bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of FOLFIRI/aflibercept in second‐line treatment of metastatic colorectal cancer in a real‐world population: Prognostic and predictive markers
Authors: Fernández Montes Ana , Martínez Lago Nieves , Covela Rúa Marta , de la Cámara Gómez Juan , González Villaroel Paula , Méndez Méndez José Carlos , Jorge Fernández Mónica , Salgado Fernández Mercedes , Reboredo López Margarita , Quintero Aldana Guillermo , Luz Pellón Augusto María , Graña Suárez Begoña , García Gómez Jesús
Published: January 2019

Purpose

The phase III VELOUR trial demonstrated efficacy with combined FOLFIRI‐aflibercept in patients with metastatic colorectal cancer previously treated with oxaliplatin with or without bevacizumab versus placebo. The effect of FOLFIRI‐aflibercept in routine clinical practice was evaluated.

Methods/Patients

Overall survival (OS), progression‐free survival (PFS), response and safety were analysed for 78 patients treated with FOLFIRI‐aflibercept at six GITuD institutions. Exploratory analyses of prognostic and predictive markers of efficacy were performed.

Results

Patients had good general status (PS 0‐1 96.2%), tumours were mostly RAS‐mutant (75.6%), synchronous (71.8%), and left‐sided (71.8%). Prior therapy included bevacizumab (47.4%) and anti‐EGFR agents (12.8%). PFS was longer for metachronous than synchronous tumours (11.0 vs 5.0 months, P = 0.028), and for left‐colon tumours (7.0 vs 3.0 months, P = 0.044). RAS‐mutant status, first‐line treatment and primary tumour surgery did not impact PFS. The disease control rate was 70.5%. The most common grade 3/4 toxicities were neutropenia (15.3%), asthenia (10.3%), diarrhea and mucositis (6.4% each). Dysphonia was reported in 39.7% of patients, and grade 3 hypertension in 3.8%. Development of hypertension (any grade) was significantly associated with a reduced risk of progression by multivariate analysis (HR = 2.7; 95%CI 1.3‐5.4; P = 0.001).

Conclusions

Efficacy with FOLFIRI‐aflibercept in a real‐life population was in line with results from the pivotal trial and toxicity was manageable with treatment adaptation. Survival outcomes were not impacted by primary tumour location, RAS‐mutant status, first‐line treatment or primary tumour surgery. Hypertension may be a surrogate marker of efficacy in this patient population.
Monocyte‐predominant engraftment, cytokine levels and early transplant‐related complications in pediatric hematopoietic stem cell recipients
Authors: Maximova Natalia , Granzotto Marilena , Barbieri Francesca , Marcuzzi Annalisa , Tommasini Alberto , Monasta Lorenzo , Simeone Roberto , Zanon Davide , Sala Roberto
Published: January 2019

Myeloablative conditioning is a well‐established procedure that precedes hematopoietic stem cell transplantation (HSCT), particularly in pediatric patients. In the period directly following transplantation, several factors may contribute to complications that lead to the activation or damage of endothelial cells, involved in the pathogenesis of vascular endothelial syndromes (VES). However, to date, sufficiently specific and sensitive diagnostic markers for the various forms of VES have not been identified. This was a retrospective single‐center study of patients who underwent allogeneic HSCT. For this cohort of patients, parameters including type of engraftment, donor characteristics, and cytokine production were measured and correlated with a high prevalence of short‐term complications after HSCT. The aim of this study was to identify specific parameters useful for improving diagnostics and predicting adverse effects in VES. We confirmed that monocyte‐predominant engraftment was related to a higher risk for an early transplant‐related complication termed sinusoidal obstruction syndrome (SOS). The increased production of specific cytokines, in particular RANTES, represents a marker associated with prevalent engraftment. In addition, patients undergoing prophylaxis with defibrotide had “classical” engraftment, a common cytokine profile and a lower incidence of life‐threatening transplant‐related complications. The beneficial effect of defibrotide might be a starting point for developing selective prophylaxis for patients with monocyte engraftment to prevent severe early transplant‐related complications.
Left ventricular remodeling and function after transapical versus transfemoral transcatheter aortic valve replacement
Authors: Al‐Hijji Mohammed A. , Zack Chad J. , Nkomo Vuyisile T. , Pislaru Sorin V. , Pellikka Patricia A. , Reeder Guy S. , Greason Kevin L. , Rihal Charanjit S. , Eleid Mackram F.
Published: January 2019

Background

The effect of utilizing transapical (TA) access for transcatheter aortic valve replacement (TAVR) on cardiac function has not been well studied.

Aims

The aim of this retrospective study is to determine the direct effects of TA access for TAVR on myocardial function parameters and their correlation with 4‐year survival.

Methods

Three hundred and thirty propensity matched patients, who underwent TAVR using Sapien valve (Edwards Lifesciences Corp, Irvine, CA) between February 15, 2012 and June 17, 2016 (115 TA and 115 transfemoral [TF] routes) were studied. The pre‐ and 1 month post‐TAVR echocardiographic features of both groups were compared. The 4‐year survival in both groups was analyzed.

