bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors and prevention of dabigatran‐related gastrointestinal bleeding in patients with atrial fibrillation
Authors: Nantsupawat Teerapat , Soontrapa Suthipong , Nantsupawat Nopakoon , Sotello David , Klomjit Saranapoom , Adabag Selcuk , Perez‐Verdia Alejandro
Published: February 2018

Introduction

Dabigatran, as compared with warfarin, was associated with lower rates of stroke and systemic embolism with similar rates of major hemorrhage. But it has a significantly higher risk of gastrointestinal bleeding (GIB). There are limited data on how to prevent GIB from dabigatran and what are the risk factors.

Methods

We performed a retrospective cohort study of patients with atrial fibrillation who have ever taken dabigatran for thromboprophylaxis from October 2010 to February 2013.

Results

A total of 247 patients were identified. There were 10 (4%) patients who developed GIB (6 (6.5%) in PPI/H2RA users vs 4 (2.6%) in non‐PPI/H2RA users; P = .184). History of GIB within 1 year prior to dabigatran initiation and HAS‐BLED score ≥3 are independent risk factors for GIB, with odds ratio of 25.14 (95% CI, 2.85‐221.47; P < .01) and 5.85 (95% CI, 1.31‐26.15; P = .021), respectively.

Conclusion

In this real‐world cohort, PPI/H2RA use was not associated with reduced GIB events. HAS‐BLED score ≥3 and prior history of GIB within 1 year are independent risk factors for GIB among dabigatran users.
Comparison of triple‐site ventricular pacing versus conventional cardiac resynchronization therapy in patients with systolic heart failure: A meta‐analysis of randomized and observational studies
Authors: Zhang Baowei , Guo Junfang , Zhang Guohui
Published: February 2018

Background

Conventional cardiac resynchronization therapy (CRT, Bi‐V) is associated with no response in about 40% patients due to an insufficient resynchronization. Some studies showed triple‐site ventricular (Tri‐V) pacing had greater benefits compared with Bi‐V pacing, but the results of these studies were conflicting. We hypothesized that Tri‐V pacing had greater benefits on long‐term outcomes compared with Bi‐V pacing in patients with heart failure.

Methods

PubMed, EMBASE, and the Cochrane Library were searched for clinical studies with related outcomes. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated to compare the change in left ventricular ejection fraction (LVEF), left ventricular geometry, functional capacity, and quality of life between Tri‐V pacing group and control group.

Results

Five trials with 251 patients were included in the analysis. Patients in the Tri‐V pacing group had a greater improvement in LVEF (WMD 4.04; 95% CI 2.15‐5.92, P < .001) and NYHA classes (WMD −0.27; 95% CI −0.42 to −0.11, P = .001) compared with control group. However, there were no significant differences in left ventricular geometry, six‐min walk distance, or Minnesota Living With Heart Failure Questionnaire score between the two groups. The subgroup analyses showed there might be a greater improvement in LVEF in the Tri‐V pacing group in patients with QRS duration ≥ 155 ms (WMD 5.60; 95% CI 3.09‐8.10, P < .001).

Conclusions

The present analysis suggests that Tri‐V pacing has greater benefits in terms of an improvement in LVEF and functional capacity in patients with systolic heart failure, especially in patients with the duration of QRS ≥ 155 ms.
Ventricular tachycardia storm originating from interventricular septum successfully treated with surgical cryoablation with electroanatomic and electrophysiological mapping before dual valve replacement
Authors: Kawamura Iwanari , Fukamizu Seiji , Miyazawa Satoshi , Hojo Rintaro , Ito Fusahiko , Watanabe Masazumi , Nishizaki Mitsuhiro , Sakurada Harumizu , Hiraoka Masayasu
Published: February 2018

A 58‐year‐old man with dilated cardiomyopathy was admitted with heart failure. He had a history of two catheter ablation procedures for ventricular tachycardia (VT) originating from the intraventricular septum (IVS). Before dual valve replacement (DVR), he suffered a VT storm. An electrophysiological study revealed an extended low‐voltage area at the IVS with the exit of the induced VT at the anterior side. Radiofrequency application was performed at the VT exit as a landmark for surgical cryoablation (SA). During the DVR, SA was performed at the IVS using this landmark. After SA, the patient had no ventricular tachyarrhythmia.
Long‐term outcomes of heart failure patients who received primary prevention implantable cardioverter‐defibrillator: An observational study
Authors: Looi Khang‐Li , Sidhu Karishma , Cooper Lisa , Dawson Liane , Slipper Debbie , Gavin Andrew , Lever Nigel
Published: February 2018

Background

Implantable cardioverter‐defibrillator (ICD) therapy is indicated for selected heart failure patients for the primary prevention of sudden cardiac death. Little is known about the outcomes in patients selected for primary prevention device therapy in the northern region of New Zealand.

Method

Heart failure patients with systolic dysfunction who underwent primary prevention ICD/cardiac resynchronization therapy‐defibrillator (CRT‐D) implantation between January 1, 2007, and June 1, 2015, were included. Complications, mortality, and hospitalization events were reviewed.

