bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Stem Cell–Like Memory T Cells in Systemic Lupus Erythematosus
Authors: Lee Ye Ji , Park Ji Ah , Kwon Hyunmi , Choi Youn Soo , Jung Kyeong Cheon , Park Seong Hoe , Lee Eun Bong
Published: April 2018

Objective

Stem cell–like memory T (Tscm) cells are long‐lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of Tscm cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify Tscm cells in patients experiencing systemic lupus erythematosus (SLE).

Methods

CD4+ and CD8+ Tscm cells were identified in SLE patients and healthy controls (HCs). In in vitro culture systems, CD4+ Tscm cells were induced to differentiate into subsets of T cells, including follicular helper T (Tfh) cells, and cytokine production patterns were assessed after stimulation. After confirming induction of transcription factors for Tfh cells, the capacity of CD4+ Tscm‐derived Tfh cells to help B cells was analyzed by measuring antibody secretion.

Results

The percentages of CD4+ and CD8+ Tscm cells among the naive CD4+/CD8+ or total CD4+ T cell populations were significantly higher in SLE patients than in HCs. Stimulated Tscm cells from SLE patients could replenish themselves and differentiate into other T lymphocyte subsets, including Tfh cells upon stimulation with T cell receptor. Production of T cell factor 1, which is an inducer of Tfh, was also increased. The differentiated Tfh cells increased antibody production by autologous B cells.

Conclusion

Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.
Water‐Soluble Phospholo[3,2‐b]phosphole‐P,P′‐Dioxide‐Based Fluorescent Dyes with High Photostability
Authors: Wang Chenguang , Fukazawa Aiko , Tanabe Yoshiyuki , Inai Naoto , Yokogawa Daisuke , Yamaguchi Shigehiro
Published: April 2018

We recently reported that fluorescent dye PB430, which consisted of a 2‐phenyl‐substituted benzophosphole P‐oxide skeleton that was reinforced by a methylene bridge, showed pronounced photostability and, thus, high utility for applications in super‐resolution stimulated emission depletion (STED) microscopy. Herein, we replaced the methylene bridge with another P=O group to 1) investigate the role of the bridging moieties; and 2) further modulate the fluorescence properties of this skeleton. We synthesized a series of phospholo[3,2‐b]phosphole‐based dyes—trans‐PO‐PB430, cis‐PO‐PB430, and trans‐PO‐PB460—all of which showed sufficient water solubility. Moreover, trans‐PO‐PB430 and trans‐PO‐PB460 exhibited intense green and orange fluorescence, respectively, and a high photostability that was comparable to that of PB430. In contrast, cis‐PO‐PB430 underwent rapid photobleaching upon continuous photoirradiation, which demonstrated the importance of steric shielding of the polycyclic skeleton by the substituents on the bridging moieties. The fluorescence properties of these dyes were insensitive to concentration, pH value, and polarity changes of the environment in solution. In addition, even in the solid state, these dyes showed strong green to orange emissions. These results demonstrate the potential utility of trans‐PO‐PB430 and trans‐PO‐PB460 as highly photostable fluorescent dyes.
Comparing outcome and recanalization results in patients with anterior circulation stroke following endovascular treatment with and without a treatment with rt‐PA: A single‐center study
Authors: Al‐Khaled Mohamed , Brüning Toralf , Gottwald Carina , Roessler Florian , Royl Georg , Eckey Thomas
Published: April 2018

Objectives

Endovascular treatment (ET), in addition to a therapy with intravenous recombinant tissue plasminogen activator IV rt‐PA in patients with acute ischemic stroke, has been found to improve outcome. However, data about ET in patients who have not received therapy with rt‐PA due to contraindications for IV rt‐PA are sparse. Comparison of ET with IV rt‐PA versus ET alone in patients with stroke is done using a proximal intracranial arterial occlusion (internal carotid artery, middle cerebral artery (M1‐Segment)).

Methods

During a 5‐year period (2011–2016), 236 patients (mean age, 69 ± 14 years; 46% women; median NIHSS score 13 ± 5) who were treated at the Department of Neurology and Neuroradiology at the University of Lübeck, undergoing ET with or without IV rt‐PA were included and analyzed.

Results

A total of 144 patients (61%) underwent ET + IV rt‐PA, and 92 patients (39%) underwent ET only. The ET with IV rt‐PA is associated with a higher rate of favorable functional outcomes (mRS≤2) at discharge from hospital (51.4% vs. 23.1%, p < .001) and lower rate of in‐hospital mortality (9% vs. 19.6%, p = .019) and symptomatic intracerebral hemorrhage [sICH] (2.1% vs. 8.7%; p = .019) compared to ET, whereas the modified treatment in cerebral infarction score (mTICI) did not differ between the groups.

In the adjusted logistic regression analysis, the ET + IV rt‐PA was associated with an increased probability of favorable functional outcome (OR, 4.3; 95% confidence interval [CI], 2.2–8.5; p < .001). For the in‐hospital mortality (OR, 0.74; 95% CI, 0.29–1.9; p = .76) and sICH (OR, 0.3; 95% CI, 0.07–1.2; p = .09), no differences were found.

