bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of Housing and Shelter among People with Histories of Unstable Housing in three Cities in Canada: A Qualitative Study
Authors: Sylvestre John , Klodawsky Fran , Gogosis Evie , Ecker John , Polillo Alexia , Czechowski Konrad , Agha Ayda , Shankar Sneha , To Matthew , Gadermann Anne , Palepu Anita , Hwang Stephen
Published: March 2018

Housing is a key social determinant of health that contributes to the well‐documented relationship between socioeconomic status and health. This study explored how individuals with histories of unstable and precarious housing perceive their housing or shelter situations, and the impact of these settings on their health and well‐being. Participants were recruited from the Health and Housing in Transition study (HHiT), a longitudinal, multi‐city study that tracked the health and housing status of people with unstable housing histories over a 5‐year period. For the current study, one‐time semi‐structured interviews were conducted with a subset of HHiT study participants (n = 64), living in three cities across Canada: Ottawa, Toronto, and Vancouver. The findings from an analysis of the interview transcripts suggested that for many individuals changes in housing status are not associated with significant changes in health due to the poor quality and precarious nature of the housing that was obtained. Whether housed or living in shelters, participants continued to face barriers of poverty, social marginalization, inadequate and unaffordable housing, violence, and lack of access to services to meet their personal needs.
Cobalt(II)/N,N′,N′′‐Trihydroxyisocyanuric Acid Catalyzed Aerobic Oxidative Esterification and Amidation of Aldehydes
Authors: Jiang Biao‐Lin , Xu Bao‐Hua , Wang Meng‐Liang , Li Zeng‐Xi , Liu Dian‐Sheng , Zhang Suo‐Jiang
Published: March 2018

A protocol for a CoII/N,N′,N′′‐trihydroxyisocyanuric acid (THICA)‐catalyzed aerobic oxidative esterification and amidation of aldehydes has been developed. Preliminary insight into the mechanism indicates that such an oxidative C−O/N cross‐coupling reaction proceeds by masking the aldehyde in a nucleophilic addition reaction with an alkoxy/amino source, thereby keeping the highly reactive formyl group from undesired oxidation. This protocol for the oxidative esterification and amidation of aldehydes proceeds through two different pathways that are characterized by the intrinsic nucleophilicity of the alkanol and amine substrates The former occurs in the presence of p‐CH3C6H4SO3H as a cocatalyst and orthoformates as the alkoxy sources, instead of alkanols, to efficiently afford the transient acetals. In contrast, the coupling of the more nucleophilic amines with aldehydes renders a readily accessible cross‐coupling reaction that occurs without any cocatalyst but is limited by the potential inhibition of THICA upon nucleophilic substitution by an amine. Consequently, only sterically hindered amines were tolerated in this catalytic system, whereas further condensation occurred in the presence of primary amines to lead to imines.
Site‐Selective δ‐C(sp3)−H Alkylation of Amino Acids and Peptides with Maleimides via a Six‐Membered Palladacycle
Authors: Zhan Bei‐Bei , Li Ya , Xu Jing‐Wen , Nie Xing‐Liang , Fan Jun , Jin Liang , Shi Bing‐Feng
Published: March 2018

The site‐selective functionalization of unactivated C(sp3)−H bonds remains one of the greatest challenges in organic synthesis. Herein, we report on the site‐selective δ‐C(sp3)−H alkylation of amino acids and peptides with maleimides via a kinetically less favored six‐membered palladacycle in the presence of more accessible γ‐C(sp3)−H bonds. Experimental studies revealed that C−H bond cleavage occurs reversibly and preferentially at γ‐methyl over δ‐methyl C−H bonds while the subsequent alkylation proceeds exclusively at the six‐membered palladacycle that is generated by δ‐C−H activation. The selectivity can be explained by the Curtin–Hammett principle. The exceptional compatibility of this alkylation with various oligopeptides renders this procedure valuable for late‐stage peptide modifications. Notably, this process is also the first palladium(II)‐catalyzed Michael‐type alkylation reaction that proceeds through C(sp3)−H activation.
A [RuRu] Analogue of an [FeFe]‐Hydrogenase Traps the Key Hydride Intermediate of the Catalytic Cycle
Authors: Sommer Constanze , Richers Casseday P. , Lubitz Wolfgang , Rauchfuss Thomas B. , Reijerse Edward J.
Published: March 2018

The active site of the [FeFe]‐hydrogenases features a binuclear [2Fe]H sub‐cluster that contains a unique bridging amine moiety close to an exposed iron center. Heterolytic splitting of H2 results in the formation of a transient terminal hydride at this iron site, which, however is difficult to stabilize. We show that the hydride intermediate forms immediately when [2Fe]H is replaced with [2Ru]H analogues through artificial maturation. Outside the protein, the [2Ru]H analogues form bridging hydrides, which rearrange to terminal hydrides after insertion into the apo‐protein. H/D exchange of the hydride only occurs for [2Ru]H analogues containing the bridging amine moiety.
Spectroscopic Identification of H2NSO and syn‐ and anti‐HNSOH Radicals
Authors: Dong Xuelin , Deng Guohai , Wu Zhuang , Xu Jian , Lu Bo , Trabelsi Tarek , Francisco Joseph S. , Zeng Xiaoqing
Published: March 2018