Results

Three hundred and eighty‐five primary prevention devices were implanted (269 ICD, 116 CRT‐D). Mean age at implant was 59.1 ± 11.4 years. Mean duration of follow‐up was 3.64 ± 2.17 years. The commonest cause of death was heart failure (41.8%). Only 2 patients died from sudden arrhythmic death. The 5‐year heart failure mortality rate was 6%, whereas the 5‐year sudden arrhythmic death rate was 0.3%. Heart failure hospitalizations were commoner in those who received ICD than CRT‐D (67.7% vs 25.8%, P < .001). Maori patients have low implant rates (14%) with relatively high rates of admissions with heart failure and ventricular arrhythmia admissions,

Conclusions

Even in appropriately selected heart failure patients who received primary prevention devices, only a small percentage died as a result of sudden arrhythmic death. CRT‐D should be the device of choice where appropriate in heart failure patients. Significant challenges remain to improve access to device therapy and maximize benefit to those who do get implanted.
Point‐of‐care activated system versus conventional intravenous admixture system at an academic medical centre in Singapore
Authors: Woon Chin Menn , Tan Thor Eng , Hooi Pik Yee , Teoh Siang Nee , Wu Tuck Seng
Published: February 2018

We aim to examine the impact of a point‐of‐care (POC)‐activated system on time and cost requirements, as compared with a conventional intravenous admixture system. Time spent on intravenous piperacillin‐tazobactam administration before and after implementation of the POC‐activated system (Mini‐bag Plus®) was measured. Resource cost difference was calculated based on the difference in required manpower and material costs. The POC‐activated system reduced IV administration time by 58% (36.7 min versus 15.4 min before and after the implementation of the POC‐activated system (p < 0.05)). The total number of drugs prepared using the POC‐activated system at our institution was estimated to be 215 920 in 2015. This translates to a total nursing time saving of 76 651.6 h and resource cost saving of SGD 3 884 400. A user satisfaction survey showed that users welcomed the POC‐activated system, due to its ease of use and safety benefits. A POC‐activated system offers significant benefits over the conventional IV admixture system in terms of nursing time and cost savings, as well as improved safety.
Nuclear Magnetic Resonance Investigation of the Effect of pH on Micelle Formation by the Amino Acid‐Based Surfactant Undecyl l‐Phenylalaninate
Authors: Rothbauer Gabriel A. , Rutter Elisabeth A. , Reuter‐Seng Chelsea , Vera Simon , Billiot Eugene J. , Fang Yayin , Billiot Fereshteh H. , Morris Kevin F.
Published: February 2018

Micelle formation by the anionic amino acid‐based surfactant undecyl l‐phenylalaninate (und‐Phe) was investigated as a function of pH in solutions containing either Na+, l‐arginine, l‐lysine, or l‐ornithine counterions. In each mixture, the surfactant's critical micelle concentration (CMC) was the lowest at low pH and increased as solutions became more basic. Below pH 9, surfactant solutions containing l‐arginine and l‐lysine had lower CMC than the corresponding solutions with Na+ counterions. Nuclear magnetic resonance (NMR) diffusometry and dynamic light scattering studies revealed that und‐Phe micelles with Na+ counterions had hydrodynamic radii of approximately 15 Å throughout the investigated pH range. Furthermore, l‐arginine, l‐lysine, and l‐ornithine were found to bind most strongly to the micelles below pH 9 when the counterions were cationic. Above pH 9, the counterions became zwitterionic and dissociated from the micelle surface. In und‐Phe/l‐arginine solution, counterion dissociation was accompanied by a decrease in the hydrodynamic radius of the micelle. However, in experiments with l‐lysine and l‐ornithine, micelle radii remained the same at low pH when counterions were bound and at high pH when they were not. This result suggested that l‐arginine is attached perpendicular to the micelle surface through its guanidinium functional group with the remainder of the molecule extending into solution. Contrastingly, l‐lysine and l‐ornithine likely bind parallel to the micelle surface with their two amine functional groups interacting with different surfactant monomers. This model was consistent with the results from two‐dimensional ROESY (rotating frame Overhauser enhancement spectroscopy) NMR experiments. Two‐dimensional NMR also showed that in und‐Phe micelles, the aromatic rings on the phenylalanine headgroups were rotated toward the hydrocarbon core of micelle.
Early and late complications in the reconstructed mandible with free fibula flaps
Authors: van Gemert Johannes T.M. , Abbink Jan H. , van Es Robert J.J. , Rosenberg Antoine J.W.P. , Koole Ron , Van Cann Ellen M.
Published: February 2018

Background and Objectives

Evaluation of mandibular reconstructions with free fibula flaps. Identification of factors associated with major recipient site complications, that is, necessitating surgical intervention under general anaesthesia.

Methods

Seventy‐nine reconstructions were included. The following factors were analyzed: fixation type, number of osteotomies, site of defect (bilateral/unilateral), surgeon, sex, ASA classification, continuous smoking, pathological N‐stage, age, defect size, flap ischemic time, and postoperative radiotherapy. Proportional hazards regression was used to test the effect on the time between reconstruction and intervention.

Results

Sixty‐nine (87%) of the 79 fibula flaps were successful at the last follow‐up. Forty‐eight major recipient site complications occurred in 41 reconstructions. Nineteen complications required surgical intervention within six weeks and were mostly vascular problems, necessitating immediate intervention. These early complications were associated with defects crossing the midline, with an estimated relative risk of 5.3 (CI 1.1‐20, P = 0.01). Twenty‐nine complications required surgical intervention more than 6 weeks after the reconstruction. These late complications generally occurred after months or years, and were associated with smoking, with an estimated relative risk of 2.8 (CI 1.0‐8.3, P = 0.05).

Conclusions

Fibula flaps crossing the midline have a higher risk of early major recipient site complications than unilateral reconstructions. Smoking increases the risk of late complications.
The value of additional bevacizumab in patients with high‐risk stroma‐high colon cancer. A study within the QUASAR2 trial, an open‐label randomized phase 3 trial
Authors: Huijbers Anouck , van Pelt Gabi W. , Kerr Rachel S. , Johnstone Elaine C. , Tollenaar Rob A.E.M. , Kerr David J. , Mesker Wilma E.
Published: February 2018

Introduction

Patients with a high stroma percentage within the primary tumor have a poor prognosis. In this study, we investigate whether anti‐angiogenic therapy might improve survival of patients with a stroma‐high profile with potentially increased angiogenesis.

