bluuebunny/crossref_metadata_2025 huggingface dataset:
Bladder and upper urinary tract cancers as first and second primary cancers
Authors: Zheng Guoqiao , Sundquist Kristina , Sundquist Jan , Försti Asta , Hemminki Otto , Hemminki Kari
Published: June 2021

Background

Previous population‐based studies on second primary cancers (SPCs) in urothelial cancers have focused on known risk factors in bladder cancer patients without data on other urothelial sites of the renal pelvis or ureter.

Aims

To estimate sex‐specific risks for any SPCs after urothelial cancers, and in reverse order, for urothelial cancers as SPCs after any cancer. Such two‐way analysis may help interpret the results.

Methods

We employed standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancer associated with urothelial cancers. Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015.

Results

We identified 46 234 urinary bladder cancers (75% male), 940 ureteral cancers (60% male), and 2410 renal pelvic cancers (57% male). After male bladder cancer, SIRs significantly increased for 9 SPCs, most for ureteral (SIR 41.9) and renal pelvic (17.2) cancers. In the reversed order (bladder cancer as SPC), 10 individual FPCs were associated with an increased risk; highest associations were noted after renal pelvic (21.0) and ureteral (20.9) cancers. After female bladder cancer, SIRs of four SPCs were significantly increased, most for ureteral (87.8) and pelvic (35.7) cancers. Female bladder, ureteral, and pelvic cancers associated are with endometrial cancer.

Conclusions

The risks of recurrent urothelial cancers were very high, and, at most sites, female risks were twice over the male risks. Risks persisted often to follow‐up periods of >5 years, motivating an extended patient follow‐up. Lynch syndrome‐related cancers were associated with particularly female urothelial cancers, calling for clinical vigilance.
The frequency and clinicopathological significance of NRAS mutations in primary cutaneous nodular melanoma in Indonesia
Authors: Rinonce Hanggoro Tri , Sastri Deflen Jumatul , Trisnawati Fita , Kameswari Bidari , Ferronika Paranita , Irianiwati
Published: June 2021

Background

Melanoma is a lethal skin malignancy with a high risk of metastasis, which prompts a need for research on treatment targets and prognostic factors. Recent studies show that the presence of neuroblastoma RAS viral oncogene homolog (NRAS) mutation can influence cell growth in melanomas. The NRAS mutation, which stimulates the mitogen‐activated protein kinase (MAPK) signaling pathway, is associated with a lower survival rate. However, evidence from Indonesia population is still very rare. Further understanding of the role of NRAS mutations in Indonesian melanoma cases will be crucial in developing new management strategies for melanoma patients with NRAS mutations.

Aims

To explore the frequency of NRAS mutations and their clinicopathological associations in patients with primary nodular cutaneous melanoma in Central Java and Yogyakarta, Indonesia.

Methods and results

Fifty‐one paraffin‐embedded tissue samples were collected from primary nodular skin melanoma cases between 2011 and 2019 from the two largest referral hospitals in Yogyakarta and Central Java, Indonesia. The NRAS mutation status was evaluated using qualitative real‐time polymerase chain reaction (qRT‐PCR). The association of NRAS mutation was analyzed with the following: age, gender, location, lymph node metastasis, ulceration, mitotic index, tumor‐infiltrating lymphocytes (TILs), necrosis, tumor thickness, lymphovascular invasion (LVI), and tumor size. NRAS mutations were detected in 10 (19.6%) samples and predominantly observed (60%) in exon 2 (G12). These mutations were significantly correlated with lymph node metastases (p = .000); however, they were not associated with other variables analyzed in this study.

Conclusions

The prevalence of NRAS mutations in primary nodular cutaneous melanoma cases from Indonesia is consistent with previous studies and is significantly associated with increased lymph node metastases. However, the predominant mutation detected in exon 2 (G12) is different from previous studies conducted in other countries. This suggests that melanoma cases in Javanese people have different characteristics from other ethnicities.
Layered Double Oxides for Sensing Reducing Volatile Organic Compounds: The Effect of Local Charge Region Modulation
Authors: Qin Yuxiang , Xu Xin , Xia Qing , Wang Xinyang
Published: June 2021

