bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive factors associated with liver fibrosis and steatosis by transient elastography in patients with HIV mono‐infection under long‐term combined antiretroviral therapy
Authors: Perazzo Hugo , Cardoso Sandra W , Yanavich Carolyn , Nunes Estevão P , Morata Michelle , Gorni Nathalia , da Silva Paula Simplicio , Cardoso Claudia , Almeida Cristiane , Luz Paula , Veloso Valdilea G , Grinsztejn Beatriz
Published: November 2018

Introduction

Non‐alcoholic fatty liver disease is characterized by the presence of hepatic steatosis and can be associated with fibrosis progression, development of cirrhosis and liver‐related complications. Data on the prevalence of liver fibrosis and steatosis in HIV patients remain contradictory in resource‐limited settings. We aimed to describe the prevalence and factors associated with liver fibrosis and steatosis in patients with HIV mono‐infection under long‐term antiretroviral therapy (ART) in Rio de Janeiro, Brazil.

Methods

Clinical assessment, fasting blood collection and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by transient elastography were performed on the same day for this cross‐sectional study (PROSPEC‐HIV study; NCT02542020). Patients with viral hepatitis co‐infection, ART‐naïve or missing data were excluded. Liver fibrosis and steatosis were defined by LSM ≥ 8.0 kPa and CAP ≥ 248 dB/m respectively. HIV history, cumulative and current ART regimens were evaluated. Multivariate logistic regression models adjusted for age and gender were performed.

Results

In total, 395 patients (60% female; median age of 45 (IQR, 35 to 52) years, body mass index = 25.7 (23.2 to 29.4) kg/m2, alanine aminotransferase = 30 (23 to 42) IU/L, duration of ART for 7 (4 to 14) years) were included. LSM and CAP were reliable in 93% (n = 367) and 87% (n = 344) respectively. The prevalence of fibrosis and steatosis were 9% (95% confidence interval (CI), 7 to 13) and 35% (95% CI, 30 to 40) respectively. The following factors were associated with fibrosis (odds ratio (OR) (95% CI)): older age (per 10 years; 1.80 (1.27 to 2.55); p = 0.001) and CD4+ count <200 cells/mm3 (7.80 (2.09 to 29.09), p = 0.002). Type 2 diabetes had a trend towards the presence of liver fibrosis (2.67 (0.96 to 7.46), p = 0.061). Central obesity (10.74 (4.40 to 26.20), p < 0.001), type 2 diabetes (9.74 (3.15 to 30.10), p < 0.001), dyslipidaemia (2.61 (1.35 to 5.05), p = 0.003) and metabolic syndrome (4.28 (2.45 to 7.46), p < 0.001) were associated with steatosis. A dominant backbone ART regimen of zidovudine (AZT), d4T, ddI or ddC was associated with steatosis (1.90 (1.07 to 3.38), p = 0.028) independently of metabolic features.

Conclusion

Integrated strategies for preventing non‐communicable diseases in people with HIV mono‐infection are necessary to decrease the burden of liver diseases.

Clinical Trial Number: NCT02542020.
Repeated isoflurane in adult male mice leads to acute and persistent motor decrements with long‐term modifications in corpus callosum microstructural integrity
Authors: Bajwa Nikita M. , Lee Jeong B. , Halavi Shina , Hartman Richard E. , Obenaus Andre
Published: November 2018

Isoflurane is a commonly used inhalational anesthetic, clinically and in animal experimental studies. Although it has been reported as safe, recent findings suggest that despite widespread use, isoflurane‐induced inhalational anesthesia can lead to various pathophysiological and cognitive alterations. Therefore, we aimed to investigate the long‐term behavioral and white matter consequences of repeated isoflurane exposure. Twenty 3‐month‐old C57BL/6J male mice received one exposure of isoflurane for 40 min or 2 exposures to isoflurane separated by 3 days. Behavioral paradigms (open field, balance beam, foot fault, rotarod, elevated zero maze, tail suspension, water maze, and social recognition tests) were administered at 1, 3, 5, 7, and 90 days post exposure. Animals exposed to repeated isoflurane showed significant motor deficits on the balance beam and increased anxiety‐like behavior. Animals exposed to single isoflurane showed impaired performance on the foot fault test. Diffusion tensor imaging showed that repeated isoflurane exposure led to long‐term disruption of water diffusivity in corpus callosum (CC) white matter. Furthermore, 2‐D structure‐tensor analysis from stained brain sections showed differences in the microstructural organization of CC white matter in mice with single versus repeated isoflurane exposures. These results suggest that behavioral deficits observed up to 90 days after repeated isoflurane exposure resulted from, at least in part, altered CC white matter microstructural integrity.
Integrated climatology and trends in the subtropical Hadley cell, sunshine duration and cloud cover over South Africa
Authors: Mahlobo D. D. , Ndarana T. , Grab S. , Engelbrecht F.
Published: November 2018

This study uses two methods to diagnose the local Hadley circulation; first the zonally averaged mass stream function, and second the stream function vector method. The two methods have been applied to the ERA‐Interim reanalysis data for the period 1979–2015, to calculate both the climatology and trends of the Hadley cell. Both diagnostics advocate downwards mass flux being dominant over the subtropics, particularly over South Africa, yet the strength of Hadley is seasonal. Contrasts have been found between linear trends of the two diagnostics. Zonally symmetric diagnostics indicate strengthening of the Hadley cell, particularly in the subtropics of the Southern Hemisphere in winter and weakening in summer. The zonally asymmetric results indicate maximum strengthening of the Hadley over South Africa to be in spring and weakening in summer. Furthermore, maximum decrease in cloud cover and increase in sunshine duration over South Africa is in spring, implying more opportunities for solar energy generation.
Extreme temperature and precipitation changes associated with four degree of global warming above pre‐industrial levels
Authors: Wang Xiaoxin , Jiang Dabang , Lang Xianmei
Published: November 2018

