bluuebunny/crossref_metadata_2025 huggingface dataset:
The dark side of glucose transporters in prostate cancer: Are they a new feature to characterize carcinomas?
Authors: Gonzalez‐Menendez Pedro , Hevia David , Mayo Juan C. , Sainz Rosa M.
Published: November 2017

One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death. The prostate gland has the particular characteristic of being more glycolytic than other non‐pathological tissues given an accumulation of citrate in the seminal fluid and the inhibition of m‐aconitase that affects to tricarboxylic acid cycle. In prostate cancer (PCa), androgens increase glucose uptake, upregulate GLUT transporters such as GLUT1 and GLUT3 and stimulate AMP‐activated protein kinase pathway, suggesting a possible connection between glycolytic and androgenic signaling. Interestingly, diabetes is not a risk factor for PCa, as it is in other cancers, while insulin stimulates progression and insulin‐like growth factor 1 pathway plays an important role in PCa progression. It was recently found that PCa cells overexpress GLUT4 and, more importantly, that it seems to be related to the castration‐resistant prostate cancer (CRPC) phenotype, although little is known about its participation in tumor progression. This review will focus on the role of GLUT transporters along with PCa progression, and the involvement of GLUT4 on CRPC phenotype transition would be considered.
Adenovirus vector‐based prime‐boost vaccination via heterologous routes induces cervicovaginal CD8+ T cell responses against HPV16 oncoproteins
Authors: Çuburu Nicolas , Khan Selina , Thompson Cynthia D. , Kim Rina , Vellinga Jort , Zahn Roland , Lowy Douglas R. , Scheper Gert , Schiller John T.
Published: November 2017

Recent advances in immunotherapy against cancer underscore the importance of T lymphocytes and tumor microenvironment, but few vaccines targeting cancer have been approved likely due in part to the dearth of common tumor antigens, insufficient immunogenicity and the evolution of immune evasion mechanisms during the progression to malignancy. Human papillomaviruses (HPVs) are the primary etiologic agents of cervical cancer and progression from persistent HPV‐infection to cervical intraepithelial lesions and eventually cancer requires persistent expression of the oncoproteins E6 and E7. This offers the opportunity to specifically target these virus‐specific antigens for vaccine‐induced clearance of infected cells before cancers develop. Here we have evaluated the immunogenicity of Adenovirus Types 26 and 35 derived vectors expressing a fusion of HPV16 E6 and E7 oncoproteins after intramuscular (IM) and/or intravaginal (Ivag) immunization in mice. The adenovirus vectors were shown to transduce an intact cervicovaginal epithelium. IM prime followed by Ivag boost maximized the induction and trafficking of HPV‐specific CD8+ T cells producing IFN‐γ and TNF‐α to the cervicovaginal tract. Importantly, the cervicovaginal CD8+ T cells expressed CD69 and CD103; hallmarks of intraepithelial tissue‐resident memory CD8+ T cells. This prime‐boost strategy targeting heterologous locations also induced circulating HPV‐specific CD8+ T cell responses. Our study prompts further evaluation of Ivag immunization with adenoviral vectors expressing modified E6 and E7 antigens for therapeutic vaccination against persistent HPV infection and cervical intraepithelial neoplasia.
Antibodies against human papillomaviruses as diagnostic and prognostic biomarker in patients with neck squamous cell carcinoma from unknown primary tumor
Authors: Schroeder Lea , Wichmann Gunnar , Willner Maria , Michel Angelika , Wiesenfarth Manuel , Flechtenmacher Christa , Gradistanac Tanja , Pawlita Michael , Dietz Andreas , Waterboer Tim , Holzinger Dana
Published: November 2017

Treatment of patients with neck lymph node metastasis of squamous cell carcinoma (SCC) from unknown primary tumor (NSCCUP) is challenging due to the risk of missing occult tumors or inducing toxicity to unaffected sites. Human papillomavirus (HPV) is a promising biomarker given its causal link to oropharyngeal SCC and superior survival of patients with HPV‐driven oropharyngeal SCC and NSCCUP. Identification of HPV‐driven NSCCUP could focus diagnostic work‐up and treatment on the oropharynx. For the first time, we assessed HPV antibodies and their prognostic value in NSCCUP patients. Antibodies against E6 and E7 (HPV16/18/31/33/35), E1 and E2 (HPV16/18) were assessed in 46 NSCCUP patients in sera collected at diagnosis, and in follow‐up sera from five patients. In 28 patients, HPV tumor status was determined using molecular markers (HPV DNA, mRNA and cellular p16INK4a). Thirteen (28%) NSCCUP patients were HPV‐seropositive for HPV16, 18, 31, or 33. Of eleven patients with HPV‐driven NSCCUP, ten were HPV‐seropositive, while all 17 patients with non‐HPV‐driven NSCCUP were HPV‐seronegative, resulting in 91% sensitivity (95% CI: 59–100%) and 100% specificity (95% CI: 80–100%). HPV antibody levels decreased after curative treatment. Recurrence was associated with increasing levels in an individual case. HPV‐seropositive patients had a better overall and progression‐free survival with hazard ratios of 0.09 (95% CI: 0.01–0.42) and 0.03 (95% CI: 0.002–0.18), respectively. For the first time, seropositivity to HPV proteins is described in NSCCUP patients, and high sensitivity and specificity for HPV‐driven NSCCUP are demonstrated. HPV seropositivity appears to be a reliable diagnostic and prognostic biomarker for patients with HPV‐driven NSCCUP.
Administration of adjuvant chemotherapy for stage II‐III colon cancer patients: An European population‐based study
Authors: Babaei Masoud , Balavarca Yesilda , Jansen Lina , Lemmens Valery , van Erning Felice N. , van Eycken Liesbet , Vaes Evelien , Sjövall Annika , Glimelius Bengt , Ulrich Cornelia M. , Schrotz‐King Petra , Brenner Hermann
Published: November 2017

