bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of 17q24.2‐q24.3 deletions with recognizable phenotype and short telomeres
Authors: Hancarova Miroslava , Malikova Marcela , Kotrova Michaela , Drabova Jana , Trkova Marie , Sedlacek Zdenek
Published: April 2018

Microdeletions of 17q24.2‐q24.3 have been described in several patients with developmental and speech delay, growth retardation, and other features. The relatively large size and limited overlap of the deletions complicate the genotype‐phenotype correlation. We identified a girl with intellectual disability, growth retardation, dysmorphic features, and a de novo 2.8 Mb long deletion of 17q24.2‐q24.3. Her phenotype was strikingly similar to one previously described boy with Dubowitz syndrome (MIM 223370) and a de novo 3.9 Mb long deletion encompassing the deletion of our patient. In addition, both patients had the shortest telomeres among normal age‐matched controls. Our review of all 17q24.2‐q24.3 deletion patients revealed additional remarkable phenotypic features shared by the patients, some of which have consequences for their management. Proposed novel genotype‐phenotype correlations based on new literature information on the region include the role of PSMD12 and BPTF, the genes recently associated with syndromic neurodevelopmental disorders, and a possible role of the complex topologically associated domain structure of the region, which may explain some of the phenotypic discrepancies observed between patients with similar but not identical deletions. Nevertheless, although different diagnoses including the Dubowitz, Nijmegen breakage (MIM 251260), Silver‐Russell (MIM 180860), or Myhre (MIM 139210) syndromes were originally considered in the 17q24.2‐q24.3 deletion patients, they clearly belong to one diagnostic entity defined by their deletions and characterized especially by developmental delay, specific facial dysmorphism, abnormalities of extremities and other phenotypes, and possibly also short telomere length.
KBG syndrome patient due to 16q24.3 microdeletion presenting with a paratesticular rhabdoid tumor: Coincidence or cancer predisposition?
Authors: Behnert Astrid , Auber Bernd , Steinemann Doris , Frühwald Michael C. , Huisinga Carolin , Hussein Kais , Kratz Christian , Ripperger Tim
Published: April 2018

KBG syndrome is a rare autosomal dominant disorder caused by constitutive haploinsufficiency of the ankyrin repeat domain‐containing protein 11 (ANKRD11) being the result of either loss‐of‐function gene variants or 16q24.3 microdeletions. The syndrome is characterized by a variable clinical phenotype comprising a distinct facial gestalt and variable neurological involvement. ANKRD11 is frequently affected by loss of heterozygosity in cancer. It influences the ligand‐dependent transcriptional activation of nuclear receptors and tumor suppressive function of tumor protein TP53. ANKRD11 thus serves as a candidate tumor suppressor gene and it has been speculated that its haploinsufficiency may lead to an increased cancer risk in KBG syndrome patients. While no systematic data are available, we report here on the second KBG syndrome patient who developed a malignancy. At 17 years of age, the patient was diagnosed with a left‐sided paratesticular extrarenal malignant rhabdoid tumor. Genetic investigations identified a somatic truncating gene variant in SMARCB1, which was not present in the germline, and a constitutional de novo 16q24.3 microdeletion leading to a loss of the entire ANKRD11 locus. Thus, KBG syndrome was diagnosed, which was in line with the clinical phenotype of the patient. At present, no specific measures for cancer surveillance can be recommended for KBG syndrome patients. However, a systematic follow‐up and inclusion of KBG syndrome patients in registries (e.g., those currently established for cancer prone syndromes) will provide empiric data to support or deny an increased cancer risk in KBG syndrome in the future.
Copper‐Promoted Tandem Radical Reaction of 2‐Oxindoles with Formamides: Facile Synthesis of Unsymmetrical Urea Derivatives
Authors: Chen Wei‐Ting , Bao Wen‐Hui , Ying Wei‐Wei , Zhu Wen‐Ming , Liang Hongze , Wei Wen‐Ting
Published: April 2018

A convenient copper‐promoted tandem radical reaction of 2‐oxindoles with formamides producing unsymmetrical urea derivatives is described. This radical‐mediated reaction enables the formation of one C=O and one C−N bond through a domino C−O coupling, ring cleavage and C−N coupling process, which features a broad substrate scope and excellent selectivity. In addition, tBuOOH not only acts as the oxidant, but also as the oxygen source. The proposed reaction mechanism is supported by control experiments.
The potential value of activin B and fibronectin for the triage of pregnancies of unknown location and prediction of first trimester viability
Authors: Al‐Memar Maya , Bobdiwala Shabnam , Madhra Mayank , Saso Srdjan , De Cock Bavo , Van Calster Ben , Brown Jeremy K. , Mukri Faizah , Bottomley Cecilia , Papageorghiou Aris , Timmerman Dirk , Horne Andrew W. , Bourne Tom
Published: April 2018

Aim

We have assessed the potential predictive ability of the biomarkers activin B and fibronectin (FN1) alone and when added to established markers for triaging patients as being at low or high risk of ectopic pregnancy (EP). We also assessed their use as predictors of viability at 12 weeks gestation.

Methods

Exploratory secondary analysis of a prospective study including all women classified as a pregnancy of known location (PUL) based on transvaginal ultrasonography between January and December 2007 at the early pregnancy unit of St Georges’ Hospital (London). We used multinomial logistic regression to assess the diagnostic potential of the biomarkers to triage PUL at high risk of complications (EP or persistent PUL), and standard binary logistic regression to predict first trimester viability at 12 weeks.

