bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial Transpedal MR-Lymphangiography of Central Lymphatics Using a Standard MR Contrast Agent: Feasibility and Initial Results in Patients with Chylous Effusions
Authors: Pieper Claus , Schild Hans
Published: April 2018

Purpose To describe a novel technique for transpedal magnetic resonance lymphangiography (tMRL) with interstitial injection of a standard gadolinium-based contrast agent, and to assess its ability to visualize the central lymphatic system (CLS) in patients with chylous effusions.

Materials and Methods Experiences with tMRL were retrospectively reviewed in seven patients with chylous effusions. High-resolution three-dimensional multi-echo (mDIXON) images of the entire torso were obtained before and after interstitial injection of an extracellular gadolinium-based contrast agent. MR examinations were assessed qualitatively by two radiologists with respect to visualization of central lymphatics, delineation of their anatomy and presence of a lymphatic pathology (chylolymphatic leakage or reflux).

Results Examination was technically successful in 6/7 patients. tMRL confirmed the location of chylolymphatic leakage in 3/7, demonstrated a lymphatic malformation in 1/7, chylolymphatic reflux in 1/7, and confirmed normal chylolymphatic flow in the central lymphatics in 1/7 patients. In one patient neither CLS enhancement nor leakage were detectable. tMRL findings were considered helpful in all technically successful cases, and considerably influenced further treatment in four patients. All examinations were well tolerated without complications. No general anesthesia or conscious sedation was necessary.

Conclusion Transpedal MR-lymphangiography with interstitial injection of a standard extracellular gadolinium-based contrast agent is feasible in clinical routine without general anesthesia and allows for assessment of pathologic conditions of central lymphatics.

Key Points 

Citation Format
Current Technique and Application of Percutaneous Cryotherapy
Authors: Mahnken Andreas , König Alexander , Figiel Jens
Published: April 2018

Purpose Local ablative therapies have become an established treatment option in interventional oncology. Radiofrequency ablation (RFA) and microwave ablation (MWA) are a standard of care in the treatment of hepatocellular carcinoma (HCC). Currently, there is an increasing interest in cryotherapy, one of the oldest ablation techniques. It has some unique characteristics with regard to technology and mechanism of action.

Materials and Methods A systematic literature search using the terms cryotherapy, cryosurgery and cryoablation was performed. Selected studies are presented dealing with the mechanism of action, cryobiology and clinical use of percutaneous, image-guided cryoablation. Recent developments and perspectives are presented.

Results Cryotherapy is increasingly used and has been included in guidelines for selected tumor entities such as renal cell carcinoma. Cryo-immunotherapy and combination treatments are future areas of interest.

Conclusion Cryoabalation may be used in many indications. Its major advantages are its unique visualization and the anesthesiologic effects of cold. While there are only a few prospectively randomized trials, the existing data on the use of cryoablation is promising. Its use appears to be justified in selected tumors, oligometastatic patients and for palliative indications.

Key Points 

Citation Format
One-pot Synthesis of 2-Substituted 4H-Chromeno[3,4-d]oxazol-4-ones from 4-Hydroxy-3-nitrocoumarin and Acids in the Presence of Triphenylphosphine and Phosphorus Pentoxide under Microwave Irradiation
Authors: Balalas T. , Stratidis G. , Papatheodorou D. , Vlachou E.-E. , Gabriel C. , Hadjipavlou-Litina D. , Litinas K.
Published: April 2018

2-Substituted 4H-chromeno[3,4-d]oxazol-4-ones are prepared from 4-hydroxy-3-nitrocoumarin and acids by one-pot reaction in the presence of PPh3 and P2O5 under microwave irradiation or by one-pot two-step reactions in the presence of Pd/C and hydrogen and then P2O5 under microwave irradiation. The fused oxazolocoumarins were also synthesized from 3-amido-4-hydroxycoumarins and P2O5 under microwave irradiation. The 3-amido-4-hydroxycoumarins are obtained almost quantitatively from 4-hydroxy-3-nitrocoumarin, acids and PPh3 under microwave irradiation, or in the presence of Pd/C and H2 on heating. Preliminary biological tests indicate significant inhibition of soybean lipoxygenase and antilipid peroxidation for both oxazolocoumarins and o-hydroxyamidocoumarins.
The Use of Bioactive Glass S53P4 as Bone Graft Substitute in the Treatment of Chronic Osteomyelitis and Infected Non-Unions – a Retrospective Study of 50 Patients
Authors: Malat Tarek Al , Glombitza Martin , Dahmen Janosch , Hax Peter-Michael , Steinhausen Eva
Published: April 2018

Background Treatment of chronic osteomyelitis (COM) remains challenging and often results in large bone defects. Dead space management and proper defect filling are essential for successful treatment. Bioactive glass S53P4 (BAG-S53P4) is an anorganic bone graft substitute with antibacterial, osteoconductive, osteostimulative and angiogenic properties. The aim of our study was to analyse the outcome of patients with COM and infected non-unions, whose bone defects were filled with BAG-S53P4.