The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients. We investigated the administration of ACT and its association with overall survival in resected Stage II (overall and stratified by low‐/high‐risk) and Stage III colon cancer patients in three European countries including The Netherlands (2009–2014), Belgium (2009–2013) and Sweden (2009–2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders. A total of 60244 resected colon cancer patients with pathological Stages II and III were analyzed. A small proportion (range 9–24%) of Stage II and over half (range 55–68%) of Stage III patients received ACT. Administration of ACT in Stages II and III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high‐risk Stage II patients (in The Netherlands (HR; 95%CI = 0.82 (0.67–0.99), Belgium (0.73; 0.59–0.90) and Sweden (0.58; 0.44–0.75)), and in Stage III patients (in The Netherlands (0.47; 0.43–0.50), Belgium (0.46; 0.41–0.50) and Sweden (0.48; 0.43–0.54)). In Stage III, results were consistent across subgroups including elderly patients. Our results show an association of ACT with higher survival among Stage III and high‐risk Stage II colon cancer patients. Further investigations are needed on the selection criteria of Stages II and III colon cancer patients for ACT.
Retrospective multicenter study of leaving the placenta in situ for patients with placenta previa on a cesarean scar
Authors: Miyakoshi Kei , Otani Toshimitsu , Kondoh Eiji , Makino Shintaro , Tanaka Mamoru , Takeda Satoru ,   the Perinatal Research Network Group in Japan
Published: November 2017

Objective

To investigate maternal outcomes after leaving the placenta in situ for placenta accreta spectrum (PAS) disorders in patients with placenta previa on a cesarean delivery scar.

Methods

The present retrospective study reviewed medical records from women with placenta previa on a cesarean scar underwent perinatal care at secondary‐ or tertiary‐level perinatal centers in Japan between January 1, 2010, and December 31, 2014. Perinatal management was conducted based on each leading obstetrician's discretion. The primary outcome was success of the leaving the placenta in situ approach for PAS disorders (defined as preserving the uterus without hysterectomy).

Results

Of 178 eligible centers, 126 (71%) participated in this study; data from 613 patients were included. Of these, 41 had the placenta left in situ owing to PAS disorders and follow‐up data were available for 36 women. Leaving the placenta in situ was successful in 25 (69%) patients, with placental resorption occurring postpartum (median 89 days; range 6–510). Hysterectomy was performed for 11 patients, primarily owing to hemorrhage and/or infection (median 30 days; range 0–95 days, postpartum).

Conclusion

Leaving the placenta in situ, with close postpartum follow‐up for at least several months, could be a uterus‐preserving option for patient with PAS disorders.
The use of cell conditioned medium for musculoskeletal tissue regeneration
Authors: Veronesi Francesca , Borsari Veronica , Sartori Maria , Orciani Monia , Mattioli‐Belmonte Monica , Fini Milena
Published: November 2017

Tissue regenerative medicine combines the use of cells, scaffolds, and molecules to repair damaged tissues. Different cell types are employed for musculoskeletal diseases, both differentiated and mesenchymal stromal cells (MSCs). In recent years, the hypothesis that cell‐based therapy is guided principally by cell‐secreted factors has become increasingly popular. The aim of the present literature review was to evaluate preclinical and clinical studies that used conditioned medium (CM), rich in cell‐factors, for musculoskeletal regeneration. Thirty‐one were in vitro, 12 in vivo studies, 1 was a clinical study, and 2 regarded extracellular vesicles. Both differentiated cells and MSCs produce CM that induces reduction in inflammation and increases synthetic activity. MSC recruitment and differentiation, endothelial cell recruitment and angiogenesis have also been observed. In vivo studies were performed with CM in bone and periodontal defects, arthritis and muscle dystrophy pathologies. The only clinical study was performed with CM from MSCs in patients needing alveolar bone regeneration, showing bone formation and no systemic or local complications. Platelet derived growth factor receptor β, C3a, vascular endothelial growth factor, monocyte chemoattractant protein‐1 and ‐3, interleukin 3 and 6, insulin‐like growth factor‐I were identified as responsible of cell migration, proliferation, osteogenic differentiation, and angiogenesis. The use of CM could represent a new regenerative treatment in several musculoskeletal pathologies because it overcomes problems associated with the use of cells and avoids the use of exogenous GFs or gene delivery systems. However, some issues remain to be clarified.
Diffusion‐weighted MRI and intravoxel incoherent motion model for diagnosis of pediatric solid abdominal tumors
Authors: Meeus Emma M. , Zarinabad Niloufar , Manias Karen A. , Novak Jan , Rose Heather E.L. , Dehghani Hamid , Foster Katharine , Morland Bruce , Peet Andrew C.
Published: November 2017

Background

Pediatric retroperitoneal tumors in the renal bed are often large and heterogeneous, and their diagnosis based on conventional imaging alone is not possible. More advanced imaging methods, such as diffusion‐weighted (DW) MRI and the use of intravoxel incoherent motion (IVIM), have the potential to provide additional biomarkers that could facilitate their noninvasive diagnosis.