In 2012, the World Bank released a report and stated that a 4 °C increase in global temperature relative to the pre‐industrial levels would be devastating. However, there is a lack of scientific literature on the changes in climate associated with a 4 °C temperature increase. Based on the daily temperature and precipitation data from the Coupled Model Intercomparison Project Phase 5 (CMIP5), we project the global terrestrial changes in the extreme values of temperature and precipitation in association with a warming of 4 °C above the pre‐industrial levels using the Representative Concentration Pathways 8.5 (RCP8.5) scenario. The results indicated that cold extremes will decrease and warm extremes will increase. More remarkable signals in temperature extremes based on daily minimum temperature are expected, and local changes in temperature extremes generally extend beyond the natural internal variability. Significant signals in the frequency of temperature extremes appear in low latitudes, while the temperature changes of the coldest and hottest days are great in northern high latitudes. Large signal‐to‐noise ratios for warm extremes mainly occur in low latitudes, while those of cold extremes are not uniformly distributed. More intense and frequent heavy precipitation is also projected. Signals in high‐precipitation extremes are prominent in high latitudes and usually exceed the local natural internal variability. Changes in extreme dry events are high in the extratropics and generally lie within the background noise. Relative to the 1.5 °C global warming scenario, there would be more violent temperature and precipitation extremes with the 4 °C warming level, and these extremes would pose more threats to natural and human systems. Additionally, small inter‐model uncertainty occurs in the regions with remarkable signals for high precipitation‐related extremes and cold days and nights, while the opposite trend is seen for extreme dry events and other temperature extremes.
Pembrolizumab: a case of drug‐induced autoimmune diabetes mellitus and colitis
Authors: Singh Nikhil R.
Published: November 2018

Background

Immunosuppressive molecules such as cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4), programmed cell death protein (PD‐1) and its ligand (PD‐L1) are markedly overexpressed in the tumour microenvironment, providing a means for immune escape. Targeting these molecules, novel immunotherapies manipulate the host immune system to better detect and kill cancer cells. This paper describes a case of drug‐induced autoimmune colitis and type 1 diabetes mellitus (T1DM) attributed to pembrolizumab.

Clinical details

A 70‐year‐old male presented with a 1‐week history of diarrhoea, vomiting, mucositis and loss of appetite following his third treatment with pembrolizumab infusion for metastatic melanoma. The patient's pathology results and clinical symptoms were consistent with a diagnosis of colitis and diabetic ketoacidosis (DKA).

Outcomes

The patient's symptoms resolved with interventions from the intensive care unit (ICU), endocrinology and gastroenterology teams. Due to the severity of the adverse drug reaction, pembrolizumab was ceased. The patient was discharged from the hospital with insulin for his T1DM and a 1‐month course of weaning prednisolone for his colitis.

Conclusion

The potential for autoimmune side effects associated with pembrolizumab may not be fully recognised by all clinicians. This case report highlights the potential for serious adverse events and serves to demonstrate the requirement for clinicians to develop a routine approach for early identification and management of these events.
Screening of Musa balbisiana Colla. seeds for antidiabetic properties and isolation of apiforol, a potential lead, with antidiabetic activity
Authors: Gopalan Greeshma , Prabha Bernard , Joe Alfred , Reshmitha Thankappan R , Sherin Daisy R , Abraham Billu , Sabu Mamiyil , Manojkumar Thanathu K , Radhakrishnan Kokkuvayil V , Nisha Prakasan
Published: November 2018

BACKGROUND

‘Phytonutrients’ have been reported to exert an incredible impact on the healthcare system and offer medical benefits including the prevention or treatment of lifestyle‐associated diseases. We chose one of the most common and important plant families, Musaceae, for our present study and explored its antidiabetic potential.

RESULTS

Seeds of the edible fruits of Musa balbisiana Colla. were investigated for their antidiabetic potential. After estimating the proximate composition, the seeds were extracted with various solvents and evaluated for antidiabetic potential in terms of the inhibition of digestive enzymes, antiglycation activity and in vitro glucose uptake. The acetone extract demonstrated the highest inhibition of α‐amylase and α‐glucosidase enzymes with IC50 values of 36.67 ± 0.367 and 100.61 ± 0.707 µg mL–1, respectively. The extract also exhibited significant glycation inhibition with an IC50 value of 86.48 ± 0.751 µg mL–1. Furthermore, a major phytochemical, apiforol, was isolated from the acetone extract for the first time, which demonstrated promising α‐glucosidase inhibition (IC50 = 48.25 ± 0.255 µmol L–1), antiglycation property (IC50 = 114.23 ± 0.567 µmol L–1) and enhanced glucose uptake in L6 myoblasts. In molecular docking studies, apiforol efficiently bonded to the active sites of α‐glucosidase enzyme 3A4A.

