2/SiO2 nanocomposites were prepared and stabilized onto glass beads by coupling two methods of dip coating and heat attachment. The prepared nanocomposites were characterized by DRS‐UV/vis, FTIR, XRD, FESEM, EDX, TEM, XPS, and N2 adsorption/desorption analyses. The operational parameters of pH, flow rate, and the photoreactor's angle against sunlight were optimized to achieve the highest degradation efficiency. Then, the photocatalytic efficacy of the prepared substrates was examined in a novel fabricated photoreactor on a complex pollutant mixture consisting of Cr (VI), BR‐29, BB‐41, and BY‐51, under two irradiation sources of visible light and sunlight. Moreover, to virtualize the process under natural irradiation conditions, the effectiveness of the performance was evaluated in various outdoor climate circumstances. Consequently, the results demonstrated the enhanced photocatalytic activity of the prepared nanocomposites under visible and solar irradiations. The removal percentages were also considerable under a partly cloudy sky and were 91.73%, 85.64%, 87.23%, and 58.59% for Cr (VI), BR‐29, BB‐41, and BY‐51, respectively. The results showed the promising activity of the innovative photoreactor and the as‐prepared nanocomposites for photocatalytic remediation of the water pollutants under natural climate conditions.
Effect of Edge Functionalization on the Bottom‐Up Synthesis of Nano‐Graphenes
Authors: Ohtomo Manabu , Hayashi Hironobu , Hayashi Kenjiro , Jippo Hideyuki , Zhu Juanjuan , Hayashi Ryunosuke , Yamaguchi Junichi , Ohfuchi Mari , Yamada Hiroko , Sato Shintaro
Published: October 2019

We demonstrate the effect of edge functionalization on the on‐surface Ullmann coupling of nano‐carbon materials. Unlike 10,10′‐Dibromo‐9,9′‐bianthryl (DBBA), which is widely known to form anthracene polymers and armchair‐edge graphene nanoribbons on Au(111), newly‐developed precursor named 5‐bromo‐11(10‐bromoanthracene‐9‐yl)anthra[2,3‐b : 7,6‐b′]dithiophene (BABAT) with isomers, which has similar structure as DBBA with one anthracene substituted with anthradithiophene, was found to make intramolecular C−C bonding instead of long anthracene polymers after annealing at 200 °C on Au(111). The mechanism was investigated using first‐principle density functional theory, which revealed that on‐surface polymerization is not kinetically preferred in case of BABAT. The reaction rate of intramolecular C−C bonding of BABAT is ∼206 times faster than that of DBBA. The intramolecular C−C bonding in DBBA biradicals, on the other hand, do not take place because of faster reverse reaction. By referring to electron density of BABAT biradicals, it was concluded that thiophene functionalization modifies distribution of electron density in BABAT radicals and facilitates electrophilic addition, leading to intramolecular C−C bonding after 200 °C annealing. These results indicate that the design of radical moiety is particularly important in the on‐surface Ullmann‐type coupling.
Bottom‐Up Fabrication of 1D Cu‐based Conductive Metal–Organic Framework Nanowires as a High‐Rate Anode towards Efficient Lithium Storage
Authors: Guo Lingzhi , Sun Jinfeng , Zhang Wenheng , Hou Linrui , Liang Longwei , Liu Yang , Yuan Changzhou
Published: October 2019

Conductive metal–organic frameworks (MOFs), as a newly emerging multifunctional material, hold enormous promise in electrochemical energy‐storage systems owing to their merits including good electronic conductivity, large surface area, appropriate pore structure, and environmental friendliness. In this contribution, a scalable solvothermal strategy was devised for the bottom‐up fabrication of 1D Cu‐based conductive MOF, that is, Cu3(2,3,6,7,10,11‐hexahydroxytriphenylene)2 (Cu‐CAT) nanowires (NWs), which were further utilized as a competitive anode for lithium‐ion batteries (LIBs). The intrinsic Li storage mechanism of the Cu‐CAT electrode was also explored. Benefiting from its structural virtues, the resultant 1D Cu‐CAT NWs were endowed with superb Li+ diffusion coefficients and electrochemical conductivities and exhibited remarkably high‐rate reversible capacities of approximately 631 mAh g−1 at 0.2 A g−1 and even approximately 381 mAh g−1 at 2 A g−1, along with striking capacity retention of 81 % after 500 cycles at 0.5 A g−1. In addition, a Cu‐CAT NWs‐based full cell assembled with LiNi0.8Co0.1Mn0.1O2 as the cathode displayed a large energy density of approximately 275 Wh kg−1 as well as excellent cycling behavior. These results manifest the promising application of 1D conductive Cu‐CAT NWs in advanced LIBs and even other potential versatile energy‐related fields.
Bioturbation by a reintroduced digging mammal reduces fuel loads in an urban reserve
Authors: Ryan C. M. , Hobbs R. J. , Valentine L. E.
Published: October 2019