Conclusion

Recanalization results after endovascular treatment are not relevantly improved in patients receiving rt‐PA. However, an additional therapy with IV rt‐PA has a positive impact on functional outcome.
Target‐setting for ecological resilience: Are companies setting environmental sustainability targets in line with planetary thresholds?
Authors: Haffar Merriam , Searcy Cory
Published: April 2018

The purpose of this research is to explore the extent to which companies are setting organization‐centric versus resilience‐based environmental targets in their sustainability reports. We define ecological resilience through the planetary thresholds identified by the Planetary Boundaries (PB) framework. On this basis, we define resilience‐based targets as corporate environmental targets that are connected (quantitatively or qualitatively) to these thresholds. Sustainability reports issued by 50 sustainability leader firms in Canada were analyzed to identify environmental sustainability targets. These targets were classified as resilience‐based and organization‐centric based on their connection to the PB framework. A total of 303 targets were identified, distributed across eight different corporate performance areas. None of these targets was found to be quantitatively tied to any PB thresholds. A small number of targets did nevertheless make reference to the global/regional ecological processes that underpin some of the Boundaries. These targets made reference to only five of the nine Boundaries described by the framework. This study highlights the extent of organization‐centric environmental targets in corporate sustainability reports. The implications of setting such targets are discussed, along with the challenges of adopting resilience‐based targets. This study also discusses the reasons why companies may not be adopting a resilience‐based approach to set sustainability targets and measure performance, despite increasing calls from stakeholders to do so. On this basis, several recommendations are also provided for managers to guide resilience‐based target‐ and goal‐setting.
Demographic, mental health, and offending characteristics of online child exploitation material offenders: A comparison with contact‐only and dual sexual offenders
Authors: Henshaw Marie , Ogloff James R. P. , Clough Jonathan A.
Published: April 2018

Technological advances have dramatically increased the ability to access, distribute and produce child exploitation material (CEM) online, resulting in increased numbers of individuals being charged with CEM offences. This study examined the demographic, mental health, and offending characteristics of CEM offenders (n = 456) in comparison to child contact sexual offenders (n = 493) and offenders with a history of both CEM and contact offences (dual offenders, n = 256). A robust data linkage methodology was employed to link records from statewide corrections services with policing and mental health records in Victoria, Australia. The results indicated that CEM offenders differed from both contact and dual offenders, and that the groups were primarily differentiated based on two factors: antisocial orientation and sexual deviance. CEM offenders demonstrated high rates of sexual deviance but low rates of antisociality, contact offenders exhibited the opposite pattern, and dual offenders had both high sexual deviance and antisociality. The findings suggest that existing sexual offender assessment and treatment frameworks are unlikely to be suitable for exclusive CEM offenders. The implications for future research are discussed.
The bidirectional association among female hormone‐related cancers: breast, ovary, and uterine corpus
Authors: Chen Min‐Chi , Lee Kuan‐Der , Lu Chang‐Hsien , Wang Ting‐Yao , Huang Shih‐Hao , Chen Chao‐Yu
Published: April 2018

Breast, ovarian, and uterine corpus cancers are common female cancers and categorized as hormone‐related diseases. Previous studies reported a unidirectional relationship for each cancer, but few studied the reciprocal association in the same cohort. A population‐based study was carried out in Taiwan to test the hypothesis that there are pairwise bidirectional associations among these cancers. Using the same cohort of 110,112 cases with primary female cancers including uterine corpus cancer (11,146 cases), ovarian cancer (12,139 cases), or breast cancer (86,827 cases) from the Taiwan Cancer Registry from 1979 to 2008, the pairwise risks of second cancer among uterine corpus, ovary, and breast cancer cases were evaluated by standardized incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) to quantify the excess of second malignancies. A reciprocal relationship was found for these three female cancers, particularly most prominent between uterine and ovarian cancers, followed by breast and uterine cancers as well as breast and ovarian cancers. The overall risk of second cancers was highest within the first 5 years after the diagnosis of primary cancer. The bidirectional relationships suggest common risk factors among these three female cancers. This is the largest cohort study to focus on the bidirectional associations among hormone‐related cancers in Asian women, and these results could aid in the development of early prevention strategies and follow‐up surveillance programs.
Lipin‐1 determines lung cancer cell survival and chemotherapy sensitivity by regulation of endoplasmic reticulum homeostasis and autophagy
Authors: Fan Xueyu , Weng Yuanyuan , Bai Yongfeng , Wang Zongpan , Wang Siwei , Zhu Jin , Zhang Feng
Published: April 2018

Cancer cells undergo comprehensive metabolic reprogramming to meet the increased requirements of energy and building blocks for proliferation. Lipin‐1, a phosphatidic acid phosphatase converting phosphatidic acid (PA) to diacylglycerol (DAG), is upregulated in lung adenocarcinoma (LUAD) cell lines and tumor tissues. In this study, we reveal high lipin‐1 expression is correlated with poor prognosis of patients with LUAD. Knockdown of lipin‐1 decreases cell viability and proliferation in LUAD cells, whereas it has less effect on nontumorigenic lung cells. Autophagy and ER stress play important roles in tumor initiation and progression. Lipin‐1 knockdown induces the initiation of autophagy while disrupts formation of autolysosome. Lipin‐1 silencing induces the activation of ER stress through the IRE1α pathway. Furthermore, we demonstrate disrupted ER homeostasis contributes to the cell phenotype, and the elevated autophagy initiation is due to the ER stress in part. For the first time, we show lack of lipin‐1 enhances the sensitivity of LUAD cells to cisplatin treatment. Our results suggest that lipin‐1 is a potential target, alone or combined with other treatment, for lung cancer therapy.
Analysis of potential genes and pathways associated with the colorectal normal mucosa–adenoma–carcinoma sequence
Authors: Wu Zhuoxuan , Liu Zhen , Ge Weiting , Shou Jiawei , You Liangkun , Pan Hongming , Han Weidong
Published: April 2018