Results

Baseline clinical characteristics, diastolic function parameters, left ventricular (LV) chamber size, and ejection fraction were similar between matched TA and TF groups. At 1 month following TAVR, there was a significant increase in stroke volume index (SVI) in both TA (mean increase 7 cm3/m2; P = 0.03) and TF groups (mean increase 7 cm3/m2; P < 0.001). Left ventricular ejection fraction (LVEF) significantly increased post TF TAVR (mean increase 2%; P = 0.008), but no significant increase was observed post TA TAVR (mean increase 1%; P = 0.27). Both groups had significant improvement in aortic valve (AV) hemodynamics post‐TAVR (P < 0.001). Overall, there were no significant differences in the mean change of SVI, LVEF, or left ventricular end diastolic dimensions (LVEDDs) post TA versus TF TAVR. There was no significant difference in 4‐year survival in the TF compared to TA group (49% vs 50%, P = 0.43).

Conclusion

Both TA and TF TAVR were equally associated with favorable changes in LV SVI and AV hemodynamics in 30 days. TA TAVR patients had similar 4 year survival to propensity matched TF TAVR; therefore, TA TAVR remains an acceptable alternative access route in patients not amenable to TF TAVR.
Transulnar access for coronary intervention in a 23‐year‐old with accelerated coronary atherosclerosis due to congenital aortic hypoplasia
Authors: Dawkins Jonathan D. , Cedars Ari M. , Schussler Jeffrey M.
Published: January 2019

Key Clinical Message

The use of alternative arterial access and advanced imaging is not only applicable to mainstream adult cardiology, but helpful and sometimes necessary in taking care of adult patients with complex congenital heart disease.
Bladder stone: “Must know” ultrasonographic signs
Authors: Koratala Abhilash , Vangapalli Ananthalaxmi , Bhattacharya Deepti , Lee Loy Justin
Published: January 2019

Key Clinical Message

Point‐of‐care ultrasonography by non‐radiology physicians has become a valuable bedside diagnostic tool. As urolithiasis is one of the commonest indications for sonographic examination, physicians need to be familiar with the characteristic features of stones, that is, acoustic shadowing on gray scale and twinkle artefact on color doppler imaging.
General Method for Synthesis Transition‐Metal Phosphide/Nitrogen and Phosphide Doped Carbon Materials with Yolk‐Shell Structure for Oxygen Reduction Reaction
Authors: Yu Yue , Ma Jun , Chen Changli , Fu Yuanyuan , Wang Yefei , Li Kai , Liao Yi , Zheng Lirong , Zuo Xia
Published: January 2019

The transition metal phosphides have gradually emerged as promising electrocatalysts candidate for oxygen reduction reaction in recent years. As a research hotspot of transition metal phosphides, exploring their mechanism of catalytic activity and the influence of unique morphology is of great significance. In this study, a series of yolk‐shell structure catalysts are fabricated only by pyrolyzing cyclophosphazene microspheres and metal salt without using any other templates, which M2P (M=Fe, Co, Ni) act as the core and N, P co‐doped carbon as the shell. The yolk‐shell structures aim to overcome the inferior conductivity and aggregation problems traditionally existed in application of transition metal phosphides through combination of transition metal phosphides and doped carbon materials. The prepared Fe2P/NPC, Co2P/NPC and Ni2P/NPC catalysts exhibit excellent ORR catalytic activity through the four‐electron pathway, together with large electrochemically active surface area, superior stability and admiring methanol tolerance.
Simulating Non‐linear Chemical and Physical (CAP) Dynamics of Signal Amplification By Reversible Exchange (SABRE)
Authors: Pravdivtsev Andrey N. , Hövener Jan‐Bernd
Published: January 2019

The hyperpolarization of nuclear spins by using parahydrogen (pH2) is a fascinating technique that allows spin polarization and thus the magnetic resonance signal to be increased by several orders of magnitude. Entirely new applications have become available. Signal amplification by reversible exchange (SABRE) is a relatively new method that is based on the reversible exchange of a substrate, catalyst and parahydrogen. SABRE is particularly interesting for in vivo medical and industrial applications, such as fast and low‐cost trace analysis or continuous signal enhancement. Ever since its discovery, many attempts have been made to model and understand SABRE, with various degrees of simplifications. In this work, we reduced the simplifications further, taking into account non‐linear chemical and physical (CAP) dynamics of several multi‐spin systems. A master equation was derived and realized using the MOIN open‐source software. The effects of different parameters (exchange rates, concentrations, spin–spin couplings) on relaxation and the polarization level have been evaluated and the results provide interesting insights into the mechanism of SABRE.
Ionic Liquid Stabilized Niobium Oxoclusters Catalyzing Oxidation of Sulfides with Exceptional Activity
Authors: Zhou Qingqing , Ye Man , Ma Wenbao , Li Difan , Ding Bingjie , Chen Manyu , Yao Yefeng , Gong Xueqing , Hou Zhenshan
Published: January 2019