The simplest aminosulfinyl radical H2NSO has been generated in the gas phase through flash vacuum pyrolysis of CF3S(O)NH2 at approximately 1000 K. Upon UV light irradiation (365 nm), 1,3‐H migration occurs in H2NSO and furnishes an elusive N‐amidyl radical HNSOH in syn and anti conformations in cryogenic matrices (N2 or Ar, 15 K). Further 266 nm laser irradiation results in dissociation of HNSOH to H2O and SN and concomitant reformation of H2NSO in trace amount. The identification of H2NSO, syn‐HNSOH, and anti‐HNSOH by matrix‐isolation IR spectroscopy is supported by high‐level quantum chemical computations.
Electrospinning of poly(γ‐benzyl–α,L‐glutamate) microfibers for piezoelectric polymer applications
Authors: Nguyen Duc‐Nam , Yu S. Michael , Moon Wonkyu
Published: March 2018

One of the latest developments in the field of piezoelectric polymers is the use of poly(γ‐benzyl‐α,L‐glutamate) (PBLG), a poly(amino acid) that can be poled along its α‐helical axis and fabricated into thermally stable piezoelectric microfibers via electrospinning. This study demonstrates a method for improving the piezoelectricity of electrospun PBLG microfibers by controlling the orientation of fibers using a method based on a concentrated electric field. The piezoelectricity is verified via customized quasi‐static and dynamic measurement methods, while the correlation between fiber alignment and the piezoelectric constant, d33, in the longitudinal mode of the electrospun PBLG fibers is investigated. When the level of alignment was varied from 50% to 90%, the piezoelectric constant increased linearly, showing a maximum d33 of 27 pC N−1 and a maximum force sensitivity of 65 mV N−1 at peak alignment. A fabricated flexible prototype based on electrospun PBLG fibers provides a new solution for the use of PBLG fibers in wearable energy harvesters or composites based on piezoelectric polymer fibers. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46440.
One‐step facile process to obtain insoluble polysaccharides fibrous mats from electrospinning of water‐soluble PMDA/cyclodextrin polymer
Authors: Cecone Claudio , Caldera Fabrizio , Anceschi Anastasia , Scalarone Dominique , Trotta Francesco , Bracco Pierangiola , Zanetti Marco
Published: March 2018

Herein, we used an electrospinning process to develop nanofibers based on poly‐cyclodextrin. This article describes a simple and effective method to produce fibers of a water‐soluble hyperbranched polymer based on β‐CD and pyromellitic dianhydride via electrospinning. The obtained fibers were made insoluble in water with a simple thermal crosslinking without the use of further reactive or solvent. After 24 h of dipping in distilled water or phosphate buffer solution morphology and size of fibers remain unaltered as observed in scanning electron microscopy. The crosslinking mechanism was studied with thermogravimetric analysis, attenuated total reflectance–Fourier infrared spectroscopy, and elemental analysis and a reaction mechanism is proposed. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46490.
Assessing the impact of the Graduate Certificate in Anatomical Sciences Instruction: A post‐degree survey
Authors: Richardson‐Hatcher April , MacPherson Brian , Gould Douglas , Brueckner‐Collins Jennifer
Published: March 2018

There are few graduate programs available for pursuing a doctorate in anatomy where students gain specific training in gross anatomy dissection and the responsibilities of a medical educator. In light of this fact, the University of Kentucky created a Graduate Certificate in Anatomical Sciences Instruction in 2006. This 12‐credit hour curriculum includes detailed training in gross anatomy and/or neuroscience courses, practicum experiences, a seminar class in pedagogical literature, and a course in educational strategies for the anatomical sciences. The award of certificate completion affirms that the candidate has demonstrated faculty‐supervised proficiency in anatomy dissection, instruction in anatomy topics, and teaching strategies for anatomy. Seventeen graduate students have earned the certificate since its inception; nine students accepted teaching positions in anatomy following their graduate training and currently nine certificate graduates have assistant (six) or associate (three) professor positions in academia. In 2016, an anonymous survey including Likert‐style and open‐ended questions was emailed to all certificate graduates. Graduates favorably responded (each question averaged 4.4 or greater out of 5) that the certificate increased their awareness of teaching‐faculty responsibilities, adequately prepared them for teaching‐related duties, and positively contributed toward their first employment. Graduates indicated that the lecturing and dissection experience, awareness of faculty responsibilities, and job preparation (e.g., teaching philosophy development) were the most helpful aspects of the certificate. These results indicate that the Graduate Certificate in Anatomical Sciences Instruction is viewed by its graduates and their employers as a valuable teaching credential that can be attained alongside a basic science degree. Anat Sci Educ 11: 516–524. © 2018 American Association of Anatomists.
Multi‐Invasion‐Induced Rearrangements as a Pathway for Physiological and Pathological Recombination
Authors: Piazza Aurèle , Heyer Wolf‐Dietrich
Published: March 2018

Cells mitigate the detrimental consequences of DNA damage on genome stability by attempting high fidelity repair. Homologous recombination templates DNA double‐strand break (DSB) repair on an identical or near identical donor sequence in a process that can in principle access the entire genome. Other physiological processes, such as homolog recognition and pairing during meiosis, also harness the HR machinery using programmed DSBs to physically link homologs and generate crossovers. A consequence of the homology search process by a long nucleoprotein filament is the formation of multi‐invasions (MI), a joint molecule in which the damaged ssDNA has invaded more than one donor molecule. Processing of MI joint molecules can compromise the integrity of both donor sites and lead to their rearrangement. Here, two mechanisms for the generation of rearrangements as a pathological consequence of MI processing are detailed and the potential relevance for non‐allelic homologous recombination discussed. Finally, it is proposed that MI‐induced crossover formation may be a feature of physiological recombination.
Optimal model‐based control of non‐viral siRNA delivery
Authors: Jamili Elnaz , Dua Vivek
Published: March 2018