CONCLUSIONS

As dietary intervention is one of the effective strategies for addressing diabetes, special attention is always given to natural food bio‐actives or agro‐products for better human health. The results of our study suggest that Musa balbisiana has significant potential as an ingredient in health food formulations by reducing postprandial hyperglycaemia. © 2018 Society of Chemical Industry
Effect of processing on quality attributes and phenolic profile of quince dried bar snack
Authors: Torres Carolina A , Sepúlveda Gloria , Concha‐Meyer Anibal A
Published: November 2018

BACKGROUND

Fruit and vegetable processing can often alter and damage antioxidants. Phenolic compounds, which are major antioxidants in these products, can suffer dissociation and changes in their concentration. Quince is an excellent source of antioxidants, with health‐improving potential for consumers. The phenolic profile (by ultra‐high‐performance liquid chromatography‐mass spectrometry) and quality attributes (pH, soluble solids, acidity, water activity) were determined for processed quince products (fresh fruit puree, cooked puree and dried bars), in addition to the effect of puree cooking time (5, 10, 15 and 20 min).

RESULTS

Soluble solids in purees averaged 14.4 °Brix and increased to 75 °Brix in bars, as did titratable acidity, reaching 1.5 g malic acid kg−1 fresh weight after 20 min of cooking at 120 °C. Quercetin, p‐coumaric acid and trans‐cinnamic acid were predominant in fresh fruit puree. Thermal processing significantly increased the concentration of p‐coumaric acid, trans‐cinnamic acid, apigenin and quercetin, and decreased gallic acid. This increase was 242%, on average, for all of them when comparing fresh fruit puree with bars on a fresh weight basis, demonstrating their concentration throughout the dehydration process during bar production.

CONCLUSION

Although a minimum puree cooking time of 5 min was sufficient to obtain the highest concentration of most phenolics, p‐coumaric acid showed a higher concentration after 20 min of cooking. © 2018 Society of Chemical Industry
Increased lumbar spinal column laxity due to low‐angle, low‐load cyclic flexion may predispose to acute injury
Authors: Gale Nicole C. , Zeigler Stacey L. , Towler Christopher , Mondal Sumona , Issen Kathleen A. , Mesfin Addisu , Michalek Arthur J. , Kuxhaus Laurel
Published: November 2018

Lumbar spinal column laxity contributes to instability, increasing the risk of low back injury and pain. Until the laxity increase due to the cyclic loads of daily living can be quantified, the associated injury risk cannot be predicted clinically. This work cyclically loaded 5‐vertebra lumbar motion segments (7 skeletally‐mature cervine specimens, 5 osteoporotic human cadaver specimens) for 20 000 cycles of low‐load low‐angle (15°) flexion. The normalized neutral zone lengths and slopes of the load‐displacement hysteresis loops showed a similar increase in spinal column laxity across species. The intervertebral kinematics also changes with cyclic loading. Differences in the location and magnitude of surface strain on the vertebral bodies (0.34% ± 0.11% in the cervine specimens, and 3.13% ± 1.69% in the human cadaver specimens) are consistent with expected fracture modes in these populations. Together, these results provide biomechanical evidence of spinal column damage during high‐cycle low‐load low‐angle loading.
Historical aerial and terrestrial photographs for the investigation of mass movement dynamics in the Ethiopian Highlands
Authors: Kropáček Jan , Vařilová Zuzana , Nyssen Jan
Published: November 2018

The edges of the Ethiopian Plateau are affected by frequent landslides predisposed by pronounced seasonality in precipitation, thick weathering mantle of volcanic material, and rough relief. We analyzed the three‐dimensional dynamics of three large landslides in Dessie using digital elevation models and ortho‐images derived from a time‐series of aerial photographs reaching back to 1936. Furthermore, we utilized repeated photography based on terrestrial photographs from the 1930s and 1940s to analyze landscape changes. It was revealed that the large sliding zone (25.4 ha) in lacustrine sediments at Kerra locality existed approximately in the present extent already before 1936. The volume of depleted material of the 1986–1994 rock slide at Doro Mezleya locality was assessed as 1.82 106 m3 with mean vertical thickness of 48 m. Additionally, we described the nowadays inactive Hot Spring landslide (12.9 ha). We documented a large scale reforestation of the area carried out as a remediation measure and rapid changes in land cover and settlement structure. We conclude that two out of three studied large landslides existed before 1936 and thus are not induced by the increased human pressure on the landscape of the last decades. Additionally, we provide an overview about collections of historical aerial photographs of Ethiopia, and we discuss their potential and drawbacks for mass wasting studies.
The effect of brief subway station noise exposure on commuter hearing
Authors: Shah Ravi R. , Suen Jonathan J. , Cellum Ilana P. , Spitzer Jaclyn B. , Lalwani Anil K.
Published: November 2018

Objective

To demonstrate that brief exposure to subway noise causes temporary threshold shift and is preventable with noise protection.

Methods

The study was conducted as a randomized crossover trial. Twenty subjects were randomly assigned to two groups, one with hearing protection and one without. Subjects were exposed to subway platform noise for 15 minutes. Pre‐ and post‐exposure pure tone audiometry (PTA) and otoacoustic emissions were compared. After a washout period, subjects switched hearing protection groups and repeated the process.

Results

A statistically significant reduction in PTA thresholds after subway noise exposure was identified, for subjects with and without hearing protection (P < .001). For exposure without hearing protection, the mean threshold was 5.19 dB pre‐exposure and 3.91 dB post‐exposure (decrease of 1.28 dB; 95% confidence interval, 0.82–1.74). For exposure with hearing protection, the mean threshold was 4.81 dB pre‐exposure and 3.47 dB post‐exposure (decrease of 1.34 dB; 95% confidence interval, 0.89–1.79).