Materials and Methods

Tissue samples of the primary tumor of 965 colon cancer patients participating in the QUASAR2 trial were analyzed for tumor‐stroma ratio (TSR). Stroma‐high (>50%) and stroma‐low (≤50%) groups were evaluated with respect to survival.

Results

Disease free survival (DFS) was significantly lower in the stroma‐high group (HR 1.53, 95%CI 1.19‐1.95, P = 0.001). No difference in DFS was seen with respect to treatment with capecitabine alone (CAP) or capecitabine with bevacizumab (CAPBEV) (Stroma‐high HR 1.00, 95%CI 0.69‐1.46, P = 0.996; stroma‐low HR 1.02, 95%CI 0.75‐1.41, P = 0.883). A significant difference in survival was seen comparing groups with or without vascular invasion (DFS P < 0.001). A correlation between vascular invasion and stroma‐high was seen (χ2‐test P = 0.043).

Discussion and Conclusions

The TSR confirmed to be a strong prognosticator for disease‐free survival in a selected high‐risk patient population. No benefit was found in response to treatment with bevacizumab when stratified for TSR. TSR showed to have an additional prognostic value in patients with vascular invasion present in the primary tumor.
Retroperitoneal laparoscopic adrenalectomy with transient renal artery occlusion for large adrenal tumors (≥8 cm)
Authors: Gong Binbin , Ma Ming , Xie Wenjie , Yang Xiaorong , Sun Ting
Published: February 2018

Objectives

To analyze our experience in retroperitoneal laparoscopic adrenalectomy (RLA) with transient renal artery occlusion for large adrenal tumors (≥8 cm) and to explore the safety and feasibility of this surgical procedure.

Methods

A retrospective cohort study was conducted with a surgical data review of 18 patients with large adrenal tumors who underwent RLA with transient renal artery occlusion in our hospital.

Results

Eighteen patients were treated by RLA with transient occlusion of the renal artery, and none were converted to open adrenalectomy. The renal artery occlusion time, operative time, estimated blood loss, perirenal drainage time, postoperative hospital stay, and postoperative drainage were 7.6 ± 1.0 min, 176.3 ± 49.7 min, 247.2 ± 274.1 mL, 4.1 ± 1.02 days, 6.3 ± 1.4 days, and 73.6 ± 47.9 mL, respectively. No severe complications occurred, with the exception of hemodynamic instability in one patient with a pheochromocytoma and one transfusion during the operation. Only one case of adrenal crisis occurred postoperatively. Pathological examination revealed 9 cases of pheochromocytoma, 6 cases of adrenal myelolipoma, 1 case of adrenal ganglioneuroma, 1 case of hygromata, and 1 case of adrenal teratoma. No recurrence or evidence of metastasis was observed during the 7‐to‐30‐month follow‐up period.

Conclusion

RLA with transient renal artery occlusion is a feasible, effective, and safe treatment for large adrenal tumors (≥8 cm).
Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases
Authors: Fonseca Gilton M. , de Mello Evandro S. , Faraj Sheila F. , Kruger Jaime A. P. , Coelho Fabricio F. , Jeismann Vagner B. , Lupinacci Renato M. , Cecconello Ivan , Alves Venancio A. F. , Pawlik Timothy M. , Herman Paulo
Published: February 2018

Background

Histomorphological features have been described as prognostic factors after resection of colorectal liver metastases (CLM). The objectives of this study were to assess the prognostic significance of tumor budding (TB) and poorly differentiated clusters (PDC) among CLM, and their association with other prognostic factors.

Methods

We evaluated 229 patients who underwent a first resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory infiltrate. Lymphatic and portal invasion were evaluated through D2‐40 and CD34 antibody.

Results

Factors independently associated with poor overall survival were nodules>4 (P = 0.002), presence of PDC G3 (P = 0.007), portal invasion (P = 0.005), and absence of tumor pseudocapsule (P = 0.006). Factors independently associated with disease‐free survival included number of nodules>4 (P < 0.001), presence of PDC G3 (P = 0.005), infiltrative border (P = 0.031), portal invasion (P = 0.006), and absent/mild peritumoral inflammatory infiltrate (P = 0.002). PDC and TB were also associated with histological factors, as portal invasion (TB), peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of tumor pseudocapsule (TB and PDC).

Conclusions

This is the first study demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor, but it was not an independent predictor of survival.
Application of off‐line two‐dimensional high‐performance countercurrent chromatography on the chloroform‐soluble extract of Cuscuta auralis seeds
Authors: Rho Taewoong , Yoon Kee Dong
Published: February 2018