This study aimed to identify differentially expressed genes (DEGs) related to the colorectal normal mucosa–adenoma–carcinoma sequence using bioinformatics analysis. Raw data files were downloaded from Gene Expression Omnibus (GEO) and underwent quality assessment and preprocessing. DEGs were analyzed by the limma package in R software (R version 3.3.2). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with the DAVID online tool. In a comparison of colorectal adenoma (n = 20) and colorectal cancer (CRC) stage I (n = 31), II (n = 38), III (n = 45), and IV (n = 62) with normal colorectal mucosa (n = 19), we identified 336 common DEGs. Among them, seven DEGs were associated with patient prognosis. Five (HEPACAM2, ITLN1, LGALS2, MUC12, and NXPE1) of the seven genes presented a sequentially descending trend in expression with tumor progression. In contrast, TIMP1 showed a sequentially ascending trend. GCG was constantly downregulated compared with the gene expression level in normal mucosa. The significantly enriched GO terms included extracellular region, extracellular space, protein binding, and carbohydrate binding. The KEGG categories included HIF‐1 signaling pathway, insulin secretion, and glucagon signaling pathway. We discovered seven DEGs in the normal colorectal mucosa–adenoma–carcinoma sequence that was associated with CRC patient prognosis. Monitoring changes in these gene expression levels may be a strategy to assess disease progression, evaluate treatment efficacy, and predict prognosis.
Train the child and teach the adult: Developing intervention strategies for increasing seafood consumption
Authors: Birch Dawn , Dean David , Fazal‐e‐Hasan Syed Muhammad , Lawley Meredith
Published: April 2018

Despite increasing levels of per capita seafood consumption globally, consumption levels across the population vary with many consumers eating less than recommended weekly intakes. This study investigates the influence of childhood patterns of seafood consumption, consumer confidence in selecting and preparing seafood, adult eating habits, and lifestyle on seafood consumption. Partial least squares structural equation modelling analysis was conducted using a sample of 1,318 Australian adults. The results show that consuming seafood regularly in childhood and developing the confidence to select and prepare seafood as an adult contribute to the development of seafood eating habits. Subsequently, a habit of consuming seafood leads to a lifestyle involving regular consumption of seafood. The results indicate the need to develop and implement intervention strategies for encouraging childhood seafood consumption (“train the child”) and increasing adults' confidence in selecting and preparing seafood (“teach the adult”). Intervention strategies proposed include educational programmes targeted at both children and adults, combined with the development of seafood products that appeal to children and suit the changing lifestyle needs of today's 21st century consumers.
Characterization of Carboxylic Acid Reductases for Biocatalytic Synthesis of Industrial Chemicals
Authors: Kramer Levi , Hankore Erome Daniel , Liu Yilan , Liu Kun , Jimenez Esteban , Guo Jiantao , Niu Wei
Published: April 2018

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids into aldehydes, which can serve as common biosynthetic precursors to many industrial chemicals. This work presents the systematic biochemical characterization of five carboxylic acid reductases from different microorganisms, including two known and three new ones, by using a panel of short‐chain dicarboxylic acids and hydroxy acids, which are common cellular metabolites. All enzymes displayed broad substrate specificities. Higher catalytic efficiencies were observed when the carbon chain length, either of the dicarboxylates or of the terminal hydroxy acids, was increased from C2 to C6. In addition, when substrates of the same carbon chain length are compared, carboxylic acid reductases favor hydroxy acids over dicarboxylates as their substrates. Whole‐cell bioconversions of eleven carboxylic acid substrates into the corresponding alcohols were investigated by coupling the CAR activity with that of an aldehyde reductase in Escherichia coli hosts. Alcohol products were obtained in yields ranging from 0.5 % to 71 %. The de novo stereospecific biosynthesis of propane‐1,2‐diol enantiomer was successfully demonstrated with use of CARs as the key pathway enzymes. E. coli strains accumulated 7.0 mm (R)‐1,2‐PDO (1.0 % yield) or 9.6 mm (S)‐1,2‐PDO (1.4 % yield) from glucose. This study consolidates carboxylic acid reductases as promising enzymes for sustainable synthesis of industrial chemicals.
An unusual case of coronary artery compression that did not preclude successful transcatheter pulmonary valve placement
Authors: Schwartz Matthew C. , Felix Donald , Iacono Karen , Nykanen David
Published: April 2018

During transcatheter pulmonary valve placement, coronary compression observed during simultaneous right ventricular outflow tract angioplasty and coronary angiography typically contraindicates valve implantation. We present a unique patient with tetralogy of Fallot who underwent successful transcatheter Melody valve placement despite coronary compression observed during right ventricular outflow tract balloon angioplasty.
Correlative Multiscale 3D Imaging of a Hierarchical Nanoporous Gold Catalyst by Electron, Ion and X‐ray Nanotomography
Authors: Fam Yakub , Sheppard Thomas L. , Diaz Ana , Scherer Torsten , Holler Mirko , Wang Wu , Wang Di , Brenner Patrice , Wittstock Arne , Grunwaldt Jan‐Dierk
Published: April 2018