Conclusion

Brief exposure to subway noise did not cause hearing loss with or without noise protection. Though clinically insignificant, the unexpected finding of reduction in PTA suggests that there are complex heterogeneous short‐ and long‐term cochlear responses to noise exposure that should be further explored.

Level of Evidence

1b
MHA's State of MH report reveals gaps remain in access to care
Authors: Canady Valerie A.
Published: November 2018

While lack of access to mental health treatment is slowly improving, more than 50 percent of adults with a mental illness received no treatment, according to a new report from Mental Health America (MHA), which ranks all 50 states and the District of Columbia based on several mental health and access measures.
On uniform exponential stability of linear switching system
Authors: Zada Akbar , Zada Bakht
Published: November 2018

We prove that the linear switching system
, where
is bounded valued square matrices and ϑ:[0,1,2,…)→Ω is an arbitrary switching signals, is uniformly exponentially stable if the sequence
is bounded, where s(k) is bounded valued sequence.
Model‐based reconstruction framework for correction of signal pile‐up and geometric distortions in prostate diffusion MRI
Authors: Usman Muhammad , Kakkar Lebina , Kirkham Alex , Arridge Simon , Atkinson David
Published: November 2018

Purpose

Prostate diffusion‐weighted MRI scans can suffer from geometric distortions, signal pileup, and signal dropout attributed to differences in tissue susceptibility values at the interface between the prostate and rectal air. The aim of this work is to present and validate a novel model based reconstruction method that can correct for these distortions.

Methods

In regions of severe signal pileup, standard techniques for distortion correction have difficulty recovering the underlying true signal. Furthermore, because of drifts and inaccuracies in the determination of center frequency, echo planar imaging (EPI) scans can be shifted in the phase‐encoding direction. In this work, using a B0 field map and a set of EPI data acquired with blip‐up and blip‐down phase encoding gradients, we model the distortion correction problem linking the distortion‐free image to the acquired raw corrupted k‐space data and solve it in a manner analogous to the sensitivity encoding method. Both a quantitative and qualitative assessment of the proposed method is performed in vivo in 10 patients.

Results

Without distortion correction, mean Dice similarity scores between a reference T2W and the uncorrected EPI images were 0.64 and 0.60 for b‐values of 0 and 500 s/mm2, respectively. Compared to the Topup (distortion correction method commonly used for neuro imaging), the proposed method achieved Dice scores (0.87 and 0.85 versus 0.82 and 0.80) and better qualitative results in patients where signal pileup was present because of high rectal gas residue.

Conclusion

Model‐based reconstruction can be used for distortion correction in prostate diffusion MRI.
Evaluating corrections for Eddy‐currents and other EPI distortions in diffusion MRI: methodology and a dataset for benchmarking
Authors: Irfanoglu M. Okan , Sarlls Joelle , Nayak Amritha , Pierpaoli Carlo
Published: November 2018

Purpose

To propose a methodology for assessment of algorithms that correct distortions due to motion, eddy‐currents, and echo planar imaging in diffusion weighted images (DWIs).

Methods

The proposed method evaluates correction performance by measuring variability across datasets of the same object acquired with images having distortions in different directions, thereby overcoming the unavailability of ground‐truth, undistorted DWIs. A comprehensive diffusion MRI dataset, collected using a suitable experimental design, is made available to the scientific community, consisting of three DWI shells (Bmax = 5000 s/mm2), 30 gradient directions, a replicate set of antipodal gradient directions, four phase‐encoding directions, and three different head orientations. The proposed methodology was tested using the TORTOISE diffusion MRI processing pipeline.

Results

The median variability of the original distorted data was 123% higher for DWIs, 100–168% higher for tensor‐derived metrics and 28–111% higher for MAPMRI metrics, than in the corrected versions. EPI distortions induced substantial variability, nearly comparable to the contribution of eddy‐current distortions.

Conclusions

The dataset and the evaluation strategy proposed herein enable quantitative comparison of different methods for correction of distortions due to motion, eddy‐currents, and other EPI distortions, and can be useful in benchmarking newly developed algorithms.
Fast tomoelastography of the mouse brain by multifrequency single‐shot MR elastography
Authors: Bertalan Gergely , Guo Jing , Tzschätzsch Heiko , Klein Charlotte , Barnhill Eric , Sack Ingolf , Braun Jürgen
Published: November 2018

Purpose

To introduce in vivo multifrequency single‐shot magnetic resonance elastography for full‐FOV stiffness mapping of the mouse brain and to compare in vivo stiffness of neural tissues with different white‐to‐gray matter ratios.

Methods

Viscous phantoms and 10 C57BL‐6 mice were investigated by 7T small‐animal MRI using a single‐shot spin‐echo planar imaging magnetic resonance elastography sequence with motion‐encoding gradients positioned before the refocusing pulse. Wave images were acquired over 10 minutes for 6 mechanical vibration frequencies between 900 and 1400 Hz. Stiffness maps of shear wave speed (SWS) were computed using tomoelastography data processing and compared with algebraic Helmholtz inversion (AHI) for signal‐to‐noise ratio (SNR) analysis. Different brain regions were analyzed including cerebral cortex, corpus callosum, hippocampus, and diencephalon.