We present here a new class of niobium oxoclusters that are stabilized effectively by carboxylate ionic liquids. These functionalized ILs are designated as [TBA][LA], [TBA][PA], and [TBA][HPA] in this work, in which TBA represents tetrabutylammonium and LA, PA, and HPA refer to lactate, propionate, 3‐hydroxypropionate anions, respectively. The as‐synthesized Nb oxoclusters have been characterized by use of elemental analysis, NMR, IR, XRD, TGA, HRTEM. It was found that [TBA][LA]‐stabilized Nb oxoclusters (Nb−OC@[TBA][LA]) are uniformly dispersed with an average particle size of 2–3 nm and afforded exceptionally high catalytic activity for the selective oxidation of various thioethers. The turnover number with Nb−OC@[TBA][LA] catalyst was over 56 000 at catalyst loading as low as 0.0033 mol % (1 ppm). Meantime, the catalyst also showed the high activity for the epoxidation of olefins and allylic alcohols by using only 0.065 mol % of catalyst (50 ppm). The characterization of 93Nb NMR spectra revealed that the Nb oxoclusters underwent structural transformation in the presence of H2O2 but regenerated to their initial state at the end of the reaction. In particular, the highly dispersed Nb oxoclusters can absorb a large amount of polar organic solvents and thus were swollen greatly, which exhibited “pseudo” liquid phase behavior, and enabled the substrate molecules to be highly accessible to the catalytic center of Nb oxocluster units.
Trapping of Stable [4n+1] π‐Electron Species from Peripherally Substituted, Conformationally Rigid, Antiaromatic Hexaphyrins
Authors: Firmansyah Dikhi , Hong Seong‐Jin , Dutta Ranjan , He Qing , Bae Jinhee , Jo Hongil , Kim Hakwon , Ok Kang Min , Lynch Vincent M. , Byon Hye Ryung , Sessler Jonathan L. , Lee Chang‐Hee
Published: January 2019

Peripherally substituted antiaromatic naphthorosarins have been synthesized for the first time. The synthesis was accomplished by acid‐catalyzed condensation of naphthobipyrrole building blocks with aromatic aldehydes. The naphthobipyrrole building blocks were synthesized by simple oxidative coupling of the corresponding pyrrole substituted aromatics. Solid‐state structural analyses of the synthesized naphthorosarins revealed that the presence of meso‐2,6‐dichlorophenyl‐ and 5,6‐difluoro‐substitution substantially alter the geometry and properties of the naphthorosarins. The substituents affect the redox potentials as well and, in turn, the proton‐coupled electron‐transfer processes leading to the formation of one‐ and two‐electron reduced forms of the corresponding naphthorosarins. One particular naphthorosarin that bears both peripheral fluorine and meso‐2,6‐dichlorophenyl substituents forms a stable 25 π‐electron species upon treating with TFA that was characterized by single‐crystal X‐ray diffraction analysis. The current study underscores how structural modifications can be used to fine‐tune the electronic features of naphthorosarins, including stabilization of odd electron species.
Organic‐Inorganic Hybrid Perovskite Single Crystals: Crystallization, Molecular Structures, and Bandgap Engineering
Authors: Zuo Tiantian , He Xuexia , Hu Peng , Jiang Hui
Published: January 2019

As a novel active semiconducting material for optoelectronics, organic‐inorganic hybrid perovskites have attracted much attention due to the special advantages of the high light absorption coefficient, long diffusion length and high charge carrier mobility. The single crystals with low defects and free grain boundaries can provide an ideal platform to study the intrinsic photophysical properties and show better performance compared with its amorphous or polycrystalline states. The excellent physical properties of perovskite single crystals make them applied in many fields of solar cells, photodetectors, light‐emitting diodes, lasers, catalysis, etc. Here, the recent progress in the single crystal growth, molecular structures and the bandgap engineering of organic‐inorganic hybrid perovskite single crystals are introduced. The perspective and the future challenge are also provided.
Preparation of Ordered Mesoporous Alumina Supported‐ZnO/NiO Nanocomposite Using Supercritical Carbon Dioxide Impregnation and Its Photocatalytic Performance
Authors: Sun Lili , Han Pei , Tang Shaokun
Published: January 2019

ZnO/NiO nanoparticles supported on ordered mesoporous alumina (OMA) have been prepared by supercritical carbon dioxide impregnation using Zn(NO3)2 ⋅ 6H2O and Ni(NO3)2 ⋅ 6H2O as the precursors, supercritical carbon dioxide as the solvent and methanol as the co‐solvent. The ordered mesostructures of OMA were well‐maintained during the preparation. Ordered mesoporous alumina was prepared via solvent evaporation self‐assembly. The photocatalytic performance of ZnO/NiO/OMA composites for degradation of Congo Red was studied under simulated sunlight irradiation. The results showed that photocatalytic activity of the ZnO/NiO/OMA prepared by supercritical carbon dioxide impregnation was superior to those of commercial P‐25 and the composites prepared via the incipient wetness impregnation. The removal rate of Congo Red was found to be dependent on both the microstructure of the prepared ZnO/NiO/OMA composites and also the molar ratio of ZnO/NiO nanoparticles in OMA. The optimal molar ratio of ZnO/NiO was investigated to achieve a maximum photocatalytic activity.
Oxygen‐Functionalized Ultrathin Ti3C2Tx MXene for Enhanced Electrocatalytic Hydrogen Evolution
Authors: Jiang Yanan , Sun Tao , Xie Xi , Jiang Wei , Li Jia , Tian Bingbing , Su Chenliang
Published: January 2019

Two‐dimensional (2D) transition‐metal carbides (MXenes) are widely adopted as potential electrocatalysts for the hydrogen evolution reaction (HER) owing to their metallic conductivity, rich tunable surface chemistry, and atomic thickness with highly exposed active sites. Previously published theoretical results indicate that MXenes functionalized entirely with oxygen have lower ΔGH* for HER. However, MXenes contain many terminal F groups on the basal plane, which is detrimental to the HER. Herein, the development of an ultrathin Ti3C2 MXene nanosheet fully functionalized with oxygen is reported for the HER. The obtained oxygen‐functionalized Ti3C2 (Ti3C2Ox) exhibits a much higher HER activity (190 mV at 10 mA cm−2) than that of Ti3C2Tx (T=F, OH, and O). The improved HER performance is attributed to the highly active O sites on the basal plane of Ti3C2Tx MXenes. This study paves way for electrocatalytic applications of MXene materials by tuning their surface functional groups.
Lignin Valorization by Cobalt‐Catalyzed Fractionation of Lignocellulose to Yield Monophenolic Compounds
Authors: Rautiainen Sari , Di Francesco Davide , Katea Sarmad Naim , Westin Gunnar , Tungasmita Duangamol N. , Samec Joseph S. M.
Published: January 2019