In this study, the chloroform‐soluble extract of Cuscuta auralis was separated successfully using off‐line two‐dimensional high‐performance countercurrent chromatography, yielding a γ‐pyrone, two alkaloids, a flavonoid, and four lignans. The first‐dimensional countercurrent separation using a methylene chloride/methanol/water (11:6:5, v/v/v) system yielded three subfractions (fractions I–III). The second‐dimensional countercurrent separations, conducted on fractions I–III using n‐hexane/ethyl acetate/methanol/water/acetic acid (5:5:5:5:0, 3:7:3:7:0, and 1:9:1:9:0.01, v/v/v/v/v) systems, gave maltol (1), (−)‐(13S)‐cuscutamine (2), (+)‐(13R)‐cuscutamine (3), (+)‐pinoresinol (4), (+)‐epipinoresinol (5), kaempferol (6), piperitol (7), and (9R)‐hydroxy‐d‐sesamin (8). To the best of our knowledge, maltol was identified for the first time in Cuscuta species. Furthermore, this report details the first full assignment of spectroscopic data of two cuscutamine epimers, (−)‐(13S)‐cuscutamine and (+)‐(13R)‐cuscutamine.
Ultrasound‐Guided Microinvasive Carpal Tunnel Release Using a Novel Retractable Needle‐Mounted Blade: A Cadaveric Study
Authors: Hebbard Peter D. , Hebbard Andrew I. T. , Tomka Janos , Appleyard Richard
Published: February 2018

Ultrasound (US)‐guided microinvasive procedures are defined as those performed via needles without notable scarring. Ten cadaver hands underwent US‐guided microinvasive carpal tunnel release using a novel needle‐based tool, the micro i‐Blade (Summit Medical Products, Inc, Sandy, UT). A US‐imaged landmark, the inflexion point of the ligaments distal to the hook of the hamate, was used to position the distal extent of the cut. The transverse carpal ligament was successfully released in all hands without damage to nerves or arteries. In 3 specimens, the fascia between the thenar and hypothenar muscles was partly preserved, whereas the palmar aponeurosis was partly cut in 1 specimen. The micro i‐Blade with the cutting knife retracted was also useful as a probe palpated through the palm of the cadaver hand, to test the release of the transverse carpal ligament and to guide the procedure.
Seasonal plasticity in photoprotection modulates UV‐induced hsp gene expression in copepods from a clear lake
Authors: Tartarotti B. , Alfreider A. , Egg M. , Saul N. , Schneider T. , Sommaruga R. , Tischler A. , Vetter J.
Published: February 2018

Zooplankton from clear alpine lakes is exposed to stressful levels of solar UV radiation (UVR). As these pelagic organisms experience high UVR and large changes in solar radiation conditions between ice‐free and ice‐cover periods, they have evolved various strategies to minimize UVR exposure and damage. Here, we studied the relation between photoprotection levels (mycosporine‐like amino acids, carotenoids), antioxidant capacities, and gene expression of heat shock proteins (hsps) as indicator of stress in the copepod Cyclops abyssorum tatricus during the course of a year. Expression of hsp60, hsp70, and hsp90 was measured in the field (baseline expression [BE]) and after UVR exposure in the laboratory. The BE differed among genes and seasons (hsp60: high during summer, hsp70 and hsp90: high during the ice‐cover period). The gene expression of hsp70 was upregulated after exposure to UVR (up to 5.2‐fold change), while hsp60 and hsp90 were only constitutively expressed. A strong seasonal pattern was found in the photoprotective compounds and antioxidant capacities, with highest levels during the ice‐free period. The extent of upregulation of hsp70 gene expression increased with decreasing photoprotection levels and peaked 24 h post UVR exposure (9.6‐fold change) at the time of lowest photoprotection (February). Our data suggest that hsp70 gene expression is modulated by seasonal plasticity in photoprotection. This ability of adequate stress response is essential for survival in highly variable ecosystems such as alpine lakes.
Sulfur Radical Transfer and Coupling Reaction to Benzoxazine Groups: A New Reaction Route for Preparation of Polymeric Materials Using Elemental Sulfur as a Feedstock
Authors: Lin Ho‐Keng , Liu Ying‐Ling
Published: February 2018

A novel approach to preparing polymeric materials using elemental sulfur as a feedstock through the newly developed sulfur radical transfer and coupling (SRTC) reaction is reported herein. Polybenzoxazines with high sulfur contents are prepared using the SRTC reaction with benzoxazine compounds as the radical acceptors. The reactions between elemental sulfur and benzoxazine rings are analyzed with Fourier transform infrared (FTIR), 1H NMR, and 13C DEPT spectroscopies to elucidate the SRTC reaction mechanism. Moreover, the prepared polybenzoxazine–sulfur hybrid materials show attractive repairing properties based on the dynamic S–S linkages. An effective reaction mechanism and the prepared repairable sulfur‐possessing polymeric materials are demonstrated.
Sliding free transverse rectus abdominis myocutaneous flap for closure of a massive abdominal wall defect: A case report
Authors: Senghaas Annika , Kremer Thomas , Schmidt Volker J. , Harhaus Leila , Hirche Christoph , Kneser Ulrich , Bigdeli Amir K.
Published: February 2018

Despite considerable advances in reconstructive surgery, massive abdominal wall defects continue to pose a significant surgical challenge. We report the case of a 72‐year‐old morbidly obese female patient with Clostridium septicum‐related gas gangrene of the abdominal wall. After multidisciplinary treatment and multiple extensive debridements, a massive full‐thickness defect (40 cm × 35 cm) of the right abdominal wall was present. The abdominal contents were covered with a resorbable mesh to prevent evisceration. Finally, the composite defect was successfully reconstructed through a contralateral extended free transverse rectus abdominis myocutaneus (TRAM) flap (50 cm × 38 cm). An arterio‐venous loop to the superficial femoral vessels using the great saphenous vein was necessary to allow the flap to reach the defect. Postoperatively, a minor wound healing disorder of the flap was successfully treated with split skin grafting. Six month after surgery, the patient presented with a completely healed flap coverage area and a small abdominal hernia without the need of further surgical revision. This case illustrates the use of a sliding free TRAM flap for closure of a massive abdominal wall defect.
Lipid‐Modifying Effects of Chitosan Supplementation in Humans: A Pooled Analysis with Trial Sequential Analysis
Authors: Huang Haohai , Zou Ying , Chi Honggang , Liao Dan
Published: February 2018

Scope

We performed a pooled analysis with trial sequential analysis (TSA) to evaluate the efficacy and safety of chitosan supplementation on serum lipids in humans.