Digging animals may alter many characteristics of their environment as they disrupt and modify the ground's surface by creating foraging pits or burrows. Extensive disturbance to the soil and litter layer changes litter distribution and availability, potentially altering fuel loads. In many landscapes, including peri‐urban areas, fire management to reduce fuel loads is complex and challenging. The reintroduction of previously common digging animals, many of which are now threatened, may have the added benefit of reducing fuel loads. We experimentally examined how the reintroduction of a marsupial bandicoot, quenda (Isoodon fusciventer), altered surface fuel loads in an urban bush reserve in Perth, Western Australia. Foraging activities of quenda (where they dig for subterranean food) were substantial throughout the reserve, creating a visibly patchy distribution in surface litter. Further, in open plots where quenda had access, compared to fenced plots where quenda were excluded, quenda foraging significantly reduced litter cover and litter depth. Similarly, estimated surface fuel loads were nearly halved in open plots where quenda foraged compared to fenced plots where quenda were absent (3.6 cf. 6.4 Mg/ha). Fire behavior modeling, using the estimated surface fuel loads, indicated the predicted rate of spread of fire were significantly lower for open plots where quenda foraged compared to fenced plots under both low (29.2 cf. 51.4 m/h; total fuels) and high (74.3 cf. 130.4 m/h; total fuels) fire conditions. Although many environments require fire, including the bushland where this study occurred, fire management can be a considerable challenge in many landscapes, including urban bushland reserves, which are usually small and close to human infrastructure. The reintroduction of previously common digging species may have potential value as a complimentary tool for reducing fuel loads, and potentially, fire risk.
Helianthus maximiliani and species fine‐scale spatial pattern affect diversity interactions in reconstructed tallgrass prairies
Authors: McKenna Thomas P. , McDonnell Jack , Yurkonis Kathryn A. , Brophy Caroline
Published: October 2019

Biodiversity and Ecosystem Function analyses aim to explain how individual species and their interactions affect ecosystem function. With this study, we asked in what ways do species interact, are these interactions affected by species planting pattern, and are initial (planted) proportions or previous year (realized) proportions a better reference point for characterizing grassland diversity effects?

We addressed these questions with experimental communities compiled from a pool of 16 tallgrass prairie species. We planted all species in monocultures and mixtures that varied in their species richness, evenness, and spatial pattern. We recorded species‐specific biomass production over three growing seasons and fitted Diversity‐Interactions (DI) models to annual plot biomass yields.

In the establishment season, all species interacted equally to form the diversity effect. In years 2 and 3, each species contributed a unique additive coefficient to its interaction with every other species to form the diversity effect. These interactions were affected by Helianthus maximiliani and the species planting pattern. Models based on species planted proportions better‐fit annual plot yield than models based on species previous contributions to plot biomass.

Outcomes suggest that efforts to plant tallgrass prairies to maximize diversity effects should focus on the specific species present and in what arrangement they are planted. Furthermore, for particularly diverse grasslands, the effort of collecting annual species biomass data may not be necessary when quantifying diversity effects with DI models.
Thiol‐ene photoclick reaction: An eco‐friendly and facile approach for preparation of MPEG‐g‐keratin biomaterial
Authors: Ye Xianpan , Yuan Jiugang , Jiang Zhe , Wang Shuoxuan , Wang Ping , Wang Qiang , Cui Li
Published: October 2019