Further quantitative understanding of the biological effects and mechanisms involved in cellular and intracellular delivery of nucleic acid materials is required to produce clinical applications of gene therapy. Several modeling approaches have been used in this field; however, a comprehensive approach that integrates all the key pharmacological issues into a holistic framework that is applicable for in vivo conditions is still lacking. This contribution presents a pharmacokinetic/pharmacodynamic model‐based control study of non‐viral siRNA delivery describing the dynamics of the delivery process and takes into account the main multi‐objective optimization issues such as efficacy and toxicity, as well as the effect of uncertainty in cell doubling time. The methodology developed in this work is used to predict the optimal dosage injection rate and optimal intracellular exposure of siRNAs in order to improve the pharmacological effects before cell division occurs. The present analysis successfully provides quantitative predictions of non‐viral siRNA activity paving the path for further experimental work to probe more efficient delivery systems.
Multicentre study of laparoscopic or open assessment of the peritoneal cancer index (BIG-RENAPE)
Authors: Passot G , Dumont F , Goéré D , Arvieux C , Rousset P , Regimbeau J-M , Elias D , Villeneuve L , Glehen O , Abba J , Abboud K , Carere S , Durand-Fontanier S , Eveno C , Facy O , Gelli M , Gilly F-N , Karoui M , Lo Dico R , Ortega-Deballon P , Pocard M , Quenet F , Rat P , Sabbagh C , Sgarbura O , Thibaudeau E , Vaudoyer D , Wernert R
Published: March 2018

Background

The peritoneal cancer index (PCI) is a comparative prognostic factor for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to determine the PCI in consideration of cytoreductive surgery remains undetermined, and this study was designed to compare it with laparotomy.

Methods

A prospective multicentre study was conducted for patients with no known CRPM, but at risk of peritoneal disease. Surgery began with laparoscopic exploration followed by open exploration to determine the PCI. Concordance between laparoscopic and open assessment was evaluated for the diagnosis of CRPM and for the PCI.

Results

Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34 (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52 per cent (26 of 50). Among the 25 evaluable patients with satisfactory laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI respectively. Where there were discrepancies, it was laparoscopy that underestimated the PCI.

Conclusion

Laparoscopy may underestimate the extent of CRPM.
Initial experience with purely laparoscopic living-donor right hepatectomy
Authors: Hong S K , Lee K W , Choi Y , Kim H S , Ahn S W , Yoon K C , Kim H , Yi N J , Suh K S
Published: March 2018

Background

There may be concerns about purely laparoscopic donor right hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when performed by surgeons accustomed to open surgery. This study aimed to describe technical tips and pitfalls in PLDRH.

Methods

Data from donors who underwent PLDRH at Seoul National University Hospital between December 2015 and July 2017 were analysed retrospectively. Endpoints analysed included intraoperative events and postoperative complications. All operations were performed by a single surgeon with considerable experience in open living donor hepatectomy.

Results

A total of 26 donors underwent purely laparoscopic right hepatectomy in the study interval. No donor required transfusion during surgery, whereas two underwent reoperation. In two donors, the dissection plane at the right upper deep portion of the midplane was not correct. One donor experienced portal vein injury during caudate lobe transection, and one developed remnant left hepatic duct stenosis. One donor experienced remnant portal vein angulation owing to a different approach angle, and one experienced arterial damage associated with the use of a laparoscopic energy device. One donor had postoperative bleeding due to masking of potential bleeding foci owing to intra-abdominal pressure during laparoscopy. Two donors experienced right liver surface damage caused by a xiphoid trocar.

Conclusion

Purely laparoscopic donor hepatectomy differs from open donor hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in open donor hepatectomy must gain adequate experience in laparoscopic liver surgery and make adjustments when performing PLDRH.
Biomarkers in colorectal liver metastases
Authors: Yamashita S , Chun Y S , Kopetz S E , Vauthey J-N
Published: March 2018

Background

Despite a 5-year overall survival rate of 58 per cent after liver resection for colorectal liver metastases (CLMs), more than half of patients develop recurrence, highlighting the need for accurate risk stratification and prognostication. Traditional prognostic factors have been superseded by newer outcome predictors, including those defined by the molecular origin of the primary tumour.

Methods

This review synthesized findings in the literature using the PubMed database of articles in the English language published between 1998 and 2017 on prognostic and predictive biomarkers in patients undergoing resection of CLMs.

Results

Responses to preoperative chemotherapy define prognosis in patients undergoing CLM resection. There are differences by embryological origin too. Somatic mutations in the proto-oncogenes KRAS and NRAS are associated with positive surgical margins and tumour regrowth after ablation. Other mutations (such as BRAF) and co-occurring mutations in RAS/TP53 and APC/PIK3CA have emerged as important biomarkers that determine an individual patient's tumour biology and may be used to predict outcome after CLM resection.