Results

For discriminating high‐risk (n = 16) from low‐risk PUL (n = 93), the area under the receiver operating characteristic curve (AUC) was 0.75 (95% confidence interval 0.60–0.85) for activin B and 0.55 (0.41–0.68) for FN1. Adding activin B to a multinomial logistic regression model incorporating β‐hCG ratio and initial progesterone yielded odds ratios of 0.16 (0.05–0.55) for failing vs high‐risk PUL and 0.29 (0.07–1.19) for intrauterine vs high‐risk PUL and increased the model's AUC from 0.84 to 0.89. At a risk threshold of 5% for high‐risk PUL, sensitivity increased from 84% to 87% and specificity from 48% to 64%. For discriminating viable (n = 28) from non‐viable (n = 81) pregnancies at 12 weeks, both markers had an AUC of 0.54.

Conclusions

Our results suggested that activin B may be a promising marker to improve PUL triage in addition to established markers.
Improving precision of second‐trimester biometry
Authors: Loiacono Christy , Bethune Michael , Schneider Michal , Lombardo Paul
Published: April 2018

Objective

To utilise image score‐based criteria for second‐trimester fetal biometry as an educational tool to improve biometry quality.

Methods

Five sonographers regularly performing obstetric ultrasound examinations were recruited for this study. Biometry images were collected from fifteen second‐trimester examinations for each sonographer prior to participating in a biometry education session, and another set of biometry images were collected from fifteen second‐trimester examinations following the education session. The education session was a one‐hour presentation that explained image score‐based criteria to evaluate and grade the quality of the bi‐parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) and humeral length (HL) biometry parameters. Each of the five sonographers performed a total of 30 examinations (15 pre‐ and 15 post‐education session). From these examinations, a total of 150 images were collected for each biometry parameter (75 pre‐ and 75 post‐education). A total of 600 biometry images were evaluated. Images from both the pre‐ and post‐education session were assessed by an obstetrician sonologist using the same image score‐based criteria. Pre‐ and post‐image scores were compared using paired t‐tests.

Results

Improvement in the mean image scores for all biometry parameters was observed after the education session. The difference between pre‐ and post‐education image quality scores was significant for the AC (P = 0.01), FL (P = 0.002) and for the overall score (P = 0.001).

Conclusion

Implementing an image score‐based criteria evaluation technique is a simple and useful method to improve fetal biometry precision.
A Two‐Dimensional Ruddlesden–Popper Perovskite Nanowire Laser Array based on Ultrafast Light‐Harvesting Quantum Wells
Authors: Zhang Haihua , Wu Yishi , Liao Qing , Zhang Zhaoyi , Liu Yanping , Gao Qinggang , Liu Peng , Li Meili , Yao Jiannian , Fu Hongbing
Published: April 2018

Miniaturized nanowire nanolasers of 3D perovskites feature a high gain coefficient; however, room‐temperature optical gain and nanowire lasers from 2D layered perovskites have not been reported to date. A biomimetic approach is presented to construct an artificial ligh‐harvesting system in mixed multiple quantum wells (QWs) of 2D‐RPPs of (BA)2(FA)n−1PbnBr3n+1, achieving room‐temperature ASE and nanowire (NW) lasing. Owing to the improvement of flexible and deformable characteristics provided by organic BA cation layers, high‐density large‐area NW laser arrays were fabricated with high photostability. Well‐controlled dimensions and uniform geometries enabled 2D‐RPPs NWs functioning as high‐quality Fabry–Perot (FP) lasers with almost identical optical modes, high quality (Q) factor (ca. 1800), and similarly low lasing thresholds.
A Self‐Reporting Photocatalyst for Online Fluorescence Monitoring of High Throughput RAFT Polymerization
Authors: Yeow Jonathan , Joshi Sanket , Chapman Robert , Boyer Cyrille
Published: April 2018

Translating controlled/living radical polymerization (CLRP) from batch to the high throughput production of polymer libraries presents several challenges in terms of both polymer synthesis and characterization. Although recently there have been significant advances in the field of low volume, high throughput CLRP, techniques able to simultaneously monitor multiple polymerizations in an “online” manner have not yet been developed. Here, we report our discovery that 5,10,15,20‐tetraphenyl‐21H,23H‐porphine zinc (ZnTPP) is a self‐reporting photocatalyst that can mediate PET‐RAFT polymerization as well as report on monomer conversion via changes in its fluorescence properties. This enables the use of a microplate reader to conduct high throughput “online” monitoring of PET‐RAFT polymerizations performed directly in 384‐well, low volume microtiter plates.
An Ultra‐Robust and Crystalline Redeemable Hydrogen‐Bonded Organic Framework for Synergistic Chemo‐Photodynamic Therapy
Authors: Yin Qi , Zhao Peng , Sa Rong‐Jian , Chen Guang‐Cun , Lü Jian , Liu Tian‐Fu , Cao Rong
Published: April 2018

The low structural stability of hydrogen‐bonded organic frameworks (HOFs) is a thorny issue retarding the development of HOFs. A rational design approach is now proposed for construction of a stable HOF. The resultant HOF (PFC‐1) exhibits high surface area of 2122 m2 g−1 and excellent chemical stability (intact in concentrated HCl for at least 117 days). A new method of acid‐assisted crystalline redemption is used to readily cure the thermal damage to PFC‐1. With periodic integration of photoactive pyrene in the robust framework, PFC‐1 can efficiently encapsulate Doxorubicin (Doxo) for synergistic chemo‐photodynamic therapy, showing comparable therapeutic efficacy with the commercial Doxo yet considerably lower cytotoxicity. This work demonstrates the notorious stability issue of HOFs can be properly addressed through rational design, paving a way to develop robust HOFs and offering promising application perspectives.
A Persulfide Donor Responsive to Reactive Oxygen Species: Insights into Reactivity and Therapeutic Potential
Authors: Powell Chadwick R. , Dillon Kearsley M. , Wang Yin , Carrazzone Ryan J. , Matson John B.
Published: April 2018