Wool keratin is a natural material with excellent properties, which is considered as scaffold biomaterial for tissue engineering. Polyethylene glycol can improve the mechanical properties of keratin materials because of its excellent biocompatibility and plasticity. In the present work, poly (ethylene glycol) methyl ether methacrylate (MPEGMA) was grafted onto keratin by thiol‐ene photoclick reaction. The results of FTIR and SDS‐PAGE verified the successful reaction between MPEGMA and keratin. Compared with the keratin, circular dichroism and XRD results showed that the β‐sheet ratio increased in MPEG‐g‐keratin. Additionally, it can be found that the exposure of keratin hydrophobic amino acids increased quickly and the micelle size became larger due to the introduction of MPEG from the results of fluorescence spectroscopy and particle size analysis. The MPEG‐g‐ keratin was formed into a membrane to further study the application of the modified keratin. Compared with the keratin membrane, the flexibility and biocompatibility of modified keratin have been improved. This work provides an eco‐friendly and facile approach for preparation of the keratin biomaterials.
Properties of human astrocytes and NG2 glia
Authors: Bedner Peter , Jabs Ronald , Steinhäuser Christian
Published: October 2019

Since animal models are inevitable for medical research, information on species differences in glial cell properties is critical for successful translational research. Here, we review current knowledge about morphological and functional properties of human astrocytes and NG2 glial cells and compare these data with those obtained for the comparable cells in rodents. Morphological analyses of astrocytes in the neocortex of rodents versus humans have demonstrated clear differences. In contrast, the functional properties of astrocytes or NG2 glial cells in these species are surprisingly similar. However, these findings should be interpreted with caution, as so far functional analyses of human cells are only available from neocortex and hippocampus, and it is known from rodent studies that the properties of astrocytes in different brain regions may vary considerably. Moreover, technical challenges render astrocyte electrophysiological measurements in situ unreliable, and human cell properties may be affected by medications. Nevertheless, based on the limited data currently available, there is substantial similarity between human and rodent astrocytes with regard to those functional properties studied to date. The unique morphological characteristics of astrocytes in human neocortex call for further physiological analysis. The basic properties for NG2 glia are even less completely evaluated with regard to the question of species differences but no glaring differences have been reported so far. In conclusion, it remains justifiable to employ mouse or rat models to investigate the etiology of human CNS diseases that might involve astrocytes or NG2 glia.
Comparative Assessment of Vegetative and Reproductive Terrestrial Plant Species Endpoints from Exposure to Herbicides and Potential Environmental Implications: A Review
Authors: Christl Heino , Hoen Thierry , Zumkier Ulrich
Published: October 2019

To investigate whether vegetative endpoints are protective of reproductive endpoints in terrestrial plant risk assessments (RAs) for authorization of plant protection products (PPPs), we assessed differences in sensitivity to herbicides between these parameters. Published literature and unpublished proprietary data generated for the registration of PPPs were used to compile a database. If reproductive endpoints were systematically more sensitive than the vegetative endpoints on which regulatory decisions are presently based, a concern could be raised about the protectiveness of the current RA process. Vegetative and reproductive endpoints were assessed considering further potentially relevant parameters. Reproductive endpoints were compared with vegetative endpoints of juvenile plants or with those of mature plants. Direct comparison by substance–species combination proved to be most adequate and was used to calculate quotients by effect level. In addition, we assessed the spread between different effect levels, estimating by which factor the conservatism would increase if effect rate (ER)50 endpoints were replaced by ER25 or ER10 endpoints with otherwise unchanged test parameters. Reproductive endpoints were found to be similarly sensitive as vegetative endpoints derived in nontarget terrestrial plant (NTTP) studies conducted following Organisation for Economic Co-operation and Development (OECD) or US Office of Chemical Safety and Pollution Prevention (OCSPP) guidelines. A switch from vegetative to reproductive endpoints would therefore not significantly change the conservatism (less than a factor of 1.5), whereas the change from ER50 to ER10 would (by a factor of ~5 to 6). However, because ecotoxicological tests on terrestrial plants bear intrinsic high variability that prevents the reliable detection of effects at the 10% effect level, ER10 endpoints are not a reliable basis for RA. No particular family, genus, or species with clusters of distinctly insensitive vegetative and sensitive reproductive endpoints could be identified that would call for regular testing of reproductive endpoints. Also, from the data set available, no specific herbicidal modes of action could be singled out for acting particularly on reproductive endpoints. Integr Environ Assess Manag 2020;16:166–183. © 2019 SETAC
Continuing increased risk of second cancer in long‐term testicular cancer survivors after treatment in the cisplatin era
Authors: Hellesnes Ragnhild , Kvammen Øivind , Myklebust Tor Å. , Bremnes Roy M. , Karlsdottir Ása , Negaard Helene F.S. , Tandstad Torgrim , Wilsgaard Tom , Fosså Sophie D. , Haugnes Hege S.
Published: October 2019

