bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiomics and Machine Learning Accurately Predict Clinical Response to Adalimumab and Etanercept Therapy in Patients With Rheumatoid Arthritis
Authors: Tao Weiyang , Concepcion Arno N. , Vianen Marieke , Marijnissen Anne C. A. , Lafeber Floris P. G. J. , Radstake Timothy R. D. J. , Pandit Aridaman
Published: September 2020

Objective

To predict response to anti–tumor necrosis factor (anti‐TNF) prior to treatment in patients with rheumatoid arthritis (RA), and to comprehensively understand the mechanism of how different RA patients respond differently to anti‐TNF treatment.

Methods

Gene expression and/or DNA methylation profiling on peripheral blood mononuclear cells (PBMCs), monocytes, and CD4+ T cells obtained from 80 RA patients before they began either adalimumab (ADA) or etanercept (ETN) therapy was studied. After 6 months, treatment response was evaluated according to the European League Against Rheumatism criteria for disease response. Differential expression and methylation analyses were performed to identify the response‐associated transcription and epigenetic signatures. Using these signatures, machine learning models were built by random forest algorithm to predict response prior to anti‐TNF treatment, and were further validated by a follow‐up study.

Results

Transcription signatures in ADA and ETN responders were divergent in PBMCs, and this phenomenon was reproduced in monocytes and CD4+ T cells. The genes up‐regulated in CD4+ T cells from ADA responders were enriched in the TNF signaling pathway, while very few pathways were differential in monocytes. Differentially methylated positions (DMPs) were strongly hypermethylated in responders to ETN but not to ADA. The machine learning models for the prediction of response to ADA and ETN using differential genes reached an overall accuracy of 85.9% and 79%, respectively. The models using DMPs reached an overall accuracy of 84.7% and 88% for ADA and ETN, respectively. A follow‐up study validated the high performance of these models.

Conclusion

Our findings indicate that machine learning models based on molecular signatures accurately predict response before ADA and ETN treatment, paving the path toward personalized anti‐TNF treatment.
Designing Metallogelators Derived from NSAID‐based Zn(II) Coordination Complexes for Drug‐Delivery Applications
Authors: Mondal Swapneswar , Dastidar Parthasarathi
Published: September 2020

A crystal engineering approach has been invoked to design a new series of eight Zn(II) coordination complexes derived from various non‐steroidal anti‐inflammatory drugs (NSAIDs), namely diclofenac (DIC), ibuprofen (IBU), naproxen (NAP), flufenamic acid (FLU) and meclofenamic acid (MEC), and two co‐ligands, namely N‐phenyl‐3‐pyridylamide (3‐Py) and N‐phenyl‐4‐pyridylamide (4‐Py), and Zn(NO3)2 as potential supramolecular gelators. Half of the coordination complexes thus synthesized were able to form aqueous gels (MG‐3‐PyMEC, MG‐3‐PyDIC, MG‐4‐PyNAP and MG‐4‐PyMEC). Single‐crystal structures of all eight complexes revealed that they possessed a gelation‐inducing 1D hydrogen‐bonded network including amide…amide synthon in some cases, which supported strongly the design principles based on which these complexes were synthesized. Interestingly, one such metallogelator complex, namely 3‐PyMEC, showed an intriguing anticancer property against a human breast cancer cell line (MDA‐MB‐231), as revealed by both MTT and cell migration assays.
Main Belt asteroid as a Possible Younger Dryas impactor
Authors: Usatov Maxim
Published: September 2020

The Younger Dryas (YD) cosmic impact hypothesis is gaining support due to the increasing amount of proxy evidence from 26 Younger Dryas Boundary sites that includes depositions of magnetic, silicate, and carbon spherules; high‐temperature meltglass and melt accretions; nanodiamonds, and Ir and Pt deposits, as well as evidence of major biomass burning and widespread extinctions in stratigraphic layers dated ∼12.8 kyr ago. Among the possible causes, an encounter with a swarm of fragments on an orbit similar to that of 2P/Encke is proposed. This work suggests another potential source of impacting material that requires no special events in the Solar System: Main Belt asteroids excited into highly eccentric Earth‐crossing orbits via mean‐motion resonance with Jupiter and the ν6 secular resonance with Saturn—the established mechanisms of Main Asteroid Belt depletion and Earth‐bound meteorite delivery. It is shown that the probability of and the time between collisions of ejected material with Earth (Δt ∼ 32 kyr), as well as the energy of impacts, are broadly compatible with the YD impact proxy evidence. Such events may reoccur via bombardments of fragment swarms, potentially challenging existing asteroid deflection concepts.
Isolating cost drivers in interstitial lung disease treatment using nonparametric Bayesian methods
Authors: Kurz Christoph F. , Stafford Seth
Published: September 2020

Mixture modeling is a popular approach to accommodate overdispersion, skewness, and multimodality features that are very common for health care utilization data. However, mixture modeling tends to rely on subjective judgment regarding the appropriate number of mixture components or some hypothesis about how to cluster the data. In this work, we adopt a nonparametric, variational Bayesian approach to allow the model to select the number of components while estimating their parameters. Our model allows for a probabilistic classification of observations into clusters and simultaneous estimation of a Gaussian regression model within each cluster. When we apply this approach to data on patients with interstitial lung disease, we find distinct subgroups of patients with differences in means and variances of health care costs, health and treatment covariates, and relationships between covariates and costs. The subgroups identified are readily interpretable, suggesting that this nonparametric variational approach to inference can discover valid insights into the factors driving treatment costs. Moreover, the learning algorithm we employed is very fast and scalable, which should make the technique accessible for a broad range of applications.
Microcarrier expansion of c‐MycERTAM‐modified human olfactory mucosa cells for neural regeneration
Authors: Valinhas Ana , Santiago‐Toledo Gerardo , Wall Ivan B.
Published: September 2020