Persulfides (RSSH) have been hypothesized as critical components in sulfur‐mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H2S). Hindering the study of persulfides is a lack of persulfide‐donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS‐responsive (ROS=reactive oxygen species), self‐immolative persulfide donor. The donor, termed BDP‐NAC, showed selectivity towards H2O2 over other potential oxidative or nucleophilic triggers, resulting in the sustained release of the persulfide of N‐acetyl cysteine (NAC) over the course of 2 h, as measured by LCMS. Exposure of H9C2 cardiomyocytes to H2O2 revealed that BDP‐NAC mitigated the effects of a highly oxidative environment in a dose‐dependent manner over relevant controls and to a greater degree than common H2S donors sodium sulfide (Na2S) and GYY4137. BDP‐NAC also rescued cells more effectively than a non‐persulfide‐releasing control compound in concert with common H2S donors and thiols.
Synthesis of CuS and ZnO/Zn(OH)2 nanoparticles and their evaluation for in vitro antibacterial and antifungal activities
Authors: Zare Khafri Hossein , Ghaedi Mehrorang , Asfaram Arash , Javadian Hamedreza , Safarpoor Mohammad
Published: April 2018

In this study, the copper sulfide nanoparticles (CuS‐NPs) and the zinc oxide/zinc hydroxide nanoparticles ((ZnO/Zn(OH)2‐NPs) were synthesized by a simple and low‐cost method, and the synthesized nanoparticles were characterized and identified by UV–Vis, field emission scanning electron microscopy (FE‐SEM), transmission electron microscopy (TEM) and X‐ray diffraction (XRD). The antimicrobial activity of the CuS‐NPs and the ZnO/Zn(OH)2‐NPs were examined by broth dilution to determine the minimal inhibitory concentration (MIC) of antibacterial agent required to inhibit the growth of a pathogen and the minimum bactericidal concentration (MBC) required to kill a particular bacterium. Agar disc diffusion method was used to determine the zone of inhibition. The nanoparticles demonstrated potent antibacterial activity against Klebsiella pneumonia (ATCC 1827), Acinetobacter baumannii (ATCC 150504), Escherichia coli (ATCC 33218) and Staphylococcus aureus (ATCC 25293). Antifungal activity against Aspergillus oryzae (PTCC 5164) was also obtained. The data obtained from antimicrobial activities by broth dilution and agar disc diffusion methods exhibited the CuS‐NPs were more effective than the ZnO/Zn(OH)2‐NPs. A good correlation was observed between the data obtained by both methods.
Regulation of Integrated Stress Response Sensitizes U87MG Glioblastoma Cells to Temozolomide Through the Mitochondrial Apoptosis Pathway
Authors: He Yichun , Meng Hao , Xu Huadan , Fan Linghua , Zhou Zijian , Xu Bo , Sun Liankun , Gao Yufei
Published: April 2018

Glioblastomas are the most frequently diagnosed and worst primary malignancy of the central nervous system, with very poor prognosis. The first‐line antiglioma drug temozolomide shows decreasing therapeutic efficacy as treatment progresses. As the integrated stress response (ISR) may be a resistance factor and severe stress might transform the protective effect of the ISR into a damage effect, pharmacological regulation of ISR may be an effective way to sensitize glioma to temozolomide. The aim of the present study was to investigate the mechanisms of the ISR in regulating the therapeutic effect of temozolomide in the human glioblastoma multiforme cell line U87MG. Cultured U87MG cells were treated with temozolomide and PCR array was used to screen key factors in the response to treatment. Cells were co‐treated with temozolomide and the eIF2α phosphatase inhibitor salubrinal, and cell apoptosis was measured. Combination treatment with temozolomide and salubrinal had a synergistic effect on cell viability. Salubrinal could upregulate the expression of ATF4, a key factor in the ISR, and enhance temozolomide‐induced apoptosis. ATF4 transcriptionally regulated expression of the BH3‐ONLY protein NOXA, thus inducing mitochondrial apoptosis. These findings suggest that ISR and ATF4 are involved in the death crosstalk between the endoplasmic reticulum and mitochondria and might be a potential target to enhance the therapeutic effect of temozolomide in patients with glioblastoma multiforme. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.
Molecular Profiling and Clonal Tracking of Secreted Rheumatoid Factors in Primary Sjögren's Syndrome
Authors: Wang Jing J. , Reed Joanne H. , Colella Alex D. , Russell Amanda J. , Murray‐Brown William , Chataway Tim K. , Jackson Katherine J. L. , Goodnow Christopher C. , Gordon Tom P.
Published: April 2018

Objective

Rheumatoid factors (RFs) are associated with systemic disease in primary Sjögren's syndrome (SS) and may be pathogenic as mixed cryoglobulins. Current detection methods cannot resolve RFs at a molecular level. This study was undertaken to perform the first proteomic and transcriptomic analysis of secreted and membrane‐bound IgM‐RF in primary SS and identify unique heavy‐chain peptide signatures for RF clonotype tracking.