Using complete information on total treatment burden, this population‐based study aimed to investigate second cancer (SC) risk in testicular cancer survivors (TCS) treated in the cisplatin era. The Cancer Registry of Norway identified 5,625 1‐year TCS diagnosed 1980–2009. Standardized incidence ratios (SIRs) were calculated to evaluate the total and site‐specific incidence of SC compared to the general population. Cox regression analyses evaluated the effect of treatment on the risk of SC. After a median observation time of 16.6 years, 572 TCS developed 651 nongerm cell SCs. The SC risk was increased after surgery only (SIR 1.28), with site‐specific increased risks of thyroid cancer (SIR 4.95) and melanoma (SIR 1.94). After chemotherapy (CT), we observed 2.0‐ to 3.7‐fold increased risks for cancers of the small intestine, bladder, kidney and lung. There was a 1.6‐ to 2.1‐fold increased risk of SC after ≥2 cycles of cisplatin‐based CT. Radiotherapy (RT) was associated with 1.5‐ to 4.4‐fold increased risks for cancers of the stomach, small intestine, liver, pancreas, lung, kidney and bladder. After combined CT and RT, increased risks emerged for hematological malignancies (SIR 3.23). TCS treated in the cisplatin era have an increased risk of developing SC, in particular after treatment with cisplatin‐based CT and/or RT.
Fraser extracellular matrix complex subunit 1 promotes liver metastasis of gastric cancer
Authors: Umeda Shinichi , Kanda Mitsuro , Miwa Takashi , Tanaka Haruyoshi , Tanaka Chie , Kobayashi Daisuke , Hayashi Masamichi , Yamada Suguru , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro
Published: October 2019

Liver metastasis is often fatal in patients with gastric cancer, therefore, we aimed to identify genes associated with the mechanisms of liver metastasis of gastric cancer (GC) and to investigate their potential to predict recurrence and to serve as targets of therapy. Recurrence pattern‐specific transcriptome analysis was performed to identify liver metastasis‐associated genes. A stable knockout cell line was generated to investigate metabolic pathways that contribute to the malignant phenotype in vitro and vivo. Three hundred GC patients were analyzed to demonstrate an association between gene expression levels and clinicopathological parameters. As a results extracellular matrix complex subunit 1 (FRAS1) was identified as a liver metastasis‐associated gene. Pathway analysis revealed that FRAS1 expression was significantly correlated with the expression of genes encoding TGFB1, MAP1B, AHNAK, BMP2, MUC1, BIRC5, MET, CDH1, RB1 and MKI67. FRAS1 expression was associated with the activation of the EGFR and PI3K signaling pathways. The proliferation ability of FRAS1 knockout cell line (FRAS1‐KO) was inhibited compared to that of the parent cell line through caspase activity increment and cell cycle alteration. FRAS1‐KO cells exhibited increased responsiveness to oxygen stress and diminished stemness, invasiveness, and migration. Mouse models of GC revealed decreases in tumor formation and generation of metastasis by FRAS1‐KO cells. Moreover, the cumulative liver recurrence rate was significantly increased in patients with GC with high FRAS1 expression levels. We concluded that FRAS1 contributes to the malignant phenotype of GC, especially liver metastasis, and may therefore serve as a predictive marker or a target for treating liver metastasis.
Effect of novel porphyrazine photosensitizers on normal and tumor brain cells
Authors: Mishchenko Tatiana A. , Turubanova Victoria D. , Mitroshina Elena V. , Alzeibak Razan , Peskova Nina N. , Lermontova Svetlana A. , Klapshina Larisa G. , Balalaeva Irina V. , Vedunova Maria V. , Krysko Dmitri V.
Published: October 2019