Multi‐metal oxides with uniform distribution of various metal elements have potential for an enhanced gas‐sensing response due to the strong heterogeneous and synergistic effects involved. In this study, three layered double oxides, labeled as CuCr‐, ZnCr‐, and ZnTi‐LDOs, respectively, were prepared with corresponding LDHs (layered double hydroxides) as precursors and self‐sacrificial templates. The elemental mapping confirms the uniform distribution of hetero‐metal elements in whole LDOs. The CuCr‐LDOs exhibits a much larger sensing response towards reducing VOCs at room temperature, which is 3.5 or 13.3 times that of ZnCr‐ or ZnTi‐LDOs, respectively. The response differences are analyzed in terms of the local charge region modulation associated with heterojunction formation, and it is further demonstrated based on first‐principles calculations and valence electron theory. The present work suggests a possible strategy for developing highly sensitive oxide‐based gas sensors for VOCs detection.
Synthesis and Characterization of the Potential Melt‐Castable Explosive 3‐(1,2,4‐Oxadiazolyl)‐5‐Nitratomethyl Isoxazole
Authors: Johnson Eric C. , Reid Tristen A. , Miller Christopher W. , Sabatini Jesse J. , Sausa Rosario C. , Byrd Edward F. C. , Orlicki Joshua A.
Published: June 2021

The synthesis of 3‐(1,2,4‐oxadiazolyl)‐5‐nitratomethyl isoxazole (C6H4N4O5), its physical properties, and its theoretical performances are described. This energetic material was found to have a melting point range of 76.6–79.2 °C, and a thermal onset decomposition temperature of 184.5 °C. These thermal features put this material into the standalone melt‐castable explosive class. The material was found to have TNT performance, and was found to be insensitive to impact, friction, and electrostatic discharge, despite having a nitric ester functionality. A critical reaction in making this molecule was the desymmetrization of diaminoglyoxime. The optimization of this transformation is described. Previous reports of this desymmetrization were found to be inaccurate, as the desymmetrization reaction produces a co‐crystal of mono‐ and bi‐1,2,4‐oxadiazole products.
Addressing virtual reality misclassification: A hardware‐based qualification matrix for virtual reality technology
Authors: Takac Marcel , Collett James , Conduit Russell , De Foe Alexander
Published: June 2021

Through its unique sensory synchronized design, virtual reality (VR) provides a convincing, user‐centred experience of highly controllable scenarios. Importantly, VR is a promising modality for healthcare, where treatment efficacy has been recognized for a range of conditions. It is equally valuable across wider research disciplines. However, there is a lack of suitable criteria and consistent terminology with which to define VR technology. A considerable number of studies have misclassified VR hardware (e.g. defining laptops as VR), hindering validity and research comparisons. This review addresses these limitations and establishes a standardized VR qualification framework. As a result of a comprehensive theoretical and literature review, the hardware‐based VR qualification matrix is proposed. The matrix criteria consist of (1) three‐dimensional (3D) synchronized sensory stimulation; (2) degrees of freedom tracking; and (3) visual suppression of physical stimuli. To validate the model and quantify the current scale/diversity of VR misclassification, a 2019 sectional review of health‐related studies was conducted. Of the 115 studies examined against standardized criteria, 35.7% utilized VR, 31.3% misclassified VR, 18.3% were considered quasi‐VR, and 14.8% omitted critical specifications. The proposed model demonstrates good validity and reliability for qualifying and classifying VR.

Key Practitioner Messages

Virtual reality (VR) therapy has gained rapid empirical support, although many practitioners do not understand the difference between genuine and less‐realistic VR variations.

That has resulted from an evident lack of suitable criteria to define VR across a range of studies and protocols.

Our proposed hardware‐based virtual reality qualification matrix addresses issues to do with misclassification, via the introduction of standardised criteria.

Applying the matrix to existing literature has revealed that more than 30% of VR studies use hardware that does not fit the high standards of rigour required for immersion in a simulated space.