Methods

Purified heavy chains of serum RFs from 15 patients with primary SS were subjected to de novo mass spectrometric sequencing. The circulating B cell Ig repertoire was determined by massively parallel sequencing of IGH RNA from matched peripheral blood mononuclear cells (n = 7). RF‐specific heavy‐chain third complementarity‐determining region (CDR3) peptides were identified by searching RF heavy‐chain peptide sequences against the corresponding IGH RNA sequence libraries. Heavy‐chain CDR3 peptides were used as biomarkers to track serum RF clonotypes using quantitative multiple reaction monitoring.

Results

Serum RFs were clonally restricted and composed of shared sets of IgM heavy‐chain variable region (Ig VH) 1–69, 3–15, 3–7, and 3–74 subfamilies. Cryoprecipitable RFs from patients with mixed cryoglobulinemia (MC) were distinguishable from nonprecipitating RFs by a higher frequency of amino acid substitutions and identification of stereotypic heavy‐chain CDR3 transcripts. Potentially pathogenic RF clonotypes were detected in serum by multiple reaction monitoring years before patients presented with MC. Levels of Ig VH4–34 IgM‐RF decreased following immunosuppression and remission of MC.

Conclusion

Cryoprecipitable RF clonotypes linked to vasculitis in primary SS have different molecular profiles than nonprecipitating RFs, suggesting different underlying mechanisms of production. The combined omics workflow presented herein provides molecular biomarkers for tracking and removal of pathogenic RF clones.
Bayesian planning of step‐stress accelerated degradation tests under various optimality criteria
Authors: Zhao Xiujie , Pan Rong , Xie Min
Published: April 2018

Step‐stress accelerated degradation testing (SSADT) has become a common approach to predicting lifetime for highly reliable products that are unlikely to fail in a reasonable time under use conditions or even elevated stress conditions. In literature, the planning of SSADT has been widely investigated for stochastic degradation processes, such as Wiener processes and gamma processes. In this paper, we model the optimal SSADT planning problem from a Bayesian perspective and optimize test plans by determining both stress levels and the allocation of inspections. Large‐sample approximation is used to derive the asymptotic Bayesian utility functions under 3 planning criteria. A revisited LED lamp example is presented to illustrate our method. The comparison with optimal plans from previous studies demonstrates the necessity of considering the stress levels and inspection allocations simultaneously.
Constructing Proton‐conducting Channels within Sulfonated(Poly Arylene Ether Ketone) Using Sulfonated Graphene Oxide: A Nano‐Hybrid Membrane for Proton Exchange Membrane Fuel Cells
Authors: Jang Hye Ri , Vinothkannan Mohanraj , Kim Ae Rhan , Yoo Dong Jin
Published: April 2018

Nano‐hybrid membranes made up using sulfonated (poly‐arylene ether ketone) (SPAEK) and sulfonated graphene oxide (SGO) with various weight ratio i.e., 0.5, 1 and/or 1.5 wt % were fabricated with a traditional solvent casting approach and their appropriateness for the potential application of proton exchange membrane fuel cells (PEMFCs) was probed. Structural characteristics of membranes were substantiated by 1H NMR, FT‐IR, and XRD. The composite membranes revealed the outstanding thermal property with a primary weight drop at temperature of 200 °C, as proved by TGA analysis. TM‐AFM images of composite membrane revealed the phase separated morphology of hydrophobic and hydrophilic regions, which afford the wide pathways for swift and easy conduction of protons. Additionally, integration of SGO dramatically raises the water absorption and consequently proton conductivity, whereas it decreases activation energy needed to transfer the protons via membrane. Proton conductivity value of 124 mS/cm was acquired using 1.5 wt % SGO/SPAEK composite membrane with a higher volume of water absorption i.e., 19%.
Recording routine forensic mental health evaluations should be a standard of practice in the 21st century
Authors: Siegel David M. , Kinscherff Robert
Published: April 2018

The standard of practice for forensic interviews in criminal and delinquency cases, other than those conducted as part of brief preliminary screening evaluations or in emergency situations, should include a digital recording requirement. This standard should be adopted because of the greater availability of, and familiarity with, recording technology on the part of mental health professionals, the greater use and proven effectiveness of recording in other contexts of the criminal justice system, and the improvement in court presentation and accuracy of judicial determinations involving forensic assessments that recording will provide. The experience of practitioners with recording since professional associations last studied the issue should be taken into account, as informal data suggest it has been positive. Unfortunately, the legal system is unlikely to prompt this advance without its reconsideration by the forensic mental health professions, because current constitutional jurisprudence does not require recording and effectively makes it contingent upon request by examiners. Forensic evaluators thus have a valuable opportunity to educate the legal system on the utility and importance of this key reform, and so should adopt it as a best practice.
Molecular interactions between vinculin and phospholipids
Authors: Goldmann Wolfgang H.
Published: April 2018

The focal adhesion protein vinculin has been implicated in associating with soluble and membranous phospholipids. Detailed investigations over the past ten years describe the intermolecular interactions of the vinculin tail domain with soluble and membrane phospholipids. Previous studies have implied that the tail's unstructured C‐terminal region affects the mechanical behavior of cells and that the same region, at the molecular level, has bi‐stable behavior sensitive to different protonation states. The aim of this short communication is to discuss whether the C‐terminal vinculin tail (Vt) domain interacts favorably with membrane‐embedded phospholipids such as PIP2 and that the region is also an anchor for lipid membranes.
From a stone to rupture: calyceal rupture secondary to obstructive uropathy
Authors: Kheiri Babikir , Kazmi Ismail , Madala Seetharamprasad , Abu Sitta Emad
Published: April 2018