Results

In phantoms, algebraic Helmholtz inversion–based SWS was systematically biased by noise and discretization, whereas tomoelastography‐derived SWS was consistent over the full SNR range analyzed. Mean in vivo SWS of the whole brain was 3.76 ± 0.33 m/s with significant regional variation (hippocampus = 4.91 ± 0.49 m/s, diencephalon = 4.78 ± 0.78 m/s, cerebral cortex = 3.53 ± 0.29 m/s, and corpus callosum = 2.89 ± 0.17 m/s).

Conclusion

Tomoelastography retrieves mouse brain stiffness within shorter scan times and with greater detail resolution than classical algebraic Helmholtz inversion–based magnetic resonance elastography. The range of SWS values obtained here indicates that mouse white matter is softer than gray matter at the frequencies investigated.
Infrared Imagery and Inert Media Used in Treating Upwelling Groundwater with Rotenone
Authors: Haukebø Trond , Steinkjer Jarle , Finlayson Brian
Published: November 2018

Untreated upwelling groundwater from seeps and springs in and adjacent to surface water bodies has been long suspected of causing failed rotenone treatments by providing a refugia of nontoxic water. A possible solution involves the use of an inert media to carry the liquid rotenone to the source of upwelling groundwater and release rotenone over an extended period of time sufficient to affect the mortality of the target fish. In our initial study to address this problem, we used thermal infrared imagery (FLIR One) on a smartphone to locate groundwater that was subsequently treated with mixtures of the liquid rotenone formulation CFT Legumine (3.3% rotenone) utilizing two commercially available inert carriers: (1) CatSan Hygiene Litter (mixture of quartz sand and calcite) and (2) Vectocarb (fine powder of modified CaCO3). Trials on the mixtures were conducted in 2015 in upwelling groundwater areas of the Skibotn River drainage, Troms County, Norway, the site of previously failed eradication efforts. Following application, mean concentrations of 75.6 to 131 μg/L rotenone were present at 0.5 h in the pools and the brooks downstream of the upwelling groundwater that decreased and stabilized to 11.5 to 16.8 μg/L rotenone at 3 h. Both carriers have large surface areas (porosity) that transport (through sorption) the rotenone liquid to the source of upwelling groundwater and release (through desorption) concentrations of rotenone over at least 3 h. Both mixtures show promise in treating upwelling groundwater to eradicate fish from those areas and were used successfully in the 2016 retreatment of Skibotn River for the eradication of Atlantic Salmon Salmo salar infested with the ectoparasite Gyrodactylus salaris.
Raphael Lemkin in Remote Australia: The Logic of Cultural Genocide and Homelands
Authors: Altman Jon
Published: November 2018

In the 1970s, Aboriginal people in remote Australia took decisive steps to decentralize from government settlements and missions to live and make a living on their ancestral lands at places that have become known as homelands. Over time, this migration garnered some state support and saw the emergence of new facilitating institutions. But in the last decade homeland living has been discursively demeaned by politicians, and policies have been put in place to undermine the possibility of residing and making a livelihood in these smallest, most remote places mainly located on Indigenous‐titled lands. As Indigenous territorial rights expand, the state looks to extinguish possibilities for current and future generations to utilize the land and its resources for livelihood. In this article, I draw on evidence from political discourse, policy documents and programme design and implementation to outline this state project to eliminate a contemporary lifeway. I provide ethnographic evidence from work with Kuninjku people in Arnhem Land that documents this destruction. I engage with the work of Raphael Lemkin to document and theorize the techniques being deployed in terms of the logic of cultural genocide. I end by asking what homelands people might do to push back and what role anthropologists might play in such a process.
In‐situ polymerization of aliphatic‐aromatic polyamide nanocomposites in the presence of Halloysite nanotubes
Authors: Taherian Sara , Rahmani Sima , Sharif Alireza , Zeinolebadi Ahmad , Abdollahi Mahdi
Published: November 2018

Nanocomposites consisting of semi‐aromatic polyamide (PA) and pristine or alkali activated halloysite nanotubes (HNT or mHNT, respectively) were synthesized by the in‐situ interfacial polymerization method. The condensation reactions were carried out between isophthaloyl dichloride in hexane and triethylenetetramine in water containing different amounts of HNT or mHNT. The interactions and crystallinity of the nanocomposites were studied by Fourier transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) analysis, respectively. Development of hydrogen bonds between the functional groups of PA and hydroxyl groups of nanotubes was indicated by FTIR spectroscopy. According to the XRD analysis, the addition of HNT and mHNT nanotubes increased the crystallinity of the PA. This was ascribed to the role of nanotubes as nucleating agents in the PA matrix. Thermal resistance and char residue of PA, as revealed by thermogravimetric analysis, were enhanced by incorporating both HNT and mHNT and the latter was more effective in this regard. Furthermore, while the addition of pristine HNTs decreased the glass transition temperature (Tg) of the PA, the Tg could be increased by about 5°C, in the presence of 5 wt% of mHNTs. Finally, the facilely activated mHNT nanotubes were found to be highly efficient in improving the thermal and structural properties of semi‐aromatic PAs.
Higher incidence of surgery‐related complications in Wilms tumor nephrectomy from clinical records analysis compared with central database registration
Authors: van Poll Daan , Wilde Jim , van de Ven Kees , Asimakidou Maria , Heij Hugo , Wijnen Marc
Published: November 2018

Background/Objectives

Central database registrations are widely used tools for assessment of clinical results, but their reliability is subject to debate. The aim of this study is to evaluate the reliability of central database registration for Wilms tumor (WT) nephrectomy‐related complications.