The model is a practical tool researchers and practitioners can use to quality and verify VR standards across research studies.
Changes in intolerance of uncertainty over the course of treatment predict posttraumatic stress disorder symptoms in an inpatient sample
Authors: Badawi Amalia , Steel Zachary , Harb Merrylord , Mahoney Christopher , Berle David
Published: June 2021

Intolerance of uncertainty (IU) is the inability to tolerate distress that arises in response to the absence of important information. The level of IU has been investigated across various psychological disorders; however, few studies have examined IU in trauma‐affected samples. We aimed to investigate the relationship between IU and posttraumatic stress disorder (PTSD) across the course of treatment. Participants (n = 106) had a diagnosis of PTSD and were from first responder, military, and occupational injury backgrounds. Participants completed self‐report questionnaires pre‐ and post‐engagement in an inpatient group trauma‐informed psychoeducation and skills (TIPS) intervention. Regression analyses indicated that decreases in overall and inhibitory IU were associated with decreases in PTSD severity overall and at the symptom cluster level. However, prospective IU was only associated with changes in the re‐experiencing, avoidance, and arousal PTSD symptom clusters. Our findings are congruent with the nascent literature indicating that IU may be a maintaining factor for PTSD, suggesting clinical relevance for attendance to IU within the course of treatment.
Is personality the key in cognitive‐behavioural therapy for eating disorders? A review
Authors: Fumagalli Giovanni , Margola Davide
Published: June 2021

The efficacy of individual cognitive‐behavioural therapy (CBT) for eating disorders can be assessed by investigating the potential predictors, mediators and moderators of treatment. The present review focused on personality since its crucial role has been emphasized both by research and practice. Sixteen studies were collected, and data were extracted through a highly operationalized coding system. Overall, personality disorders were the most investigated construct; however, their influence was somewhat contradictory. A more cogent result occurred for borderline personality disorder (BPD) when considered as a moderator (not a predictor nor a mediator). Patients with a more disturbed borderline personality benefited to a greater extent from treatments including booster modules on affects, interpersonal relationships and mood intolerance, rather than symptoms exclusively. Nine additional personality dimensions, beyond BPD, were investigated sparsely, and results regarding them were barely indicative in this review. However, some of these dimensions (e.g., affective lability and stimulus‐seeking behaviours) could be traced back to BPD, thereby strengthening evidence of the role of borderline disorder as a moderator. Although research on the relationship between personality and eating disorders needs to be increased and methodologically improved, personality, taken as a whole, emerged as a promising variable for enhancing the efficacy of CBT.
Charging scheduling strategy for linear wireless power transfer network with external power injection
Authors: Yang Jingjing , Jiang Yanwei , Xu Zhezhuang , Chen Wei
Published: June 2021

Wireless power transfer network (WPTN) can provide efficient, timely, and dynamic charging service for multiple devices wirelessly by adopting mobile chargers. However, there are still urgent requirements to reduce the cost and improve the charging performance of WPTN. Therefore, this paper proposes the charging scheduling strategy for linear WPTN in which devices are distributed linearly or approximately linearly. An improved energy consumption model of the WPTN node is discussed firstly. Then, considering the charging capability of the wireless power transfer module, a charging threshold is selected to improve energy use efficiency. Moreover, the regional charging of mobile chargers is realized, so the distribution of carried energy on mobile chargers could be balanced and the maximum required energy that a single mobile charger carried could be reduced. Meanwhile, the processes of charging scheduling and energy delivery are analyzed in detail. Finally, simulation analysis and experimental data verify the effectiveness of the proposed charging scheduling strategies.
Nonsurgical fat reduction: Cryolipolysis, RF skin tightening, HIFEM, and injectable lipolysis
Authors: Gold Michael , Kleinrock Marci L. , Utley Collette , Bauknecht Caroline , Goldberg David
Published: June 2021

Nonsurgical fat reduction has become a very popular cosmetic treatment category with energy‐based devices demonstrating, in clinical trials, safety, and efficacy. These devices, which use both radiofrequency and cold, will be presented in this manuscript, and their documented efficacy will be reviewed. As well, the new field of high intensity focused electromagnetic technology is gaining excitement for not only muscle stimulation, but also for fat reduction and now skin tightening. And finally, pharmaceutical agents are being used and investigated for their clinical effects on reducing fat. The myriad of treatment options now available provide clinicians with great choices, with documented safety and efficacy, to reduce fat, tighten the skin, and stimulate muscle formation.
Advances in tissue engineering of vasculature through three‐dimensional bioprinting
Authors: Zhu Junjin , Wang Yuting , Zhong Linna , Pan Fangwei , Wang Jian
Published: June 2021

Background

A significant challenge facing tissue engineering is the fabrication of vasculature constructs which contains vascularized tissue constructs to recapitulate viable, complex and functional organs or tissues, and free‐standing vascular structures potentially providing clinical applications in the future. Three‐dimensional (3D) bioprinting has emerged as a promising technology, possessing a number of merits that other conventional biofabrication methods do not have. Over the last decade, 3D bioprinting has contributed a variety of techniques and strategies to generate both vascularized tissue constructs and free‐standing vascular structures.