Invited for this month's cover is the group of Joseph S. M. Samec at Stockholm University together with Duangamol Tungasmita from Chulalongkorn University. The image shows cobalt‐based heterogeneous catalyst on nitrogen‐doped carbon support outperforming the noble‐metal‐based competitors. The Communication itself is available at 10.1002/cssc.201802497.
A cleft lip and palate gene, Irf6, is involved in osteoblast differentiation of craniofacial bone
Authors: Thompson Jake , Mendoza Fabian , Tan Ethan , Bertol Jessica Wildgrube , Gaggar Arju S , Jun Goo , Biguetti Claudia , Fakhouri Walid D.
Published: January 2019

Background: Interferon regulatory factor 6 (IRF6) plays a critical role in embryonic tissue development, including differentiation of epithelial cells. Besides orofacial clefting due to haploinsufficiency of IRF6, recent human genetic studies indicated that mutations in IRF6 are linked to small mandible and digit abnormalities. The function of IRF6 has been well studied in oral epithelium; however, its role in craniofacial skeletal formation remains unknown. In this study, we investigated the role of Irf6 in craniofacial bone development using comparative analyses between wild‐type (WT) and Irf6‐null littermate mice. Results: Immunostaining revealed the expression of IRF6 in hypertrophic chondrocytes, osteocytes, and bone matrix of craniofacial tissues. Histological analysis of Irf6‐null mice showed a remarkable reduction in the number of lacunae, embedded osteocytes in matrices, and a reduction in mineralization during bone formation. These abnormalities may explain the decreased craniofacial bone density detected by micro‐CT, loss of incisors, and mandibular bone abnormality of Irf6‐null mice. To validate the autonomous role of IRF6 in bone, extracted primary osteoblasts from calvarial bone of WT and Irf6‐null pups showed no effect on osteoblastic viability and proliferation. However, a reduction in mineralization was detected in Irf6‐null cells. Conclusions: Altogether, these findings suggest an autonomous role of Irf6 in regulating bone differentiation and mineralization. Developmental Dynamics 248:221‐232, 2019. © 2019 Wiley Periodicals, Inc.
S,O‐Ligand‐Promoted Pd‐Catalyzed C–H Olefination of Thiophenes
Authors: Álvarez‐Casao Yolanda , Fernández‐Ibáñez M. Ángeles
Published: January 2019

An efficient PdII catalyzed C–H olefination of thiophenes has been developed using an easily accessible bidentate S,O‐ligand. The catalytic system promotes the C‐2 olefination of a wide range of thiophenes bearing both, electron donating and withdrawing groups under mild conditions. This methodology provides a direct path towards the synthesis of 2,3‐disubstituted thiophenes, which are difficult to obtain via other C–H functionalization routes. The S,O‐ligand is responsible for the broad substrate scope and high levels of C‐2 selectivity in 3‐substituted thiophenes.
ACEME: Reducing of CO2 and H2S for biogas upgrading using accelerated mineralization
Authors: Sakowski Bastian Alexander , Kaiser Martin , Mollekopf Norbert
Published: January 2019

To reduce carbon dioxide and hydrogen sulfide concentration in simulated biogas, experiments were performed on a laboratory scale. The main goal was to use calcium, lead and zinc from fly ash from waste combustion power plants to form carbonates and sulfides for biogas upgrading within a process water cycle. Thereby, the contact time between the simulated biogas and the ionized process water was limited to less than 1 s. The investigation focused on the influence of hydrogen sulfide partial pressure, reaction time, reaction temperature, and process water volume flows. The experiments were performed with two different ashes.

The results show that the kinetics for hydrogen sulfide reactions were better than for carbon dioxide where the mass transfer into the liquid phase slows down the upgrading process. This led to fast reactions for H2S in the initial volume and therefore to a bottleneck for further sequestration. For carbon dioxide the kinetics limit the process in the beginning until all reactants for carbonates and the process water volume flow limit the process also. For the process temperature, slightly better separation efficiencies were realized for carbon dioxide at 40 °C while the effect for hydrogen sulfide separation was contradictory for the used ashes. With higher process water volume flow, best results were achieved and the bottleneck of reactants ratios was compensated. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13144, 2019
Neural networks for sentence comprehension and production: An ALE‐based meta‐analysis of neuroimaging studies
Authors: Walenski Matthew , Europa Eduardo , Caplan David , Thompson Cynthia K.
Published: January 2019