Conclusion

Knowledge of somatic mutations can guide the use of preoperative therapy, extent of surgical margin and selection for ablation alone.
One‐Pot Hydrothermal Synthesis of Highly Fluorescent Polyethyleneimine‐capped Copper Nanoclusters for Specific Detection of Rifampicin
Authors: Tan Nai‐Di , Yin Jian‐Hang , Yuan Yaqing , Meng Lei , Xu Na
Published: March 2018

Herein, a novel bright‐green and highly fluorescent polyethyleneimine capped copper nanoclusters (CuNCs@PEI) has been hydrothermally synthesized, which is employed as a fluorescence probe to determine rifampicin. Under optimum synthetic conditions, the morphology, surface chemistry and optical features of resulting CuNCs@PEI are well characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, UV–Vis absorption spectra, transient and steady‐state fluorescence. In comparison to previous reports, the new species with a larger diameter of approximately 3 nm exhibit higher fluorescence quantum yield (QY) up to nearly 10.7%, and demonstrate tolerability to extreme pH, high ionic strengths as well as long‐term UV irradiation. These excellent optical properties ascribe to unique grain size and surface chemical features of products, which are further discussed in this work. In addition, we employed as‐prepared CuNCs@PEI to detect rifampicin based on fluorescence quenching phenomenon. The fluorescence intensity of probe is linearly proportional to rifampicin over the concentration rage from 0 to 20 μM, where the limit of detection (LOD) is 50 nM. Besides, this probe can be also used to assay rifampicin in serum samples with satisfactory recoveries.
Exploring the impact of chronic high‐altitude exposure on visual spatial attention using the ERP approach
Authors: Zhang Delong , Ma Hailin , Huang Jiaqun , Zhang Xinjuan , Ma Huifang , Liu Ming
Published: March 2018

Introduction

Previous studies have reported the slowing of reaction times to attentionally demanding tasks due to a reduction in cognitive resource as a result of chronic high‐altitude exposure. However, it is still largely unknown whether this reaction slowness can be attributed to the attentional allocation change and/or response patterns.

Methods

To clarify this issue, this study investigated attention‐related (N2pc and N2 cc) and response‐related (MP and RAP) event‐related potentials (ERPs) to identify the performance of a visual search task by individuals who had lived in high‐altitude areas for three years compared with those living at sea level.

Results

This study showed that the reaction times in response to a visual search task were significantly longer in the high‐altitude subjects than in the sea level subjects. Corresponding to this behavioral observation, we found a significantly lower N2pc amplitude and a larger N2 cc amplitude in the high‐altitude subjects, suggesting a reduction in spatial attention allocation to the target (N2pc) in these subjects, indicating they need to work harder to preclude cross‐talk between response selection and attention direction (N2 cc). Moreover, we also discovered higher MP amplitudes and longer RAP latencies in the high‐altitude subjects, which further indicated that these subjects were slower and required greater cortical activation while preparing and executing correctly selected responses (MP and RAP).

Conclusion

Nevertheless, this study collectively provided new insights into the attention reaction slowness from high‐altitude exposure.
A novel rapid quantitative method reveals stathmin‐1 as a promising marker for esophageal squamous cell carcinoma
Authors: Yan Lu , Dong Xiu , Gao Jiajia , Liu Fang , Zhou Lanping , Sun Yulin , Zhao Xiaohang
Published: March 2018

Stathmin‐1 is a microtubule depolymerization protein that regulates cell division, growth, migration, and invasion. Overexpression of stathmin‐1 has been observed to be associated with metastasis, poor prognosis, and chemoresistance in various human cancers. Our previous studies found that serum stathmin‐1 was significantly elevated in patients with esophageal squamous cell carcinoma (ESCC) by ELISAs. Here, we constructed high‐affinity monoclonal antibodies and then developed a competitive AlphaLISA for rapid, accurate quantitation of stathmin‐1 in serum. Compared to ELISA, our homogeneous AlphaLISA showed better sensitivity and accuracy, a lower limit of detection, and a wider linear range. The measurements of nearly 1000 clinical samples showed that serum stathmin‐1 level increased dramatically in patients with squamous cell carcinoma (SCC), especially in ESCC, with a sensitivity and a specificity of 81% and 94%, respectively. Even for early stage ESCC, stathmin‐1 achieved an area under the receiver operating characteristic curve (AUC) of 0.88. Meanwhile, raised concentrations of stathmin‐1 were associated with lymph node metastasis and advanced cancer stage. Notably, various types of SCC showed significantly higher AUCs in serum stathmin‐1 detection compared to adenocarcinoma. Furthermore, we confirmed that stathmin‐1 was enriched in the oncogenic exosomes, which can explain the reason why it enters into the blood to serve as a tumor surrogate. In conclusion, this large‐scale and systematic study of serum stathmin‐1 measured by our newly established AlphaLISA showed that stathmin‐1 is a very promising diagnostic and predictive marker for SCC in the clinic, especially for ESCC.
Association of family history and survival in patients with colorectal cancer: a pooled analysis of eight epidemiologic studies
Authors: Chong Dawn Q. , Banbury Barbara L. , Phipps Amanda I. , Hua Xinwei , Kocarnik Jonathan , Peters Ulrike , Berndt Sonja I. , Huang Wen‐Yi , Potter John D. , Slattery Martha L. , White Emily , Campbell Peter T. , Harrison Tabitha , Newcomb Polly A. , Chan Andrew T.
Published: March 2018