Design/Methods

All Dutch patients undergoing WT nephrectomy according to the International Society of Paediatric Oncology (SIOP) 2001 protocol between 2001 and 2013 were evaluated. Results from the central database were analyzed and compared with data found via individual medical records analysis (gold standard).

Results

A total of 179 patients were included. Fourteen (7.8%) patients with a total of 17 complications were identified in the central database. The medical records revealed that 33 (18.4%) of patients had undergone a total of 41 complications (P < 0.001). Operative complications were similar between the groups (P = 0.157). Eleven short‐term complications were noted in the central database versus 27 in the medical records (P = 0.059). Significantly more long‐term complications, namely, adhesive small‐bowel obstruction, were noted from the medical records compared with the central database (7 vs 1, respectively, P < 0.001). Postoperative chemotherapy was significantly delayed by on average 6 days (P < 0.0001) in patients with complications. No significant effect of complications on event‐free survival, overall survival, or the relapse rate was recorded.

Conclusion

Central database registrations underestimate the incidence of surgery‐related complications after WT nephrectomy and need to be regarded with caution.
Bone marrow transplant and pediatric multiple myeloma
Authors: Davidow Kimberly A. , Walter Andrew W. , Kolb E. Anders
Published: November 2018

Multiple myeloma is a malignant plasma cell disorder that is rare in the pediatric population, with only approximately 0.3% of cases diagnosed before the age of 30. In this report, we present two patients diagnosed with multiple myeloma between the ages of 12 and 16. Their respective treatment regimens are discussed, including the use of both autologous and allogeneic stem cell transplant.
Sentinel lymph node biopsy in head and neck rhabdomyosarcoma
Authors: Turpin Brian , Pressey Joseph G. , Nagarajan Rajaram , Weiss Brian D. , Trout Andrew T. , Gelfand Michael J. , Pater Luke , Vatner Ralph E. , Breneman John C. , Dasgupta Roshni
Published: November 2018

Head and neck rhabdomyosarcoma lymph node staging is challenging due to varied patterns of lymphatic drainage and the suboptimal predictive value of available imaging modalities. Furthermore, regional relapse rates are unacceptably high, and the toxicity of empiric radiation is undesirable in the pediatric and young adult population. In an attempt to improve locoregional control without excess morbidity, we have adopted routine sentinel lymph node biopsy in head and neck rhabdomyosarcoma, which is safe and feasible in pediatric patients. Of six procedures reported here, pathologic findings led to intensification of regional and/or systemic therapy in two patients.
How I approach iron deficiency with and without anemia
Authors: Powers Jacquelyn M. , O'Brien Sarah H.
Published: November 2018

Iron deficiency anemia remains a common referral to the pediatric hematology–oncology subspecialist. Improved understanding of iron homeostasis, including the effects of the regulatory hormone hepcidin, recent adult and pediatric clinical trial data, as well as the availability of safer formulations of intravenous iron, have resulted in additional considerations when making treatment recommendations in such patients. Young children and adolescent females remain the most commonly affected groups, but children with complex medical or chronic inflammatory conditions including comorbid gastrointestinal disorders also require special consideration.
Tunable mechanical properties of core‐shell polymers of poly(hexyl methacrylate) and poly(methyl methacrylate) by semicontinuous heterophase polymerization
Authors: Sahagún Aguilar L. O. , Ceja Andrade I. , Alvarado Mendoza A. G. , Puig Arevalo J. E. , Rabelero Velasco M.
Published: November 2018

The synthesis of core/shell polymers with tunable mechanical properties made of poly(hexyl methacrylate) (PHeMA) and poly(methyl methacrylate) (PMMA) by a two‐stage semicontinuous heterophase polymerization, is presented here. This polymerization technique is characterized by employing low surfactant concentrations to produce large polymer‐to‐surfactant ratios. In this process, monomer is added in a continuous low rate to achieve monomer starved conditions, allowing to control particle size (usually smaller than 50 nm). To modulate the mechanical properties, the weight ratio of core/shell polymers are varied from 10/90 to 90/10 for direct and reverse compositions, respectively. Conversion was followed gravimetrically; nanoparticles were characterized with quasi‐elastic light scattering, IR spectroscopy, differential scanning calorimetry, transmission electron microscopy, and mechanical tests (tensile and hardness). Highly stable latex formed of nanoparticles, with high conversions are obtained. Tensile tests show that the mechanical properties can be tuned according to core/shell composition, mainly in the system formed by PMMA/PHeMA. These results are explained in terms of core‐and‐shell polymers location, composition and hardness. As expected, an increment in concentration of PMMA produces a more rigid material independently of its position. POLYM. ENG. SCI., 59:365–371, 2019. © 2018 Society of Plastics Engineers
Composite polymer electrolytes based on electrospun thermoplastic polyurethane membrane and polyethylene oxide for all‐solid‐state lithium batteries
Authors: Gao Minghao , Wang Chao , Zhu Lin , Cheng Qin , Xu Xin , Xu Gewen , Huang Yiping , Bao Junjie
Published: November 2018