Results

This review focuses on different strategies to print two kinds of vasculature constructs, namely vascularized tissue constructs and vessel‐like tubular structures, highlighting the feasibility and shortcoming of the current methods for vasculature constructs fabrication. Generally, both direct printing and indirect printing can be employed in vascularized tissue engineering. Direct printing allows for structural fabrication with synchronous cell seeding, while indirect printing is more effective in generating complex architecture. During the fabrication process, 3D bioprinting techniques including extrusion bioprinting, inkjet bioprinting and light‐assisted bioprinting should be selectively implemented to exert advantages and obtain the desirable tissue structure. Also, appropriate cells and biomaterials matter a lot to match various bioprinting techniques and thus achieve successful fabrication of specific vasculature constructs.

Conclusion

The 3D bioprinting has been developed to help provide various fabrication techniques, devoting to producing structurally stable, physiologically relevant, and biologically appealing constructs. However, although the optimization of biomaterials and innovation of printing strategies may improve the fabricated vessel‐like structures, 3D bioprinting is still in the infant period and has a great gap between in vitro trials and in vivo applications. The article reviews the present achievement of 3D bioprinting in generating vasculature constructs and also provides perspectives on future directions of advanced vasculature constructs fabrication.
Habitat segregation of plate phenotypes in a rapidly expanding population of three‐spined stickleback
Authors: Eriksson Britas Klemens , Yanos Casey , Bourlat Sarah J. , Donadi Serena , Fontaine Michael C. , Hansen Joakim P. , Jakubavičiūtė Eglė , Kiragosyan Karine , Maan Martine E. , Merilä Juha , Austin Åsa N. , Olsson Jens , Reiss Katrin , Sundblad Göran , Bergström Ulf , Eklöf Johan S.
Published: June 2021

Declines of large predatory fish due to overexploitation are restructuring food webs across the globe. It is now becoming evident that restoring these altered food webs requires addressing not only ecological processes, but evolutionary ones as well, because human‐induced rapid evolution may in turn affect ecological dynamics. We studied the potential for niche differentiation between different plate armor phenotypes in a rapidly expanding population of a small prey fish, the three‐spined stickleback (Gasterosteus aculeatus). In the central Baltic Sea, three‐spined stickleback abundance has increased dramatically during the past decades. The increase in this typical mesopredator has restructured near‐shore food webs, increased filamentous algal blooms, and threatens coastal biodiversity. Time‐series data covering 22 years show that the increase coincides with a decline in the number of juvenile perch (Perca fluviatilis), the most abundant predator of stickleback along the coast. We investigated the distribution of different stickleback plate armor phenotypes depending on latitude, environmental conditions, predator and prey abundances, nutrients, and benthic production; and described the stomach content of the stickleback phenotypes using metabarcoding. We found two distinct lateral armor plate phenotypes of stickleback, incompletely and completely plated. The proportion of incompletely plated individuals increased with increasing benthic production and decreasing abundances of adult perch. Metabarcoding showed that the stomach content of the completely plated individuals more often contained invertebrate herbivores (amphipods) than the incompletely plated ones. Since armor plates are defense structures favored by natural selection in the presence of fish predators, the phenotype distribution suggests that a novel low‐predation regime favors stickleback with less armor. Our results suggest that morphological differentiation of the three‐spined stickleback has the potential to affect food web dynamics and influence the persistence and resilience of the stickleback take‐over in the Baltic Sea.
Clinical outcomes among patients with chronic kidney disease hospitalized with diabetic foot disorders: A nationwide retrospective study
Authors: Salim Michael
Published: June 2021

Introduction

Diabetic foot ulcerations or infections (DFUs/DFIs) are common complications of patients with diabetes. This study aimed to explore the impact of non‐dialysis and dialysis CKD on hospitalized patients with DFUs/DFIs.

Methods

A retrospective cohort study was conducted using the National Inpatient Sample database for the years 2017 and 2018. Patients hospitalized for DFUs/DFIs were included in the study. The primary outcome was lower limb amputations. The secondary outcomes were inpatient mortality, sepsis, length of stay (LOS), total hospitalization charges (THC) and disposition.