Tomographic imaging of catalysts allows non‐invasive investigation of structural features and chemical properties by combining large fields of view, high spatial resolution, and the ability to probe multiple length scales. Three complementary nanotomography techniques, (i) electron tomography, (ii) focused ion beam—scanning electron microscopy, and (iii) synchrotron ptychographic X‐ray computed tomography, were applied to render the 3D structure of monolithic nanoporous gold doped with ceria, a catalytically active material with hierarchical porosity on the nm and μm scale. The resulting tomograms were used to directly measure volume fraction, surface area and pore size distribution, together with 3D pore network mapping. Each technique is critically assessed in terms of approximate spatial resolution, field of view, sample preparation and data processing requirements. Ptychographic X‐ray computed tomography produced 3D electron density maps with isotropic spatial resolution of 23 nm, the highest so far demonstrated for a catalyst material, and is highlighted as an emerging method with excellent potential in the field of catalysis.
Enantiopure Phospha[1]ferrocenophanes: Textbook Examples of Through‐Space Nuclear Spin–Spin Coupling
Authors: Sadeh Saeid , Cao My P. T. , Quail J. Wilson , Zhu Jianfeng , Müller Jens
Published: April 2018

Three enantiopure phospha[1]ferrocenophanes (2R) equipped with either a phenyl, an isopropyl, or a tert‐butyl group at the bridging phosphorus atom were synthesized by a salt‐metathesis approach in isolated yields between 52 and 63 %. The chirality in these strained sandwich compounds stems from the planar‐chiral ferrocene moiety, which is symmetrically equipped with two iPr groups adjacent to phosphorus. Surprisingly, all three phospha[1]ferrocenophanes show an uncommon through‐space nuclear 1H–31P coupling. As a result of the embedded symmetry, these new compounds are ideal examples to differentiate between through‐space and through‐bond coupling mechanisms in NMR spectroscopy.
Evolution from S3 to S4 States of the Oxygen‐Evolving Complex in Photosystem II Monitored by Quantum Mechanics/Molecular Mechanics (QM/MM) Dynamics
Authors: Narzi Daniele , Capone Matteo , Bovi Daniele , Guidoni Leonardo
Published: April 2018

Water oxidation in the early steps of natural photosynthesis is fulfilled by photosystem II, which is a protein complex embedded in the thylakoid membrane inside chloroplasts. The water oxidation reaction occurs in the catalytic core of photosystem II, which consists of a Mn4Ca metal cluster, at which, after the accumulation of four oxidising equivalents through five steps (S0–S4) of the Kok–Joliot cycle, two water molecules are split into electrons, protons, and molecular oxygen. In recent years, by combining experimental and theoretical approaches, new insights have been achieved into the structural and electronic properties of different steps of the catalytic cycle. Nevertheless, the exact catalytic mechanism, especially concerning the final stages of the cycle, remains elusive and greatly debated. Herein, by means of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations, from the structural, electronic, and magnetic points of view, the S3 state before and upon oxidation has been characterised. In contrast with the S2 state, the oxidation of the S3 state is not followed by a spontaneous proton‐coupled electron‐transfer event. Nevertheless, upon modelling the reduction of the tyrosine residue in photosystem II (TyrZ) and the protonation of Asp61, spontaneous proton transfer occurs, leading to the deprotonation of an oxygen atom bound to Mn1; thus making it available for O−O bond formation.
Toward a general mixed quantum/classical method for the calculation of the vibronic ECD of a flexible dye molecule with different stable conformers: Revisiting the case of 2,2,2‐trifluoro‐anthrylethanol
Authors: Cerezo Javier , Aranda Daniel , Avila Ferrer Francisco J. , Prampolini Giacomo , Mazzeo Giuseppe , Longhi Giovanna , Abbate Sergio , Santoro Fabrizio
Published: April 2018

We extend a recently proposed mixed quantum/classical method for computing the vibronic electronic circular dichroism (ECD) spectrum of molecules with different conformers, to cases where more than one hindered rotation is present. The method generalizes the standard procedure, based on the simple Boltzmann average of the vibronic spectra of the stable conformers, and includes the contribution of structures that sample all the accessible conformational space. It is applied to the simulation of the ECD spectrum of (S)‐2,2,2‐trifluoroanthrylethanol, a molecule with easily interconvertible conformers, whose spectrum exhibits a pattern of alternating positive and negative vibronic peaks. Results are in very good agreement with experiment and show that spectra averaged over all the sampled conformational space can deviate significantly from the simple average of the contributions of the stable conformers. The present mixed quantum/classical method is able to capture the effect of the nonlinear dependence of the rotatory strength on the molecular structure and of the anharmonic couplings among the modes responsible for molecular flexibility. Despite its computational cost, the procedure is still affordable and promises to be useful in all cases where the ECD shape arises from a subtle balance between vibronic effects and conformational variety.
PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside
Authors: Turk Anita A. , Wisinski Kari B.
Published: April 2018

Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA‐mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate‐ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA‐mutant cells while sparing normal cells—a concept called synthetic lethality. PARP inhibitors are the first cancer therapeutics designed to exploit synthetic lethality. Recent clinical trials in BRCA‐mutant, metastatic breast cancer demonstrated improved outcomes with single‐agent PARP inhibitors (olaparib and talazoparib) over chemotherapy. However, resistance to PARP inhibitors remains a challenge. Primarily due to myelosuppression, the combination of PARP inhibitors with chemotherapy has been difficult. Novel combinations with chemotherapy, immunotherapy, and other targeted therapies are being pursued. In this review, the authors discuss current knowledge of PARP inhibitors in BRCA‐mutant breast cancer and potential future directions for these agents. Cancer 2018;124:2498‐506. © 2018 American Cancer Society.
Temporal trends in management and outcomes of testicular cancer: A population‐based study
Authors: Leveridge Michael J. , Siemens D. Robert , Brennan Kelly , Izard Jason P. , Karim Safiya , An Howard , Mackillop William J. , Booth Christopher M.
Published: April 2018

BACKGROUND

Treatment guidelines for early‐stage testicular cancer have increasingly recommended de‐escalation of therapy with surveillance strategies. This study was designed to describe temporal trends in routine clinical practice and to determine whether de‐escalation of therapy is associated with inferior survival in the general population.

METHODS

The Ontario Cancer Registry was linked to electronic records of treatment to identify all patients diagnosed with testicular cancer treated with orchiectomy in Ontario during 2000‐2010. Treatment after orchiectomy was classified as radiotherapy (RT), retroperitoneal lymph node dissection (RPLND), chemotherapy, or none. Surveillance was defined as no identified treatment within 90 days of orchiectomy. Overall survival (OS) and cancer‐specific survival (CSS) were measured from the date of orchiectomy.

RESULTS

The study population included 1564 and 1086 cases of seminomas and nonseminoma germ cell tumors (NSGCTs), respectively. Among patients with seminomas, there was a significant increase in the proportion of patients with no treatment within 90 days of orchiectomy (from 56% to 84%; P < .001); the use of RT decreased over time (from 38% to 8%; P < .001); and the use of chemotherapy remained stable (from 6% to 9%; P = .289). Practice patterns 90 days after orchiectomy remained stable over time among patients with NSGCTs: from 51% to 57% for no treatment (P = .435), from 43% to 43% for chemotherapy (P = .336), and from 9% to 3% for RPLND (P = .476). The OS rates for the entire cohort at 5 and 10 years were 97% and 96%, respectively; the CSS rates were 98% and 98%, respectively. There was no significant change in OS or CSS for patients with seminomas or NSGCTs during the study period.

CONCLUSIONS

There has been substantial de‐escalation in the treatment of testicular cancer in routine practice since 2000. Long‐term survival in routine practice is excellent and has not decreased with the uptake of surveillance strategies. Cancer 2018;124:2724‐2732. © 2018 American Cancer Society
Final results of a phase 2, open‐label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high‐risk myelodysplastic syndrome
Authors: Assi Rita , Kantarjian Hagop M. , Kadia Tapan M. , Pemmaraju Naveen , Jabbour Elias , Jain Nitin , Daver Naval , Estrov Zeev , Uehara Taisuke , Owa Takashi , Cortes Jorge E. , Borthakur Gautam
Published: April 2018

BACKGROUND

Indisulam possesses anticancer properties through down‐regulation of various cell‐cycle checkpoint molecules, thereby blocking the phosphorylation of retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with nucleoside analogs and topoisomerase inhibitors.

METHODS

The authors designed a phase 2 study of indisulam in combination with idarubicin and cytarabine in patients who had relapsed/refractory acute myeloid leukemia AML and high‐risk myelodysplastic syndrome. In stage 1, patients received intravenous indisulam at 400 mg/m2 on days 1 and 8 of a 28‐day cycle. If they had no response, then patients received same dose schedule of indisulam followed by intravenous idarubicin 8 mg/m2 daily for 3 days and cytarabine 1.0 g/m2 over 24 hours daily on days 9 through 12 (for those aged < 60 years) or days 9 through 11 (for those aged > 60 years) of a 28‐day cycle. Primary endpoints included the overall response rate, and secondary objectives included overall survival.

RESULTS

Forty patients were enrolled. Of the 37 evaluable patients, 31 received indisulam with chemotherapy. Of these, 11 (35%) responded for a median duration of 5.3 months. The estimated 1‐year overall survival rate was 51% for responders compared with 8 % for nonresponders (P < .001). The most common grade ≥3 nonhematologic toxicities were electrolyte abnormalities (50%) and febrile neutropenia (28%).

CONCLUSIONS

The combination of indisulam with idarubicin and cytarabine yielded a 35% response rate in heavily pretreated patients with AML. With emerging data identifying the expression of DCAF15 (DDB1 and CUL4‐associated factor 15) as a potential biomarker for activity, the combination of indisulam with idarubicin and cytarabine should be studied in a biomarker‐driven trial or in patients who have splicing factor mutations. Cancer 2018;124:2758‐65. © 2018 American Cancer Society. Cancer 2018;124:2758‐2765. © 2018 American Cancer Society
Symptom and function profiles of men with localized prostate cancer
Authors: Reeve Bryce B. , Tan Xianming , Chen Ronald C. , Usinger Deborah S. , Pinheiro Laura C.
Published: April 2018

BACKGROUND

Men diagnosed with localized prostate cancer seek information on how treatment options may impact their health‐related quality of life (HRQOL). The authors used latent profile analysis (LPA) to group men according to their symptom burden and functional status and to identify patient characteristics associated with each HRQOL profile.