Photodynamic therapy (PDT) is a clinically approved procedure for targeting tumor cells. Though several different photosensitizers have been developed, there is still much demand for novel photosensitizers with improved properties. In this study we aim to characterize the accumulation, localization and dark cytotoxicity of the novel photosensitizers developed in‐house derivatives of porphyrazines (pz I‐IV) in primary murine neuronal cells, as well as to identify the concentrations at which pz still effectively induces death in glioma cells yet is nontoxic to nontransformed cells. The study shows that incubation of primary neuronal and glioma cells with pz I‐IV leads to their accumulation in both types of cells, but their rates of internalization, subcellular localization and dark toxicity differ significantly. Pz II was the most promising photosensitizer. It efficiently killed glioma cells while remaining nontoxic to primary neuronal cells. This opens up the possibility of evaluating pz II for experimental PDT for glioma.
Effects of human placenta‐derived mesenchymal stem cells with NK4 gene expression on glioblastoma multiforme cell lines
Authors: Jabbarpour Zahra , Kiani Jafar , Keshtkar Somayeh , Saidijam Massoud , Ghahremani Mohammad H. , Ahmadbeigi Naser
Published: October 2019

Poor prognosis and low survival are commonly seen in patients with glioblastoma multiforme (GBM). Due to the specific nature of solid tumors such as GBM, delivery of therapeutic agents to the tumor sites is difficult. So, one of the major challenges in the treatment of these tumors is a selection of appropriate method for drug delivery. Mesenchymal stem cells (MSCs) have a unique characteristic in migration toward the tumor tissue. In this regard, the present study examined the antitumor effects of manipulating human placenta‐derived mesenchymal stem cells (PDMSCs) with NK4 expression (PDMSC‐NK4) on GBM cells. After separation and characterization of PDMSCs, these cells were transduced with NK4 which was known as the antagonist of hepatocyte growth factor (HGF). The results indicated that engineered PDMSCs preferably migrate into GBM cells by transwell coculture system. In addition, the proliferation of the GBM cells significantly reduced after coculture with these cells. In fact, manipulated PDMSCs inhibited growth of tumor cells by induction of apoptosis. Our findings suggested that besides having antitumor effects, PDMSCs can also be applied as an ideal cellular vehicle to target the glioblastoma multiforme.
Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels
Authors: Evans Mark Francis , Vacek Pamela Mary , Sprague Brian Lee , Stein Gary Stephen , Stein Janet Lee , Weaver Donald Lee
Published: October 2019

Breast tumor stratification by recurrence‐risk is critical for deciding patient treatment. Here an approach combining cancer pathways microarray data complemented by RNA in situ hybridization (ISH) was investigated as a means for recurrence marker discovery and visualization in pathology specimens. LncRNA and mRNA expressions in breast carcinomas with low (n = 8) vs intermediate/high (n = 10) recurrence‐scores as estimated by 21‐gene assay and pathology review were compared by microarray assay. Tissue microarrays were prepared from breast carcinomas (n = 20) and ductal carcinoma in situ (DCIS) specimens (n = 84 patients) with known outcomes. Thirteen RNA ISH assays were performed: lncRNAs (BBC3‐1, FER3, RAD21‐AS1, ZEB1‐2) and mRNAs (GLO1, GLTSCR2, TGFB1, TLR2) (implicated by the microarray data); MKI67; a pooled panel of recurrence‐associated proliferation markers (BIRC5, Cyclin B1, MKI67, MYBL2, STK15); a pooled panel of non‐proliferation recurrence‐associated markers (CEACAM5, HTF9C, NDRG1, TP53, SLC7A5); and lncRNAs H19 and HOTAIR. Seven lncRNAs and 10 mRNAs showed significantly (P < .05) altered upregulation or downregulation by microarray assay: carcinoma RNA ISH staining did not mirror these patterns. HOTAIR staining was associated with a higher breast cancer recurrence score (P = .0152); qualitatively, H19 was massively expressed in a metaplastic triple negative breast carcinoma. Among the DCIS cohort, significant associations with multiple outcome variables were noted for TGFB1 and the non‐proliferation panel (P‐value range: .0001 to .047); proliferation panel staining showed an association with increasing DCIS grade (P = .0269) but not with outcomes. The findings support recurrence‐risk estimation by the use of multi‐marker panels that are representative of diverse cellular pathways rather than over‐reliance on proliferation targets. H19, HOTAIR, and TGFB1 RNA ISH show potential for selective diagnostics.
The economic efficiency of clinical laboratories in public hospitals: A case study in Iran
Authors: Alinejhad Mina , Aghlmand Siamak , Feizollahzadeh Sadegh , Yusefzadeh Hasan
Published: October 2019