Human olfactory mucosa cells (hOMCs) have potential as a regenerative therapy for spinal cord injury. In our earlier work, we derived PA5 cells, a polyclonal population that retains functional attributes of primary human OMCs. Microcarrier suspension culture is an alternative to planar two‐dimensinal culture to produce cells in quantities that can meet the needs of clinical development. This study aimed to screen the effects of 10 microcarriers on PA5 hOMCs yield and phenotype. Studies performed in well plates led to a 2.9‐fold higher cell yield on plastic compared to plastic plus microcarriers with upregulation of neural markers β‐III tubulin and nestin for both conditions. Microcarrier suspension culture resulted in concentrations of 1.4 × 105 cells/ml and 4.9 × 104 cells/ml for plastic and plastic plus, respectively, after 7 days. p75NTR transcript was significantly upregulated for PA5 hOMCs grown on Plastic Plus compared to Plastic. Furthermore, coculture of PA5 hOMCs grown on Plastic Plus with a neuronal cell line (NG108‐15) led to increased neurite outgrowth. This study shows successful expansion of PA5 cells using suspension culture on microcarriers, and it reveals competing effects of microcarriers on cell expansion versus functional attributes, showing that designing scalable bioprocesses should not only be driven by cell yields.
Obese patients and robotic colorectal surgery: systematic review and meta-analysis
Authors: Suwa Y , Joshi M , Poynter L , Endo I , Ashrafian H , Darzi A
Published: September 2020

Background

Obesity is a major health problem, demonstrated to double the risk of colorectal cancer. The benefits of robotic colorectal surgery in obese patients remain largely unknown. This meta-analysis evaluated the clinical and pathological outcomes of robotic colorectal surgery in obese and non-obese patients.

Methods

MEDLINE, Embase, Global Health, Healthcare Management Information Consortium (HMIC) and Midwives Information and Resources Service (MIDIRS) databases were searched on 1 August 2018 with no language restriction. Meta-analysis was performed according to PRISMA guidelines. Obese patients (BMI 30 kg/m2 or above) undergoing robotic colorectal cancer resections were compared with non-obese patients. Included outcome measures were: operative outcomes (duration of surgery, conversion to laparotomy, blood loss), postoperative complications, hospital length of stay and pathological outcomes (number of retrieved lymph nodes, positive circumferential resection margins and length of distal margin in rectal surgery).

Results

A total of 131 full-text articles were reviewed, of which 12 met the inclusion criteria and were included in the final analysis. There were 3166 non-obese and 1420 obese patients. A longer duration of surgery was documented in obese compared with non-obese patients (weighted mean difference −21·99 (95 per cent c.i. −31·52 to −12·46) min; P < 0·001). Obese patients had a higher rate of conversion to laparotomy than non-obese patients (odds ratio 1·99, 95 per cent c.i. 1·54 to 2·56; P < 0·001). Blood loss, postoperative complications, length of hospital stay and pathological outcomes were not significantly different in obese and non-obese patients.

Conclusion

Robotic surgery in obese patients results in a significantly longer duration of surgery and higher conversion rates than in non-obese patients. Further studies should focus on better stratification of the obese population with colorectal disease as candidates for robotic procedures.
Case series of fluoroscopic findings and 3D reconstruction of human spinal MRIs of the space of Okada
Authors: Reina Miguel A. , Avellanal Martín , Boezaart André P. , Tubbs R. Shane , De Andrés José , Nin Olga C. , Prats‐Galino Alberto
Published: September 2020

Objective

To better understand the unexpected spread of contrast medium observed by conventional fluoroscopic X‐ray images during standard neuraxial techniques used in the treatment of pain. The support of 3D reconstruction of MRI images of structures within the lumbar spine was used to better understand the space of Okada.

Methods

Lumbar facet joint and epidural corticosteroid injections in five patients under fluoroscopic guidance with loss of resistance to air or saline to identify the facet joints or epidural space. Next, in a retrospective study, the authors examined the retrodural space of Okada and the neighboring tissues with 3D reconstruction of spinal MRIs of seven patients without any demonstrable spinal pathology to better understand the characteristics of the space of Okada.

Results

Contrast medium spread to the ipsilateral and contralateral sides was observed in five patients. The contralateral spread was thought to be through the retrodural space of Okada, which is a potential space between the anterior surface of the vertebral lamina and the posterior surface of the ligamentum flavum. It facilitates communication between the contralateral articular facet joints of the spine.