Comprehending and producing sentences is a complex endeavor requiring the coordinated activity of multiple brain regions. We examined three issues related to the brain networks underlying sentence comprehension and production in healthy individuals: First, which regions are recruited for sentence comprehension and sentence production? Second, are there differences for auditory sentence comprehension vs. visual sentence comprehension? Third, which regions are specifically recruited for the comprehension of syntactically complex sentences? Results from activation likelihood estimation (ALE) analyses (from 45 studies) implicated a sentence comprehension network occupying bilateral frontal and temporal lobe regions. Regions implicated in production (from 15 studies) overlapped with the set of regions associated with sentence comprehension in the left hemisphere, but did not include inferior frontal cortex, and did not extend to the right hemisphere. Modality differences between auditory and visual sentence comprehension were found principally in the temporal lobes. Results from the analysis of complex syntax (from 37 studies) showed engagement of left inferior frontal and posterior temporal regions, as well as the right insula. The involvement of the right hemisphere in the comprehension of these structures has potentially important implications for language treatment and recovery in individuals with agrammatic aphasia following left hemisphere brain damage.
Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer
Authors: Ferrera Annabelle , Valladares Wendy , Cabrera Yessy , de la Luz Hernandez Maria , Darragh Teresa , Baena Armando , Almonte Maribel , Herrero Rolando
Published: January 2019

HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV‐tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow‐up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18‐related HSIL+ was 96.8% (95%CI = 83.8–99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3–68.6). Specificity was 97.5% (95%CI = 93.7–99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18‐related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.
Circulating androgens and postmenopausal ovarian cancer risk in the Women's Health Initiative Observational Study
Authors: Trabert Britton , Michels Kara A. , Anderson Garnet L. , Brinton Louise A. , Falk Roni T. , Geczik Ashley M. , Harris Holly R. , Pan Kathy , Pfeiffer Ruth M. , Qi Lihong , Rohan Thomas , Wentzensen Nicolas , Xu Xia
Published: January 2019

Our knowledge of epidemiologic risk factors for ovarian cancer supports a role for androgens in the pathogenesis of this disease; however, few studies have examined associations between circulating androgens and ovarian cancer risk. Using highly sensitive LC–MS/MS assays, we evaluated associations between pre‐diagnostic serum levels of 12 androgens, including novel androgen metabolites that reflect androgen activity in tissues, and ovarian cancer risk among postmenopausal women in a nested case–control study in the Women's Health Initiative (WHI) Observational Study (OS). We frequency‐matched 169 ovarian cancer cases to 410 controls from women enrolled in WHI‐OS who were not using menopausal hormones at enrollment/blood draw. We estimated associations overall and by subtype (n = 102 serous/67 non‐serous) using multivariable adjusted logistic regression. Androgen/androgen metabolite levels were not associated with overall ovarian cancer risk. In analyses by subtype, women with increased levels of androsterone‐glucuronide (ADT‐G) and total 5‐α reduced glucuronide metabolites (markers of tissue‐level androgenic activity) were at increased risk of developing non‐serous ovarian cancer: ADT‐G tertile (T)3 versus T1 odds ratio [OR] (95% confidence interval [CI]) 4.36 (1.68–11.32), p‐heterogeneity 0.002; total glucuronide metabolites 3.63 (1.47–8.95), 0.002. Risk of developing serous tumors was unrelated to these markers. ADT‐G and total glucuronide metabolites, better markers of tissue‐level androgenic activity in women than testosterone, were associated with an increased risk of developing non‐serous ovarian cancer. Our work demonstrates that sex steroid metabolism is important in the etiology of non‐serous ovarian cancers and supports a heterogeneous hormonal etiology across histologic subtypes of ovarian cancer.
Neonatal phototherapy and future risk of childhood cancer
Authors: Auger Nathalie , Laverdière Caroline , Ayoub Aimina , Lo Ernest , Luu Thuy Mai
Published: January 2019

We sought to determine if neonatal phototherapy is associated with a greater risk of childhood cancer. We conducted a retrospective cohort study of 786,998 infants born in hospitals of Quebec, Canada between 2006 and 2016, with 4,660,868 person‐years of follow‐up over an 11‐year period. The exposures were neonatal phototherapy (32,314 or 4.1% of infants) and untreated jaundice (91,855 or 11.7% of infants). The outcome was hospitalization for solid or hematopoietic childhood tumours between 2 months and 11 years of age. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of phototherapy with childhood cancer, adjusted for infant characteristics. The incidence of childhood cancer was higher for infants with phototherapy (25.1 per 100,000 person‐years) and untreated jaundice (23.0 per 100,000) compared to unexposed infants (21.6 per 100,000). Phototherapy appeared to be associated with late onset solid tumours, including brain/central nervous system cancers. Between age 4 and 11 years, children who received neonatal phototherapy had more than 2 times the risk of any solid tumour compared to unexposed children (HR 2.26, 95% CI 1.34–3.81). Results were similar for phototherapy compared against untreated jaundice. A similar trend was however less apparent for hematopoietic cancer. We conclude that neonatal phototherapy may be associated with a slightly increased risk of solid tumours in childhood, but cannot rule out an effect of bilirubin. Minimizing unnecessary exposure to phototherapy through adherence to recommended thresholds for treatment is encouraged.
In silico prediction of chemical reproductive toxicity using machine learning
Authors: Jiang Changsheng , Yang Hongbin , Di Peiwen , Li Weihua , Tang Yun , Liu Guixia
Published: January 2019