Key Clinical Message

Renal collecting system rupture is a rare manifestation of obstructive uropathy. The majority of cases are attributed to ureteric calculi and extrinsic ureteric compression. The optimal diagnostic image is contrast‐enhanced CT scan with delayed phase protocol. Management is usually conservative and generally depends on the etiology, urinomas size, and the presence or absence of kidney failure or infections.
Impact of Catalyst Geometry on Diffusion and Selective Catalytic Reduction Kinetics under Elevated Pressures
Authors: Peitz Daniel , Elsener Martin , Kröcher Oliver
Published: April 2018

In marine diesel engine applications, selective catalytic reduction (SCR) upstream of the turbocharger may become the preferred technology when dealing with high sulfur fuels and low exhaust gas temperatures. The target nitrogen oxide reductions in combination with minimum ammonia slip and reduced gas diffusion rates under elevated pressures require understanding of the impact of catalyst geometry on the SCR kinetics. The extent, trends, and sources for this observation are elucidated in this work by systematic testing of catalysts with equal geometry and/or intrinsic activity.
Zigzag pore based molecular simulation on the separation of CO2/CH4 mixture by carbon membrane
Authors: Pan Yanqiu , He Liu , Wang Wei , Wang Tonghua , Yu Lu
Published: April 2018

A zigzag‐type pore structure was proposed for the separation of a CO2/CH4 binary mixture by carbon molecular sieve membrane (CMSM). A defect‐free pore and three kinds of defect pores, i.e., random, uniform, and partial defect, were considered to improve the separation performance. Adsorption and diffusion behaviours of pure gases and a gas mixture were simulated by the grand canonical Monte Carlo (GCMC) method and non‐equilibrium molecular dynamics (NEMD) method, respectively. The pressure ranged from 10–100 kPa and the temperature was between 273–348 K during simulation. The calculated isotherms of CO2 and CH4 showed an acceptable agreement with the experimental data for the defect‐free pores of 0.67 nm in size at 298 K. Examination on the effect of pore sizes showed that 0.67 nm was the appropriate option for separation. The total selectivity was 20.1 at 298 K and 100 kPa with the pore size of 0.67 nm, which is consistent with the experimental value. The adsorption was determined as the dominant separation mechanism between adsorption and diffusion. Compared with the defect‐free pores, the introduction to the random and uniform defect pores can improve the total selectivities and the random defect provided superior separation performance. An appropriately low temperature and small pore size were beneficial to the separation.
Long‐term results of combined cardiac contractility modulation and subcutaneous defibrillator therapy in patients with heart failure and reduced ejection fraction
Authors: Röger Susanne , Rudic Boris , Akin Ibrahim , Shchetynska‐Marinova Tetyana , Fastenrath Fabian , Tülümen Erol , Liebe Volker , El‐Battrawy Ibrahim , Baumann Stefan , Kuschyk Jürgen , Borggrefe Martin
Published: April 2018

Background

Cardiac contractility modulation (CCM) is an electrical‐device therapy for patients with heart failure with reduced ejection fraction (HFrEF). Patients with left ventricular ejection fraction (LVEF) ≤35% also have indication for an implantable cardioverter‐defibrillator (ICD), and in some cases subcutaneous ICD (S‐ICD) is selected.

Hypothesis

CCM and S‐ICD can be combined to work efficaciously and safely.

Methods

We report on 20 patients with HFrEF and LVEF ≤35% who received CCM and S‐ICD. To exclude device interference, patients received intraoperative crosstalk testing, S‐ICD testing, and bicycle exercise testing while CCM was activated. Clinical and QOL measures before CCM activation and at last follow‐up were analyzed. S‐ICD performance was evaluated while both CCM and S‐ICD were active.

Results

Mean follow‐up was 34.3 months. NYHA class improved from 2.9 ± 0.4 to 2.1 ± 0.7 (P < 0.0001), Minnesota Living With Heart Failure Questionnaire score improved from 50.2 ± 23.7 to 29.6 ± 22.8 points (P < 0.0001), and LVEF improved from 24.4% ± 8.1% to 30.9% ± 9.6% (P = 0.002). Mean follow‐up time with both devices active was 22 months. Three patients experienced a total of 6 episodes of sustained ventricular tachycardia, all successfully treated with first ICD shock. One case received an inappropriate shock unrelated to the concomitant CCM. One patient received an LVAD, so CCM and S‐ICD were discontinued.

Conclusions

CCM and S‐ICD can be successfully combined in patients with HFrEF. S‐ICD and CCM remain efficacious when used together, with no interference affecting their function.
Treatment of Crystal Violet from Synthetic Solution Using Membranes Doped with Natural Fruit Extract
Authors: Caprarescu Simona , Miron Alexandra R. , Purcar Violeta , Radu Anita‐Laura , Sarbu Andrei , Nicolae Cristian Andi , Pascu Mihaela (Neagu) , Ion‐Ebrasu Daniela , Raditoiu Valentin
Published: April 2018