Purpose

To assess the use of an IVIM model for diagnosis of childhood malignant abdominal tumors and discrimination of benign from malignant lesions.

Study Type

Retrospective.

Population

Forty‐two pediatric patients with abdominal lesions (n = 32 malignant, n = 10 benign), verified by histopathology.

Field Strength/Sequence

1.5T MRI system and a DW‐MRI sequence with six b‐values (0, 50, 100, 150, 600, 1000 s/mm2).

Assessment

Parameter maps of apparent diffusion coefficient (ADC), and IVIM maps of slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion fraction (f) were computed using a segmented fitting model. Histograms were constructed for whole‐tumor regions of each parameter.

Statistical Tests

Comparison of histogram parameters of and their diagnostic performance was determined using Kruskal–Wallis, Mann–Whitney U, and receiver‐operating characteristic (ROC) analysis.

Results

IVIM parameters D* and f were significantly higher in neuroblastoma compared to Wilms' tumors (P < 0.05). The ROC analysis showed that the best diagnostic performance was achieved with D* 90th percentile (area under the curve [AUC] = 0.935; P = 0.002; cutoff value = 32,376 × 10−6 mm2/s) and f mean values (AUC = 1.00; P < 0.001; cutoff value = 14.7) in discriminating between neuroblastoma (n = 11) and Wilms' tumors (n = 8). Discrimination between tumor types was not possible with IVIM D or ADC parameters. Malignant tumors revealed significantly lower ADC, D, and higher D* values than in benign lesions (all P < 0.05).

Data Conclusion

IVIM perfusion parameters could distinguish between malignant childhood tumor types, providing potential imaging biomarkers for their diagnosis.

Level of Evidence: 4

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:1475–1486.
Extracellular volume with bolus‐only technique in amyloidosis patients: Diagnostic accuracy, correlation with other clinical cardiac measures, and ability to track changes in amyloid load over time
Authors: Zumbo Giulia , Barton Sharon V. , Thompson Douglas , Sun Min , Abdel‐Gadir Amna , Treibel Thomas A. , Knight Daniel , Martinez‐Naharro Ana , Thirusha Lane , Gillmore Julian D. , Moon James C. , Hawkins Philip N. , Fontana Marianna
Published: November 2017

Background

Extracellular volume (ECV) by T1 mapping requires the contrast agent distribution to be at equilibrium. This can be achieved either definitively with a primed contrast infusion (infusion ECV), or sufficiently with a delay postbolus (bolus‐only ECV). For large ECV, the bolus‐only approach measures higher than the infusion ECV, causing some uncertainty in diseases such as amyloidosis.

Purpose

To characterize the relationship between the bolus‐only and current gold‐standard infusion ECV in patients with amyloidosis.

Study Type

Bolus‐only and infusion ECV were prospectively measured.

Population

In all, 186 subjects with systemic amyloidosis attending our clinic and 23 subjects with systemic amyloidosis who were participating in an open‐label, two‐part, dose‐escalation, phase 1 trial.

Field Strength

Avanto 1.5T, Siemens Medical Solutions, Erlangen, Germany.

Assessment

Bolus‐only and infusion ECV were measured in all subjects using shortened modified Look–Locker inversion recovery (ShMOLLI) T1 mapping sequence.

Statistical Tests

Pearson correlation coefficient (r); Bland–Altman; receiver operating characteristic (ROC) curve analysis. Linear regression model with a fractional polynomial transformation.

Results

The difference between the bolus‐only and infusion myocardial ECV increased as the average of the two measures increased, with the bolus‐ECV measuring higher. For an average ECV of 0.4, the difference was 0.013. The 95% limits of agreement for the two methods, after adjustment for the bias, were ±0.056. However, cardiac diagnostic accuracy was comparable (bolus‐only vs. infusion ECV area under the curve [AUC] = 0.839 vs. 0.836), as were correlations with other clinical cardiac measures, and, in the trial patients, the ability to track changes in the liver/spleen with therapy.

Data Conclusion

In amyloidosis, with large ECVs, the bolus‐only technique reads higher than the infusion technique, but clinical performance by any measure is the same. Given the work‐flow advantages, these data suggest that the bolus‐only approach might be acceptable for amyloidosis, and might support its use as a surrogate endpoint in future clinical trials.