Reproductive toxicity is an important regulatory endpoint in health hazard assessment. Because the in vivo tests are expensive, time consuming and require a large number of animals, which must be killed, in silico approaches as the alternative strategies have been developed to assess the potential reproductive toxicity (reproductive toxicity) of chemicals. Some prediction models for reproductive toxicity have been developed, but most of them were built only based on one single endpoint such as embryo teratogenicity; therefore, these models may not provide reliable predictions for toxic chemicals with other endpoints, such as sperm reduction or gonadal dysgenesis. Here, a total of 1823 chemicals for reproductive toxicity characterized by multiple endpoints were used to develop structure‐activity relationship models by six machine‐learning approaches with nine molecular fingerprints. Among the models, MACCSFP‐SVM model has the best performance for the external validation set (area under the curve = 0.900, classification accuracy = 0.836). The applicability domain was analyzed, and a rational boundary was found to distinguish inaccurate predictions and accurate predictions. Moreover, several structural alerts for characterizing reproductive toxicity were identified using the information gain combining substructure frequency analysis. Our results would be helpful for the prediction of the reproductive toxicity of chemicals.
Forty years of the Japanese Society for Biomaterials looking back at my term of office as the chairperson
Authors: Ikada Yoshito
Published: January 2019

The compatibility of artificial materials with living system, such as antithrombogenicity and antiimmunogenicity, has been an important issue in the field of the biomaterials researches at the early periods of the biomaterials research. After that, the bioabsorbable materials have been subsequently incorporated as biomaterials. As a result, biomaterial researchers started participating in the field of drug delivery system (DDS), and combining biomaterials and cells not only led to bioartificial organs, but also tissue engineering. The bioabsorbable biomaterials function as scaffolds for the cells and play an important role in the field of regenerative medicine researches. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 930–932, 2019.
Mechanical behavior of bovine pericardium treated with hyaluronic acid derivative for bioprosthetic aortic valves
Authors: Marinho Enesio , Carbonari Ronny Calixto , Malmonge Sonia M. , Leão Cedric Rocha
Published: January 2019

We studied the mechanical behavior of bovine pericardium (BP) after anticalcification treatment using hyaluronic acid (HA) derivative. To simulate the physiological environment and stimulate the calcification process, the BP samples were immersed into simulated body fluid solution. We conducted scanning electron microscopy with energy dispersive X‐ray spectrometry, and uniaxial mechanical tests of HA‐treated and non‐treated samples. Although our microstructural analyses indicated that the HA treatment actually prevents the formation of calcium phosphate deposits, the mechanical tests show significant increase of stiffness of the HA‐treated samples. Using data from our mechanical tests as input parameters, we performed finite element (FE) computer simulations to estimate how this increase in the BP stiffness affects the stress distribution in the bioprosthetic leaflet. Although the maximum stress observed during the closing phase of the membrane in vivo is below the experimental yield stress in all cases we analyzed, our FE results indicate that increase of BP stiffness due to HA anticalcification treatment results in higher risk of disruption and failure of the leaflets in bioprosthetic heart valves. Since our FE results indicate that the commissure and the fixed edge are the regions that withstand the highest mechanical stresses during the closing phase, new designs of the valve might be efficient to enhance the endurance of the prosthesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2273–2280, 2019.
Effects of a Home‐Based Physical Rehabilitation Program on Tibial Bone Structure, Density, and Strength After Hip Fracture: A Secondary Analysis of a Randomized Controlled Trial
Authors: Suominen Tuuli H , Edgren Johanna , Salpakoski Anu , Arkela Marja , Kallinen Mauri , Cervinka Tomas , Rantalainen Timo , Törmäkangas Timo , Heinonen Ari , Sipilä Sarianna
Published: January 2019

Weight‐bearing physical activity may decrease or prevent bone deterioration after hip fracture. This study investigated the effects of a home‐based physical rehabilitation program on tibial bone traits in older hip fracture patients. A population‐based clinical sample of men and women operated for hip fracture (mean age 80 years, 78% women) was randomly assigned into an intervention (n = 40) and a standard care control group (n = 41) on average 10 weeks postfracture. The intervention group participated in a 12‐month home‐based rehabilitation intervention, including evaluation and modification of environmental hazards, guidance for safe walking, nonpharmacological pain management, motivational physical activity counseling, and a progressive, weight‐bearing home exercise program comprising strengthening exercises for the lower legs, balance training, functional exercises, and stretching. All participants received standard care. Distal tibia (5% proximal to the distal end plate) compressive bone strength index (BSI; g2/cm4), total volumetric BMD (vBMDTOT; mg/cm3), and total area (CSATOT; mm2), as well as midtibia (55%) strength–strain index (SSI; mm3), cortical vBMD (vBMDCO; mg/cm3), and ratio of cortical to total area (CSACO/CSATOT)were assessed in both legs by pQCT at baseline and at 3, 6, and 12 months. The intervention had no effect (group × time) on either the distal or midtibial bone traits. At the distal site, BSI of both legs, vBMDTOTof the fractured side, and CSATOTof the nonfractured side decreased significantly over time in both groups 0.7% to 3.1% (12 months,p < 0.05). At the midshaft site, CSACO/CSATOTand SSI of both legs, and vBMDCOof the fractured leg, decreased significantly over time in both groups 1.1% to 1.9% (12 months,p < 0.05). Trabecular and cortical bone traits of the tibia on the fractured and the nonfractured side deteriorated throughout follow‐up. The home‐based physical rehabilitation intervention aimed at promoting mobility recovery was unable to prevent bone deterioration in older people after hip fracture. © 2019 The Authors.JBMR Pluspublished by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Differentiating supraclavicular from gluteal adipose tissue based on simultaneous PDFF and T2* mapping using a 20‐echo gradient‐echo acquisition
Authors: Franz Daniela , Diefenbach Maximilian N. , Treibel Franziska , Weidlich Dominik , Syväri Jan , Ruschke Stefan , Wu Mingming , Holzapfel Christina , Drabsch Theresa , Baum Thomas , Eggers Holger , Rummeny Ernst J. , Hauner Hans , Karampinos Dimitrios C.
Published: January 2019

Background

Adipose tissue (AT) can be classified into white and brown/beige subtypes. Chemical shift encoding‐based water–fat MRI‐techniques allowing simultaneous mapping of proton density fat fraction (PDFF) and T2* result in a lower PDFF and a shorter T2* in brown compared with white AT. However, AT T2* values vary widely in the literature and are primarily based on 6‐echo data. Increasing the number of echoes in a multiecho gradient‐echo acquisition is expected to increase the precision of AT T2* mapping.