Conclusions

This study provides new evidence for the existence of the space of Okada where an unexpected contralateral spread occurred following facet joint and attempted epidural injection. The 3D reconstructions of MRIs may help us better understand the nature of the retrodural space of Okada and its clinical implications.
Did university discriminate against student?
Authors: Lyerly Eric
Published: September 2020

After graduating from Methodist University's undergraduate program with a Bachelor of Science in biology, the plaintiff was admitted into the university's physician assistant program in 2014. The plaintiff was granted double time on exams during her undergraduate education due to test‐anxiety issues. Similarly, she was granted extra time to take exams for the physician assistant program as an accommodation for her disability. Despite her testing accommodations, the plaintiff failed several of her April 2015 exams and was dismissed from the program after failing a course in October.
Second primary breast cancer after unilateral mastectomy alone or with contralateral prophylactic mastectomy
Authors: Agarwal Shailesh , Pappas Lisa , Matsen Cindy B. , Agarwal Jayant P.
Published: September 2020

Background

An increasing number of patients undergo contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. However, the benefit of CPM has not been quantified in the setting of contemporary breast cancer therapy.

Methods

We performed an analysis of 180 068 patients in the Surveillance, Epidemiology, and End Results (SEER) database, diagnosed with unilateral ductal breast carcinoma between 1998 and 2013 and treated with unilateral mastectomy (UM) or CPM. UM was performed in 146 213 patients (81.2%); CPM was performed in 33 855 patients (19.8%). Primary outcome of interest was cumulative incidence of a second primary breast cancer in the ipsilateral or contralateral breast greater than 3 months after initial diagnosis. Cumulative incidence analysis was based on a Cox proportional model to generate curves of second primary breast cancer in any breast, ipsilateral breast only, or contralateral breast only.

Results

Patients who underwent CPM had a significantly reduced incidence of second primary breast cancer 10 and 15 years after surgery (CPM 0.93% [0.73%, 1.12%] vs UM 4.44% [4.28%, 4.60%]). Patients who underwent CPM had significantly lower adjusted hazard of second primary breast cancer when compared with UM (HR 0.38 vs 1.0, P < .0001).

Conclusions

CPM offers some protection from a second primary breast cancer, attributable to a reduced incidence in the contralateral breast. These findings provide additional information to providers and patients as they make decisions regarding surgical management. They should also be interpreted in the context of the absolute incidence of second primary breast cancer after UM and previous literature demonstrating no survival benefit.
Cancer associated thrombosis and mortality in patients with cancer stratified by khorana score risk levels
Authors: Khorana Alok A. , Kuderer Nicole M. , McCrae Keith , Milentijevic Dejan , Germain Guillaume , Laliberté François , MacKnight Sean D. , Lefebvre Patrick , Lyman Gary H. , Streiff Michael B.
Published: September 2020

Background

The Khorana score (KS) clinical algorithm is used to predict VTE risk in cancer patients. The study objective was to evaluate VTE and survival rates among patients newly diagnosed with cancer and stratified by KS in a real‐world population.

Methods

Data from the Optum® Clinformatics® DataMart database between 01/01/2012–09/30/2017 was used to identify adults with ≥ 1 hospitalization or ≥ 2 outpatient claims with a cancer diagnosis (index date). Only patients who were initiated on chemotherapy or radiation therapy were included. Patients were classified based on KS (KS = 0, 1, 2 or ≥ 3). Time‐to‐first VTE and survival were evaluated from the index date to the earliest among end of data availability or insurance coverage, death, or 12 months post‐index using Kaplan‐Meier (KM) analyses.

Results

A total of 2,488 (KS = 0); 2,125 (KS = 1), 1,074 (KS = 2), and 507 (KS ≥ 3) cancer patients were included. The 12‐month KM rates of VTE were 3.1%, 5.4%, 7.9%, and 14.9% (associated median time to VTE of 2.7, 3.0, 1.4, and 1.7 months) among KS = 0, 1, 2, and ≥ 3 cohorts, respectively. Corresponding adjusted hazard ratios (95% CIs) relative to the KS = 0 cohort were 1.72 (1.25‐2.38), 2.46 (1.73‐3.50), and 4.99 (3.40‐7.31) for the KS = 1, 2, and ≥ 3 cohorts, respectively (all P < .001). Regardless of KS, patients with VTE had significantly lower survival rates than those without.

Conclusions

This real‐world claims‐based cohort study of newly diagnosed cancer patients showed significantly higher rates of VTE with increased KS, confirming its predictive ability. Moreover, VTE was associated with lower survival rates within each KS cohort.
Development of an IFNγ response‐related signature for predicting the survival of cutaneous melanoma
Authors: Hu Baohui , Wei Qian , Li Xueping , Ju Mingyi , Wang Lin , Zhou Chenyi , Chen Lianze , Li Zinan , Wei Minjie , He Miao , Zhao Lin
Published: September 2020

Background

The tumor microenvironment (TME) plays a critical role in tumorigenesis, development, and therapeutic efficacy. Major advances have been achieved in the treatment of various cancers through immunotherapy. Nevertheless, only a minority of patients have positive responses to immunotherapy, which is partly due to conditions of the immunosuppressive microenvironment. Therefore, it is essential to identify prognostic biomarkers that reflect heterogeneous landscapes of the TME.

Methods and materials

Based upon the ESTIMATE algorithm, we evaluated the infiltrating levels of immune and stromal components derived from patients afflicted by various types of cancer from The Cancer Genome Atlas database (TCGA). According to respective patient immune and stromal scores, we categorized cases into high‐ and low‐scoring subgroups for each cancer type to explore associations between TME and patient prognosis. Gene Set Enrichment Analyses (GSEA) were conducted and genes enriched in IFNγ response signaling pathway were selected to facilitate establishment of a risk model for predicting overall survival (OS). Furthermore, we investigated the associations between the prognostic signature and tumor immune infiltration landscape by using CIBERSORT algorithm and TIMER database.