Level of Evidence: 1

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2018;47:1677–1684.
Accelerated, untargeted metabolomics analysis of cutaneous T‐cell lymphoma reveals metabolic shifts in plasma and tumor adjacent skins of xenograft mice
Authors: Le Yunchen , Shen Xiaoyan , Kang Hongyan , Wang Qizheng , Li Kejia , Zheng Jie , Yu Yunqiu
Published: November 2017

Cutaneous T‐cell lymphoma (CTCL) is a heterogeneous group of skin‐homing T‐cell neoplasms. Clinical management is stage based but diagnosis and prognosis could be extremely challenging. The presented study aims to explore the metabolic profiling of CTCL by an accelerated untargeted metabolomics data analysis tool “Mummichog” to facilitate the discoveries of potential biomarkers for clinical early stage diagnosis, prognosis, and treatments in CTCL. Ultra high‐performance liquid chromatography–quadrupole time‐of‐flight–based untargeted metabolomics were conducted on the skin and plasma of CTCL mice. It showed that the metabolism of skin changed greatly versus control samples in the development of CTCL. Increased l‐glutamate and decreased adenosine monophosphate were the most essential metabolic features of CTCL tumor and tumor adjacent skins. Unique metabolism changes in tumor adjacent non‐involved skin tissues (ANIT) occurred in the progress of carcinogenesis, including upregulated cytidine‐5′‐triphosphate, aberrant biosynthesis of prostaglandins, pyrimidine, mevalonate pathway, and tryptophan degradation. Sharply elevated 5‐phospho‐α‐d‐ribose 1‐diphosphate (PRPP) marked the final state of tumor in CTCL. In the plasma, systematic shifts in corticosterone, sphingolipid, and ceramide metabolism were found. These uncovered aberrant metabolites and metabolic pathways suggested that the metabolic reprogramming of PRPP in tumor tissues may cause the disturbance of cytidine and uridine metabolic homeostasis in ANIT. Accumulative cytidine‐5′‐triphosphate in ANIT may exert positive feedback on the PRPP level and leads to CTCL further development. In addition, the accelerated data analysis tool “Mummichog” showed good practicability and can be widely used in high‐resolution liquid chromatography mass spectrometry–based untargeted metabolomics.
Threshold detection for visible light communication using parametric distribution fitting
Authors: Usman Mohammed , Al‐Rayif Mohammed Ibrahim
Published: November 2017

Visible light communication has gained widespread attention in recent times and is expected to complement existing network infrastructure such as wireless local area networks, cellular networks as well as power line communications to provide high speed connectivity. The intensity of the received light depends on the intensity and wavelength of the transmitter, wavelength sensitivity range of the receiver, and also on the ambient light. Depending on the intensity of the received light, a photo‐sensor has to detect and decode the received data, with minimum probability of error. For binary transmission, this is achieved by choosing a decision threshold. In this paper, a threshold detection mechanism is presented by fitting parametric probability distributions to the sensed signal levels. It is shown that the threshold value obtained using this method yields error probability close to zero.
Learning from Gandhi: Addressing the current dilemmas in microfinance
Authors: Hannam Mark , Ashta Arvind
Published: November 2017

Gandhi would have argued that microfinance should focus on the poorest. Gandhism would require that microfinance revert to its initial objective of helping the poor to help themselves out of poverty. Social impacts should come before financial profits. The greater impact would require providing a wider panorama of financial services. Microfinance providers should be encouraged to experiment and learn.
Poverty scoring and financial inclusion of the poor
Authors: Bumacov Vitalie , Ashta Arvind , Singh Pritam
Published: November 2017

The use of poverty scoring is associated with increased outreach towards poor borrowers only in nonprofit microfinance institutions while, in for‐profit microfinance institutions, poverty scoring is associated with increased availability of financing. Poverty scoring allows for‐profit microfinance institutions to borrow funds from social investors in addition to funds borrowed from the market. As long as these social funds do not substitute market funds used in financing poor microborrowers, the share of poor clients served increases, so does financial inclusion of the poor.
Understanding microfinance institutions and commercial banks’ relationships and innovations in the Cameroon financial environment
Authors: Messomo Elle Serge
Published: November 2017

The relationships between microfinance institutions (MFIs) and commercial banks in Cameroon are dominated by competition and innovations in products, processes, and markets. The supply of microfinance services by commercial banks and the lack of a competitive government‐controlled body are two key factors that spur the competition between commercial banks and MFIs. The two types of financial institutions increase their cooperation as a result of technology and high supply of microfinance services by commercial banks. Regulation can lead to a positive integration of the two sectors.
Proposed typology of different publics of Austrian crowdfunding platforms
Authors: Attuel‐Mendès Laurence , Caseau Cornelia , Bonescu Mihaela
Published: November 2017

Crowdfunding, as a social media, benefits from an audience of different types of publics which can be categorized according to relational proximity and degree of expertise. Different publics interact in the field of crowdfunding. From the perspective of strategic management, “direct expert” must be mobilized in the short term when “indirect expert” should continue to be mobilized in the long term. From a theoretical point of view, this new typology raises the question of the relevance of segmentation criteria.
The Effect of Sleep Disorders, Sedating Medications, and Depression on Cognitive Processing Therapy Outcomes: A Fuzzy Set Qualitative Comparative Analysis
Authors: Haynes Patricia L. , Emert Sarah E. , Epstein Dana , Perkins Suzanne , Parthasarathy Sairam , Wilcox James
Published: November 2017

Cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) is an effortful process requiring engagement in cognitive restructuring. Sleep disorders may lead to avoidance of effortful tasks and cognitive performance deficits. We explored whether sleep disorders, as assessed by polysomnography, were consistently associated with treatment response in combination with other factors. This study included 32 U.S. veterans who were examined both before and after CPT for combat‐related PTSD. We employed a novel, case‐comparative technique, fuzzy set qualitative comparative analysis (fsQCA), to identify combinations of fuzzy and crisp factors (recipes) that achieve a clinically significant outcome. Approximately one‐quarter of cases experiencing clinically significant change were either (a) Vietnam era veterans without sedating medications, moderate sleep disordered breathing, and severe depression; or (b) non–Vietnam era veterans with sedating medications and without severe periodic limb movements (or significant periodic limb movement arousals). Recipes involving the absence of the relevant sleep disorder were associated with the highest coverage values. These results using fsQCA (a) provide valuable information about the heterogeneity of CPT response and (b) suggest that sleep disorders are important factors to consider in theoretical discussions of who responds to CPT for PTSD.
A Functional Near‐Infrared Spectroscopy Study of Trauma‐Related Auditory and Olfactory Cues: Posttraumatic Stress Disorder or Combat Experience?
Authors: Gramlich Michael A. , Neer Sandra M. , Beidel Deborah C. , Bohil Corey J. , Bowers Clint A.
Published: November 2017

The prevalence of posttraumatic stress disorder (PTSD) among U.S. veterans deployed to Iraq or Afghanistan necessitates the need for comprehensive assessment and treatment strategies. This study investigated the utility of a combat‐related PTSD symptom provocation paradigm to elicit unique neurological responses across three groups: combat veterans with PTSD, combat veterans without PTSD, and nonmilitary participants without PTSD. Using functional near‐infrared spectroscopy (fNIRS) the results indicated that combat veterans with PTSD demonstrated significant activation to a trauma‐related sound compared with nonmilitary personnel, channel 14: d = 1.03, 95% confidence interval (CI) [0.28, 1.76]; channel 15: d = 1.30, 95% CI [0.53, 2.06]; and combat veterans without PTSD, channel 14: d = 0.87, 95% CI [0.14, 1.59]. Specifically, this increased neural activation was approximately located in the right medial superior prefrontal cortex (Brodmann areas 9/10), an area associated with experiencing negative or threatening stimuli and emotional detachment. There were no differences across the groups for nontrauma‐related sounds. Results were less clear with respect to a combat‐related odor. These results suggest a specific neurophysiological response to trauma‐related cues and, if replicated, may offer a biomarker for combat‐related PTSD. Such a response could provide incremental validity over diagnostic assessments alone and assist in planning and monitoring of treatment outcome.
Ultrasound Microbubbles Enhance the Activity of Vancomycin Against Staphylococcus epidermidis Biofilms In Vivo
Authors: Dong Ying , Li Junshuai , Li Pan , Yu Jialin
Published: November 2017

Objectives

Staphylococcus epidermidis is the predominant pathogen of device‐associated infections. By forming biofilms on the device surface, S epidermidis has substantial resistance to antibiotics and is difficult to eradicate. This study aimed to explore the synergistic effect of ultrasound (US)‐mediated microbubbles combined with vancomycin on S epidermidis biofilms in a rabbit model.

Methods

Two polytetrafluoroethene catheters with preformed S epidermidis biofilms were implanted subcutaneously in a rabbit, one on either side of the spine. Animals were randomized into different treatment groups, with each rabbit acting as its own control and treatment. Ultrasound was applied from 24 to 72 hours after surgery 2 times a day. The parameters were 300 kHz and 0.5 W/cm2 in a 50% duty cycle, with or without microbubbles injected subcutaneously into the implantation site. After treatments, animals were euthanized, and implants were removed for a scanning electron microscopic examination and bacterial counting. The hearts, kidneys, livers, and subcutaneous tissues were sent for histopathologic examinations.

Results

Ultrasound + microbubbles increased the bactericidal action of vancomycin by decreasing biofilm viability from a mean ± SD of 6.44 ± 0.03 log10 colony‐forming units per catheter in the control group to 3.49 ± 0.02 log10 colony‐forming units per catheter in US + microbubble + vancomycin group (P < .001). The antibacterial effect of US + microbubbles + vancomycin was more pronounced than that of US + vancomycin (P < .001). Under scanning electron microscopy, biofilms exposed to US + microbubbles + vancomycin showed a greater reduction in thickness and bacterial density than other treatments. Histopathologic examinations showed no abnormalities in organs and skins.