Methods and results

Medline, EMBASE, and CENTRAL databases were queried. Impact was expressed as a weighted mean difference (WMD) and 95% confidence interval (CI). Sensitivity analysis was conducted using the leave‐one‐out method. Statistical heterogeneity, publication bias, TSA, and subgroup analyses were also assessed. Fourteen trials (21 treatment arms) encompassing 1108 participants were suitable for statistical pooling. Chitosan supplementation significantly improved the total cholesterol (TC) and low‐density lipoprotein cholesterol (LDL‐C) concentrations in all patients. The WMDs were −0.20 mmol L−1 (95% CI, −0.35 to −0.05; p = 0.009) for TC, and −0.20 mol L−1 (95% CI, −0.26 to −0.15; p = 0.0001) for LDL‐C, respectively. TSA demonstrated that the cumulative Z‐curve crossed the trial sequential monitoring boundary for benefit providing conclusive evidence for the benefit of chitosan. However, no significant changes were seen with high‐density lipoprotein cholesterol (HDL‐C) and triglycerides. Our findings were robust after sensitivity analyses, and no serious adverse events were reported with chitosan intake.

Conclusion

Supplementation with chitosan effectively reduces plasma concentrations of TC and LDL‐C. Current evidence indicates daily chitosan supplementation as a candidate for therapeutic lipid management strategies.
High spatiotemporal resolution bSSFP imaging of hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate with spectral suppression of alanine and pyruvate‐hydrate
Authors: Milshteyn Eugene , von Morze Cornelius , Gordon Jeremy W. , Zhu Zihan , Larson Peder E.Z. , Vigneron Daniel B.
Published: February 2018

Purpose

The balanced steady‐state free precession (bSSFP) acquisition enables high spatiotemporal resolution for hyperpolarized 13C MRI at 3T but is limited by spectral contamination from adjacent resonances. The purpose of this study was to develop a framework for in vivo dynamic high resolution imaging of hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate generated in vivo at 3T by simplifying the spectrum through the use of selective suppression pulses.

Methods

Spectral suppression pulses were incorporated into the bSSFP sequence for suppression of [1‐13C]alanine and [1‐13C]pyruvate‐hydrate signals, leaving only the pyruvate and lactate resonances. Subsequently, the bSSFP pulse width, time‐bandwidth, and repetition time were optimized for imaging these dual resonances.

Results

The spectral suppression reduced both the alanine and pyruvate‐hydrate signals by 85.5 ± 4.9% and had no significant effect on quantitation of pyruvate to lactate conversion (liver: P = 0.400, kidney: P = 0.499). High resolution (2 × 2 mm2 and 3 × 3 mm2) subsecond 2D coronal projections and 3D 2.5 mm isotropic images were obtained in rats and tumor‐bearing mice with 1.8–5 s temporal resolution, allowing for calculation of lactate‐to‐pyruvate ratios and kPL.

Conclusion

The developed framework presented here shows the capability for dynamic high resolution volumetric hyperpolarized bSSFP imaging of pyruvate‐to‐lactate conversion on a clinical 3T MR scanner.
Animal remains from Neolithic settlements of the Middle Dnieper area (Ukraine)
Authors: Kovalchuk O. , Gorobets L. , Veiber A. , Lukashov D. , Yanenko V.
Published: February 2018

The paper deals with the role of different branches of economy in the life of Neolithic people in Eastern Europe (within the Middle Dnieper area). For this purpose, analysis of the osteological and malacological materials was made, and manufacturing bones and other auxiliary finds were used. The studied settlements (Surskyi Island, Shulaiv Island, Vovnigi, and Buz'ki) were found on small islands and banks of the Dnieper River in Ukraine and excavated in the 1930–1950. It has been shown that the economic bases for their residents were fishing and hunting, supplemented by gathering and cattle breeding. The general species list of identified animals includes 2 species of molluscs, 9 freshwater fishes (sturgeons, carp fishes, catfish, pike, zander), 1 reptile (European pond turtle), 15 species of birds (diving waterfowl, mallard, coot, black grouse, owls, cormorants), and 17 species of mammals. The latter are predominantly represented by wild species (bison, red deer, roe deer, wolf, fox, wildcat, hare, beaver, marmot, and squirrel). The number of domesticated forms (cattle, sheep, goat/sheep, pig, and dog) is less significant. Numerous animal bones from the studied settlements bear traces of butchering. Some of them were used in manufacturing (harpoons, fishhooks, devices for weaving nets, borers, pendants, spearheads).
Comparison on the properties of the wheat straw/rubber composites by adding graphite/carbon fiber
Authors: Li Yalan , Xu Min
Published: February 2018

The conductive wheat straw/rubber composites (WSRCs) were prepared with wheat straw fiber (WSF), rubber compound and graphite powder (GP), or carbon fiber (CF). WSRCs with different loading of conductive fillers were prepared. The curing properties, mechanical properties, dynamic mechanical properties, morphology structure and conductive properties of the composites were investigated with reference to the conductive filler loading. Sodium hydroxide combined with bis‐[γ‐(triethoxysily)‐propyl] tetrasulfide (NaOH‐Si69‐treated WSF) had a better bonding with the rubber matrix. The incorporation of GP and CF could restrict the mobility of matrix macromolecular chains and increase the viscosity of GP/CF‐filled WSRCs, resulting in the increases in torque, stiffness and storage modulus and the slight reduction in scorch time and tensile strength as well as the damping behavior. Moreover, the conductivity of the WSRCs was increased significantly as the increase in filler loading. It was also found that the conductivity of GP‐filled WSRCs were higher than that of the CF‐filled ones. POLYM. COMPOS., 40:E983–E992, 2019. © 2018 Society of Plastics Engineers
A novel synthetic strategy for preparing semi‐aromatic components modified polyamide 6 polymer
Authors: Peng Shumin , Peng Lu , Yi Chunwang , Zhang Wei , Wang Xi
Published: February 2018