Results

Among the cancers assessed, the immune scores for skin cutaneous melanoma (SKCM) were the most significantly correlated with patients' survival time (P < .0001). We identified and validated a five‐IFNγ response‐related gene signature (UBE2L6, PARP14, IFIH1, IRF2, and GBP4), which was closely correlated with the prognosis for SKCM afflicted patients. Multivariate Cox regression analysis indicated that this risk model was an independent prognostic factor for SKCM. Tumor‐infiltrating lymphocytes and specific immune checkpoint molecules had notably differential levels of expression in high‐ compared to low‐risk samples.

Conclusion

In this study, we established a novel five‐IFNγ response‐related gene signature that provided a better and increasingly comprehensive understanding of tumor immune landscape, and which demonstrated good performance in predicting outcomes for patients afflicted by SKCM.
Health care‐related time costs in patients with metastatic breast cancer
Authors: Rocque Gabrielle B. , Williams Courtney P. , Ingram Stacey A. , Azuero Andres , Mennemeyer Stephen T. , Young Pierce Jennifer , Nipp Ryan D. , Reeder‐Hayes Katherine E. , Kenzik Kelly M.
Published: September 2020

Background

Burdens related to time spent receiving cancer care may be substantial for patients with incurable, life‐limiting cancers such as metastatic breast cancer (MBC). Estimates of time spent on health care are needed to inform treatment‐related decision‐making.

Methods

Estimates of time spent receiving cancer‐related health care in the initial 3 months of treatment for patients with MBC were calculated using the following data sources: (a) direct observations from a time‐in‐motion quality improvement evaluation (process mapping); (b) cross‐sectional patient surveys; and (c) administrative claims. Average ambulatory, inpatient, and total health care time were calculated for specific treatments which differed by antineoplastic type and administration method, including fulvestrant (injection, hormonal), letrozole (oral, hormonal), capecitabine (oral, chemotherapy), and paclitaxel (infusion, chemotherapy).

Results

Average total time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on treatment. The greatest time contributions were time spent traveling for care and on inpatient services. Time with providers contributed modestly to total care time. Patients receiving infusion/injection treatments, compared with those receiving oral therapy, spent more time in ambulatory care. Health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents.

Conclusion

Time spent traveling and receiving inpatient care represented a substantial burden to patients with MBC, with variation in time by treatment type and administration method.
Wish list thinking: The quasi‐endowment effect's impact on online wish lists outcomes
Authors: Groening Christopher , Wiggins Jennifer , Raoofpanah Iman
Published: September 2020

Marketing practitioners encourage retailers to incorporate online wish lists into their websites, based on the presumption of increasing future purchases. However, recent papers find that purchasing wish list products is far from guaranteed. We propose that this outcome occurs because online wish lists provide a unique liminal space between ownership and non‐ownership that enables consumers to interact with products without the need to actually purchase them. Across two studies, we find that wish lists engender psychological ownership, enabling the quasi‐endowment effect and increasing the likelihood of purchase and decreasing the likelihood of removal from the wish list. However, this relationship moderated two factors. The first is social context of whether the wish list is private or publicly viewable, which can link the products to the consumer's identity. Second is the duration an item has been on the wish list, enabling a “cooling off” period and an opportunity for vicarious consumption through continued interaction. Collectively, our findings indicate that retailers need to more strategically manage their use of online wish lists in order to maximize their potential for increased sales.
Physicochemical Characterization of Hizikia fusiforme Polysaccharide and Its Hypoglycemic Activity via Mediating Insulin‐Stimulated Blood Glucose Utilization of Skeletal Muscle in Type 2 Diabetic Rats
Authors: Jia Rui‐Bo , Li Zhao‐Rong , Ou Zhi‐Rong , Wu Juan , Sun Baoguo , Lin Lianzhu , Zhao Mouming
Published: September 2020

In the current study, a functional polysaccharide fraction (HFP) was obtained from Hizikia fusiforme by ultrasound‐assisted enzymatic extraction, and its structural characterization and hypoglycemic activity and potential molecular mechanism were investigated. The results indicated that HFP with high uronic acid was a heterogeneous polysaccharide composed of six monosaccharides. Congo red test explained that HFP had no triple helix conformation. AFM analysis revealed that HFP was spherical particle with flame‐like aggregates and multiple strands closely arranged. Rheological analysis showed that HFP exhibited shear‐thinning flow behavior. HFP significantly ameliorated diabetes‐related symptoms and serum profiles and increased muscle glycogen storage in rats. HFP administration at 400 mg/kg body weight/day displayed greater advantages than metformin in controlling the levels of fasting blood glucose, triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA) of diabetic rats. Intervention of HFP up‐regulated markedly the expression of AMPK‐α, GLUT4, PI3K and Akt in skeletal muscle of diabetic rats at the mRNA and protein levels, revealing hypoglycemic effects of HFP may be related closely to improving insulin resistance and mitochondrial function of skeletal muscle.
Mechanistic Insights for Iodane Mediated Aromatic Halogenation Reactions
Authors: Qu Zheng‐Wang , Zhu Hui , Grimme Stefan
Published: September 2020