A family history of colorectal cancer (CRC) in first‐degree relatives (FDRs) increases the risk of CRC. However, the influence of family history on survival among CRC patients remains unclear. We conducted a pooled analysis of survival in 5010 incident CRC cases. Cox proportional hazards models were used to estimate the association of family history with overall survival (OS) and CRC‐specific survival (CSS). We also assessed the impact of the number of affected FDRs and age at CRC diagnosis in the affected FDRs on survival. Among CRC cases, 819 (16%) patients reported a family history of CRC. There were 1580 total deaths over a median follow‐up of 4.6 years, of which 1046 (66%) deaths were due to CRC. Having a family history of CRC was not associated with OS [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.89–1.19] or CSS (HR, 1.13; 95% CI, 0.95–1.36)]. There were no associations between the number of affected relatives or age at CRC diagnosis of the affected relative with survival (all Ptrend > 0.05). However, a family history of CRC did confer worse CSS in patients diagnosed with distal colon cancer (HR, 1.45, 95% CI, 1.03–2.04). A family history of CRC was generally not associated with survival after CRC diagnosis. However, having a family history of CRC was associated with worse CRC prognosis in individuals with distal colon cancer, suggesting a possible genetic predisposition with distinct pathogenic mechanism that may lead to worse survival in this group.
Conducting community‐based participatory research in an urban Malaysian community: Lessons learned and challenges in establishing partnerships
Authors: Teoh Gaik Kin , Tan Maw Pin , Tan Joo Siang , Chong Mei Chan
Published: March 2018

This paper presents the process of how partnerships are established between an urban residential community and an academic institution in Malaysia by employing community‐based participatory research, which involves researchers, community members, and organizational representatives as coresearchers. The research process encompasses colearning, power sharing, and coconstructing of knowledge, with the community members driving the research direction. The research paradigm is grounded on conducting research with the community. This paper highlights the experience and lessons learned while applying the principles of community‐based participatory research that promotes social participation of older persons living in a residential community. Two pertinent challenges surface in the research process. The first challenge involves the complexity noted in the gap between the emancipation of community‐based participatory research and the hierarchical social structure of the society. The second challenge is the prevalence of unspoken yet subtle domination that undermines the local cultural values affecting the process of coconstructing knowledge with the community. Recommendations for addressing these challenges include future partnerships with other Malaysian communities as well as cross‐border research partnerships.
A Forkhead Box Protein C2 Inhibitor: Targeting Epithelial–Mesenchymal Transition and Cancer Metastasis
Authors: Castaneda Maria , Chen Luxi , Pradhan Lagnajeet , Li Shichang , Zein Ruba , Lee Yeongju , Lim Hyun‐Suk , Nam Hyun‐Joo , Lee Jiyong
Published: March 2018

The epithelial–mesenchymal transition (EMT) has been suggested as a new target for therapeutic intervention of metastatic cancer. Forkhead box protein C2 (FOXC2) is known to be necessary for initiating and maintaining EMT, and therefore bestows on cancer cells metastatic and cancer stem cell (CSC)‐like phenotypes, allowing cells to acquire higher motility, invasiveness, self‐renewal, and therapy resistance. Here, we describe the first inhibitor of FOXC2, MC‐1‐F2. MC‐1‐F2 was able to induce cadherin switching and reverse EMT through the degradation of FOXC2 and blocking of its nuclear localization. In addition, MC‐1‐F2 was very effective in inhibiting cancer cell migration and invasion. As the first small‐molecule inhibitor of FOXC2 and the first compound targeting EMT‐associated transcription factor, MC‐1‐F2 will pave the way for a new anticancer therapeutic agent targeting metastatic cancer and help to elucidate the network of EMT signaling pathways.
Robust Organocatalysts for the Cleavage of Vegetable Oil Derivatives to Aldehydes through Retrobenzoin Condensation
Authors: Vu Nam Duc , Bah Souleymane , Deruer Elsa , Duguet Nicolas , Lemaire Marc
Published: March 2018

A series of thiazolium salts was prepared and tested for the cleavage of the α‐hydroxyketone derived from methyl oleate. The robustness of these precatalysts was determined by dynamic thermogravimetric analyses (TGA). It has been shown that the stability of these species is mainly governed by the nature of the counter‐anion and some of them were found to be stable until 350–400 °C. The α‐hydroxyketone derived from methyl oleate was cleaved under reactive distillation conditions using optimized, thermally robust N‐butylthiazolium triflate to give the cleavage product, namely, nonanal and methyl azelaaldehydate, with 85 and 70 % yields. A range of α‐hydroxyketones derived from several fatty acids was cleaved to give the corresponding bio‐based aldehydes with up to 98 % isolated yields. Finally, this protocol was successfully applied to a high‐oleic sunflower oil derivative.
Heterogeneous catalytic ozonation of naphthenic acids in water
Authors: Al jibouri Ali Kamel H. , Wu Jiangning , Upreti Simant Ranjan
Published: March 2018