Purpose

1) To mitigate issues of current T2*‐measurement techniques through experimental design, and 2) to investigate gluteal and supraclavicular AT T2* and PDFF and their relationship using a 20‐echo gradient‐echo acquisition.

Study Type

Prospective.

Subjects

Twenty‐one healthy subjects.

Field Strength/Sequence Assessment

First, a ground truth signal evolution was simulated from a single‐T2* water–fat model. Second, a time‐interleaved 20‐echo gradient‐echo sequence with monopolar gradients of neck and abdomen/pelvis at 3 T was performed in vivo to determine supraclavicular and gluteal PDFF and T2*. Complex‐based water–fat separation was performed for the first 6 echoes and the full 20 echoes. AT depots were segmented.

Statistical Tests

Mann‐Whitney test, Wilcoxon signed‐rank test and simple linear regression analysis.

Results

Both PDFF and T2* differed significantly between supraclavicular and gluteal AT with 6 and 20 echoes (PDFF: P < 0.0001 each, T2*: P = 0.03 / P < 0.0001 for 6/20 echoes). 6‐echo T2* demonstrated higher standard deviations and broader ranges than 20‐echo T2*. Regression analyses revealed a strong relationship between PDFF and T2* values per AT compartment (R2 = 0.63 supraclavicular, R2 = 0.86 gluteal, P < 0.0001 each).

Data Conclusion

The present findings suggest that an increase in the number of sampled echoes beyond 6 does not affect AT PDFF quantification, whereas AT T2* is considerably affected. Thus, a 20‐echo gradient‐echo acquisition enables a multiparametric analysis of both AT PDFF and T2* and may therefore improve MR‐based differentiation between white and brown fat.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:424–434.
Quantitative myocardial perfusion in coronary artery disease: A perfusion mapping study
Authors: Knott Kristopher D. , Camaioni Claudia , Ramasamy Anantharaman , Augusto Joao A. , Bhuva Anish N. , Xue Hui , Manisty Charlotte , Hughes Rebecca K. , Brown Louise A.E. , Amersey Rajiv , Bourantas Christos , Kellman Peter , Plein Sven , Moon James C
Published: January 2019

Background

Cardiac MR stress perfusion remains a qualitative technique in clinical practice due to technical and postprocessing challenges. However, automated inline perfusion mapping now permits myocardial blood flow (MBF, ml/g/min) quantification on‐the‐fly without user input.

Purpose

To investigate the diagnostic performance of this novel technique in detecting occlusive coronary artery disease (CAD) in patients scheduled to undergo coronary angiography.

Study Type

Prospective, observational.

Subjects

Fifty patients with suspected CAD and 24 healthy volunteers.

Field Strength

1.5T.

Sequence

"Dual" sequence multislice 2D saturation recovery.

Assessment

All patients underwent cardiac MR with perfusion mapping and invasive coronary angiography; the healthy volunteers had MR with perfusion mapping alone.

Statistical Tests

Comparison between numerical variables was performed using an independent t‐test. Receiver operator characteristic (ROC) curves were generated for transmyocardial, endocardial stress MBF, and myocardial perfusion reserve (MPR, the stress:rest MBF ratio) to diagnose severe (>70%) stenoses as measured by 3D quantitative coronary angiography (QCA). ROC curves were compared by the method of DeLong et al.

Results

Compared with volunteers, patients had lower stress MBF and MPR even in vessels with <50% stenosis (2.00 vs. 3.08 ml/g/min, respectively). As stenosis severity increased (<50%, 50–70%, >70%), MBF and MPR decreased. To diagnose occlusive (>70%) CAD, endocardial and transmyocardial stress MBF were superior to MPR (area under the curve 0.92 [95% CI 0.86–0.97] vs. 0.90 [95% CI 0.84–0.95] and 0.80 [95% CI 0.72–0.87], respectively). An endocardial threshold of 1.31 ml/g/min provided a per‐coronary artery sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90%, 82%, 50%, and 98%, with a per‐patient diagnostic performance of 100%, 66%, 57%, and 100%, respectively.

Data Conclusion

Perfusion mapping can diagnose occlusive CAD with high accuracy and, in particular, high sensitivity and NPV make it a potential "rule‐out" test.