Results

A total of 121,815 hospitalizations were included (26.1% non‐dialysis CKD; 8.4% dialysis CKD). There was no significant difference in amputation rates between those on non‐dialysis CKD (adjusted odds ratio [aOR]: 0.96; 95% confidence interval [CI]: 0.87–1.06) and dialysis CKD (aOR: 1.04, [95% CI: 0.91–1.12]) when compared to non‐CKD group. Dialysis CKD group had increased odds of undergoing major amputation (aOR: 1.74, [95% CI: 1.32–2.29]), in‐hospital mortality (aOR: 3.77 [95% CI: 1.94–7.31]), sepsis (aOR: 1.83 [95% CI: 1.27–2.62]), longer LOS (adjusted mean difference [aMD]: 1.46 [95 CI: 1.12–1.80) and higher THC (adjusted mean difference [aMD]: $20,148 [95% CI: $15,968‐$24,327]). Non‐dialysis CKD group had increased odds of sepsis (aOR: 1.36 [95% CI: 1.02–1.82]), less likely to be discharged home (aOR: 0.87 [95% CI: 0.80–0.95]), longer LOS (aMD: 0.91 [95% CI 0.69–1.13]) and higher THC (aMD: $20,148 [95% CI: $15,968–$24,327]).

Conclusion

Patients with CKD on dialysis had higher odds of undergoing major amputation. CKD increased the odds of in‐hospital morbidity and resource utilization, with the most significant is for those on dialysis.
Forest and water policy integration: A process and output‐oriented policy network analysis
Authors: Baulenas Eulàlia , Kruse Sylvia , Sotirov Metodi
Published: June 2021

Natural resource management requires cross‐sectoral policy integration because the scope of current environmental and sustainability issues surpasses traditional sectoral boundaries. While the emergence of policy networks in such cases has been observed in the policy integration literature, little is known about how these networks are formed and how they influence the processes and outputs of policy integration. Accordingly, the main aim of this article is to combine the policy integration and policy network literatures to answer two research questions: How can the formation of a policy network for the case of forest and water policy integration be explained? What are the effects of the policy network on policy integration outputs? We use qualitative interviews and social network analysis to inform the study of two regional case studies in Germany and Spain. Our results show the relevance of a policy broker in steering the interactions between forest and water policy actors, combined with the presence of synergetic interdependencies, which facilitated the activation of the network. Additionally, the activities performed contributed to ideational homogenization between the forest and water sectors in terms of problem definition and preferred solutions, despite initial divergences. We conclude that a policy network perspective is an important contribution to the policy integration literature because it allows differentiating the influence of actor‐level and network‐level factors on integrated processes and outputs. In conclusion, both actors and their relationships should be accounted for as key intermediary variables to better understand and steer policy integration between natural resource sectors.
Enantiopure 2,9‐Dideuterodecane – Preparation and Proof of Enantiopurity
Authors: Mitschke Nico , Eruçar Gülsera , Fsadni Miriam H. , Roberts Amy R. , Sadeghi Majid M. , Golding Bernard T. , Christoffers Jens , Wilkes Heinz
Published: June 2021

(R,R)‐ and (S,S)‐(2,9‐2H2)‐n‐Decane were prepared regio‐ and stereospecifically in 25–26 % yield over five steps from commercially available enantiopure (R)‐ and (S)‐propylene oxide, respectively. The synthetic procedure involved nucleophilic displacement of (R)‐ and (S)‐4‐toluenesulfonic acid 1‐methyl‐4‐pentenyl ester with LiAlD4 to furnish the respective (5‐2H)‐1‐hexenes. Subsequent olefin metathesis and reduction of the double bond furnished the title compounds. The optical purity of (R,R)‐ and (S,S)‐(2,9‐2H2)‐n‐decane could not be determined by chromatography or polarimetry. Therefore, (R,R)‐ and (R,S)‐(5‐2H)‐3‐hydroxy‐2‐hexanone were prepared from their respective hexenes by Wacker oxidation, followed by enantioselective α‐hydroxylation. The enantiopurity could then be determined by NMR spectroscopy because the stereospecifically deuterated hydroxyketones showed separated signals for the subterminal carbon atom (C‐5) in the 13C NMR spectrum.
Development of Bio‐inspired Composite Materials for the Detection of Traces of Silver Present in Water: Use of Taguchi Methodology to Design Low‐cost Carbon Paste Electrodes
Authors: García‐Melendrez Jaime , Warren‐Vega Walter M. , Zárate‐Guzmán Ana I. , Carrasco‐Marín Francisco , González‐Gutiérrez Linda V. , Romero‐Cano Luis A.
Published: June 2021