Innovative polymer membranes with and without natural fruit extract (rosehip) are characterized in terms of their ability of treating a solution containing Crystal violet by a three‐compartment laboratory scale electro‐dialysis cell. Electro‐dialysis is performed at different time intervals and using a constant voltage of 15 V. The dye removal percentage (%) and energy consumption are calculated. The highest value of dye removal is obtained for 90 min (>96%) for membranes doped with natural fruit extract. Water uptake is also determined for the prepared membranes. The physical and chemical properties of the final membranes are investigated by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and thermal gravimetric analysis‐differential scanning calorimetry (TGA‐DSC). FTIR spectra indicated no significant modifications of membrane structure due to the small amount of natural fruit extract. The surface morphology shows that the prepared membranes doped with natural fruit extract is more dense and compact. TGA results shows that the prepared membranes are stable up to 330 °C.
Regimen of procarbazine, lomustine, and vincristine versus temozolomide for gliomas
Authors: Wick Wolfgang , Winkler Frank
Published: April 2018

Both temozolomide and the regimen of procarbazine, lomustine, and vincristine (PCV) prolong survival in patients with malignant gliomas when used as an adjuvant to radiotherapy (temozolomide in patients with newly diagnosed glioblastoma and 1p/19q non‐codeleted anaplastic gliomas and PCV in both those patients with newly diagnosed high‐risk low‐grade gliomas and those with 1p/19q codeleted anaplastic oligodendrogliomas). However, there is debate regarding the appropriate alkylating regimen to use for individuals with glial neoplasms. Balancing survival advantages versus risks of toxicity and impact on quality of life are important elements of this debate.
Planar Perovskite Solar Cells with High Open‐Circuit Voltage Containing a Supramolecular Iron Complex as Hole Transport Material Dopant
Authors: Saygili Yasemin , Turren‐Cruz Silver‐Hamill , Olthof Selina , Saes Bartholomeus Wilhelmus Henricus , Pehlivan Ilknur Bayrak , Saliba Michael , Meerholz Klaus , Edvinsson Tomas , Zakeeruddin Shaik M. , Grätzel Michael , Correa‐Baena Juan‐Pablo , Hagfeldt Anders , Freitag Marina , Tress Wolfgang
Published: April 2018

In perovskite solar cells (PSCs), the most commonly used hole transport material (HTM) is spiro‐OMeTAD, which is typically doped by metalorganic complexes, for example, based on Co, to improve charge transport properties and thereby enhance the photovoltaic performance of the device. In this study, we report a new hemicage‐structured iron complex, 1,3,5‐tris(5′‐methyl‐2,2′‐bipyridin‐5‐yl)ethylbenzene Fe(III)‐tris(bis(trifluoromethylsulfonyl)imide), as a p‐type dopant for spiro‐OMeTAD. The formal redox potential of this compound was measured as 1.29 V vs. the standard hydrogen electrode, which is slightly (20 mV) more positive than that of the commercial cobalt dopant FK209. Photoelectron spectroscopy measurements confirm that the iron complex acts as an efficient p‐dopant, as evidenced in an increase of the spiro‐OMeTAD work function. When fabricating planar PSCs with the HTM spiro‐OMeTAD doped by 5 mol % of the iron complex, a power conversion efficiency of 19.5 % (AM 1.5G, 100 mW cm−2) is achieved, compared to 19.3 % for reference devices with FK209. Open circuit voltages exceeding 1.2 V at 1 sun and reaching 1.27 V at 3 suns indicate that recombination at the perovskite/HTM interface is low when employing this iron complex. This work contributes to recent endeavors to reduce recombination losses in perovskite solar cells.
Functional Pituitary Tissue Generation from Human Embryonic Stem Cells
Authors: Kano Mayuko , Suga Hidetaka , Kasai Takatoshi , Ozone Chikafumi , Arima Hiroshi
Published: April 2018

The anterior pituitary gland produces several hormones essential for regulation of the somatic endocrine system. Deficiency of these hormones can cause life‐threatening diseases, including adrenal crisis. Pituitary tissue generated from human pluripotent stem cells is expected to provide better treatment than current hormone replacement therapy. During early mammalian development, the pituitary anlage (Rathke's pouch) develops from non‐neural ectoderm adjacent to the developing ventral hypothalamus. The close interaction between these two tissues is crucial for Rathke's pouch development and involves several signaling molecules. Early exposure of human embryonic stem cells in 3D floating culture to sonic hedgehog and bone morphogenetic protein 4 promoted the cells’ differentiation into oral ectoderm and, subsequently, hormone‐producing cells such as corticotrophs (adrenocorticotropic hormone–producing cells). The differentiation approach described herein, which induces the formation of pituitary tissue in contact with hypothalamic neural tissue, mimics mammalian pituitary development. The differentiated corticotrophs are functional, responding normally to both release and feedback signals. © 2018 by John Wiley & Sons, Inc.
Interpretation of the Ultrasonic Effect on Induction Time During BaSO4 Heterogeneous Nucleation by a Cluster Coagulation Model
Authors: Guo Zhichao , Zhang Xiaoguo , Han Wenxiang , Li Liye , Wang Lixia
Published: April 2018

The effect of ultrasound on BaSO4 nucleation is studied by measuring the induction time when nucleation is predominantly heterogeneous. In the experiments, barium sulphate is used as the working substance precipitated by mixing aqueous BaCl2 and Na2SO4 solutions with relatively low concentrations compared to the experiments of homogeneous nucleation. It is observed that at a given supersaturation level, the induction time decreases significantly with increasing ultrasonic energy during heterogeneous nucleation. In addition, the effect of ultrasound on nucleation order and the nucleation coefficient in the empirical model of nucleation rate are also investigated and compared with the corresponding effects during homogeneous nucleation.
Separation of Nucleobases Using High‐performance Liquid Chromatography Coupled with Voltammetric Scanning
Authors: Zitka Ondrej , Kudr Jiri , Labuda Jan , Xhaxhiu Kledi , Adam Vojtech
Published: April 2018