A major challenge the oil sands industries are facing is the urgent need to treat large amounts of oil sands process‐affected water (OSPW). OSPW is toxic to many species mainly due to the presence of naphthenic acids (NAs). Ozonation can significantly reduce both concentration and toxicity of the NAs. Unfortunately, this method suffers from its relatively high cost. To enhance NAs removal, we initiated heterogeneous catalytic ozonation of synthetic OSPW. Two types of catalysts were investigated: i) alumina supported metal oxides, and ii) unsupported catalysts. The alumina supported oxides included MnO2, MnO2/Co3O4, and MnO2/Li2O, while the unsupported catalysts were alumina and activated carbon (AC). All tested catalysts enhanced the ozone removal of NAs. Specifically, AC was found to be a very effective catalyst in addition to its adsorbability. AC significantly enhanced the removal of NAs and COD, the detoxification of the OSPW, and the biodegradability of NAs. For 85 % removal of NAs, the AC catalyzed ozonation needed 15 min whereas over 45 min were required by its non‐catalyzed counterpart. By using AC catalyzed ozonation, the efficiencies of detoxification and COD removal were both over four times and the biodegradability of the synthetic OSPW was over five times of those treated by non‐catalyzed ozonation. The mechanism study confirmed that due to the presence of AC the hydroxyl radical concentration increased 31 %, resulting in 26.4 % reduction in ozone consumption compared to non‐catalyzed ozonation. The removal of NAs was enhanced because of the higher oxidation power of hydroxyl radicals than molecular ozone.
Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy
Authors: Greenwell I. Brian , Staton Ashley D. , Lee Michael J. , Switchenko Jeffrey M. , Saxe Debra F. , Maly Joseph J. , Blum Kristie A. , Grover Natalie S. , Mathews Stephanie P. , Gordon Max J. , Danilov Alexey V. , Epperla Narendranath , Fenske Timothy S. , Hamadani Mehdi , Park Steven I. , Flowers Christopher R. , Cohen Jonathon B.
Published: March 2018

BACKGROUND

Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki‐67 proliferative index. Single‐center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy.

METHODS

The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL.

RESULTS

A CK was found to be associated with inferior overall survival (OS) (4.5 vs 11.6 years; P<.01) and progression‐free survival (PFS) (1.9 vs 4.4 years; P<.01). In patients who underwent high‐intensity induction followed by autologous stem cell transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1 vs 11.6 years; P = .04) and PFS (3.6 vs 7.8 years; P<.01). Among patients with a CK, high‐intensity induction had no effect on OS (4.5 vs 3.8 years; P = .77) nor PFS (2.3 vs 1.5 years; P = .46). Similarly, ASCT in first remission did not improve PFS (3.5 vs 1.2 years; P = .12) nor OS (5.1 vs 4.0 years; P = .27). On multivariable analyses with Ki‐67 and MIPI, only CK was found to be predictive of OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12‐3.49 [P = .02]), whereas both CK (HR, 1.91; 95% CI, 1.17‐3.12 [P = .01]) and Ki‐67 >30% (HR, 1.86; 95% CI, 1.06‐3.28 [P = .03]) were associated with inferior PFS. Multivariable analysis did not identify any specific cytogenetic abnormalities associated with inferior survival.

CONCLUSIONS

CK appears to be independently associated with inferior outcomes in patients with MCL regardless of the intensity of induction therapy and receipt of ASCT. Cytogenetics should be incorporated into the workup of a new diagnosis of MCL and novel therapeutic approaches should be investigated for patients with CK. Cancer 2018;124:2306‐15. © 2018 American Cancer Society.
Mature results of a prospective study of deintensified chemoradiotherapy for low‐risk human papillomavirus‐associated oropharyngeal squamous cell carcinoma
Authors: Chera Bhishamjit S. , Amdur Robert J. , Tepper Joel E. , Tan Xianming , Weiss Jared , Grilley‐Olson Juneko E. , Hayes D. Neil , Zanation Adam , Hackman Trevor G. , Patel Samip , Sheets Nathan , Weissler Mark C. , Mendenhall William M.
Published: March 2018

BACKGROUND

The purpose of the current study was to determine quality of life and tumor control from a prospective phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk, human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma.

METHODS

Patients with T0‐T3, N0‐N2c, M0, p16‐positive disease and a minimal smoking history were treated with 60 grays of intensity‐modulated radiotherapy with concurrent weekly intravenous cisplatin (30 mg/m2). The primary study endpoint was the pathologic complete response rate based on biopsy of the primary site and dissection of pretreatment positive lymph node regions. The pathologic complete response rate as previously reported was 86%. Herein, the authors report secondary endpoint measures of local control, regional control, cause‐specific survival, distant metastasis‐free survival, and overall survival, and patient‐reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ‐C30] and the Patient‐Reported Outcomes version of Common Terminology Criteria for Adverse Events [PRO‐CTCAE]).

RESULTS

A total of 44 patients enrolled with a median follow‐up of 36 months (88% with ≥2 years). The 3‐year local control, regional control, cause‐specific survival, distant metastasis‐free survival, and overall survival rates were 100%, 100%, 100%, 100%, and 95%, respectively. The mean before and 3‐year after EORTC QOL scores were: global: 80 of 78; swallowing: 11 of 11; dry mouth: 16 of 41; and sticky saliva: 6 of 29. The mean before and 3‐year after PRO‐CTCAE scores were: swallowing: 0.4 of 0.7; and dry mouth: 0.4 of 1.4. Approximately 39% of patients required a feeding tube (median duration, 15 weeks; none were permanent). There were no ≥grade 3 late adverse events reported.

CONCLUSIONS

For patients with favorable‐risk human papillomavirus‐associated oropharyngeal squamous cell carcinoma, a substantially decreased intensity of therapy with 60 grays of intensity‐modulated radiotherapy and weekly low‐dose cisplatin produced better preservation of quality of life compared with standard therapies while maintaining excellent 3‐year tumor control and survival. Cancer 2018;124:2347‐54. © 2018 American Cancer Society.
Cancer survival among Alaska Native people
Authors: Nash Sarah H. , Meisner Angela L. W. , Zimpelman Garrett L. , Barry Marc , Wiggins Charles L.
Published: March 2018

BACKGROUND

Recent cancer survival trends among American Indian and Alaska Native (AN) people are not well understood; survival has not been reported among AN people since 2001.