Conclusions

Ultrasound microbubbles enhanced the antibacterial effect of vancomycin against S epidermidis biofilms in vivo without exerting obvious harms to the animals.
Extremely Painful Multifocal Acquired Predominant Axonal Sensorimotor Neuropathy of the Upper Limb
Authors: Lieba‐Samal Doris , van Eijk Jeroen J. J. , van Rosmalen Marieke H. J. , van Balken Irene M. F. , Verrips Aad , Mostert Jop , Pillen Sigrid , van Alfen Nens
Published: November 2017

The differential diagnosis of upper extremity mononeuritis multiplex includes neuralgic amyotrophy, vasculitic neuropathy, and Lewis‐Sumner syndrome. We describe 3 patients initially suspected of neuralgic amyotrophy, who had an extremely painful, protracted, progressive disease course, not fitting one of these established diagnoses. Nerve ultrasonography showed focal caliber changes of the roots, plexus, and limb nerves. Electromyography showed predominant multifocal axonopathy. Ongoing autoimmune neuropathy was suspected. Steroid treatment provided temporary relief, and intravenous immunoglobulin A sustained pain decrease and functional improvement. These patients appear to have extremely painful axonal inflammatory neuropathy, with a good response to immune‐modulating treatment.
Digital object identifier and its use in core Chinese academic journals: A Chinese perspective
Authors: Wang Weilang , Deng Lvxiang , You Bin , Zhang Ping , Chen Yifeng
Published: November 2017

Digital object identifiers (DOIs) are widely used across the world but not very much within China. This paper investigates the current usage of DOIs in China. Using an isometric method, we sampled 238 core Chinese academic journals from the Chinese Science and Technical Journal Citation Reports (2015 version, Core Edition), which includes 2,383 journals in total. According to our investigation, we found that: (1) although 80.25% of journals assign DOIs, 42.41% have only assigned DOIs to articles published after 2010; (2) most journals (89.01%) register DOIs through Institute of Scientific and Technical Information of China; and (3) only 84.82% of journals that register DOIs include them in the articles. This paper looks at the reasons for the limited implementation of DOIs and makes suggestions as to how usage can be expanded in China.
General phase regularized reconstruction using phase cycling
Authors: Ong Frank , Cheng Joseph Y. , Lustig Michael
Published: November 2017

Purpose

To develop a general phase regularized image reconstruction method, with applications to partial Fourier imaging, water–fat imaging and flow imaging.

Theory and Methods

The problem of enforcing phase constraints in reconstruction was studied under a regularized inverse problem framework. A general phase regularized reconstruction algorithm was proposed to enable various joint reconstruction of partial Fourier imaging, water–fat imaging and flow imaging, along with parallel imaging (PI) and compressed sensing (CS). Since phase regularized reconstruction is inherently non‐convex and sensitive to phase wraps in the initial solution, a reconstruction technique, named phase cycling, was proposed to render the overall algorithm invariant to phase wraps. The proposed method was applied to retrospectively under‐sampled in vivo datasets and compared with state of the art reconstruction methods.

Results

Phase cycling reconstructions showed reduction of artifacts compared to reconstructions without phase cycling and achieved similar performances as state of the art results in partial Fourier, water–fat and divergence‐free regularized flow reconstruction. Joint reconstruction of partial Fourier + water–fat imaging + PI + CS, and partial Fourier + divergence‐free regularized flow imaging + PI + CS were demonstrated.

Conclusion

The proposed phase cycling reconstruction provides an alternative way to perform phase regularized reconstruction, without the need to perform phase unwrapping. It is robust to the choice of initial solutions and encourages the joint reconstruction of phase imaging applications. Magn Reson Med 80:112–125, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Reconstruction of bladder function and prevention of renal deterioration by means of end‐to‐side neurorrhaphy in rats with neurogenic bladder
Authors: Li Yun Long , Wen Jian Jun , Wen Yi Bo , He Xiang Fei , Wu Jun Wei , Li Yan Wei , Han Zhong Jiang , Feng Jin Jin , Yan Shao Hua , Li Shou Lin , Heesakkers John PFA , Gao Wan Sheng , Wen Jian Guo
Published: November 2017

Aims

To investigate the feasibility of restoring bladder function and prevention of renal deterioration by neurorrhaphy in rats with neurogenic bladder (NB).

Methods

Forty‐two rats were assigned to the end‐to‐side nerve coaptation group (ECG, n = 16), no nerve coaptation group (NCG, n = 16), and control group (CG, n = 10). In the ECG, the left ventral root (VR) and dorsal root (DR) of L6 and S1 were transected, and the distal stump of L6VR was sutured to the lateral face of L4VR. In the NCG, the left VR and DR of L6 and S1 were transected, but coaptation was not performed. In the CG, no operation was performed. Nerve regeneration, bladder function, and renal function were evaluated by FluoroGold (FG) retrograde tract tracing, cystometry, electrical stimulation, MRI, histology and biochemical assays.

Results

In the ECG, FG‐labeled neurons were observed in the left ventral horn of L4 spinal cord. There was a significant increase in intravesical pressure upon stimulation of the left L4VR proximal to the coaptation. Maximum cystometric capacity, post‐void residual urine, bladder compliance and weight, serum creatinine, blood urea nitrogen, and fibrotic area of bladder and kidney were lower in the ECG than in the NCG, but higher than the CG. Hydronephrosis was noticed in ECG and NCG rats. Maximum detrusor voiding pressure was higher in the ECG and CG than in the NCG.