In this paper, a method based on chromatographic separation of analytes and their quantification using on‐line cyclic voltammetry is reported. The method based on high performance liquid chromatography on reverse phase column was optimized using free nucleobases‐guanine, adenine, thymine, and cytosine. The optimal separation of nucleobases was detected when using 0.05 M borate buffer (pH 9.0) as the mobile phase, at isocratic flow rate 1 mL min−1, and at separation column temperature of 30 °C. The accurate timing of the cyclic voltammetry enabled us to quantify the concentrations of individual nucleobases by oxidation on glassy carbon electrode.
A chemical activity approach to exposure and risk assessment of chemicals
Authors: Gobas Frank A.P.C. , Mayer Philipp , Parkerton Thomas F. , Burgess Robert M. , van de Meent Dik , Gouin Todd
Published: April 2018

To support the goals articulated in the vision for exposure and risk assessment in the twenty-first century, we highlight the application of a thermodynamic chemical activity approach for the exposure and risk assessment of chemicals in the environment. The present article describes the chemical activity approach, its strengths and limitations, and provides examples of how this concept may be applied to the management of single chemicals and chemical mixtures. The examples demonstrate that the chemical activity approach provides a useful framework for 1) compiling and evaluating exposure and toxicity information obtained from many different sources, 2) expressing the toxicity of single and multiple chemicals, 3) conducting hazard and risk assessments of single and multiple chemicals, 4) identifying environmental exposure pathways, and 5) reducing error and characterizing uncertainty in risk assessment. The article further illustrates that the chemical activity approach can support an adaptive management strategy for environmental stewardship of chemicals where “safe” chemical activities are established based on toxicological studies and presented as guidelines for environmental quality in various environmental media that can be monitored by passive sampling and other techniques. Environ Toxicol Chem 2018;37:1235–1251. © 2018 The Authors. Published by Wiley Periodicals, Inc. on behalf of SETAC.
The anticipation and outcome phases of reward and loss processing: A neuroimaging meta‐analysis of the monetary incentive delay task
Authors: Oldham Stuart , Murawski Carsten , Fornito Alex , Youssef George , Yücel Murat , Lorenzetti Valentina
Published: April 2018

The processing of rewards and losses are crucial to everyday functioning. Considerable interest has been attached to investigating the anticipation and outcome phases of reward and loss processing, but results to date have been inconsistent. It is unclear if anticipation and outcome of a reward or loss recruit similar or distinct brain regions. In particular, while the striatum has widely been found to be active when anticipating a reward, whether it activates in response to the anticipation of losses as well remains ambiguous. Furthermore, concerning the orbitofrontal/ventromedial prefrontal regions, activation is often observed during reward receipt. However, it is unclear if this area is active during reward anticipation as well. We ran an Activation Likelihood Estimation meta‐analysis of 50 fMRI studies, which used the Monetary Incentive Delay Task (MIDT), to identify which brain regions are implicated in the anticipation of rewards, anticipation of losses, and the receipt of reward. Anticipating rewards and losses recruits overlapping areas including the striatum, insula, amygdala and thalamus, suggesting that a generalised neural system initiates motivational processes independent of valence. The orbitofrontal/ventromedial prefrontal regions were recruited only during the reward outcome, likely representing the value of the reward received. Our findings help to clarify the neural substrates of the different phases of reward and loss processing, and advance neurobiological models of these processes.
Demand of long‐term care and benefit eligibility across European countries
Authors: Carrino Ludovico , Orso Cristina Elisa , Pasini Giacomo
Published: April 2018

In this paper, we study how elderly individuals adjust their informal long‐term care utilization to changes in the provision of formal care. Despite this is crucial to design effective policies of formal elderly care, empirical evidence is scant due to the lack of credible identification strategies to account for the endogeneity of formal care. We propose a novel instrument, an index that captures individuals' eligibility status for the long‐term care programs implemented in the region of residence. Our estimates, which are robust to a number of different specifications, suggest that higher formal care provision would lead to an increase in informal care utilization as well. In the context of current theoretical economic model of care use, this result points to the existence of a substantial unmet demand of care among older people in Europe.
Parabacteroides distasonis attenuates toll‐like receptor 4 signaling and Akt activation and blocks colon tumor formation in high‐fat diet‐fed azoxymethane‐treated mice
Authors: Koh Gar Yee , Kane Anne , Lee Kyongbum , Xu Qiaobing , Wu Xian , Roper Jatin , Mason Joel B. , Crott Jimmy W.
Published: April 2018

Gut dysbiosis may play an etiological role in colorectal tumorigenesis. We previously observed that the abundance of Parabacteroides distasonis (Pd) in stool was inversely associated with intestinal tumor burden and IL‐1β concentrations in mice. Here, we assessed the anti‐inflammatory capacity of Pd membrane fraction (PdMb) in colon cancer cell lines. In addition, we tested whether Pd could suppress colon tumorigenesis in mice. Six‐week‐old male A/J mice were fed a low‐fat (LF) diet, high‐fat (HF) diet or HF+ whole freeze‐dried Pd (HF + Pd, 0.04% wt/wt) for 24 weeks. After 1 week on diet, mice received 4 weekly injections of azoxymethane. PdMb robustly suppressed the production of pro‐inflammatory cytokines and lowered the abundance of MyD88 and pAkt (ser473) induced by E. coli lipopolysaccharide in colon cancer cell lines. Moreover, PdMb induced apoptosis in colon cancer cell lines and blocked TLR4 activation in a reporter line. Colon tumors were observed in 0% of LF (0 of 19), 25% of HF (5 of 20) and 0% of HF + Pd mice (0 of 20) (p = 0.005). The latter group also displayed a lower abundance of MyD88 and pAkt (ser473) in colonic mucosa than HF mice. Taken together, these data suggest that Pd has anti‐inflammatory and anti‐cancer properties that are likely mediated by the suppression of TLR4 and Akt signaling, as well as promotion of apoptosis. Further work is needed to confirm these findings in additional models and fully elaborate the mechanism of action.
A time for YAP1: Tumorigenesis, immunosuppression and targeted therapy
Authors: Shibata Masahiro , Ham Kendall , Hoque Mohammad Obaidul
Published: April 2018