Stable iodanes such as PhI(OAc)2 (Ac=acetyl) may be readily activated by electrophiles and salts for useful functional group transfer reactions under mild conditions, but the underlying reaction mechanism remains controversial. In this work, a general mechanism of iodane‐mediated aromatic halogenation is revealed by extensive DFT calculations using PhI(OAc)2 and anisole PhOMe as model iodane and aromatic substrate, respectively. It is shown that facile OAc/X (X=Cl, Br) ligand exchange with electrophiles can be induced by electrophilic attack at acetyl C=O groups of PhI(OAc)2 to form more reactive iodanes, especially the non‐symmetric iodanes PhI(X)OAc that can be activated by electrophiles to reach reactive iodonium PhIX+ for further electrophilic halonium X+ transfer to aromatic substrates. Direct anionic OAc−/X− exchange of iodane are 4∼7 kcal/mol endergonic, suggesting the crucial role of electrophilic iodane activation. Hetero‐ and homolytic I−X bond cleavages of neutral iodanes are more than 28 kcal/mol endergonic and thus unlikely under ambient conditions without electrophilic activation.
The Application of HEXS and HERFD XANES for Accurate Structural Characterisation of Actinide Nanomaterials: The Case of ThO2
Authors: Amidani Lucia , Vaughan Gavin B. M. , Plakhova Tatiana V. , Romanchuk Anna Yu. , Gerber Evgeny , Svetogorov Roman , Weiss Stephan , Joly Yves , Kalmykov Stepan N. , Kvashnina Kristina O.
Published: September 2020

The structural characterisation of actinide nanoparticles (NPs) is of primary importance and hard to achieve, especially for non‐homogeneous samples with NPs less than 3 nm. By combining high‐energy X‐ray scattering (HEXS) and high‐energy‐resolution fluorescence‐detected X‐ray absorption near‐edge structure (HERFD XANES) analysis, we have characterised for the first time both the short‐ and medium‐range order of ThO2 NPs obtained by chemical precipitation. By using this methodology, a novel insight into the structures of NPs at different stages of their formation has been achieved. The pair distribution function revealed a high concentration of ThO2 small units similar to thorium hexamer clusters mixed with 1 nm ThO2 NPs in the initial steps of formation. Drying the precipitates at around 150 °C promoted the recrystallisation of the smallest units into more thermodynamically stable ThO2 NPs. HERFD XANES analysis at the thorium M4 edge, a direct probe for f states, showed variations that we have correlated with the breakdown of the local symmetry around the thorium atoms, which most likely concerns surface atoms. Together, HEXS and HERFD XANES are a powerful methodology for investigating actinide NPs and their formation mechanism.
Implanting Atomic Dispersed Ru in PtNi Colloidal Nanocrystal Clusters for Efficient Catalytic Performance in Electro‐oxidation of Liquid Fuels
Authors: Li Binsheng , Yang Shaohan , Chen Guozhu , Li Cuncheng , Lv Yipin , Yang Xiaodong , Gao Daowei
Published: September 2020

Although PtRu alloy nanocatalysts have been certified to possess excellent electrocatalytic performance and CO‐poisoning tolerance toward formic acid and methanol electro‐oxidation, the unaffordable usages of ruthenium (Ru) and platinum (Pt) have greatly limited their widespread adoption. Here, a facile one‐pot method is reported for implanting atomic dispersed Ru in PtNi colloidal nanocrystal clusters with different Ru/Pt/Ni molar ratios, greatly reducing the dosages of Pt and Ru, and further improving the catalytic performances for the electro‐oxidation of formic acid and methanol. Through simple control of the amount of Ni(acac)2 precursor, trimetallic Ru0.3Pt70.5Ni29.2, Ru0.6Pt55.9Ni43.5, Ru0.2Pt77.3Ni22.5, and Ru0.9Pt27.3Ni71.8 colloidal nanocrystal clusters (CNCs) are obtained. In particular, the Ru0.3Pt70.5Ni29.2 CNCs exhibit excellent specific activities for formic acid and methanol electro‐oxidation, that is, 14.2 and 15.3 times higher, respectively, than those of the Pt/C catalyst. Moreover, the Ru0.3Pt70.5Ni29.2 CNCs also possess better anti‐CO‐poisoning properties and diffusion ability than the other RuPtNi CNCs. The excellent formic acid and methanol electro‐oxidation activities of RuPtNi CNCs are ascribed to the optimal ligand effects derived from the Pt, Ni, and atomic dispersed Ru atoms, which can improve the OH adsorption ability and further the anti‐CO‐poisoning capability. This research opens a new door for increasing the electro‐oxidation properties of liquid fuels by using lower dosages of noble metals in Pt‐based catalysts.
How Does Iron Storage Protein Ferritin Interact with Plutonium (and Thorium)?
Authors: Zurita Cyril , Tsushima Satoru , Bresson Carole , Garcia Cortes Marta , Solari Pier Lorenzo , Jeanson Aurélie , Creff Gaëlle , Den Auwer Christophe
Published: September 2020