Carbon Paste Electrodes (CPE) modified with Grapefruit‐Peels (GP) functionalized with Urea (GPU) and, Melamine (GPM) were designed for the detection of Ag+ in water. Taguchi L9 methodology was used to determine the optimal graphite‐Active material ratio. The best electrochemical response was for CPE‐GPU with an 80 : 20 ratio. The results obtained showed a linear detection range between 0.5 to 28 μg L−1, with a detection limit of 0.73 μg L−1 and a limit of quantification of 1.04 μg L−1. Attributable to CPE‐GPU characteristics: electroactive surface area 0.175 cm2, roughness factor 3.87, resistance 0.09 Ω and, mostly −NH2 groups on its surface. The composite material offers a viable option to be used for the determination of silver traces in situ in industrial processes.
Growth mechanism and kinetics of vertically aligned carbon nanotube arrays
Authors: Liu Qingxiong , Shi Xiaofei , Jiang Qinyuan , Li Run , Zhong Sheng , Zhang Rufan
Published: June 2021

Carbon nanotubes (CNTs) exhibit excellent mechanical, electrical, thermal, and chemical properties and show promising application potentials in numerous fields. Among different types of CNTs, vertically aligned CNT arrays (VACNTs) exhibit more superiors due to their good alignment, controllable structures and morphologies, and easy mass‐production, and so forth. During the past years, extensive efforts were put into the controlled synthesis of VACNTs with desired structures and morphologies. Among these efforts, it should be noted that, it is of significant importance to improve the array lengths of VACNTs, especially for the fabrication of VACNTs‐based fibers, transparent flexible films, and other functional materials, and so forth. However, it still remains a big challenge to synthesize VACNTs with length over centimeters. In this review, we summarize the growth mechanism, kinetics, growth factors of VACNTs, and the strategies for how to improve their array lengths. Finally, we also propose our outlook on the future development of VACNTs.

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Phytochemical screening and the effect of Trichosanthes dioica in high‐fat diet induced atherosclerosis in Wistar rats
Authors: Shrivastava Amit Kumar , Thapa Samul , Shrestha Laxmi , Mehta Roshan Kumar , Gupta Anamika , Koirala Niranjan
Published: June 2021

Trichosanthes dioica fruit pericarp has a powerful hypolipidemic and antioxidant properties. Wistar rats were divided into five groups (n = 30). The normal control group received vehicle and standard diet throughout the experimental period. Groups II, III, IV, and V were given a high‐fat diet and free access of water for 21 days. Experimental groups IV and V were given high‐fat diet along with T. dioica extract 400 and 800 mg/kg, respectively. Blood was collected at 21 days, and lipid profile estimation was performed. The phytochemical screening was performed by different phytochemical screening methods. Lipid peroxidation and catalase activity were done by taking a liver tissue sample. The phytochemical screening of extract showed good results and indicated the presence of phytoconstituents in extract. 2,2‐Diphenyl‐1‐picrylhydrazyl scavenging activity of T. dioica was found to be 65.79% at a concentration of 100 μg/ml extract, whereas that of the control was 94.06%. The Wistar rats fed with a high‐fat diet with T. dioica showed a significant decrease in total cholesterol (TC), triglycerides (TG), very‐low‐density lipoprotein (VLDL), and low‐density lipoprotein (LDL) levels and an increase in high‐density lipoprotein (HDL) level. The lipid peroxidation and catalase activity of methanol extract of T. dioica were significantly reduced with individual comparison with all groups. The methanol extract of T. dioica has the hypolipidemic effect, which showed a decrease in TC, TG, VLDL, and LDL levels and an increase in HDL level in Wistar rats. It also has antioxidant properties. In this study, we have evaluated the antioxidant and the antihyperlipidemic activities of T. dioica in high‐fat diet induced hyperlipidemia in Wistar rats.
Disentangling the relationship between internationalization, incremental and radical innovation, and firm performance
Authors: Freixanet Joan , Rialp Josep
Published: June 2021