In this work, a novel synthetic path for preparing semi‐armotic components modified polyamide 6 was developed by caprolactam as solvent of purified terephthalic acid and 1,6‐hexanediamine. First, the ring opening reaction and poly‐addition of caprolactam were initiated by 1,6‐hexanediamine to generate a prepolymer containing amino groups in both ends, then followed by the poly‐condensation reaction with purified terephthalic acid, a long chain copolymer was produced, which the reaction time was reduced by 4 h compared with conventional hydrolytic ring‐opening polymerization of pure caprolactam. By varying the ratio of terephthalic acid and 1,6‐hexanediamine, a series of copolymers with different number average molecular weight and physical properties were prepared. Analytical results showed that the conversion percentage of caprolactam is significantly increased by the proposed method. Furthermore, this new copolymers exhibited excellent transparence and high decomposition temperature. Besides, the copolymers with average molecular weight ≥15,000 present good mechanical properties, making it a potentially useful application in plastics, textile yarn, and membranes. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 959–967
Ultrafast shock compression of PDMS‐based polymers
Authors: Armstrong Michael R. , Grivickas Paulius V. , Sawvel April M. , Lewicki James P. , Crowhurst Jonathan C. , Zaug Joseph M. , Radousky Harry B. , Stavrou Elissaios , Alviso Cynthia T. , Hamilton Julie , Maxwell Robert S.
Published: February 2018

The shock response of polymers is important for a number of commercial and defense‐related applications, but it is difficult to obtain empirical shock response data over the wide range of preparations and aging conditions typically found in such applications. Ultrafast compression is useful to characterize polymer shock response over a wide range of polymer initial conditions due to the high throughput of this method. To establish greater confidence in ultrafast compression experiments and to characterize the detailed shock response of several variations in a single base polymer, the results of sub‐nanosecond shock compression experiments in ∼5 μm thick layers of the polydimethylsiloxane (PDMS)‐based elastomeric rubbers Sylgard‐184, SE1700, and an unfilled, end‐linked model PDMS network are presented. The results of conventional ultrafast shock etalon measurements to time‐of‐flight measurements for similar thickness layers of irradiated and unirradiated SE1700 are compared. Good agreement between the shock response measured by these two ultrafast shock methods, as well as consistency between ultrafast data and long time scale gas gun data is found. From measurements across a variety of PDMS formulations, a statistically significant variation in the shock response with the quasistatic elastic modulus is presented. Published 2018.† J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 827–832
Electronic Properties of Ag Reconstructions on Si(111): Coulomb Blockade Behavior at Room Temperature
Authors: Chandola Sandhya , McGilp John , Esser Norbert
Published: February 2018

The electronic properties and optical response of Si(111)–Ag reconstructions, with distinct interface structures, are studied with scanning tunneling microscopy (STM), reflectance anisotropy spectroscopy (RAS), and infrared spectroscopic ellipsometry (IRSE). The results are compared to previous studies on the Si(111)‐(3 × 1)–Ag surface. Depending on the preparation conditions, STM shows hybrid surfaces comprising (√3 × √3) areas with semiconducting (3 × 1)–Ag regions or metallic Ag islands. RAS of the (√3 × √3)–Ag reconstruction mostly shows a flat response, confirming the isotropic nature of the surface while Ag islands on this surface produce a steep increase in the infrared as well as a strong optical anisotropy at 3.5 eV. Scanning tunneling spectroscopy (STS) of the islands shows a high density of states with almost no structure. STS of Ag nanodots on the (3 × 1)–Ag surface shows distinct Coulomb resonances within the Si bandgap while the Si(111)‐(3 × 1)–Ag surface reveals an expected semiconducting behavior with a band gap and no sign of resonances. Ag islands on the (3 × 1)–Ag surface also show weak Coulombic oscillations indicating that local transport depends on the electronic properties of the interface.
Silicon buckyballs versus prismanes: Influence of spatial confinement on the structural properties and optical spectra of the Si18H12 and Si19H12 clusters
Authors: Gordeychuk Mark V. , Katin Konstantin P. , Grishakov Konstantin S. , Maslov Mikhail M.
Published: February 2018

The genetic algorithm is combined with the density functional theory to predict how the cylindrical spatial confinement affects the structural characteristics and optical adsorption spectra of the low‐energy Si18H12 and Si19H12 isomers. Retrieved ground states (minimum energy states) of Si18H12 and Si19H12 isomers significantly differ from the earlier proposed “ultrastable” aromatic molecular systems and prismanes. According to our calculations, they are represented by the almost spherical endohedral buckyballs. In contrast to pure silicic clusters (Si18 or Si19), the most of Si atoms in the low‐energy Si18H12 and Si19H12 are four‐coordinated. Spatial confinement results in more oblong structures with the different optical spectra. Prismanes under confinement get some energy advantages over the spherical structures, but despite this they do not become the most energetically favorable ones. Thus, the current results warrant however further research on the spatial confinement of silicic prismanes, as our study suggests challenges in devising the method of their synthesis without additional chemical techniques.
Development and validation of a gas chromatography/tandem mass spectrometry method for simultaneous quantitation of several antipsychotics in human plasma and oral fluid
Authors: Rosado Tiago , Oppolzer David , Cruz Belinda , Barroso Mário , Varela Samira , Oliveira Victor , Leitão Carlos , Gallardo Eugenia
Published: February 2018

Rationale

Antipsychotic drugs are prescription medications used to treat psychotic disorders, such as schizophrenia, schizoaffective disorder, or psychotic depression. With several antipsychotic drugs currently available all over the world, this class of drugs has quickly gained importance in both the clinical and forensic context. This work describes the development and validation of a methodology for the determination of seven antipsychotic drugs in plasma and oral fluid samples.