METHODS

Patients completed the Patient‐Reported Outcomes Measurement Information System and the Expanded Prostate Index Composite measures 3 months after treatment initiation. Anxiety, depression, fatigue, sleep disturbance, pain, diarrhea, urinary obstruction, urinary incontinence, erectile function, and sex satisfaction were modeled jointly using LPA, and the analysis was adjusted for covariates to examine associations between patient characteristics and profiles.

RESULTS

One‐third of the 373 men were not non‐Hispanic white (26% were black). Four LPA profiles were identified. Men who experienced the “best HRQOL” were less likely to receive treatment, to be older, and to smoke. Men in the second best profile experienced symptoms similar to men in the best HRQOL group but reported poor sexual and urinary function, because they were more likely to receive therapy. The third profile included men with increased symptom burden and poor functioning who were likely to undergo prostatectomy and to have increased comorbidity. The “worst HRQOL” group experienced the worst symptoms and the poorest functioning, and these men were more likely to be younger, to have more comorbidities, and to smoke.

CONCLUSIONS

LPA revealed that men who receive the same treatment can experience very different HRQOL impact. Understanding the factors most associated with poorer HRQOL allows clinicians to focus their care on individuals most in need of symptom management and support. Cancer 2018;124:2832‐2840. © 2018 American Cancer Society
Melancholia and cancer: The bladder cancer narrative
Authors: Correa Andres F. , Smaldone Marc C.
Published: April 2018

Patients who undergo treatment for muscle‐invasive bladder cancer have a 50% risk of developing a posttreatment psychiatric diagnosis, the most prevalent of which is substance abuse, and such diagnoses are associated with worse cancer‐specific and overall survival. Further research into the application of distress instruments is paramount for the early identification and treatment of at risk patients.

See referenced original article on pages 3127‐35, this issue.
Fundamentals of Acoustic Cytometry
Authors: Ward Michael D. , Kaduchak Gregory
Published: April 2018

Acoustic cytometry uses radiation pressure forces instead of or in addition to hydrodynamic focusing to position cells or particles in a flowing stream for analysis. Commercial implementations to date combine both hydrodynamic and acoustic focusing together to enable high precision analysis of a broad dynamic range of volumetric sample input rates up to an order of magnitude higher than is practical with hydrodynamic focus alone. This capability allows great flexibility in reducing assay time or modifying or eliminating concentration requirements or concentration steps in sample preparation protocols. It also provides a practical method for processing sub‐microliter volumes using sample dilution. In order to take full advantage of this dynamic range, it is necessary to understand the fundamental benefits and limitations of acoustic focusing as applied to flow cytometry. © 2018 by John Wiley & Sons, Inc.
Isolation of Murine Skin Resident and Migratory Dendritic Cells via Enzymatic Digestion
Authors: Kashem Sakeen W. , Kaplan Daniel H.
Published: April 2018

Dendritic cells (DCs) are a highly specialized subset of professional antigen‐presenting cells (APCs) that reside in peripheral and lymphoid tissues. DCs capture antigen in the periphery and migrate to the lymph node where they prime naïve T cells. In addition, DCs have been recently appreciated to have function in innate immunity within tissues. In the skin, heterogeneous populations of DCs reside within the epidermis and the dermis. Analysis of the cutaneous DC subsets is complicated by requirements of distinct enzymatic digestion protocols for isolation of APCs from distinct anatomical compartments of the skin. Here, specific approaches for isolation of DCs from the epidermis, dermis, and the skin‐draining lymph nodes of mice are described. © 2018 by John Wiley & Sons, Inc.
Significance of Pharmacogenomics in Precision Medicine
Authors: Cascorbi Ingolf
Published: April 2018

Precision medicine—a term widely used in modern medicine—emphasizes the goal to overcome still existing limitations of therapeutic interventions by tailoring medical treatments to individual patient characteristics. Pharmacogenetics was one of the first scientific approaches taking molecular biomarkers into consideration of diagnostics and therapeutic decisions. This issue of Clinical Pharmacology & Therapeutics on the significance of pharmacogenomics inprecision medicine discusses the ongoing challenges on different levels. Access and usage of clinical biobanks, gain of specific information of medication from electronic health records, and tools to combine clinical and molecular information in order to develop advanced clinical decision support are subjects of numerous research initiatives. Implementation in clinical routine, however, remains the subject of evaluation of clinical‐ and cost‐effectiveness, so far.
Tuning the Key Properties of Singlet Oxygen‐Responsive Acene‐Doped Conjugated Polymer Nanoparticles
Authors: Frausto Fanny , Thomas Samuel W.
Published: April 2018

This paper describes the effects of nanoparticle composition on energy transfer and ratiometric fluorescent response to singlet oxygen (1O2) of a series of acene‐doped conjugated polymer nanoparticles (CPNs). These CPNs are comprised of the conjugated polymer poly [(9,9‐dioctylfluorenyl‐2,7‐diyl)‐alt‐co‐(1,4‐benzo‐(2,1′,3)‐thiadiazole) (F8BT) as the polymer donor matrix and one of four different 1O2‐sensitive acene acceptor dopants. In the dense chromophore matrix of the CPN, the quantum yield of fluorescence of each acene‐doped CPN matches or exceeds that of the undoped F8BT CPN. Reactivity with 1O2 of the acenes follows the same trend in the solid matrix of CPNs as previously found in dilute solution. The doping levels of acenes in the CP matrix have important implications for both the extent of energy transfer and the subsequent rates of ratiometric response. This study therefore lends important insight into the rational design of luminescent, stimuli‐responsive CPNs and the reactivity of singlet oxygen in heterogeneous material systems.
Hierarchically Structured FeNiOxHy Electrocatalyst Formed by In Situ Transformation of Metal Phosphate for Efficient Oxygen Evolution Reaction
Authors: Wu Xiujuan , Zhao Yimeng , Xing Tongyu , Zhang Peili , Li Fusheng , Lee Husileng , Li Fei , Sun Licheng
Published: April 2018