Material and Methods In this retrospective study (07/13 – 02/16), we analysed all patients with COM and infected non-unions, who obtained BAG-S53P4 after surgical debridement to fill their bone defects. Epidemiological data, pre-, peri- and postoperative characteristics were evaluated. The primary endpoint was the successful control of infection during the follow-up period. Secondary endpoints were the absence of BAG-S53P4-related complications, the time period to full weight bearing as well as to radiologically detectable incorporation of BAG. X-ray examinations were routinely performed 1 month, 3 – 4 months, 6 months and 12 months postoperatively.

Results 50 patients were analysed. Staphylococcus aureus was the most common pathogen involved. On average, 11.1 ± 6.7 cm3 BAG-S53P4 were implanted. Mean follow-up was at 12.3 months. After 6 months, 26/37 (70.3%) and after 12 months, 35/42 (83.3%) of the filled bone defects were healed. X-ray examinations showed a thickened neo-cortex. 40 patients (80%) have achieved full weight bearing after a mean of 4 months. There were no complications at all in 76% of patients. Seven patients suffered reinfection. BAG-associated complications were not seen.

Conclusions The use of BAG-S53P4 in patients with COM and infected non-unions is promising. Adequate debridement and proper defect filling are necessary. BAG is well tolerated. X-ray examinations showed a thickened neo-cortex. The antibacterial effect is not mediated by antibiotics and is advantageous in times of evolving antibiotic resistance. High quality studies with a longer follow-up are required.

Trial registration: TRN DRKS00011679
Perioperatives Management von Patienten mit gerinnungshemmenden Medikamenten in der Wirbelsäulenchirurgie
Authors: Gerlach Rüdiger , Lapp Harald
Published: April 2018

Einleitung Eine zunehmende Zahl von Patienten wird wegen degenerativer Erkrankungen der Wirbelsäule operativ behandelt. Der Einsatz gerinnungshemmender Medikamente nimmt zu. Beide Tatsachen bedingen, dass Patienten mit notwendigen Operationen an der Wirbelsäule und gerinnungshemmender Therapie Wirbelsäulenchirurgen vor Schwierigkeiten bei der Entscheidung über die perioperative Fortsetzung der Medikation, bzw. die Notwendigkeit einer Umstellung stellen.

Material und Methoden Indikationen der Thrombozytenfunktionshemmung und oralen Antikoagulation, das perioperative Management von Patienten sowie die Praxis der medikamentösen Prophylaxe thromboembolischer Ereignisse bei wirbelsäulenchirurgischen Patienten werden auf der Basis einer aktuellen Literaturrecherche erörtert.

Ergebnisse Im Allgemeinen ist die Datenlage relativ schwach und die Empfehlungen für die Wirbelsäulenchirurgie sind z. T. aus anderen Fachgebieten abgeleitet oder beruhen auf Erfahrungswissen. Für ASS als Monotherapie zur Sekundärprophylaxe existieren Daten, dass die kontinuierliche perioperative Fortsetzung ohne wesentlich erhöhtes Blutungsrisiko möglich ist. Das bisherige perioperative Bridging bei Patienten mit Vorhofflimmern (VHF) oder Zustand nach venösen thromboembolischen Ereignissen sollte nur bei Patienten mit hohem Risiko erfolgen. Bei Patienten mit mittlerem und niedrigem Risiko sollte nur eine übliche Thrombembolieprophylaxe erfolgen.

Schlussfolgerungen Patienten mit gerinnungshemmenden Medikamenten sind Risikopatienten; zum einen wegen der Komorbidität, die eine Gerinnungshemmung erforderlich macht und zum anderen wegen der Notwendigkeit des perioperativen Managements. Die standardisierte Gerinnungsanamnese hilft Blutungskomplikationen zu vermeiden und Patienten mit gerinnungshemmenden Medikamenten zu identifizieren. Spontane Blutungen bei medikamentöser Gerinnungshemmung und perioperative Blutungskomplikationen bei wirbelsäulenchirurgischen Patienten sind mit einer hohen Morbidität und unter Umständen Mortalität assoziiert. Das perioperative Management von Patienten mit pharmakologischer Gerinnungshemmung in der Wirbelsäulenchirurgie ist aufgrund der Komplexität (neue Antikoagulanzien, Co-Morbidität, Alter der Patienten) eine interdisziplinäre Aufgabe, die mit den Kardiologen, Neurologen und Gefäßmedizinern gemeinsam erfolgen sollte. Auch wenn hier Möglichkeiten im perioperativen Umgang bei Patienten mit Gerinnungshemmern aufgezeigt werden, muss die Entscheidung nach Abwägen des individuellen Risiko/Nutzenverhältnisses erfolgen.
Various pointer states approaches to polar modular values
Authors: Ho Le Bin , Imoto Nobuyuki
Published: April 2018