Research Summary

This study examines the impact of firm internationalization on incremental and radical product innovation, and the effects of these innovation facets on sales growth. We use a sample of 1,064 Spanish manufacturers over the period 2008–2014. We find a positive relationship between higher international scope and greater ex‐post radical innovation output, and an inverted U‐shape relationship between export intensity and both innovation forms. We also find a positive relationship between incremental innovation and sales growth for performance leaders, and negative for performance laggards. Conversely, radical innovation boosts performance laggards' sales growth, but reduces that of performance leaders. The study supports and qualifies the learning‐by‐exporting effect, by identifying some firm‐specific factors that shape the relationship between internationalization, innovation, and firm performance.

Managerial Summary

In this study, we examine the effect of a more intense and more geographically spread out international expansion in a firm's incremental and radical innovation performance. We argue that more internationalized firms may benefit from new knowledge and learning, which they may leverage to increase their incremental and radical product innovations. In turn, we posit that incremental product innovation may be beneficial for performance leaders, but useless for a turnaround of performance laggards. Conversely, radical innovation may be useful for performance laggards, but may disrupt the current position of performance leaders and lead to reduced sales growth. These results point to the importance for exporters to use their new knowledge and capabilities to develop innovation forms that are consistent with their position in the market.
Considerations for using reproduction data in toxicokinetic–toxicodynamic modeling
Authors: Jager Tjalling , Trijau Marie , Sherborne Neil , Goussen Benoit , Ashauer Roman
Published: June 2021

Toxicokinetic–toxicodynamic (TKTD) modeling is essential to make sense of the time dependence of toxic effects, and to interpret and predict consequences of time-varying exposure. These advantages have been recognized in the regulatory arena, especially for environmental risk assessment of pesticides, where time-varying exposure is the norm. We critically evaluate the link between the modeled variables in TKTD models and the observations from laboratory ecotoxicity tests. For the endpoint reproduction, this link is far from trivial. The relevant TKTD models for sublethal effects are based on dynamic energy budget (DEB) theory, which specifies a continuous investment flux into reproduction. In contrast, experimental tests score egg or offspring release by the mother. The link between model and data is particularly troublesome when a species reproduces in discrete clutches and, even more so, when eggs are incubated in the mother's brood pouch (and release of neonates is scored in the test). This situation is quite common among aquatic invertebrates (e.g., cladocerans, amphipods, mysids), including many popular test species. In this discussion paper, we treat these and other issues with reproduction data, reflect on their potential impact on DEB-TKTD analysis, and provide preliminary recommendations to correct them. Both modelers and users of model results need to be aware of these complications, as ignoring them could easily lead to unnecessary failure of DEB-TKTD models during calibration, or when validating them against independent data for other exposure scenarios. Integr Environ Assess Manag 2022;18:479–487. © 2021 SETAC

KEY POINTS

Toxicokinetic-toxicodynamic (TKTD) models are receiving increasing attention for risk assessment of pesticides; for sublethal effects, these models are based on Dynamic-Energy Budget (DEB) theory. For reproduction, the modeled property (mass investment into reproduction) does not match what is observed in experimental tests (egg or neonate release), requiring auxiliary hypotheses. Ignoring (or incorrect) auxiliary hypotheses has the potential to bias TKTD analyses, and can lead to unnecessary failure of the analysis in a risk-assessment context. We present and discuss these issues in detail, and provide preliminary recommendations to ensure effective application of DEB-based TKTD models.
Prognostic significance of histopathological response to preoperative chemotherapy in unilateral Wilms' tumor: An analysis of 899 patients treated on the SIOP WT 2001 protocol in the UK‐CCLG and GPOH studies
Authors: Vujanić Gordan M. , D'Hooghe Ellen , Graf Norbert , Vokuhl Christian , Al‐Saadi Reem , Chowdhury Tanzina , Pritchard‐Jones Kathy , Furtwängler Rhoikos
Published: June 2021