Conclusions

End‐to‐side neurorrhaphy is a useful method for restoring bladder function and preventing renal injury in rats with NB.
Visualization of calcium phosphate cement in teeth by zero echo time 1H MRI at high field
Authors: Dou Weiqiang , Mastrogiacomo Simone , Veltien Andor , Alghamdi Hamdan S. , Walboomers X. Frank , Heerschap Arend
Published: November 2017

1H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high‐field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T1 and T2* values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T2* relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T2* values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T2 values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T1 values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal‐to‐noise‐ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC‐filled lesions showed less homogeneous structures, a lower T1 value and T2* separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed.
Application of the state‐dependent Riccati equation for flexible‐joint arms: Controller and estimator design
Authors: Korayem M. H. , Lademakhi N. Y. , Nekoo S. R.
Published: November 2017

Full feedback data is mostly essential in control design. Measuring the links' variation of a flexible‐joint robot (FJR) is easy but not for its actuators. The measurement of states and workspace are also affected by noise and disturbance, respectively; hence, a state observer or a nonlinear estimator is very helpful to improve the control performance of a dynamic system. The state‐dependent Riccati equation (SDRE) is one of the most promising methods in the field of nonlinear optimal observers for estimating variables of multiple‐input–multiple‐output systems. Systematic procedure, simple structure, and incorporation of a wide range of systems (under an observability condition) are some of the advantages of the method. Therefore, the aim of this study is to compose the SDRE controller and estimator simultaneously to reduce the state error of the system in the presence of external disturbance and noise. The application of this method is shown for FJRs in the estimation of changes in motion behind the connection of the motor and link where there is no easy way to measure. The proposed composition of the SDRE controller and estimator was implemented on a 6R robot to examine the various aspects of FJR systems.
Do pregnancy characteristics contribute to rising childhood cancer incidence rates in the United States?
Authors: Kehm Rebecca D. , Osypuk Theresa L. , Poynter Jenny N. , Vock David M. , Spector Logan G.
Published: November 2017

Background

Since 1975, childhood cancer incidence rates have gradually increased in the United States; however, few studies have conducted analyses across time to unpack this temporal rise. The aim of this study was to test the hypothesis that increasing cancer incidence rates are due to secular trends in pregnancy characteristics that are established risk factors for childhood cancer incidence including older maternal age, higher birthweight, and lower birth order. We also considered temporal trends in sociodemographic characteristics including race/ethnicity and poverty.

Procedure

We conducted a time series county‐level ecologic analysis using linked population‐based data from Surveillance, Epidemiology, and End Results cancer registries (1975–2013), birth data from the National Center for Health Statistics (1970–2013), and sociodemographic data from the US Census (1970–2010). We estimated unadjusted and adjusted average annual percent changes (AAPCs) in incidence of combined (all diagnoses) and individual types of cancer among children, ages 0–4 years, from Poisson mixed models.

Results

There was a statistically significant unadjusted temporal rise in incidence of combined childhood cancers (AAPC = 0.71%; 95% CI = 0.55–0.86), acute lymphoblastic leukemia (0.78%; 0.49–1.07), acute myeloid leukemia (1.86%; 1.13–2.59), central nervous system tumors (1.31%; 0.94–1.67), and hepatoblastoma (2.70%; 1.68–3.72). Adjustment for county‐level maternal age reduced estimated AAPCs between 8% (hepatoblastoma) and 55% (combined). However, adjustment for other county characteristics did not attenuate AAPCs, and AAPCs remained significantly above 0% in models fully adjusted for county‐level characteristics.

Conclusion

Although rising maternal age may account for some of the increase in childhood cancer incidence over time, other factors, not considered in this analysis, may also contribute to temporal trends.
The influence of coping strategies on subsequent well‐being in older patients with cancer: A comparison with 2 control groups
Authors: Baitar Abdelbari , Buntinx Frank , De Burghgraeve Tine , Deckx Laura , Schrijvers Dirk , Wildiers Hans , van den Akker Marjan
Published: November 2017

Objective

To evaluate dispositional coping strategies as predictors for changes in well‐being after 1 year in older patients with cancer (OCP) and 2 control groups.

Methods

OCP were compared with 2 control groups: middle‐aged patients with cancer (MCP) (aging effect) and older patients without cancer (ONC) (cancer effect). Patients were interviewed shortly after a cancer diagnosis and 1 year later. Dispositional coping was measured with the Short Utrecht Coping List. For well‐being, we considered psychological well‐being (depression, loneliness, distress) and physical health (fatigue, ADL, IADL). Logistic regression analyses were performed to study baseline coping as predictor for subsequent well‐being while controlling for important baseline covariates.

Results

A total of 1245 patients were included in the analysis at baseline: 263 OCP, 590 ONC, and 392 MCP. Overall, active tackling was employed most often. With the exception of palliative reacting, OCP utilized each coping strategy less frequently than MCP. At 1‐year follow‐up, 833 patients (66.9%) were interviewed. Active coping strategies (active tackling and seeking social support) predicted subsequent well‐being only in MCP. Avoidance coping strategies did not predict well‐being in any of the patient groups. Palliative reacting predicted distress in OCP; depression and dependency for ADL in MCP.