To improve the electrochemical properties and enhance the mechanical strength of solid polymer electrolytes, series of composite polymer electrolytes (CPEs) were fabricated with hybrids of thermoplastic polyurethane (TPU) electrospun membrane, polyethylene oxide (PEO), SiO2 nanoparticles and lithium bis(trifluoromethane)sulfonamide (LiTFSI). The structure and properties of the CPEs were confirmed by SEM, XRD, DSC, TGA, electrochemical impedance spectroscopy and linear sweep voltammetry. The TPU electrospun membrane as the skeleton can improve the mechanical properties of the CPEs. In addition, SiO2 particles can suppress the crystallization of PEO. The results show that the TPU‐electrospun‐membrane‐supported PEO electrolyte with 5 wt% SiO2 and 20 wt% LiTFSI (TPU/PEO‐5%SiO2‐20%Li) presents an ionic conductivity of 6.1 × 10−4 S cm−1 at 60 °C with a high tensile strength of 25.6 MPa. The battery using TPU/PEO‐5%SiO2‐20%Li as solid electrolyte and LiFePO4 as cathode shows an attractive discharge capacity of 152, 150, 121, 75, 55 and 26 mA h g−1 at C‐rates of 0.2C, 0.5C, 1C, 2C, 3C and 5C, respectively. The discharge capacity of the cell remains 110 mA h g−1 after 100 cycles at 1C at 60 °C (with a capacity retention of 91%). All the results indicate that this CPE can be applied to all‐solid‐state rechargeable lithium batteries. © 2018 Society of Chemical Industry
Licht ins Dunkle
Authors: Loos Andreas
Published: November 2018

Wollte man belegen, dass sich das Interesse für Physik und andere Naturwissenschaften vererbt, dann wäre seine Familie ein Paradebeispiel. Der Vater des Gesuchten, ein Professor für angewandte Physik, entdeckt er zusammen mit seinem Vater (also dem Großvater des Gesuchten) den lichtelektrischen Effekt. Der Sohn des Gesuchten wird Festkörperphysiker, ein Neffe berühmter Botaniker und ein Onkel einflussreicher Arzt.
Effect of pH and content of reduction‐sensitive copolymer on the guest exchange kinetics of micelles
Authors: Li Yixia , Si Jianhao , Fan Haiyan , Ye Xiaodong
Published: November 2018

The micelles formed by reduction‐sensitive amphiphilic copolymer have emerged as promising drug nanocarriers due to the controlled drug release and effective anticancer activity triggered by the reducing stimulation. However, the effect of pH on the stability and guest exchange of the micelles formed by reduction‐sensitive copolymer have not been systemically investigated. Herein, the micelles formed by a reduction‐sensitive copolymer poly(ε‐caprolactone)‐b‐poly[oligo(ethylene glycol) methyl ether methacrylate] (PCL–SS–POEGA) with a single disulfide group at different pH values loaded with dyes 3,3′‐dioctadecyloxacarbocyanine perchlorate/1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiO/DiI) were prepared through the precipitation‐dialysis method. In addition, mixed micelles formed by different contents of reduction‐sensitive and reduction‐insensitive copolymers encapsulated with DiO/DiI at pH 7.5 were also prepared by the similar approach. The effects of pH and the content of reduction‐sensitive copolymer on guest exchange of these micelles were studied by the fluorescence resonance energy transfer method. Results show that the pH value in the environment has great influence on the guest exchange rate of reduction‐sensitive micelles in the presence of 10 mM dithiothreitol (DTT) and slight effect on that in the absence of DTT. Under a reducing environment, the guest exchange rate of the micelles containing various contents of disulfide‐linked copolymer increases with the increasing content of PCL–SS–POEGA. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 1636–1644
Thermal stability of single‐domain antibodies estimated by molecular dynamics simulations
Authors: Bekker Gert‐Jan , Ma Benson , Kamiya Narutoshi
Published: November 2018

Single‐domain antibodies (sdAbs) function like regular antibodies, however, consist of only one domain. Because of their low molecular weight, sdAbs have advantages with respect to production and delivery to their targets and for applications such as antibody drugs and biosensors. Thus, sdAbs with high thermal stability are required. In this work, we chose seven sdAbs, which have a wide range of melting temperature (Tm) values and known structures. We applied molecular dynamics (MD) simulations to estimate their relative stability and compared them with the experimental data. High‐temperature MD simulations at 400 K and 500 K were executed with simulations at 300 K as a control. The fraction of native atomic contacts, Q, measured for the 400 K simulations showed a fairly good correlation with the Tm values. Interestingly, when the residues were classified by their hydrophobicity and size, the Q values of hydrophilic residues exhibited an even better correlation, suggesting that stabilization is correlated with favorable interactions of hydrophilic residues. Measuring the Q value on a per‐residue level enabled us to identify residues that contribute significantly to the instability and thus demonstrating how our analysis can be used in a mutant case study.
Suppression, disaggregation, and modulation of γ‐Synuclein fibrillation pathway by green tea polyphenol EGCG
Authors: Roy Sneha , Bhat Rajiv
Published: November 2018