The impact of the contamination of living organisms by actinide elements has been a constant subject of attention since the 1950s. But to date still little is understood. Ferritin is the major storage and regulation protein of iron in many organisms, it consists of a protein ring and a ferrihydric core at the center. This work sheds light on the interactions of early actinides (Th, Pu) at oxidation state +IV with ferritin and its ability to store those elements at physiological pH compared to Fe. The ferritin–thorium load curve suggests that ThIV saturates the protein (2840 Th atoms per ferritin) in a similar way that Fe does on the protein ring. Complementary spectroscopic techniques (spectrophotometry, infrared spectroscopy, and X‐ray absorption spectroscopy) were combined with molecular dynamics to provide a structural model of the interaction of ThIV and PuIV with ferritin. Comparison of spectroscopic data together with MD calculations suggests that ThIV and PuIV are complexed mainly on the protein ring and not on the ferrihydric core. Indeed from XAS data, there is no evidence of Fe neighbors in the Th and Pu environments. On the other hand, carboxylates from amino acids of the protein ring and a possible additional carbonate anion are shaping the cation coordination spheres. This thorough description from a molecular view point of ThIV and PuIV interaction with ferritin, an essential iron storage protein, is a cornerstone in comprehensive nuclear toxicology.
Selective Modification for Red‐Shifted Excitability: A Small Change in Structure, a Huge Change in Photochemistry
Authors: Becker Yvonne , Roth Sina , Scheurer Maximilian , Jakob Andreas , Gacek Daniel A. , Walla Peter J. , Dreuw Andreas , Wachtveitl Josef , Heckel Alexander
Published: September 2020

We developed three bathochromic, green‐light activatable, photolabile protecting groups based on a nitrodibenzofuran (NDBF) core with D‐π‐A push–pull structures. Variation of donor substituents (D) at the favored ring position enabled us to observe their impact on the photolysis quantum yields. Comparing our new azetidinyl‐NDBF (Az‐NDBF) photolabile protecting group with our earlier published DMA‐NDBF, we obtained insight into its excitation‐specific photochemistry. While the “two‐photon‐only” cage DMA‐NDBF was inert against one‐photon excitation (1PE) in the visible spectral range, we were able to efficiently release glutamic acid from azetidinyl‐NDBF with irradiation at 420 and 530 nm. Thus, a minimal change (a cyclization adding only one carbon atom) resulted in a drastically changed photochemical behavior, which enables photolysis in the green part of the spectrum.
Surface Propensity of Anions in a Binary Ionic‐Liquid Mixture Assessed by Full‐Range Angle‐Resolved X‐ray Photoelectron Spectroscopy and Surface‐Tension Measurements
Authors: Oz Erdinc , Sahin Ozgur , Okur Halil I. , Suzer Sefik
Published: September 2020

Angle‐resolved X‐ray photoelectron spectroscopy and contact‐angle measurements guided by a signal attenuation model are utilized to extract molar composition and anion enrichment in the vacuum interface of a binary ionic liquid mixture, having a common quaternary ammonium cation and two different anions. By using the intensity ratio of the F1s peaks belonging to the two different anions recorded at the full electron take‐off angle range, from 0° to 80°, we have determined that only a fractionally covered and anion enriched surface layer can predict the AR‐XPS data, which is also consistent with surface tension measurements. Moreover, the more bulky and non‐spherical anion enrichment is evident even at the conventional and the so assumed bulk sensitive take‐off angle of 0°. This methodology provides a surface enrichment factor of the molecular ions and clearly serves as an experimental evidence for recently debated surface layering and/or island structure in ionic liquid systems.
Scaled Isolation of Mesenchymal Stem/Stromal Cell‐Derived Extracellular Vesicles
Authors: Börger Verena , Staubach Simon , Dittrich Robin , Stambouli Oumaima , Giebel Bernd
Published: September 2020

Mesenchymal stem/stromal cells (MSCs) provide therapeutic effects in many diseases. Contrary to initial hypotheses, they act in a paracrine rather than a cellular manner. To this end, extracellular vesicles (EVs) have been found to mediate the therapeutic effects, even when harvested from MSC‐conditioned cell culture supernatants. Lacking self‐replicating activity and being so small that MSC‐EV preparations can be sterilized by filtration, EVs provide several advantages as therapeutic agents over cellular therapeutics. At present, methods allowing EV preparation from larger volumes are scarce and regularly require special equipment. We have developed a polyethylene glycol−based precipitation protocol allowing extraction of EVs from several liters of conditioned medium. MSC‐EVs prepared with this method have been successfully applied to a human graft‐versus‐host disease patient and to several animal models. Although the method comes with its own limitations, it is extremely helpful for the initial evaluation of EV‐based therapeutic approaches. Here, we introduce the technique in detail and discuss all critical steps. © 2020 The Authors.

Basic Protocol 1: Preparation of MSC‐conditioned medium for scaled MSC‐EV production

Basic Protocol 2: PEG precipitation OF MSC‐EV from MSC‐conditioned medium
Novel methodology for measuring intraoral wear in enamel and dental restorative materials
Authors: F. Esquivel‐Upshaw Josephine , Hsu Shu‐Min , Bohórquez Ana C. , Abdulhameed Nader , Scheiffele Gary W. , Kim Mijin , Neal Dan , Chai John , Ren Fan
Published: September 2020

Objectives

To test the hypotheses that (a) the chairside/handheld dental scanner combined with a metrology software will measure clinical wear in vivo in agreement with measurements from X‐ray computed microtomography and; (b) polished monolithic zirconia does not cause accelerated wear of opposing enamel.