We theoretically analyze the polar decomposition for quantum modular values under various pointer states approaches. We consider both the finite-dimensional discrete pointer state and continuous pointer state cases. In contrast to that, a weak value of an observable is usually divided into its real and imaginary parts; here, we show that separation from the modulus and phase is necessary to a modular value. We show that the modulus of the modular value is related to the pointer post-selection conditional probability, and the phase of the modular value is connected to the summation of a geometric phase and an intrinsic phase. We also discuss a relationship between the modulus and phase, and therein, the derivative of the phase is related to the derivative of the logarithm of the modulus via a Berry-Simon-like connection which is in the form of a weak value. As a consequence, the modulus-phase relation allows us to obtain these polar components whenever the connection is specified. One of the possible applications of our results is to evaluate the weak value (the Berry-Simon-like connection) when the polar modular value is experimentally obtained.
Particle-in-cell simulations of anomalous transport in a Penning discharge
Authors: Carlsson Johan , Kaganovich Igor , Powis Andrew , Raitses Yevgeny , Romadanov Ivan , Smolyakov Andrei
Published: April 2018

Electrostatic particle-in-cell simulations of a Penning discharge are performed in order to investigate azimuthally asymmetric, spoke-like structures previously observed in experiments. Two-dimensional simulations show that for Penning-discharge conditions, a persistent nonlinear spoke-like structure forms readily and rotates in the direction of E × B and electron diamagnetic drifts. The azimuthal velocity is within about a factor of 2 of the ion acoustic speed. The spoke frequency follows the experimentally observed scaling with ion mass, which indicates the importance of ion inertia in spoke formation. The spoke provides enhanced (anomalous) radial electron transport, and the effective cross-field conductivity is several times larger than the classical (collisional) value. The level of anomalous current obtained in the simulations is in good agreement with the experimental data. The rotating spoke channels most of the radial current, observable by an edge probe as short pulses.
Site-specific magnetic anisotropies in R2Fe14B systems
Authors: Yoshioka T. , Tsuchiura H.
Published: April 2018

The local magnetic anisotropy of R ions in R2Fe14B (R = Dy, Ho) systems is studied based on a microscopic effective spin model constructed from the information obtained by using first-principles calculations. By taking into account up to 6-th order crystal electric field parameters, the model satisfactory describes the observed magnetization curves and the temperature dependence of anisotropy constants. We found that at low temperatures, the noncollinear structure appears in the Ho2Fe14B system reflecting the local magnetic anisotropy.
Boxcar detection for high-frequency modulation in stimulated Raman scattering microscopy
Authors: Fimpel P. , Riek C. , Ebner L. , Leitenstorfer A. , Brida D. , Zumbusch A.
Published: April 2018

Stimulated Raman scattering (SRS) microscopy is an important non-linear optical technique for the investigation of unlabeled samples. The SRS signal manifests itself as a small intensity exchange between the laser pulses involved in coherent excitation of Raman modes. Usually, high-frequency modulation is applied in one pulse train, and the signal is then detected on the other pulse train via lock-in amplification. While allowing shot-noise limited detection sensitivity, lock-in detection, which corresponds to filtering the signal in the frequency domain, is not the most efficient way of using the excitation light. In this manuscript, we show that boxcar averaging, which is equivalent to temporal filtering, is better suited for the detection of low-duty-cycle signals as encountered in SRS microscopy. We demonstrate that by employing suitable gating windows, the signal-to-noise ratios achievable with lock-in detection can be realized in shorter time with boxcar averaging. Therefore, high-quality images are recorded at a faster rate and lower irradiance which is an important factor, e.g., for minimizing degradation of biological samples.
Electrode redox reactions with polarizable molecules
Authors: Matyushov Dmitry V.
Published: April 2018

A theory of redox reactions involving electron transfer between a metal electrode and a polarizable molecule in solution is formulated. Both the existence of molecular polarizability and its ability to change due to electron transfer distinguish this problem from classical theories of interfacial electrochemistry. When the polarizability is different between the oxidized and reduced states, the statistics of thermal fluctuations driving the reactant over the activation barrier becomes non-Gaussian. The problem of electron transfer is formulated as crossing of two non-parabolic free energy surfaces. An analytical solution for these free energy surfaces is provided and the activation barrier of electrode electron transfer is given in terms of two reorganization energies corresponding to the oxidized and reduced states of the molecule in solution. The new non-Gaussian theory is, therefore, based on two theory parameters in contrast to one-parameter Marcus formulation for electrode reactions. The theory, which is consistent with the Nernst equation, predicts asymmetry between the cathodic and anodic branches of the electrode current. They show different slopes at small electrode overpotentials and become curved at larger overpotentials. However, the curvature of the Tafel plot is reduced compared to the Marcus-Hush model and approaches the empirical Butler-Volmer form with different transfer coefficients for the anodic and cathodic currents.
Electric field tuning of magnetism in heterostructure of yttrium iron garnet film/lead magnesium niobate-lead zirconate titanate ceramic
Authors: Lian Jianyun , Ponchel Freddy , Tiercelin Nicolas , Chen Ying , Rémiens Denis , Lasri Tuami , Wang Genshui , Pernod Philippe , Zhang Wenbin , Dong Xianlin
Published: April 2018