Introduction

Clinical laboratories are identified as one of the most important and expensive units of the health system. Therefore, it is essential to pay attention to these units' cost efficiency. This study purpose was to evaluate the economic efficiency of hospitals' laboratory units affiliated to Urmia University of Medical Sciences (UMSU), in order to assess their performance.

Methods

This research was a descriptive‐analytic study that was accomplished in 2017. The statistical population of the study included all of the hospitals' clinical laboratories affiliated to UMSU. Moreover, DEA method and Deap2.1 software were used to analyze data. In this study, technical and allocative efficiencies of the studied laboratory units were also calculated in addition to the determination of the economic efficiency of the laboratories.

Results

The average economic efficiency of clinical laboratories calculated by DEA in 2017 was 0.676. This value was lower than the allocative and technical efficiency scores, which indicates that these units could attain full efficiency by reducing their costs without having any effect on output values. Moreover, about 14 percent of the clinical laboratory units were economically efficient. In addition, it is noteworthy to state that, from total of university hospital laboratories, only three hospitals had no economic excess or deficiency values of inputs.

Conclusion

Considering that 76% of laboratory units have not been economically efficient, it is necessary for the laboratory managers to consider optimum allocating of resources, with respect to the cost of laboratory equipment and inputs in order to increase their units' economic efficiency.
The circ_0021977/miR‐10b‐5p/P21 and P53 regulatory axis suppresses proliferation, migration, and invasion in colorectal cancer
Authors: Lu Chen , Jiang Wei , Hui Bingqing , Rong Dawei , Fu Kai , Dong Chaoxi , Tang Weiwei , Cao Hongyong
Published: October 2019

An in‐depth understanding of circular RNAs (circRNAs) indicates that they are abundant in the eukaryotic transcriptome. Many circRNAs act as microRNA sponges; thus, they represent a new type of regulatory factor. However, the role of circRNA in colorectal cancer (CRC) remains largely unknown. Low circ_0021977 expression in patients with CRC is associated with higher tug‐lymph node metastasis (TNM) stage and poorer prognosis compared with patients with high circ_0021977 expression. Moreover, miR‐10b‐5p was shown to be a target of circ_0021977, and p21 and p53 are suggested to be putative target genes of miR‐10b‐5p. The results showed that the circ_0021977/miR‐10b‐5p/p21&p53 regulatory axis suppresses proliferation, migration, and invasion by CRC cells. This evidence reveals new relationships and brings new highlights to the treatment of CRC.
RNA‐binding protein PUM2 regulates mesenchymal stem cell fate via repression of JAK2 and RUNX2 mRNAs
Authors: Lee Myon‐Hee , Wu Xinjun , Zhu Yong
Published: October 2019

The differentiation of mesenchymal stem cells (MSCs) into unwanted lineages can generate potential problems in clinical trials. Thus, understanding the molecular mechanisms, involved in this process, would help prevent unexpected complications. Regulation of gene expression, at the posttranscriptional level, is a new approach in cell therapies. PUMILIO is a conserved posttranscriptional regulator. However, the underlying mechanisms of PUMILIO, in vertebrate stem cells, remain elusive. Here, we show that depletion of PUMILIO2 (PUM2) blocks MSC adipogenesis and enhances osteogenesis. We also demonstrate that PUM2 works as a negative regulator on the 3′‐untranslated regions of JAK2 and RUNX2 via direct binding. CRISPR/Cas9‐mediated gene silencing of Pum2 inhibited lipid accumulation and induced excessive bone formation in zebrafish larvae. Our findings reveal novel roles of PUM2 in MSCs and provide potential therapeutic targets for related diseases.
Interactive effects of salinity and silicon application on Solanum lycopersicum growth, physiology and shelf‐life of fruit produced hydroponically
Authors: Costan Andrei , Stamatakis Aristeidis , Chrysargyris Antonios , Petropoulos Spyridon A , Tzortzakis Nikos
Published: October 2019