A simple and low‐cost fabrication method is needed to obtain effective and robust heterogeneous catalysts for the oxygen evolution reaction (OER). In this study, an electrocatalyst FeNiOxHy with a hierarchical structure is synthesized on nickel foam by a simple fabrication method through anion exchange from a metal phosphate to a metal hydroxide. The as‐fabricated FeNiOxHy electrode requires overpotentials of 206 and 234 mV to deliver current densities of 10 and 50 mA cm−2, respectively. The catalytic performance of FeNiOxHy is superior to that of most previously reported FeNi‐based catalysts, including NiFe layered double hydroxide. The catalyst also shows good long‐term durability at a current density of 50 mA cm−2 over 50 h with no activity decay under 1 m KOH. By comparison to the directly electrodeposited FeNi hydroxide in morphology and electrochemical properties, the improved activity of the catalyst could be mainly attributed to an enhancement of its intrinsic activity, which was caused by the anion exchange of phosphate to (oxy)hydroxide. Further studies by cyclic voltammetry indicated a stronger interaction between Ni and Fe from the negative shift of the oxidation peak of Ni2+/Ni3+ in comparison with reported FeNiOxHy, which promoted the generation of active Ni3+ species more easily. This work may provide a new approach to the simple preparation of effective and robust OER catalysts by anion exchange.
Selective Fragmentation of Biorefinery Corncob Lignin into p‐Hydroxycinnamic Esters with a Supported Zinc Molybdate Catalyst
Authors: Wang Shuizhong , Gao Wa , Li Helong , Xiao Ling‐Ping , Sun Run‐Cang , Song Guoyong
Published: April 2018

Lignin is the largest renewable resource of bioaromatics, and the catalytic fragmentation of lignin into phenolic monomers is increasingly recognized as an important starting point for lignin valorization. Herein, we report that ZnMoO4 supported on MCM‐41 can catalyze the fragmentation of biorefinery technical lignin, enzymatic mild acidolysis lignin, and native lignin derived from corncob to yield lignin oily products that contain 15–37.8 wt % phenolic monomers, in which the high selectivities towards methyl coumarate (1) and methyl ferulate (2) were obtained (up to 78 %). The effects of some key parameters such as the influence of the solvent, reaction temperature, time, H2 pressure, and catalyst dosage were examined in view of activity and selectivity. The loss of Zn from the catalyst is discussed as the primary cause of deactivation, and the catalytic activity and selectivity can be well preserved in at least six runs by thermal calcination. The high selectivity to 1 and 2 leads to their easy separation and purification from lignin oily product to provide sustainable monomers for the preparation of functional polyether esters and polyesters.
Quantification of airway fibrosis in asthma by flow cytometry
Authors: Reichard Andrew , Wanner Nicholas , Stuehr Eric , Alemagno Mario , Weiss Kelly , Queisser Kimberly , Erzurum Serpil , Asosingh Kewal
Published: April 2018

Airway fibrosis is a prominent feature of asthma, contributing to the detrimental consequences of the disease. Fibrosis in the airway is the result of collagen deposition in the reticular lamina layer of the subepithelial tissue. Myofibroblasts are the leading cell type involved with this collagen deposition. Established methods of collagen deposition quantification present various issues, most importantly their inability to quantify current collagen biosynthesis occurring in airway myofibroblasts. Here, a novel method to quantify myofibroblast collagen expression in asthmatic lungs is described. Single cell suspensions of lungs harvested from C57BL/6 mice in a standard house dust mite model of asthma were employed to establish a flow cytometric method and compare collagen production in asthmatic and non‐asthmatic lungs. Cells found to be CD45–αSMA+, indicative of myofibroblasts, were gated, and median fluorescence intensity of the anti‐collagen‐I antibody labeling the cells was calculated. Lung myofibroblasts with no, medium, or high levels of collagen‐I expression were distinguished. In asthmatic animals, collagen‐I levels were increased in both medium and high expressers, and the number of myofibroblasts with high collagen‐I content was elevated. Our findings determined that quantification of collagen‐I deposition in myofibroblastic lung cells by flow cytometry is feasible in mouse models of asthma and indicative of increased collagen‐I expression by asthmatic myofibroblasts. © 2018 International Society for Advancement of Cytometry
Achieving maximum bit rate in a cognitive radio network with physical layer network coding
Authors: Khosroazad Somayeh , Abedi Ali , Neda Naaser
Published: April 2018