METHODS

This study examined cause‐specific survival among AN cancer patients for lung, colorectal, female breast, prostate, and kidney cancers. It evaluated whether survival differed between cancers diagnosed in 1992‐2002 (the earlier period) and cancers diagnosed in 2003‐2013 (the later period) and by the age at diagnosis (<65 vs ≥65 years), stage at diagnosis (local or regional/distant/unknown), and sex. Kaplan‐Meier and Cox proportional hazards models were used to estimate univariate and multivariate‐adjusted cause‐specific survival for each cancer.

RESULTS

An improvement was observed in 5‐year survival over time from lung cancer (hazard ratio [HR] for the later period vs the earlier period, 0.83; 95% confidence interval [CI], 0.72‐0.97), and a marginally nonsignificant improvement was observed for colorectal cancer (HR, 0.81; 95% CI, 0.66‐1.01). Site‐specific differences in survival were observed by age and stage at diagnosis.

CONCLUSIONS

This study presents the first data on cancer survival among AN people in almost 2 decades. During this time, AN people have experienced improvements in survival from lung and colorectal cancers. The reasons for these improvements may include increased access to care (including screening) as well as improvements in treatment. Improving cancer survival should be a priority for reducing the burden of cancer among AN people and eliminating cancer disparities.Cancer2018;124:2570‐7. ©2018 American Cancer Society.
Variation in sleep and metabolic function is associated with latitude and average temperature in Drosophila melanogaster
Authors: Brown Elizabeth B. , Torres Joshua , Bennick Ryan A. , Rozzo Valerie , Kerbs Arianna , DiAngelo Justin R. , Keene Alex C.
Published: March 2018

Regulation of sleep and metabolic homeostasis is critical to an animal's survival and under stringent evolutionary pressure. Animals display remarkable diversity in sleep and metabolic phenotypes; however, an understanding of the ecological forces that select for, and maintain, these phenotypic differences remains poorly understood. The fruit fly, Drosophila melanogaster, is a powerful model for investigating the genetic regulation of sleep and metabolic function, and screening in inbred fly lines has led to the identification of novel genetic regulators of sleep. Nevertheless, little is known about the contributions of naturally occurring genetic differences to sleep, metabolic phenotypes, and their relationship with geographic or environmental gradients. Here, we quantified sleep and metabolic phenotypes in 24 D. melanogaster populations collected from diverse geographic localities. These studies reveal remarkable variation in sleep, starvation resistance, and energy stores. We found that increased sleep duration is associated with proximity to the equator and elevated average annual temperature, suggesting that environmental gradients strongly influence natural variation in sleep. Further, we found variation in metabolic regulation of sleep to be associated with free glucose levels, while starvation resistance associates with glycogen and triglyceride stores. Taken together, these findings reveal robust naturally occurring variation in sleep and metabolic traits in D. melanogaster, providing a model to investigate how evolutionary and ecological history modulate these complex traits.
Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry
Authors: Savarese Gianluigi , Carrero Juan‐Jesus , Pitt Bertram , Anker Stefan D. , Rosano Giuseppe M.C. , Dahlström Ulf , Lund Lars H.
Published: March 2018

Aim

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF), but are underutilized. Hyperkalaemia may be one reason, but the underlying reasons for underuse are unknown. The aim of this study was to investigate the independent predictors of MRA underuse in a large and unselected HFrEF cohort.

Methods and results

We included patients with HFrEF (ejection fraction <40%), New York Heart Association (NYHA) class II–IV and heart failure (HF) duration ≥6 months from the Swedish HF Registry. Logistic regression analysis identified independent associations between 39 demographic, clinical, co‐treatment, and socioeconomic predictors and MRA non‐use. Of 11 215 patients, 27% were women; mean age was 75 ± 11 years; only 4443 (40%) patients received MRA. Selected characteristics independently associated with MRA non‐use were in descending order of magnitude: lower creatinine clearance (<60 mL/min), no need for diuretics, no cardiac resynchronization therapy/implantable cardioverter‐defibrillator, higher blood pressure, no digoxin use, higher ejection fraction, outpatient setting, older age, lower income, ischaemic heart disease, male sex, follow‐up in primary vs. specialty care, lower NYHA class, and absence of hypertension diagnosis. Plasma potassium and N‐terminal pro B‐type natriuretic peptide levels were not associated with MRA non‐use.

Conclusion

Mineralocorticoid receptor antagonists remain underused in HFrEF. Their use does not decrease with elevated potassium but does with impaired renal function, even in the creatinine clearance 30–59.9 mL/min range where MRAs are not contraindicated. MRA underuse may be further related to non‐specialist care, milder HF and no use of other HF therapy.
Theoretical Insights into the Unique Ligation of [Fe4S4] Iron–Sulfur Clusters
Authors: Kubas Adam , Maszota Paweł
Published: March 2018