In this paper, the converse magnetoelectric (CME) effect by electric field tuning of magnetization in an original heterostructure composed of a polycrystalline yttrium iron garnet (YIG) film and a lead magnesium niobate-lead zirconate titanate (PMN-PZT) ceramic is presented. The magnetic performances of the YIG films with different thicknesses under a DC electric field applied to the PMN-PZT ceramics and a bias magnetic field are investigated. All the magnetization-electric field curves are found to be in good agreement with the butterfly like strain curve of the PMN-PZT ceramic. Both the sharp deformation of about 2.5‰ of PMN-PZT and the easy magnetization switching of YIG are proposed to be the reasons for the strongest CME interaction in the composite at the small electric coercive field of PMN-PZT (4.1 kV/cm) and the small magnetic coercive field of YIG (20 Oe) where the magnetic susceptibility reaches its maximum value. A remarkable CME coefficient of 3.1 × 10−7 s/m is obtained in the system with a 600 nm-thick YIG film. This heterostructure combining multiferroics and partially magnetized ferrite concepts is able to operate under a small or even in the absence of an external bias magnetic field and is more compact and power efficient than the traditional magnetoelectric devices.
High density liquid structure enhancement in glass forming aqueous solution of LiCl
Authors: Camisasca G. , De Marzio M. , Rovere M. , Gallo P.
Published: April 2018

We investigate using molecular dynamics simulations the dynamical and structural properties of LiCl:6H2O aqueous solution upon supercooling. This ionic solution is a glass forming liquid of relevant interest in connection with the study of the anomalies of supercooled water. The LiCl:6H2O solution is easily supercooled and the liquid state can be maintained over a large decreasing temperature range. We performed simulations from ambient to 200 K in order to investigate how the presence of the salt modifies the behavior of supercooled water. The study of the relaxation time of the self-density correlation function shows that the system follows the prediction of the mode coupling theory and behaves like a fragile liquid in all the range explored. The analysis of the changes in the water structure induced by the salt shows that while the salt preserves the water hydrogen bonds in the system, it strongly affects the tetrahedral hydrogen bond network. Following the interpretation of the anomalies of water in terms of a two-state model, the modifications of the oxygen radial distribution function and the angular distribution function of the hydrogen bonds in water indicate that LiCl has the role of enhancing the high density liquid component of water with respect to the low density component. This is in agreement with recent experiments on aqueous ionic solutions.
Effect of interface reaction and diffusion on stress-oxidation coupling at high temperature
Authors: Yue Mengkun , Dong Xuelin , Fang Xufei , Feng Xue
Published: April 2018

High-temperature structural materials undergo oxidation during the service, and stress would generate in the oxide film. Understanding the coupling effect between stress and oxidation contributes to the understanding of material degradation and failure during the oxidation process. Here, we propose a model to investigative the coupling effect of stress and oxidation at high temperature by considering the three-stage oxidation process, where both the interface reaction and the diffusion process are present. The governing equations including the oxidation kinetics and stress equilibrium for isothermal oxidation under stress-oxidation coupling effect have been derived. The theory is validated by comparing with the experimental results of SiO2 grown on Si substrate. Results show that the coupling of stress and oxidation influences the growth of the oxide film by affecting all three stages of the oxidation process.
Nuclear export of ubiquitinated proteins via the UBIN-POST system
Authors: Hirayama Shoshiro , Sugihara Munechika , Morito Daisuke , Iemura Shun-ichiro , Natsume Tohru , Murata Shigeo , Nagata Kazuhiro
Published: April 2018

Significance

It is commonly observed that proteasome impairment results in accumulation of ubiquitinated proteins in the cytosol. Even proteins originally located in the nucleus show similar cytosolic accumulation, suggesting that unidentified machinery proactively transports them to the cytosol. Here, we report that a protein complex, UBIN–polyubiquitinated substrate transporter, harboring ubiquitin binding domain and nuclear export signal specifically mediates this process. In addition, their worm homologues showing similar transportation activity are important to maintain the lifespan of worms under natural condition. Our findings provide an answer to the long-standing question of why ubiquitinated proteins are deposited in the cytosol by proteasome impairment; they provide definite identification of underlying molecular machinery and show its essential involvement in the proteostasis in animal cells.
Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses
Authors: Deng Tanggang , Yan Guobei , Song Xin , Xie Lin , Zhou Yu , Li Jianglin , Hu Xiaoxiao , Li Zhen , Hu Jun , Zhang Yibin , Zhang Hui , Sun Yang , Feng Peifu , Wei Dong , Hu Bin , Liu Jing , Tan Weihong , Ye Mao
Published: April 2018

Significance

Previous studies have demonstrated that p21 occupies a central position in cell-cycle regulation and DNA damage responses. As an unstable protein, the regulation of p21 stability has been extensively investigated over the past 20 years. Although p21 degradation by the ubiquitin-proteasome pathway has been well characterized, it is unclear whether ubiquitylated p21 can be recycled. Here, we identify USP11 as a deubiquitylase that directly removes p21 polyubiquitylation and stabilizes p21 protein, revealing that cellular p21 protein is finely regulated by a dynamic balance of USP11-mediated stabilization and proteasome-mediated degradation. Meanwhile, we also provide evidence that the USP11-p21 axis plays a crucial role in G1/S transition under physiological conditions and in regulating the balance between cytostasis and apoptosis.
Desynchronization of slow oscillations in the basal ganglia during natural sleep
Authors: Mizrahi-Kliger Aviv D. , Kaplan Alexander , Israel Zvi , Bergman Hagai
Published: April 2018