YAP1 is one of the most important effectors of the Hippo pathway and has crosstalk with other cancer promoting pathways. YAP1 contributes to cancer development in various ways that include promoting malignant phenotypes, expansion of cancer stem cells and drug resistance of cancer cells. Because pharmacologic or genetic inhibition of YAP1 suppresses tumor progression and increases the drug sensitivity, targeting YAP1 may open a fertile avenue for a novel therapeutic approach in relevant cancers. Recent enormous studies have established the efficacy of immunotherapy, and several immune checkpoint blockades are in clinical use or in the phase of development to treat various cancer types. Immunosuppression in the tumor microenvironment (TME) induced by cancer cells, immune cells and associated stromal cells promotes tumor progression and causes drug resistance. Accumulated evidences of scientific efforts from the last few years suggest that YAP1 influences macrophages, myeloid‐derived suppressor cells and regulatory T‐cells to facilitate immunosuppressive TME. Although the underlying mechanisms is not clearly discerned, it is evident that YAP1 activating pathways in different cellular components induce immunosuppressive TME. In this review, we summarize the evidences involved in the dual roles of YAP1 in cancer development and immunosuppression in the TME. We also discuss the possibility of YAP1 as a novel therapeutic target.
Therapeutic targeting of tumor‐associated macrophages in pancreatic neuroendocrine tumors
Authors: Krug Sebastian , Abbassi Rami , Griesmann Heidi , Sipos Bence , Wiese Dominik , Rexin Peter , Blank Annika , Perren Aurel , Haybaeck Johannes , Hüttelmaier Stefan , Rinke Anja , Gress Thomas M. , Michl Patrick
Published: April 2018

Pancreatic neuroendocrine tumors (PNETs) represent a heterogeneous group of neuroendocrine neoplasms with varying biological behavior and response to treatment. Although targeted therapies have been shown to improve the survival for patients at advanced stage, resistance to current therapies frequently occurs during the course of therapy. Previous reports indicate that the infiltration of tumor‐associated macrophages (TAMs) in PNETs might correlate with tumor progression and metastasis formation. We aimed to evaluate the prognostic and functional impact of TAMs in human PNETs in vitro and in vivo and to investigate the effect of therapeutic targeting TAMs in a genetic PNET mouse model. TAM expression pattern was assessed immunohistochemically in human PNET tissue sections and a tissue‐micro‐array of PNET tumors with different functionality, stage, and grading. The effect of liposomal clodronate on TAM cell viability was analyzed in myeloid cell lines and isolated murine bone macrophages (mBMM). In vivo, RIP1Tag2 mice developing insulinomas were treated with liposomal clodronate or PBS‐Liposomes. Tumor progression, angiogenesis and immune cell infiltration were assessed by immunohistochemistry. In human, insulinomas TAM density was correlated with invasiveness and malignant behavior. Moreover, TAM infiltration in liver metastases was significantly increased compared to primary tumors. In vitro, Liposomal clodronate selectively inhibited the viability of myeloid cells and murine bone macrophages, leaving PNET tumor cell lines largely unaffected. In vivo, repeated application of liposomal clodronate to RIP1Tag2 mice significantly diminished the malignant transformation of insulinomas, which was accompanied by a reduced infiltration of F4/80‐positive TAM cells and simultaneously by a decreased microvessel density, suggesting a pronounced effect of clodronate‐induced myeloid depletion on tumor angiogenesis. Concomitant treatment with the antiangiogenic TKI sunitinib, however, did not show any synergistic effects with liposomal clodronate. TAMs are crucial for malignant transformation in human PNET and correlate with metastatic behavior. Pharmacological targeting of TAMs via liposomal clodronate disrupts tumor progression in the RIP1Tag2 neuroendocrine tumor model and was associated with reduced tumor angiogenesis. Based on these results, using liposomal clodronate to target proangiogenic myeloid cells could be employed as novel therapeutic avenue in highly angiogenic tumors such as PNET.
The potential of ICT‐supported participatory communication interventions to challenge local power dynamics: Lessons from the case of Togo
Authors: Breuer Anita , Blomenkemper Laura , Kliesch Stefan , Salzer Franziska , Schädler Manuel , Schweinfurth Valentin , Virchow Stephen
Published: April 2018

This paper adds to the debate on the contribution of ICT towards improving the quality of local governance. The data presented were collected during the scoping phase of an ICT‐based participation platform aimed at improving local governance in Togo. We combine original data from a social network analysis and a representative household survey. Based on these data, we conclude that the success of ICT interventions to transform local power structures depends on their adequate adaption to the political and technical environment. Decisions about the stage of the public policy cycle at which ICT projects intervene must be informed by the nature of local power relations and the distribution of access to ICT and participation opportunities across the intervention's target population.