In this paper, the power allocation problem in a relay‐assisted cognitive radio network (CRN) is considered where the secondary users exchange information in an interweave mode on the basis of physical layer network coding. In order to enhance the capacity of CRN, using multiple‐input multiple‐output and orthogonal frequency division multiplexing has become very popular in the literature. This paper goes one step further to improve the throughput of secondary users using physical layer network coding by drawing off the transmission time. The main goal is to maximize the capacity of CRN, while keeping the total interference imposed on the primary users under a certain threshold. An optimal solution to this power allocation problem with limited relay power constraint, due to the limited budget, is derived; however, because of the high complexity of this method, an efficient suboptimal solution is also proposed.
Web service discovery utilizing logical reasoning and semantic similarity
Authors: Fang Mingzhe , Wang Dandan , Mi Zhenqiang , Obaidat Mohammad S.
Published: April 2018

Web service discovery facilitates the implementation of complex and reconfigurable applications in service‐oriented architecture, such as service selection, composition, and provision. This paper presents an approach for semantic and automated Web service discovery. Our approach to semantic Web service discovery consists of ontology‐based service preprocessor, reasoning‐based service filter, and parameter‐based service matcher. An important feature of this approach is that the relationship among concepts in ontology is quantified and considered as an important factor in the matching process, which results in high precision and recall. Additionally, we propose a filtering method based on logical reasoning to preprocess the large amount of Web services. Through the filtering method, Web services which are feasible in logic are selected to be matched with user requests. So there is a great improvement in the run‐time performance of service discovery approach. Experiments show that our approach is feasible and effective to discover the required Web services.
Label‐QoS switching protocol for quality of service assurance in dynamic swarm robot local network
Authors: Irawan Addie , Mat Jusoh Mohd Falfazli , Abas Mohammad Fadhil
Published: April 2018

This paper presents the modeling and analysis of a proposed label–quality of service (QoS) switching protocol for heterogeneous robot in a swarm. Establishing the data communication and network in multirobot task allocation is an important aspect in robot collaboration. Instead of passing the data through the cloud network, each robot can be configured as a node in its swarm for intercommunication. This research was conducted to model and propose aggregation and classification methods in a swarm robot network inspired from multiprotocol label switching, namely, label‐QoS switching protocol. Each packet of data is forwarded with a proposed 2‐side label values that are concerned with addressing and QoS. This proposed protocol was applied in each of the node's routing, and it was set up with forwarding information table. The simulation and analysis were conducted in 2 situations: (1) with a constant n–label switch mobile robot and a number of packet data increasing with time and (2) with a constant number of packet and varying n–label switch mobile robot by time. With reference to the network parameter performances, it shows that the anomaly treatment by the proposed protocol is able to prioritize the data forwarding between the robots at the edge of the swarm with class of service although the robot community at the center is increasing or getting crowded.
PAPR reduction for OFDM‐based visible light communication systems using proposed hybrid technique
Authors: Freag Haitham , Hassan Emad S. , El‐Dolil Sami A. , Dessouky Moawad I.
Published: April 2018

Orthogonal Frequency Division Multiplexing (OFDM) is utilized with visible light communication (VLC) systems to decrease the impacts of inter‐symbol interference and to achieve communication with high speed of data transmission and huge bandwidth. In any case, the main problem in OFDM‐based VLC systems is high peak‐to‐average power ratios (PAPRs). This paper proposes a hybrid PAPR reduction technique based on signal transformation combined with clipping. The Hadamard transform is used in the proposed technique to reduce the PAPR without affecting the bit error rate (BER) of the VLC systems. The optimum clipping threshold at which the PAPR is reduced simultaneously with the improvement the BER of the VLC systems is also determined. The performance of the proposed system is assessed in terms of complementary cumulative distribution function and the BER. The obtained results demonstrate that the proposed procedure can simultaneously decrease the PAPR and achieve good BER performance compared to the OFDM‐based VLC system.
A meta‐analysis of the relationships between body checking, body image avoidance, body image dissatisfaction, mood, and disordered eating
Authors: Walker D. Catherine , White Emily K. , Srinivasan Vamshek J.
Published: April 2018

Objective

Body checking (BC) and body image avoidance (BIA) have been proposed as etiological and maintaining mechanisms for eating disorder (ED) pathology. To date, no comprehensive review summarizes the relationships of BC and BIA with ED pathology, body image dissatisfaction, or mood/affect.

Method

Meta‐analyses examined the relationships of BC and BIA with ED pathology, body image dissatisfaction, and mood/affect. Gender, publication status, and presence or absence of ED diagnoses were examined as potential moderators.

Results

Results showed strong relationships between BC and ED pathology (ρ = 0.588) and BC and body image dissatisfaction (ρ = 0.631) and a moderate relationship between BC and mood/affect (ρ = 0.385). Similarly, results showed strong relationships between BIA and ED pathology (ρ = 0.553) and BIA and body image dissatisfaction (ρ = 0.543) and a moderate relationship between BIA and mood/affect (ρ = 0.392). Overall, limited evidence supported publication bias; however, publication bias may exist in the relationship between BIA and body image dissatisfaction in the literature. Subgroup moderator analyses suggested that gender moderates the strength of the relationships between BC and ED pathology, body image dissatisfaction, and mood/affect and between BIA and body image dissatisfaction.

Discussion

Results are consistent with cognitive‐behavioral models of ED pathology that suggest BC and BIA are behavioral expressions of overvaluation of weight and shape. Notably, more published research has investigated BC than BIA. Future studies, incorporating methods such as meta‐analytic structural equation modeling, should examine these variables to further test cognitive‐behavioral models of ED development and maintenance.