Oligomerization of γ‐Synuclein is known to have implications for both neurodegeneration and cancer. Although it is known to co‐exist with the fibrillar deposits of α‐Synuclein (Lewy bodies), a hallmark in Parkinson's disease (PD), the effect of potential therapeutic modulators on the fibrillation pathway of γ‐Syn remains unexplored. By a combined use of various biophysical tools and cytotoxicity assays we demonstrate that the flavonoid epigallocatechin‐3‐gallate (EGCG) significantly suppresses γ‐Syn fibrillation by affecting its nucleation and binds with the unstructured, nucleus forming oligomers of γ‐Syn to modulate the pathway to form α‐helical containing higher‐order oligomers (~158 kDa and ~ 670 kDa) that are SDS‐resistant and conformationally restrained in nature. Seeding studies reveal that these oligomers although “on‐pathway” in nature, are kinetically retarded and rate‐limiting species that slows down fibril elongation. We observe that EGCG also disaggregates the protofibrils and mature γ‐Syn fibrils into similar SDS‐resistant oligomers. Steady‐state and time‐resolved fluorescence spectroscopy and isothermal titration calorimetry (ITC) reveal a weak non‐covalent interaction between EGCG and γ‐Syn with the dissociation constant in the mM range (Kd ~ 2–10 mM). Interestingly, while EGCG‐generated oligomers completely rescue the breast cancer (MCF‐7) cells from γ‐Syn toxicity, it reduces the viability of neuroblastoma (SH‐SY5Y) cells. However, the disaggregated oligomers of γ‐Syn are more toxic than the disaggregated fibrils for MCF‐7cells. These findings throw light on EGCG‐mediated modulation of γ‐Syn fibrillation and suggest that investigation on the effects of such modulators on γ‐Syn fibrillation is critical in identifying effective therapeutic strategies using small molecule modulators of synucleopathies.
Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I
Authors: Rittner Alexander , Paithankar Karthik S. , Drexler David Jan , Himmler Aaron , Grininger Martin
Published: November 2018

Modularity is a fundamental property of megasynthases such as polyketide synthases (PKSs). In this study, we exploit the close resemblance between PKSs and animal fatty acid synthase (FAS) to re‐engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by sequence and structural information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS‐like modules as well as bimodular constructs. The novel re‐engineered modules resemble all four common types of PKSs and demonstrate that this approach can be a powerful tool to deliver products with higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS‐based biosynthetic pathways for custom compound design.
Investigation of amodiaquine localization in liver lobules using matrix‐assisted laser desorption/ionization imaging mass spectrometry
Authors: Grove Kerri J. , Hoque Shaila , Rudewicz Patrick J.
Published: November 2018

Rationale

High mass and high spatial resolution matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) opens new possibilities for the detailed study of the hepatic metabolism of drugs. The spatial and temporal distribution of drug metabolites within liver lobules, anatomical subunits of the liver, may aid in the understanding of the formation of reactive metabolites that bind to liver proteins and cause drug‐induced liver injury.

Methods

Frozen livers obtained from rats dosed orally with amodiaquine (100 mg/kg) were sectioned at 10 μm and coated with a MALDI matrix. The liver sections were then analyzed using a Fourier transform ion cyclotron resonance mass spectrometer. Images corresponding to amodiaquine and its metabolites were obtained at a spatial resolution of 25 μm.

Results

Molecular images of amodiaquine within liver lobules have higher intensities near the portal triad and lower intensities near the central vein.

Conclusions

This study demonstrates that MALDI IMS can be used to investigate the metabolism of drugs within liver lobules. The results are consistent with existing knowledge of amodiaquine metabolism and reactive metabolite formation.
Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice
Authors: Watanabe Yusuke , Tsuchiya Atsunori , Seino Satoshi , Kawata Yuzo , Kojima Yuichi , Ikarashi Shunzo , Starkey Lewis Philip J. , Lu Wei-Yu , Kikuta Junichi , Kawai Hirokazu , Yamagiwa Satoshi , Forbes Stuart J. , Ishii Masaru , Terai Shuji
Published: November 2018

We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl4-induced cirrhosis. Fibrosis regression, liver regeneration, and liver-migrating host cells were evaluated. Administered cell behavior was also tracked by intravital imaging. In coculture, MSCs induced switching of id-BMMs toward the M2 phenotype with high phagocytic activity. In vivo, the combination therapy reduced liver fibrosis (associated with increased matrix metalloproteinases expression), increased hepatocyte proliferation (associated with increased hepatocyte growth factor, vascular endothelial growth factor, and oncostatin M in the liver), and reduced blood levels of liver enzymes, more effectively than MSCs or id-BMMs monotherapy. Intravital imaging showed that after combination cell administration, a large number of id-BMMs, which phagocytosed hepatocyte debris and were retained in the liver for more than 7 days, along with a few MSCs, the majority of which were trapped in the lung, migrated to the fibrotic area in the liver. Host macrophages and neutrophils infiltrated after combination therapy and contributed to liver fibrosis regression and promoted regeneration along with administered cells. Indirect effector MSCs and direct effector id-BMMs synergistically improved cirrhosis along with host cells in mice. These studies pave the way for new treatments for cirrhosis. Stem Cells Translational Medicine  2019;8:271&284
Metal‐Free Assemblage of Four C−N and Two C−C Bonds via a Cascade Five Component Diastereoselective Synthesis of Pyrido[1,2‐a]Pyrimidines
Authors: Rezvanian Atieh , Alinaghian Fereshteh , Heravi Majid M.
Published: November 2018

An efficient heteroannulation synthesis of N‐fused, pyrido[1,2‐a]pyrimidines was successfully achieved via a sequential, one‐pot five‐component reaction, involving primary amines, diketene (DK), differently substituted aromatic aldehydes, nitro ketene dithioacetal and propanediamine in ethanol at 70 °C. This new protocol constructs two rings through the formation of four C–N and two C–C bonds via a one pot sequential reaction involving ring‐opening/ Knoevenagel condensation, /nucleophilic substitution (SN)/ Michael addition followed by imine−enamine tautomerization and final N‐heterocyclization. The method is particularly attractive due to the advantages such as: atom economy, optimum convergence, commercially available or readily accessible starting materials, high bond‐forming efficiency, free metal‐catalyst and mild reaction conditions. The products were isolated by just decantation of the solvent and purification without using column chromatography method.