Materials and methods

Thirty single crowns were randomized to receive a monolithic zirconia or metal‐ceramic crown. Two non‐restored opposing teeth in the same quadrants were identified to serve as enamel controls. After cementation, quadrants were scanned using an intraoral dental scanner. Patients were recalled at 6‐months and 1‐year for re‐scanning. Scanned images were compared using a metrology software to determine maximum vertical wear of teeth. The accuracy of the scanning measurements from this new method was compared with X‐ray computed microtomography (micro‐CT) measurements. Statistical analysis was performed using Mann–Whitney U test to determine significant differences between wear of enamel against zirconia, metal‐ceramic or enamel. Linear regression analysis determined agreement between measurements obtained using intraoral scanning and micro‐CT.

Results

Regression analysis demonstrated that there is a quantitative agreement between depth and volume measurements produced using intraoral scanning and the micro‐CT methodologies. There was no significant difference between the wear of enamel against polished monolithic zirconia crowns and enamel against enamel.

Conclusions

Intraoral scanning combined with a matching software can accurately quantify clinical wear to verify that monolithic zirconia exhibited comparable wear of enamel compared with metal‐ceramic crowns and control enamel. Agreement between the intraoral scanner and the micro‐CT was 99.8%. Clinical Trials.gov NCT02289781.
Synthesis and antimicrobial activity of the hybrid molecules between amoxicillin and derivatives of benzoic acid
Authors: Li Zhonglin , Lin Hao , Zhou Junwen , Chen Liangzhu , Pan Zhikun , Fang Binghu
Published: September 2020

Due to the increasing problem of bacterial resistance worldwide, the demand for new antibiotics is becoming increasingly urgent. We wished to: (a) prepare hybrid molecules by linking different pharmacophores by chemical bonds; (b) investigate the antib acterial activity of these hybrids using drug‐sensitive and drug‐resistant pathogens in vitro and vivo. A series of hybrid molecules with a diester structure were designed and synthesized that linked amoxicillin and derivatives of benzoic acid via a methylene bridge. Synthesized compounds were evaluated for activities against Gram‐positive bacteria (Staphylococcus aureus American Type Culture Collection [ATCC] 29213, ATCC 11632; methicillin‐resistant S. aureus [MRSA] 11; Escherichia coli ATCC 25922) and Gram‐negative bacteria (Salmonella LS677, GD836, GD828, GD3625) by microdilution of broth. Synthesized compounds showed good activity against Gram‐positive and Gram‐negative bacteria in vitro. In particular, amoxicillin‐p‐nitrobenzoic acid (6d) showed good activity against Salmonella species and had better activity against methicillin‐resistant S. aureus (minimum inhibitory concentration [MIC] = 64 μg/ml) than the reference drug, amoxicillin (MIC = 128 μg/ml). Amoxicillin‐p‐methoxybenzoic acid (6b) had the best antibacterial activity in vivo (ED50 = 13.2496 μg/ml). The hybrid molecules of amoxicillin and derivatives of benzoic acid synthesized based on a diester structure can improve the activity of amoxicillin against Salmonella species and even improve the activity against MRSA.
Pretreatment motivation and therapy outcomes in eating disorders: A systematic review and meta‐analysis
Authors: Sansfaçon Jeanne , Booij Linda , Gauvin Lise , Fletcher Émilie , Islam Farah , Israël Mimi , Steiger Howard
Published: September 2020

Objective

Identifying modifiable predictors of outcomes following treatment for eating disorders may help to tailor interventions to patients' individual needs, improve treatment efficacy, and develop new interventions. The goal of this meta‐analysis was to quantify the association between pretreatment motivation and posttreatment changes in eating disorder symptomology.

Method

We reviewed 196 longitudinal studies reporting on change on indices of overall eating‐disorder symptomatology, weight gain, binge‐eating, vomiting, anxiety/depression, and treatment adherence. Meta‐analyses were performed using two complementary approaches: (a) combined probability analysis using the added Z's method; (b) effect size analyses. Using random‐effect models, effect sizes were pooled when there were at least three studies with the same type of statistical design and reporting statistics on the same outcome. Heterogeneity in study outcome was evaluated using Q and I2 statistics. Studies were reviewed qualitatively when the number of studies or reported data were insufficient to perform a meta‐analysis.

Results

Forty‐two articles were included. Although samples and treatments differed substantially across studies, results across studies were remarkably consistent. Both combined‐probability and effect‐size analyses indicated positive effects of pretreatment motivation on improvement in general eating‐disorder symptoms (Cohen's r = .17), and an absence of effects on anxiety/depression symptoms. Remaining outcome indices were subject to selective reporting and/or small sample size bias.