Significance

Slow-wave sleep is widely associated with synchronized slow oscillations recorded in the cortical mantle and elsewhere in the brain. In this study, we focused on the basal ganglia, a group of interconnected subcortical nuclei implicated in habit learning and in common neurological disorders (e.g., Parkinson’s disease). We show that unlike cortical circuits, where slow oscillation is locally synchronized, slow oscillations of firing rates within each basal ganglia nucleus are not phase-locked between adjacent neurons, and are decoupled from the local field potential. Our results establish that neuronal slow oscillations and synchrony do not always co-occur, and highlight decorrelation as a key feature of basal ganglia circuitry that persists even in the most synchronized physiological conditions.
Shared epitope–aryl hydrocarbon receptor crosstalk underlies the mechanism of gene–environment interaction in autoimmune arthritis
Authors: Fu Jiaqi , Nogueira Sarah V. , Drongelen Vincent van , Coit Patrick , Ling Song , Rosloniec Edward F. , Sawalha Amr H. , Holoshitz Joseph
Published: April 2018

Significance

This study identifies a mechanistic basis for the enigmatic, long-observed interaction between the rheumatoid arthritis shared epitope (SE)—the most significant genetic risk factor in this disease—and exposure to environmental pollutants, such as cigarette smoke. Specifically, we show that the SE, acting as a signal transduction ligand, cooperates with the aryl hydrocarbon receptor-activated pathway, and together facilitate cellular events that culminate in inflammation and bone destruction in experimental autoimmune arthritis. The cross-talk between the two pathways is mediated by nuclear factor kappa B.
eIF1 Loop 2 interactions with Met-tRNA
i
control the accuracy of start codon selection by the scanning preinitiation complex
Authors: Thakur Anil , Hinnebusch Alan G.
Published: April 2018

Significance

In translation initiation, a preinitiation complex (PIC) of the 40S ribosomal subunit, eukaryotic initiation factors (eIFs), and initiator transfer RNA (tRNA
i
) scans the mRNA for an AUG codon in favorable context. AUG recognition evokes a closed PIC conformation and triggers dissociation of eIF1. Structural data predict that a clash between eIF1 β-hairpin Loop 2 and tRNA
i
impedes selection of non-AUG start codons in the open, scanning conformation of the PIC. Supporting this model, we show that alanine substitutions of Loop 2 residues increase initiation at suboptimal start codons (UUGs and AUGs in poor context) in vivo and destabilize tRNA
i
binding at UUG codons in reconstituted PICs in vitro. These results establish Loop 2–RNA
i
interaction as a key determinant of initiation accuracy.
Muscularis macrophage development in the absence of an enteric nervous system
Authors: Avetisyan Marina , Rood Julia E. , Huerta Lopez Silvia , Sengupta Rajarshi , Wright-Jin Elizabeth , Dougherty Joseph D. , Behrens Edward M. , Heuckeroth Robert O.
Published: April 2018

Significance

Neurons and muscularis macrophages (MM) interact closely in the adult bowel and enteric neurons modulate the inflammatory response of neighboring MM. Enteric neurons also produce the essential macrophage survival factor colony stimulating factor 1. How MM–enteric neuron interactions are established during development has not been previously investigated. Surprisingly, we find that MM colonize fetal mouse bowel before enteric neurons. Furthermore, neonatal mouse and human bowel that is missing enteric neurons contains normal numbers of well-patterned, phenotypically intact MM. These data suggest that enteric neurons are not required for bowel colonization by MM and that modulatory neuro-immune circuits of the bowel mature postnatally and may be influenced by environmental factors like intestinal microbes or diet.
Anti–HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity
Authors: Dosenovic Pia , Kara Ervin E. , Pettersson Anna-Klara , McGuire Andrew T. , Gray Matthew , Hartweger Harald , Thientosapol Eddy S. , Stamatatos Leonidas , Nussenzweig Michel C.
Published: April 2018

Significance

An essential requirement for an HIV vaccine is to elicit antibodies to conserved regions of the spike protein (i.e., Env) because these antibodies can protect against infection. Although broadly neutralizing antibodies develop naturally in rare individuals after prolonged HIV infection, eliciting them by vaccination has only been possible in artificial knock-in mouse models in which the number of B cells expressing the antibody precursor is superphysiologic. To understand the relationship among precursor frequency, antigen affinity, and germinal center recruitment, we have performed adoptive transfer experiments in which fixed numbers of precursor cells are engrafted in WT mice. Our results provide a framework for an understanding of how precursor frequency and antigen affinity shape humoral immunity to HIV.
Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells
Authors: Ribeiro Kleber Silva , Vasconcellos Camilla Ioshida , Soares Rodrigo Pedro , Mendes Maria Tays , Ellis Cameron C. , Aguilera‐Flores Marcela , de Almeida Igor Correia , Schenkman Sergio , Iwai Leo Kei , Torrecilhas Ana Claudia
Published: April 2018

Trypanosoma cruzi, the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi, which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture‐derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans‐sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin‐like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle‐free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC‐MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain‐derived EVs caused higher infection of LLC‐MK2 cells than Y strain‐derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host–parasite interaction.
Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence
Authors: Yoon Ki-Jun , Vissers Caroline , Ming Guo-li , Song Hongjun
Published: April 2018