Level of Evidence: 1

Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:756–762.
What influences a tourist to return to a cultural destination?
Authors: Vareiro Laurentina , Ribeiro José Cadima , Remoaldo Paula Cristina
Published: January 2019

This study investigates the likelihood of tourists to repeat a visit to a cultural destination. We use a sample of 432 tourists who had visited Guimarães, Portugal. A cluster analysis separates visitors according to their opinion of the city's attributes. Afterward, a logistic regression analyses the variables that affect the likelihood of revisiting, taking into account the three clusters obtained. Results showed that, among the total sample, global quality of the destination had the biggest influence on the tourists' decision of whether to revisit the destination, whereas the least important reason was prior visits. These influential factors varied when different cluster group compositions were considered.
Moral Injury: An Integrative Review
Authors: Griffin Brandon J. , Purcell Natalie , Burkman Kristine , Litz Brett T. , Bryan Craig J. , Schmitz Martha , Villierme Claudia , Walsh Jessica , Maguen Shira
Published: January 2019

Individuals who are exposed to traumatic events that violate their moral values may experience severe distress and functional impairments known as “moral injuries.” Over the last decade, moral injury has captured the attention of mental health care providers, spiritual and faith communities, media outlets, and the general public. Research about moral injury, especially among military personnel and veterans, has also proliferated. For this article, we reviewed scientific research about moral injury. We identified 116 relevant epidemiological and clinical studies. Epidemiological studies described a wide range of biological, psychological/behavioral, social, and religious/spiritual sequelae associated with exposure to potentially morally injurious events. Although a dearth of empirical clinical literature exists, some authors debated how moral injury might and might not respond to evidence‐based treatments for posttraumatic stress disorder (PTSD) whereas others identified new treatment models to directly address moral repair. Limitations of the literature included variable definitions of potentially morally injurious events, the absence of a consensus definition and gold‐standard measure of moral injury as an outcome, scant study of moral injury outside of military‐related contexts, and clinical investigations limited by small sample sizes and unclear mechanisms of therapeutic effect. We conclude our review by summarizing lessons from the literature and offering recommendations for future research.
Existence of solutions to Schrödinger‐Poisson systems with critical and supercritical nonlinear terms
Authors: Li Yuhua , Gu Hua
Published: January 2019

In this paper, the existence of nontrivial solutions to a class of Schrödinger‐Poisson systems with critical and supercritical nonlinear terms is obtained via variational methods. By using the potential function, a compactness imbedding result is obtained. The properties of potential function play an important role for insuring variational setting.
Determination of the 15N chemical shift anisotropy in natural abundance samples by proton‐detected 3D solid‐state NMR under ultrafast MAS of 70 kHz
Authors: Rossi Federica , Duong Nghia Tuan , Pandey Manoj Kumar , Chierotti Michele R. , Gobetto Roberto , Nishiyama Yusuke
Published: January 2019

Chemical shift anisotropy (CSA) is a sensitive probe of electronic environment at a nucleus, and thus, it offers deeper insights into detailed structural and dynamic properties of different systems, for example, chemical, biological, and materials. Over the years, massive efforts have been made to develop recoupling methods that reintroduce CSA interaction under magic angle spinning (MAS) conditions. Most of them require slow or moderate MAS (≤20 kHz) and isotopically enriched samples. On the other hand, to the best of the authors' knowledge, no 13C or 15N CSA recoupling schemes at ultrafast MAS (≥60 kHz) suitable for cost‐effective natural abundant samples have been developed. We present here a proton‐detected 3D 15N CS/15N CSA/1H CS correlation experiment which employs 1H indirect detection for sensitivity enhancement and a γ‐encoded
‐symmetry‐based CSA recoupling scheme. In particular, two different symmetries, that is, R837 and R1049, are first tested, in a 2D 15N CSA/1H CS version, on [U‐15N]‐L‐histidine·HCl·H2O as a model sample under 70 kHz MAS. Then the 3D experiment is applied on glycyl‐L‐alanine at natural abundance, resulting in site‐resolved 15N CSA lineshapes from which CSA parameters are retrieved by SIMPSON numerical fittings. We demonstrate that this 3D R‐symmetry‐based pulse sequence is highly robust with respect to wide‐range offset mismatches and weakly dependent to rf inhomogeneity within mis‐sets of ±10% from the theoretical value.
Chemical exchange saturation transfer imaging of phosphocreatine in the muscle
Authors: Chung Julius Juhyun , Jin Tao , Lee Jung Hee , Kim Seong‐Gi
Published: January 2019

Purpose

To determine the exchange parameters for the CEST of phosphocreatine (PCrCEST) in phantoms and to characterize PCrCEST in vivo in the muscle at different saturation powers and magnetic fields.

Methods

Exchange parameters were measured in PCr solutions using varying saturation power at 15.2 T. Z‐spectra were analyzed using multipool Lorentzian fitting in the hindlimb using various powers at 2 different fields: 9.4 T and 15.2 T. Modulation of PCr signal in PCrCEST and phosphorus MRS was observed in the mouse hindlimb before and after euthanasia.

Results

The exchange rate of PCr at physiological pH in phantoms was confirmed to be in a much slower exchange regime compared with Cr: kex at pH 7.3 and below was less than 400 s–1. There was insufficient signal for detection of PCrCEST in the brain, but PCrCEST in the hindlimb was measured to be 2.98% ± 0.43 at a B1 of 0.47 μT at 15.2 T, which is 29% higher than 9.4T values. The value of PCrCEST at a B1 of 0.71 μT was not significantly different than that measured at a B1 of 0.47 μT. After euthanasia, PCrCEST signal dropped by 82.3% compared with an 85% decrease in PCr in phosphorus MRS, whereas CrCEST signal increased by 90.6%.

Conclusion

The PCrCEST technique has viable sensitivity in the muscle at high fields and shows promise for the study of metabolic dysfunction and cardiac systems.