Discussion

Our findings underscore the importance of incorporating treatment engagement approaches in the treatment of eating disorders. Optimal reporting of study findings and improving study quality would improve future efforts to obtain an in‐depth understanding of the relationship between motivation and eating disorder symptoms.
Genome structure and content of the rice root‐knot nematode (Meloidogyne graminicola)
Authors: Phan Ngan Thi , Orjuela Julie , Danchin Etienne G. J. , Klopp Christophe , Perfus‐Barbeoch Laetitia , Kozlowski Djampa K. , Koutsovoulos Georgios D. , Lopez‐Roques Céline , Bouchez Olivier , Zahm Margot , Besnard Guillaume , Bellafiore Stéphane
Published: September 2020

Discovered in the 1960s, Meloidogyne graminicola is a root‐knot nematode species considered as a major threat to rice production. Yet, its origin, genomic structure, and intraspecific diversity are poorly understood. So far, such studies have been limited by the unavailability of a sufficiently complete and well‐assembled genome. In this study, using a combination of Oxford Nanopore Technologies and Illumina sequencing data, we generated a highly contiguous reference genome (283 scaffolds with an N50 length of 294 kb, totaling 41.5 Mb). The completeness scores of our assembly are among the highest currently published for Meloidogyne genomes. We predicted 10,284 protein‐coding genes spanning 75.5% of the genome. Among them, 67 are identified as possibly originating from horizontal gene transfers (mostly from bacteria), which supposedly contribute to nematode infection, nutrient processing, and plant defense manipulation. Besides, we detected 575 canonical transposable elements (TEs) belonging to seven orders and spanning 2.61% of the genome. These TEs might promote genomic plasticity putatively related to the evolution of M. graminicola parasitism. This high‐quality genome assembly constitutes a major improvement regarding previously available versions and represents a valuable molecular resource for future phylogenomic studies of Meloidogyne species. In particular, this will foster comparative genomic studies to trace back the evolutionary history of M. graminicola and its closest relatives.
Genetic diversity, population structure, and gene flow analysis of lowland bamboo [Oxytenanthera abyssinica (A. Rich.) Munro] in Ethiopia
Authors: Oumer Oumer Abdie , Dagne Kifle , Feyissa Tileye , Tesfaye Kassahun , Durai Jayaraman , Hyder Muhammad Zeeshan
Published: September 2020

Bamboo, a member of subfamily Bambusoideae in the grass family (Poaceae), is one of the most important nontimber forest resources and a potential alternative to wood and wood products. Ethiopian lowland bamboo (Oxytenanthera abyssinica) is an economically and ecologically important species which accounts about 85% of total bamboo coverage in the country. This species is experiencing population decline due to a number of anthropogenic factors. As a foundation step, genetic diversity, population structure, and gene flow analysis of various O. abyssinica populations found in Ethiopia are studied using inter‐simple sequence repeat markers. One hundred and thirty isolates of bamboo belonging to 13 geographically diverse populations were collected for DNA extraction and analysis. Heterozygosity, level of polymorphism, marker efficiency, Nei's gene diversity (H), and Shannon's information index (I) analysis, analysis of molecular variance (AMOVA), analysis for cluster, principal coordinates (PCoA), and admixture analyses were performed based on the markers banding pattern. The results indicated high genetic variation (84.48%) at species level. The H, I, observed and effective number of alleles at the species level were 0.2702, 0.4061, 1.8448, and 1.4744, respectively, suggesting a relatively high level of genetic diversity. However, genetic differentiation at the population level was relatively low. Using grouped populations, AMOVA revealed that most (61.05%) of the diversity was distributed within the populations with FST = 0.38949, FSC = 0.10486, and FCT = 0.31797. Cluster analysis grouped the populations into markedly distinct clusters, suggesting confined propagation in distinct geographic regions. STRUCTURE analyses showed K = 2 for all populations and K = 11 excluding Gambella population. Using these markers, we found strong evidence that the genetic diversity of the lowland bamboo is associated with distinct geographic regions and that isolates of Gambella Region, with their unique genetic origin, are quite different from other bamboos found in the country.
Isotopic niche size of Coregonus artedi (sensu lato) Increases in the presence of Mysis diluviana, expanded habitat use and phenotypic diversity
Authors: Ridgway Mark S. , Piette‐Lauzière Gabriel , Bell Allan H. , Turgeon Julie
Published: September 2020

Post‐glacial colonization of lakes in Algonquin Park, Ontario, Canada resulted in food webs with cisco (Coregonus artedi sensu lato) and either Mysis diluviana or Chaoborus spp. as the dominant diel migrator. Mysis as prey, its diel movements and benthic occupancy, are hypothesized to be key elements of ecological opportunity for cisco diversity in the Laurentian Great Lakes. If correct, the hypothesis strongly implies that lakes with Mysis would have greater trophic niche size and drive greater adaptive radiation of cisco forms relative to lakes without Mysis. The dichotomy in diel migrator in Algonquin Park lakes was an opportunity to assess the isotopic niche size of cisco (δ15N and δ13C) and determine if niche size expands with Mysis presence. We found the presence of Mysis is necessary to expand isotopic niche size in our study lakes. The use of habitats not typically associated with the ancestral form of cisco (e.g., benthic habitats) and phenotypic diversity (blackfin and cisco) also continue to expand niche size in Mysis‐based food webs. Partial ecological speciation based on a large niche space appears to be present in one lake (Cauchon Lake) where use of alternative habitats is the only real difference in cisco. The presence of blackfin expands niche space in Cedar and Radiant Lakes. This was not matched in Hogan Lake where niche space was relatively smaller with similar forms. Possible reasons for this discrepancy may be related to the asymmetric basin of Hogan Lake and whether the two forms overlap during cool and cold‐water periods of the annual temperature cycle. By comparing trophic niche size among lakes with and without Mysis, we conclude that Mysis provides a key ecological opportunity for cisco diversity in our study lakes and likely more widely.