Conclusions

Coping strategies influence subsequent well‐being in patients with cancer, but the impact is different in the age groups. Palliative reacting was the only coping strategy that predicted well‐being (ie, distress) in OCP and is therefore, especially in this population, a target for coping skill interventions.
Unraveling the Mechanistic Complexity of the Glomerulocystic Phenotype in Dicer Conditional KO Mice by 2D Gel Electrophoresis Coupled Mass Spectrometry
Authors: Fiumara Claudia Vincenza , Scumaci Domenica , Iervolino Anna , Perri Angela Mena , Concolino Antonio , Tammè Laura , Petrillo Federica , Capasso Giovambattista , Cuda Giovanni
Published: November 2017

Purpose

Dicer, an RNase III type endonuclease, is a key enzyme involved in miRNA biogenesis. It has been shown that this enzyme is essential for several aspects of postnatal kidney functions and homeostasis. In this study, we have examined conditional knockout (cKO) mice for Dicer in Pax8 (Paired‐box gene 8) expressing cells to investigate the kidney protein profile. This specific model develops a glomerulocystic phenotype coupled with urinary concentration impairment, proteinuria, and severe renal failure.

Experimental design

Proteomic analysis was performed on kidney tissue extracts from cKO and control (Ctr) mice by 2D Gel Electrophoresis coupled with mass spectrometry.

Results

The analysis highlighted 120 protein spots differentially expressed in Dicer cKO tissue compared with control; some of these proteins were validated by Western blotting. Ingenuity Pathway Analysis led to the identification of some interesting networks; among them, the one having ERK as a central hub may explain, through the modulation of the expression of a number of identified protein targets, the metabolic and structural alterations occurring during kidney cyst development in Dicer cKO mouse model.

Conclusions and clinical relevance

Our results contribute to gain new insights into molecular mechanisms through which Dicer endonuclease controls kidney development and physiological functions.
Protein structure modeling and refinement by global optimization in CASP12
Authors: Hong Seung Hwan , Joung InSuk , Flores‐Canales Jose C. , Manavalan Balachandran , Cheng Qianyi , Heo Seungryong , Kim Jong Yun , Lee Sun Young , Nam Mikyung , Joo Keehyoung , Lee In‐Ho , Lee Sung Jong , Lee Jooyoung
Published: November 2017

For protein structure modeling in the CASP12 experiment, we have developed a new protocol based on our previous CASP11 approach. The global optimization method of conformational space annealing (CSA) was applied to 3 stages of modeling: multiple sequence‐structure alignment, three‐dimensional (3D) chain building, and side‐chain re‐modeling. For better template selection and model selection, we updated our model quality assessment (QA) method with the newly developed SVMQA (support vector machine for quality assessment). For 3D chain building, we updated our energy function by including restraints generated from predicted residue‐residue contacts. New energy terms for the predicted secondary structure and predicted solvent accessible surface area were also introduced. For difficult targets, we proposed a new method, LEEab, where the template term played a less significant role than it did in LEE, complemented by increased contributions from other terms such as the predicted contact term. For TBM (template‐based modeling) targets, LEE performed better than LEEab, but for FM targets, LEEab was better. For model refinement, we modified our CASP11 molecular dynamics (MD) based protocol by using explicit solvents and tuning down restraint weights. Refinement results from MD simulations that used a new augmented statistical energy term in the force field were quite promising. Finally, when using inaccurate information (such as the predicted contacts), it was important to use the Lorentzian function for which the maximal penalty arising from wrong information is always bounded.
Crystal structure of the Legionella effector Lem22
Authors: Kozlov Guennadi , Wong Kathy , Gehring Kalle
Published: November 2017

Legionella pneumophila is a pathogen causing severe pneumonia in humans called Legionnaires’ disease. Lem22 is a previously uncharacterized effector protein conserved in multiple Legionella strains. Here, we report the crystal structure of Lem22 from the Philadelphia strain, also known as lpg2328, at 1.40 Å resolution. The structure shows an up‐and‐down three‐helical bundle with a significant structural similarity to a number of protein‐binding domains involved in apoptosis and membrane trafficking. Sequence conservation identifies a putative functional site on the interface of helices 2 and 3. The structure is an important step toward a functional characterization of Lem22.
Data visualizations to detect systematic errors in laboratory assay results
Authors: Lötsch Jörn
Published: November 2017

The measurement of concentrations of drugs and endogenous substances is widely used in basic and clinical pharmacology research and service tasks. Using data science‐derived visualizations of laboratory data, it is demonstrated on a real‐life example that basic statistical exploration of laboratory assay results or advised standard visual methods of data inspection may fall short in detecting systematic laboratory errors. For example, data pathologies such as generating always the same value in all probes of a particular assay run may pass undetected when using standard methods of data quality check. It is shown that the use of different data visualizations that emphasize different views of the data may enhance the detection of systematic laboratory errors. A dotplot of single data in the order of assay is proposed that provides an overview on the data range, outliers and a particular type of systematic errors where similar values are wrongly measured in all probes.