BACKGROUND

Using water with high salinity for plant fertigation may have detrimental effects on plant development and total yield and on the quality of the crop produced. As a possible means to alleviate the negative effects of salinity, silicon (Si) can be incorporated in the nutrient solution supplied to plants. In the present study, hydroponically grown tomato (Solanum lycopersicum Mill.) plants were subjected to two different salinity levels (0 and 50 mmol L−1 NaCl) with and without the application of Si (0 and 2 mmol L−1 K2SiO3) in order to evaluate its possible positive impact on mitigation of salinity stress‐induced symptoms. An additional experiment was implemented with postharvest Si application (sodium silicate) to investigate effects on the shelf‐life of tomato fruit.

RESULTS

Salinity (50 mmol L−1 NaCl) decreased plant size, total yield and fresh fruit weight while a high percentage of blossom end rot symptoms of tomato fruit was also observed. The application of Si in the nutrient solution counteracted these detrimental effects, generating a higher yield and healthier fruit (lower blossom end rot incidence) compared to the untreated plants (no application of Si). Salinity improved several quality‐related traits in tomato fruit, resulting in higher marketability, whereas the addition of Si (pre‐ and postharvest) maintained fruit firmness following storage thereby increasing the shelf‐life of tomato fruit.

CONCLUSIONS

These findings indicate that Si application (pre‐ and postharvest) could provide an effective means of alleviating the unfavorable effects of using low‐quality water in plant fertigation on tomato plant development, fruit yield and post‐harvest quality, through increased fruit firmness. © 2019 Society of Chemical Industry
Two novel proteins, TtpB2 and TtpD2, are essential for iron transport in the TonB2 system of Vibrio vulnificus
Authors: Barnes Adel D. , Pfeifer Hailey J. , Zbylicki Brianne R. , Roberts Elena K. , Rudd Justin C. , Manzo Mario A. , Phillips Elysse A. , Berry Michael M. , Kenton Ryan J.
Published: October 2019

In gram‐negative bacteria, energy‐dependent active transport of iron‐bound substrates across the outer membrane is achieved through the TonB systems of proteins. Three TonB systems have been identified in the human pathogen Vibrio vulnificus. The TonB1 system contains three proteins: TonB1, ExbB1, and ExbD1. Both the TonB2 and TonB3 systems have been shown to also contain a fourth protein, TtpC2 and TtpC3, respectively. Here, we report and begin to characterize two additional proteins in the TonB2 and TonB3 systems: TtpB and TtpD. Both TtpB2 and TtpD2 are absolutely required for the function of the TonB2 system in V. vulnificus. However, although both TtpB3 and TtpD3 in the TonB3 system are related to the proteins in the TonB2 system, neither are active in iron transport. All six protein components of the TonB2 system—TonB2, ExbB2, ExbD2, TtpB2, TtpC2, and TtpD2—are essential for the uptake of both endogenously produced iron‐bound siderophores and exogenous siderophores produced from other organisms. Through complementation, we have shown that V. vulnificus is capable of using different TtpD2 proteins from other Vibrio species to bring in multiple siderophores. In contrast, we also demonstrate that TtpB2 must come from V. vulnificus, and not other species within the genus, to complement mutations in the TonB2 system.
Drug and Disease Effects in Parkinson's Psychosis: Revisiting the Role of Dopamine
Authors: Dave Sonali , Weintraub Daniel , Aarsland Dag , ffytche Dominic H.
Published: October 2019

Background

Levodopa and dopamine agonists (dopamine replacement therapy [DRT]) are implicated in Parkinson's disease psychosis (PDP), but the relationship between DRT and neurotransmitter dysfunction inherent to PD remains unclear.

Objectives

To examine the relationship between baseline striatal dopamine transporter (DAT) binding in drug‐naïve idiopathic PD, introduction of DRT, or dose change and incident early‐onset PDP.

Methods

Baseline DAT binding was compared between patients with and without incident psychosis (defined here as hallucinations or delusions), controlling for age, sex, baseline cognition, and prospective DRT in the Parkinson's Progression Markers Initiative cohort. Incident illusions were not considered psychosis symptoms.