During embryonic brain development, neural progenitor/stem cells (NPCs) sequentially give rise to different subtypes of neurons and glia via a highly orchestrated process. To accomplish the ordered generation of distinct progenies, NPCs go through multistep transitions of their developmental competence. The molecular mechanisms driving precise temporal coordination of these transitions remains enigmatic. Epigenetic regulation, including changes in chromatin structures, DNA methylation, and histone modifications, has been extensively investigated in the context of cortical neurogenesis. Recent studies of chemical modifications on RNA, termed epitranscriptomics, have also revealed their critical roles in neural development. In this review, we discuss advances in understanding molecular regulation of the sequential lineage specification of NPCs in the embryonic mammalian brain with a focus on epigenetic and epitranscriptomic mechanisms. In particular, the discovery of lineage-specific gene transcripts undergoing rapid turnover in NPCs suggests that NPC developmental fate competence is determined much earlier, before the final cell division, and is more tightly controlled than previously appreciated. We discuss how multiple regulatory systems work in harmony to coordinate NPC behavior and summarize recent findings in the context of a model of epigenetic and transcriptional prepatterning to explain NPC developmental competence.
Design Flaws: Consequences of the Coverage Gap in Food Programs for Children at Kindergarten Entry
Authors: Arteaga Irma , Heflin Colleen , Parsons Sarah
Published: April 2018

Children age out of the Women, Infants, and Children (WIC) program at 60 months and become eligible for the National School Lunch Program (NSLP) upon kindergarten entry. During this period of time, low‐income children experience fewer food support services than at any other time. Using the Early Childhood Longitudinal Study, we examine the effects of the duration of the coverage gap between WIC and NSLP on kindergarteners’ skills. Results show evidence of negative effects on reading, though not on math. Findings also suggest that, for children in full‐day kindergarten, effects on reading fade out in the spring term.
Nutrition Transition and the Structure of Global Food Demand
Authors: Gouel Christophe , Guimbard Houssein
Published: April 2018

Estimating future demand for food is a critical aspect of global food security analyses. The process linking dietary changes to wealth is known as the nutrition transition and presents well‐identified features that help to predict consumption changes in poor countries. This study proposes to represent the nutrition transition with a nonhomothetic, flexible‐in‐income demand system. The resulting model is estimated statistically based on cross‐sectional information from FAOSTAT. The model captures the main features of the nutrition transition: rise in demand for calories associated with income growth; diversification of diets away from starchy staples; and a large increase in caloric demand for animal‐based products, fats, and sweeteners. The estimated model is used to project food demand between 2010 and 2050 based on a set of plausible futures (trend projections and Shared Socioeconomic Pathways scenarios). The main results of these projections are: (a) global food demand will increase by 47%, less than half the growth in the previous four decades; (b) this growth will be attributable mainly to lower‐middle‐income and low‐income countries; (c) the structure of global food demand will change over the period, with a doubling of demand for animal‐based calories and a much smaller 19% increase in demand for starchy staples; and (d) the analysis of a range of population and income projections reveals important uncertainties—depending on the scenario, the projected increases in demand for animal‐based and vegetal‐based calories range from 74% to 114%, and from 20% to 42%, respectively.
Identifying differentially methylated sites in samples with varying tumor purity
Authors: Häkkinen Antti , Alkodsi Amjad , Facciotto Chiara , Zhang Kaiyang , Kaipio Katja , Leppä Sirpa , Carpén Olli , Grénman Seija , Hynninen Johanna , Hietanen Sakari , Lehtonen Rainer , Hautaniemi Sampsa
Published: April 2018

Motivation

DNA methylation aberrations are common in many cancer types. A major challenge hindering comparison of patient-derived samples is that they comprise of heterogeneous collection of cancer and microenvironment cells. We present a computational method that allows comparing cancer methylomes in two or more heterogeneous tumor samples featuring differing, unknown fraction of cancer cells. The method is unique in that it allows comparison also in the absence of normal cell control samples and without prior tumor purity estimates, as these are often unavailable or unreliable in clinical samples.

Results

We use simulations and next-generation methylome, RNA and whole-genome sequencing data from two cancer types to demonstrate that the method is accurate and outperforms alternatives. The results show that our method adapts well to various cancer types and to a wide range of tumor content, and works robustly without a control or with controls derived from various sources.

Availability and implementation

The method is freely available at https://bitbucket.org/anthakki/dmml.

Supplementary information

Supplementary data are available at Bioinformatics online.
A case with acute-on-chronic liver failure receiving liver transplantation during daclatasvir and asunaprevir therapy in chronic hepatitis C patient
Authors: Park Wonhyeong , Jung Jihwan , Yang Soo Hyun , Lee Danbi , Kang Hyo Jeong
Published: April 2018

We report a case with hepatitis C virus genotype 1 b liver cirrhosis who received liver transplantation because of acute-on-chronic liver failure during daclatasvir (DSV) and asunaprevir (ASV) combination therapy. To our knowledge, this is the first case received liver transplantation during DSV + ASV therapy. Therefore, clinicians should pay particular attention to the possibility of acute liver failure during DSV and ASV combination therapy.
Criteria for assessing the quality of mHealth apps: a systematic review
Authors: Nouri Rasool , R Niakan Kalhori Sharareh , Ghazisaeedi Marjan , Marchand Guillaume , Yasini Mobin
Published: April 2018

Objective

Review the existing studies including an assessment tool/method to assess the quality of mHealth apps; extract their criteria; and provide a classification of the collected criteria.