Methods

The antipsychotic drugs (chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, cyamemazine and, levomepromazine) were isolated from 0.2 mL of oral fluid and 0.5 mL of plasma using solid‐phase extraction (SPE) following analysis by gas chromatography/tandem mass spectrometry (GC/MS/MS). The method was validated according to the international guidelines in terms of selectivity, linearity, accuracy, precision and recovery.

Results

The procedure was linear within 2–600 ng/mL (plasma) and 2–400 ng/mL (oral fluid), the intervals varying according to the compound; a mean R2 value of 0.99 was obtained and the calibrator's accuracy (mean relative error) was within a ±15 % interval for all concentrations. The limits of detection ranged from 1 to 10 ng/mL. Within‐ and between‐run precision and accuracy were acceptable for all studied compounds. The extraction efficiency of the process ranged from 79% to 95%. The method was applied to authentic specimens.

Conclusions

The described method was proven selective and sensitive for the determination of antipsychotics in low sample volumes using SPE and GC/MS/MS. This method was considered suitable not only for routine analysis of patients undergoing antipsychotic treatment (to evaluate compliance), but also in forensic scenarios where the studied compounds may be involved. To the best of our knowledge, this is the first work that reports the determination of antipsychotic drugs in oral fluid using MS/MS.
UAV‐derived habitat predictors contribute strongly to understanding avian species–habitat relationships on the Eastern Qinghai‐Tibetan Plateau
Authors: Fritz Andreas , Li Li , Storch Ilse , Koch Barbara
Published: February 2018

Species–habitat relationships are of core interest in ecological studies. In this research, we explored the potential of small, unmanned aerial vehicles (UAVs) to derive a comprehensive set of habitat predictors to explain distribution variance of an alpine bird community in Jikdril county, on the eastern Qinghai‐Tibetan Plateau (QTP). In 2014 and 2015, we carried out two breeding season bird surveys on 140 plots, from eight sample blocks in the Nyanpo Yutse region. In summer 2014, we conducted 39 flights over the eight sample blocks, and obtained 5500 images which covered 45 km2 of alpine grassland habitat. We used photogrammetry software to generate high‐resolution orthophotos and digital surface models with an average pixel size of 13 cm. We derived both 3D‐ and 2D‐UAV‐based models as habitat predictors used to analyze explained variance in the local bird community at four different sample scales (plot radii of 50 m, 100 m, 150 m and 200 m). We performed canonical correspondence analyses (CCA), with a model‐building approach based on permutation. Furthermore, the proportion of total variance explained by each predictor group was calculated, and analysis of results showed that UAV data derived predictors played a significant role in explaining the variance of the sampled bird community on the QTP. In particular, 3D‐based predictors contributed strongly to the explanation of variance (50 m: 45.44%, 100 m: 44.60%, 150 m: 49.21%, 200 m: 36.22% of the total explained variance per sample size), followed by 2D‐based predictors over the same four sample scales (50 m: 35.45%, 100 m: 34.57%, 150 m: 31.19%, 200 m: 39.48%). Our results indicate that a sample plot scale of 150–200 m radius leads to the most comprehensive explanation of variance (all predictors: 39.59%, P < 0.0001 and 39.13% P < 0.0001). UAV data provide us with fine‐scale (10 cm resolution) continuous raster data on land cover, topographic and landscape features, which are hard to acquire with conventional habitat measurements. We therefore successfully demonstrate the performance of UAV‐derived data in facilitating ecological research at different spatial scales.
Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of Nanoparticles
Authors: Lu Hongxu , Stenzel Martina H.
Published: February 2018

Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models that can mimic the microenvironment of tissues. MCTS have gained increasing interest in the nano‐biotechnology field as they can provide easily accessible information on the performance of nanoparticles without using animal models. Considering that many countries have put restrictions on animals testing, which will only tighten in the future as seen by the recent developments in the Netherlands, 3D models will become an even more valuable tool. Here, an overview on MCTS is provided, focusing on their use in cancer research as most nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter, various types of nanoparticles—from self‐assembled block copolymers to inorganic nanoparticles, are discussed. A range of physicochemical parameters including the size, shape, surface chemistry, ligands attachment, stability, and stiffness are found to influence nanoparticles in MCTS. Some of these studies are complemented by animal studies confirming that lessons from MCTS can in part predict the behaviour in vivo. In summary, MCTS are suitable models to gain additional information on nanoparticles. While not being able to replace in vivo studies, they can bridge the gap between traditional 2D in vitro studies and in vivo models.
Highly Uniform Resistive Switching Properties of Solution‐Processed Silver‐Embedded Gelatin Thin Film
Authors: Chang Yu‐Chi , Lee Cheng‐Jung , Wang Li‐Wen , Wang Yeong‐Her
Published: February 2018