[Fe4S4] iron–sulfur clusters are typically anchored to the protein scaffold via four cysteine residues, but in a number of proteins one of the Cys is replaced with another ligand. The biological role of such a replacement is unknown although essential to maintain catalytic activity. Here, we explore the geometries and electronic structures of 3:1 site differentiated model compounds [Fe4S4][S(CH3)]3(L) using quantum chemical methods. The unique ligands L were chosen to represent biologically relevant molecules: methanethiol (represents cysteine), acetic acid (asparagine), 4‐methylimidazole (histidine), and water/hydroxyl anion. Each ligand was considered as deprotonated anion or protonated neutral molecule. We found the replacements do not influence structure of the cluster significantly. On the contrary, the impact on the reduction potentials is visible and may reach up to 0.2 V depending on the charge of the ligand. We also studied previously unconsidered asymmetry in excess charge distribution in a reduced [Fe4S4]+ cubane caused by a unique ligation. Our findings show that protonation/deprotonation reactions may provide gating mechanisms in the electron flow carried by iron–sulfur clusters. Additionally, we calculated X‐ray absorption (XAS) and emission (XES) spectra of all compounds under investigation. Particularly, theoretical XES show clear features characteristic to each unique ligand. However, their intensity may be too small to be observed experimentally.
Supplementing Grazing Dairy Ewes with Plant‐Derived Oil and Rumen‐Protected EPA+DHA Pellets Enhances Health‐Beneficial n−3 Long‐Chain Polyunsaturated Fatty Acids in Sheep Milk
Authors: Nguyen Quang V. , Le Van H. , Nguyen Don V. , Malau‐Aduli Bunmi S. , Nichols Peter D. , Malau‐Aduli Aduli E. O.
Published: March 2018

This study investigates the impact of supplementing dairy ewes in mid lactation with rumen‐protected (RPO) pellets containing eicosapentaenoic acid (EPA, 20:5n−3) and docosahexaenoic acid (DHA, 22:6n−3) or pellets infused with 50 mL kg−1 DM of either canola (CO), rice bran (RBO), flaxseed (FSO), or safflower (SFO) oils on enhancing the concentration of n−3 long‐chain (≥C20) polyunsaturated fatty acids (n−3 LC‐PUFA) in milk. It is hypothesized that including these oils in the diet of grazing dairy ewes will improve milk fatty acid (FA) composition by increasing levels of n−3 LC‐PUFA. Sixty grazing dairy ewes balanced by sire breed and parity are randomly allocated to one of 6 treatments: 1) Control: commercial pellets without oil inclusion; 2) pellets containing 50 mL kg−1 DM of CO; 3) RBO; 4) FSO; 5) SFO; and 6) RPO at the rate of 1 kg day−1 for each ewe for 8 weeks. Weekly bulked daily milk FA analysis shows RPO has the most efficiency at elevating n−3 LC‐PUFA content by twofold, threefold, and fivefold greater concentrations of EPA, DPA, and DHA, respectively, than the control (0.17 vs 0.08%, 0.23 vs 0.08%, 0.19 vs 0.04%) (P < 0.0001). FSO improves levels of EPA (0.11%) and DPA (0.15%), while CO increases DPA (0.13%) (P < 0.0001). FSO and RPO reached the “source” and good “source” of n−3 LC‐PUFA (ΣEPA + DHA + DPA) contents of 35.1 and 61.7 mg 250 mL−1, respectively. These findings recommend that rumen protected pellets containing EPA + DHA, flaxseed, and potentially canola oil supplements, can be used to improve the content of n−3 LC‐PUFA in dairy ewe milk.

Practical Applications: The results promote the potential for production of premium quality and health‐beneficial fresh milk through dietary supplementation of grazing dairy ewes with plant‐derived oil and rumen‐protected EPA + DHA.

Interactions between supplemented diets and week of supplementation on the concentrations of LA (a), ALA (b), EPA (c), DHA (d), and DPA (e) in milk.
Chiral Bisdiphenylphosphine Dioxides Bearing a Bis(triazolyl) Backbone as Promising Lewis Bases for Asymmetric Organocatalysis
Authors: Sevrain Nicolas , Volle Jean‐Noel , Pirat Jean‐Luc , Ayad Tahar , Virieux David
Published: March 2018

Two chiral C2‐symmetric diphenylphosphine dioxides bearing an original bis(triazolyl) backbone were prepared starting from inexpensive and readily available precursors. The key step involves the simultaneous formation of five bonds in one chemical step with 100 % atom efficiency through a copper‐catalyzed tandem [3+2] cycloaddition/dimerization reaction. Interestingly, these chiral inducers exhibited good to excellent catalytic activities as chiral Lewis base organocatalysts to promote useful stereoselective reactions.
Three‐dimensional microfluidic chip with twin‐layer herringbone structure for high efficient tumor cell capture and release via antibody‐conjugated magnetic microbeads
Authors: Zhang Lei , Xu Zhigang , Kang Yuejun , Xue Peng
Published: March 2018

Harvesting rare circulating tumor cells (CTCs) from human blood is distinctly substantial to monitor tumor stage and evaluate therapeutic efficacy. As a proof‐of‐concept study, a microfluidic chip with twin‐layer herringbone grooves was developed to isolate and recover tumor cells with high efficiency based on the immunoreaction between cells and antibody‐conjugated microbeads (MBs) under local magnetic field. Functional MBs were initially localized onto the internal channel wall through the magnetic guidance. Then, infused tumor cells were deviated into the herringbone groove via passive microvortex and were further trapped through an irreversible interaction with MBs. Upon the removal of magnet, the captured cells and residual MBs were released from the channel and collected for further analysis in cell adhesion and proliferation in vitro. Capture efficiency of tumor cells reached up to ∼90% and limit of detection was down to 50 cells per mL based on this approach. Furthermore, recovery rate of tumor cells was as high as ∼94%, and potencies of cell attachment and proliferation was well maintained in retrieved cells. Hence, the present technique has a great potential for the isolation, quantitation and recovery of CTCs for cancer theranostic guidance and biomolecular analysis.