Results

Of 386 patients, 30 (8%) developed PDP (predominantly hallucinations, mean onset 42 months) and 355 (92%) had either no PDP symptoms (mean follow‐up 64 months) or reported illusions only (111/355, 31%). Incident PDP was associated with reduced baseline striatal DAT binding, controlling for confounders (F1,377 = 10.9; P = 0.001), but not with a specific DRT regime. A total of 6 patients developed PDP when DRT free. There was no suggestion that PDP onset was coincident with starting levodopa or levodopa dose increase. Incident illusions were not associated with reduced DAT binding.

Conclusion

The findings highlight the role of disease‐related dopamine mechanisms in the pathophysiology of hallucinations in Parkinson's disease alongside medication. It remains to be determined how dopamine mechanisms, medication, and other neurotransmitter systems implicated in PDP interact.
Towards fast and robust 4D optimization for moving tumors with scanned proton therapy
Authors: Buti Gregory , Souris Kevin , Montero Ana Maria Barragán , Lee John Aldo , Sterpin Edmond
Published: October 2019

Purpose

Robust optimization is becoming the gold standard for generating robust plans against various kinds of treatment uncertainties. Today, most robust optimization strategies use a pragmatic set of treatment scenarios (the so‐called uncertainty set) consisting of combinations of maximum errors, of each considered uncertainty source (such as tumor motion, setup and image‐conversion errors). This approach presents two key issues. First, a subset of considered scenarios is unnecessarily improbable which could potentially compromise the plan quality. Second, the resulting large uncertainty set leads to long plan computation times, which limits the potential for robust optimization as a standard clinical tool. In order to address these issues, a method is introduced which is able to preselect a limited set of relevant treatment error scenarios.

Methods

Uncertainties due to systematic setup errors, image‐conversion errors and respiratory tumor motion are considered. A four‐dimensional (4D)‐equiprobability hypersurface is defined, which takes into account the joint probabilities of the above‐mentioned uncertainty sources. Only scenarios that lie on the predefined 4D hypersurface are considered, guaranteeing statistical consistency of the uncertainty set. In this regard, twelve scenarios are selected that cover maximum spatial displacements of the tumor during breathing. Subsequently, additional scenarios are considered (sampled from the aforementioned 4D hypersurface) in order to cover any estimated residual range errors. Two different scenario‐selection procedures were tested: (a) the maximum displacements (MD) method that only considers twelve scaled maximum displacement scenarios and (b) maximum displacements and residual range (MDR) method which, in addition to the scaled maximum displacement scenarios, considers additional maximum range uncertainty scenarios. The methods were tested for five lung cancer patients by performing comprehensive Monte Carlo robustness evaluations.

Results

A plan computation time gain of 78% is achieved by applying the MD method, whilst obtaining a target robustness of D larger than 95% of the prescribed dose, for the worst‐case scenario. Additionally, the MD method has the potential to be fully automatic which makes it a promising candidate for fast automatic planning workflows. The MDR method produced plans with excellent target robustness (D larger than 95% of the prescribed dose, even for the worst‐case scenario), whilst still obtaining a significant plan computation time gain of 57%.

Conclusions

Two scenario‐selection procedures were developed which achieved significant reduction of plan computation time and memory consumption, without compromising plan quality or robustness.
ALDH1A1‐related stemness in high‐grade serous ovarian cancer is a negative prognostic indicator but potentially targetable by EGFR/mTOR‐PI3K/aurora kinase inhibitors
Authors: Kaipio Katja , Chen Ping , Roering Pia , Huhtinen Kaisa , Mikkonen Piia , Östling Päivi , Lehtinen Laura , Mansuri Naziha , Korpela Taina , Potdar Swapnil , Hynninen Johanna , Auranen Annika , Grénman Seija , Wennerberg Krister , Hautaniemi Sampsa , Carpén Olli
Published: October 2019

Poor chemotherapy response remains a major treatment challenge for high‐grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient‐derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment‐naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment‐naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment‐naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K‐mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K‐mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment‐naive tumours. EGFR, mTOR‐PI3K and aurora kinase inhibitors are candidates for targeting this cell population. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.