The silver‐embedded gelatin (AgG) thin film produced by the solution method of metal salts dissolved in gelatin is presented. Its simple fabrication method ensures the uniform distribution of Ag dots. Memory devices based on AgG exhibit good device performance, such as the ON/OFF ratio in excess of 105 and the coefficient of variation in less of 50%. To further investigate the position of filament formation and the role of each element, current sensing atomic force microscopy (CSAFM) analysis as well as elemental line profiles across the two different conditions in the LRS and HRS are analyzed. The conductive and nonconductive regions in the current map of the CSAFM image show that the conductive filaments occur in the AgG layer around Ag dots. The migration of oxygen ions and the redox reaction of carbon are demonstrated to be the driving mechanism for the resistive switching of AgG memory devices. The results show that dissolving metal salts in gelatin is an effective way to achieve high‐performance organic–electronic applications.
Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis
Authors: Li Fei , Alderman Myles H. , Tal Aya , Mamillapalli Ramanaiah , Coolidge Alexis , Hufnagel Demetra , Wang Zhihao , Neisani Elham , Gidicsin Stephanie , Krikun Graciela , Taylor Hugh S.
Published: February 2018

Endometriosis is ectopic growth of endometrial tissue traditionally thought to arise through retrograde menstruation. We aimed to determine if cells derived from endometriosis could enter vascular circulation and lead to hematogenous dissemination. Experimental endometriosis was established by transplanting endometrial tissue from DsRed+ mice into the peritoneal cavity of DsRed- mice. Using flow cytometry, we identified DsRed+ cells in blood of animals with endometriosis. The circulating donor cells expressed CXCR4 and mesenchymal stem cell (MSC) biomarkers, but not hematopoietic stem cell markers. Nearly all the circulating endometrial stem cells originated from endometriosis rather than from the uterus. Cells expressing DsRed, CXCR4, and MSCs markers were identified in the peritoneal wall and surrounding vessels of recipient mice, contributing to both endometriosis and angiogenesis. Cells originating in endometriosis lesions migrated and implanted in lung tissue and displayed makers of differentiation, indicating retained multipotency. In vitro these cells demonstrated multipotency and were able to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Endometriosis lesions also expressed high levels of CXCL12, the CXCR4 receptor ligand. Serum CXCL12 levels were greater than in sham control mice. In humans with endometriosis, serum CXCL12 levels were significantly higher than controls, suggesting that the CXCL12/CXCR4 axis is operational in women with spontaneous endometriosis as well. Stem cells, rather than differentiated cells from endometriosis, enter the circulation in response to CXCL12. We identify an endometriosis-derived stem cell population, a potential mechanism of dissemination of this disease and a potential target for treatment of endometriosis.
Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies
Authors: Bhere Deepak , Khajuria Rajiv Kumar , Hendriks William T. , Bandyopadhyay Antara , Bagci-Onder Tugba , Shah Khalid
Published: February 2018

Stem cells are emerging as promising treatment strategies for several brain disorders and pathologies. In this study, we explored the potential of creating induced pluripotent stem cell-derived neural stem cells (ipNSC) by using either unmodified or gene-modified somatic cells and tested their fate and therapeutic efficacies in vitro and in vivo. We show that cells engineered in somatic state lose transgene-expression during the neural induction process, which is partially restored by histone deacetylase inhibitor treatment whereas cells engineered at the ipNSC state have sustained expression of transgenes. In vivo, bimodal mouse and human ipNSCs engineered to express tumor specific death-receptor ligand and suicide-inducing therapeutic proteins have profound anti-tumor efficacy when encapsulated in synthetic extracellular matrix and transplanted in mouse models of resected-glioblastoma. This study provides insights into using somatic cells for treating CNS disorders and presents a receptor-targeted cancer therapeutic approach for brain tumors.
Mesenchymal Stem Cells Protect Against Hypoxia-Ischemia Brain Damage by Enhancing Autophagy Through Brain Derived Neurotrophic Factor/Mammalin Target of Rapamycin Signaling Pathway
Authors: Zheng Zhen , Zhang Li , Qu Yi , Xiao Guoguang , Li Shiping , Bao Shan , Lu Q. Richard , Mu Dezhi
Published: February 2018

Hypoxic-ischemic encephalopathy (HIE) is a serious disease for neonates. However, present therapeutic strategies are not effective enough for treating HIE. Previous study showed that mesenchymal stem cells (MSCs) can exert neuroprotective effects for brain damage, but its mechanism remains elusive. Using in vitro coculture of rat cortical primary neurons and MSCs in HI conditions, we demonstrated that MSCs help increase brain derived neurotrophic factor (BDNF) and autophagy markers (LC3II and Beclin1) in the cultures and decrease cells death (lactate dehydrogenase levels). We demonstrated a similar mechanism using an in vivo rat model of HI in combination with MSCs transplantation. Using a behavioral study, we further showed that MSCs transplantation into the rat brain after HI injury can attenuate behavioral deficits. Finally, we found that the increase in BDNF and autophagy related factors after HI injury combined with MSCs transplantation can be reversed by anti-BDNF treatment and strengthen the point that the protective effects of BDNF work through inhibition of the mammalin target of rapamycin (mTOR) pathway. Collectively, we proposed that coculture/transplantation of MSCs after HI injury leads to increased BDNF expression and a subsequent reduction in mTOR pathway activation that results in increased autophagy and neuroprotection. This finding gives a hint to explore new strategies for treating neonates with HIE.
Cover Image, Volume 5, Issue 2
Authors: Paerregaard Karsten
Published: February 2018

The cover image, by Karsten Paerregaard, is based on the Focus Article Power in/of/as water: Revisiting the hydrologic cycle in the Peruvian Andes, DOI: 10.1002/wat2.1270.

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