Methods

In accordance with the PRISMA statement, a literature search was conducted in MEDLINE, EMBase, ISI and Scopus for English language citations published from January 1, 2008 to December 22, 2016 for studies including tools or methods for quality assessment of mHealth apps. Two researchers screened the titles and abstracts of all retrieved citations against the inclusion and exclusion criteria. The full text of relevant papers was then individually examined by the same researchers. A senior researcher resolved eventual disagreements and confirmed the relevance of all included papers. The authors, date of publication, subject fields of target mHealth apps, development method, and assessment criteria were extracted from each paper. The extracted assessment criteria were then reviewed, compared, and classified by an expert panel of two medical informatics specialists and two health information management specialists.

Results

Twenty-three papers were included in the review. Thirty-eight main classes of assessment criteria were identified. These were reorganized by expert panel into 7 main classes (Design, Information/Content, Usability, Functionality, Ethical Issues, Security and Privacy, and User-perceived value) with 37 sub-classes of criteria.

Conclusions

There is a wide heterogeneity in assessment criteria for mHealth apps. It is necessary to define the exact meanings and degree of distinctness of each criterion. This will help to improve the existing tools and may lead to achieve a better comprehensive mHealth app assessment tool.
Subrogation and the Theory of Insurance When Suits Can Be Brought for Losses Suffered
Authors: Polinsky A Mitchell , Shavell Steven
Published: April 2018

The theory of insurance is considered here when an insured individual may be able to sue another party for the losses that the insured suffered—and thus when an insured has a potential source of compensation in addition to insurance coverage. Insurance policies reflect this possibility through so-called subrogation provisions that give insurers the right to step into the shoes of insureds and to bring suits against injurers. In a basic case, the optimal subrogation provisions involve full retention by the insurer of the proceeds from a successful suit and the pursuit of all positive expected value suits. This eliminates litigation risks for insureds and results in lower premiums—financed by the litigation income of insurers, including from suits that insureds would not otherwise have brought. Moreover, optimal subrogation provisions are characterized in the presence of moral hazard, administrative costs, and non-monetary losses, and it is demonstrated that optimal provisions entail sharing litigation proceeds with insureds in the first two cases but not when losses are non-monetary. (JEL G22, K13, K41)
Ten Essential Practices for Developing or Reforming a Biostatistics Core for a NCI Designated Cancer Center
Authors: Mazumdar Madhu , Moshier Erin L , Özbek Umut , Parsons Ramon
Published: April 2018

There are 69 National Cancer Institute (NCI) designated Cancer Centers (CCs) in the United States. Biostatistical collaboration is pivotal in cancer research, and support for a cancer biostatistics shared resource facility (C-BSRF) is included in the award. Although the services and staff needed in a C-BSRF have been outlined in general terms and best practices for biostatistical consultations and collaboration in an academic health center have been agreed upon, implementing these practices in the demanding setting of cancer centers interested in pursuing or maintaining NCI designation remains challenging. We surveyed all C-BSRF websites to assess their organizational charts, governance, size, services provided, and financial models and have identified 10 essential practices for the development of a successful C-BSRF. Here, we share our success with, and barriers to, implementation of these practices. Showcasing development plans for these essential practices resulted in an NCI score of “Excellent to Outstanding” for our C-BSRF in 2015, and performance metrics in 2016–2017 demonstrated notable improvement since our original Cancer Center Support Grant (CCSG) application in 2014. We believe that the essential practices described here can be adapted and adjusted, as needed, for CCs of various sizes and with different types of cancer research programs.
Male Sexual Function and Dysfunction (DRAFT)
Authors: Albaugh Jeffrey A.
Published: April 2018

Sexual dysfunction is a common and frustrating problem in men that is often under reported and under treated. Sexual dysfunction issues identified by men may include hypoactive sexual desire disorder/lack of libido, premature ejaculation, delayed ejaculation, erectile dysfunction and/or Peyronie’s disease. This chapter covers information on how normal sexual function occurs and some of the etiologic factors leading to sexual dysfunction. Understanding each individual patient and their goals for sexual health can lead to identifying and addressing sexual issues effectively. Information is provided about some of the traditional medical treatment options typically used to treat men with common sexual problems. In addition, some lifestyle modification and psychological approaches to treating sexual dysfunction are discussed.
Homeopathy in the Prevention and Treatment of Sexual Problems (DRAFT)
Authors: Ullman Dana , Allen Karen
Published: April 2018

Homeopathic medicine is a specialized form of pharmacology used throughout the world by physicians and other health and medical care providers. Nanodoses of plants, mineral, animal, chemical, or pathogens are prescribed based on their ability to cause in overdose specific syndromes in patients. Because symptoms are considered adaptations of the human body to fight infection and/or to adapt to stress, using nanodoses of substances that could cause similar symptoms that patients experience is one way to influence gene expression, immunological development, and the genitourinary microbiome to initiate a healing process. The homeopathic approach to the prevention and treatment of sexual problems requires analysis of a person’s overall syndrome, not simply local disease. This chapter provides specific homeopathic medicines with abbreviated summaries of their indications in (a) genitourinary dysbiosis, (b) sexual trauma and psychosexual conflict, and (c) sexual pain and functional limitation.
Chiropractic (DRAFT)
Authors: Eisen Susan R.
Published: April 2018

This chapter focuses on mechanical disorders of the lumbar and pelvic spine associated with sexuality, with a detailed overview of neuromusculoskeletal anatomy. A full discussion is also included regarding the definition of chiropractic as recognized by the National Institutes of Health, as well as its place in complementary and alternative medicine. An explanation of sensory and motor functions of associated nerves is provided. Individual in-office case studies are offered along with reported clinical trials regarding the use of chiropractic in low back conditions and outcomes as reported in prestigious medical journals. Lastly, specific types of chiropractic treatment utilized in the author’s office are discussed.
The Epidemiology of Pain and Addiction
Authors: Brunner Emily , Levy Robert
Published: April 2018

The chapter on the epidemiology of pain and addiction opens with a discussion of epidemiological principles and then proceeds to review two categories of data: that which are available on the use of opioids to treat chronic pain, and that reflecting opioid use disorder (OUD). The data are provided with graphical representations that may aid in discussions and in teaching. An accompanying glossary of epidemiological terminology facilitates understanding of the data. Conclusions are drawn from the prevalence of use and of mortality that contribute to an understanding of the origins and direction of the opioid use crisis. An accompanying text box provides resources for further exploration of the topics discussed in the chapter.
Ethical Issues in Treating Pain and Addiction
Authors: Spevak Christopher J.
Published: April 2018

In addressing the ethical issues that arise in treating both pain and addiction, the author of this chapter has organized his presentation around: the history of medical ethics; theories and definitions; and the ethical challenges to providing clinical care. The theoretical underpinnings to ethical decision-making are important to providing the best possible outcome, and their evolution is described, from the Hippocratic Oath to current human subjects’ protection rules for clinical trials. The tension between patient autonomy and the physician’s obligation to protect is as high as that seen in parenthood, but commonly with even less control of the individuals involved. A framework is provided for examining clinical cases that aids in addressing such topics as treatment disagreement, confidentiality, informed consent, abandonment, pregnancy, and biases that may be seen with categorical treatment programs (e.g., abstinence-based, faith-based). A text box is added giving additional resources on the topics discussed.
Professionally Directed Non-Pharmacological Management of Chronic Pain
Authors: Przekop Peter
Published: April 2018

This chapter is a complement to Chapter 15, concentrating on the non-pharmacological approaches to chronic pain. It features a discussion on the utility of mind-body therapies, psychosocial treatments, and technology-based therapies in the context of recovery through 12-Step programs and other mutual support groups. Such settings are commonly poorly receptive to medication management of either pain or addiction; the availability of other approaches can bridge the gap, leading to effective management of both. The therapies discussed include “movement” therapies, such as internal qi gong, tai chi, yoga, and martial arts. Healing touch, reiki, external qi gong, and acupuncture are examples of “energy” therapies, requiring an intercessor. Among the psychosocial treatments are motivational interviewing, cognitive restructuring, cognitive behavioral therapy, acceptance-based cognitive therapy, operant training, hypnosis, relaxation training, and mindfulness/meditation. Addressed as procedures are massage, chiropractic and osteopathic manipulations, trans-epidermal nerve stimulation (TENS), and transcranial magnetic stimulation (TMS).
Revising the Treatment Plan and/or Ending Pain Treatment
Authors: Weiner Mark A. , Malinoff Herbert L.
Published: April 2018

This chapter describes specifically the population with chronic non-malignant pain whose illness is described as “opioid treatment failures,” perhaps 75% of the total. It addresses one of the most difficult questions in the management of comorbid pain and addiction: termination of opioid therapy. It begins by defining the problem for each patient in terms of strata of risk, and then describes the opioid discontinuation process in both outpatient medical offices and hospital settings. Timelines for discontinuation, including of benzodiazepines, are discussed, as well as the place of buprenorphine during taper or withdrawal. Both the fear of abandonment and the requirement for long-term aftercare are addressed, consistent with psychosocial principles generally accepted for the management of all chronic conditions.
Non-Pharmacological Therapies for Substance Use Disorders
Authors: Weaver Michael F.
Published: April 2018

In conjunction with chapters 16 and 17, which described non-pharmacological approaches to pain management, this chapter reviews the available non-pharmacological approaches to substance use disorders (SUD). Specific subtopics include 12-Step programs and facilitation, motivational enhancement therapy, cognitive behavioral therapy, individual and group psychotherapies, contingency management, community reinforcement, family therapy, relapse management, and the terminal consideration of all therapies, termination (what is the duration of treatment)? Each subtopic is addressed in abstract rather than in comprehensive format, to allow the primary care provider to identify her level of interest and present level of understanding, and to inform further reading. The chapter concludes with a text box providing additional resources.