In the SIOP Wilms' tumor (WT) studies, preoperative chemotherapy is used as primary treatment, and tumors are classified thereafter by pathologists. Completely necrotic WTs (CN‐WTs) are classified as low‐risk tumors. The aim of the study was to evaluate whether a subset of regressive type WTs (RT‐WTs) (67%‐99% chemotherapy‐induced changes [CIC]) showing an exceptionally good response to preoperative chemotherapy had comparably excellent survivals as CN‐WTs, and to establish a cut‐off point of CIC that could define this subset. The study included 2117 patients with unilateral, nonanaplastic WTs from the UK‐CCLG and GPOH‐WT studies (2001‐2020) treated according to the SIOP‐WT‐2001 protocol. There were 126 patients with CN‐WTs and 773 with RT‐WTs, stages I‐IV. RT‐WTs were subdivided into subtotally necrotic WTs (>95% CIC) (STN‐WT96‐99) (124 patients) and the remaining of RT‐WT (RR‐WT67‐95) (649 patients). The 5‐year event‐free survival (EFS) and overall survival (OS) for CN‐WTs were 95.3% (±2.1% SE) and 97.3% (±1.5% SE), and for RT‐WTs 85.7% (±1.14% SE, P < .01) and 95.2% (±0.01% SE, P = .59), respectively. CN‐WT and STN‐WT96‐99 groups showed significantly better EFS than RR‐WT67‐95 (P = .003 and P = .02, respectively), which remained significantly superior when adjusted for age, local stage and metastasis at diagnosis, in multivariate analysis, whereas OS were superimposable (97.3 ± 1.5% SE for CN‐WT; 97.8 ± 1.5% SE for STN‐WT96‐99; 94.7 ± 1.0% SE for RR‐WT67‐95). Patients with STN‐WT96‐99 share the same excellent EFS and OS as patients with CN‐WTs, and although this was achieved by more treatment for patients with STN‐WT96‐99 than for patients with CN‐WT, reduction in postoperative treatment of these patients may be justified.
Evaluating irrigation scheme performance in a tropical environment: The Guanacaste scheme, Costa Rica*
Authors: Benavides Juan , Mateos Luciano , García‐Vila Margarita , Fereres Elías
Published: June 2021

Irrigation is expanding in the tropics and could make an important contribution to the intensification of production in those tropical areas where a dry season limits productivity. A study was carried out to characterize irrigation performance and the yield gaps of a tropical irrigation scheme that covers more than 41 000 ha in northern Costa Rica. The study covered a 5‐year period, from 2014 to 2018. The performance indicator relative irrigation supply (RIS) ranged between 2.48 and 3.78, values higher than those typically observed in schemes of temperate areas, but in the low range of those documented in the tropics. Despite the excess of water usage, it was found that there were farms with water shortages, especially in the canal tails during the dry season, but there was also damage caused by excess of water in the rainy season. The potential yield of the two main crops (rice and sugar cane) was determined with the AquaCrop simulation model. Actual yields were determined via a farmers' survey that also inquired about irrigation management issues. Yield gaps were determined for each of the two sectors that make up the irrigation scheme (South and West canals). The mean yield gap of rice in the South Canal sector (3.34 t ha−1) was smaller than that of the West Canal sector (4.84 t ha−1). The highest yield gap of rice occurred in the rainy season in the West canal sector. The yield gap of sugar cane in the West canal sector was significantly larger than that in the South canal sector (170 and 148 t ha−1, respectively). A farmers' survey, combined with an examination of soil maps, revealed that poor drainage through the heavy soils that predominate in the West canal sector is one of the main causes of the large yield gap, in both rice and sugar cane. While users are relatively satisfied with the provision of irrigation water and its cost, several opportunities (e.g. water delivery, amount of fertilizer in sugar cane, water supply and irrigation system on farms) for improving scheme performance and for closing the yield gaps are discussed.
Validation of a two‐step approach combining serum biomarkers and liver stiffness measurement to predict advanced fibrosis
Authors: Fujii Hideki , Enomoto Masaru , Fukumoto Shinya , Kimura Tatsuo , Nadatani Yuji , Takashima Shingo , Hagihara Atsushi , Uchida‐Kobayashi Sawako , Tamori Akihiro , Nishimoto Naoki , Kawada Norifumi
Published: June 2021

Background and Aim

The Gut and Obesity in Asia Workgroup recently reported that a two‐step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non‐alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low‐risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry.

Methods

This cross‐sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis‐4 score [FIB‐4]) and LSM, alone or in combination.

Results

Of 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first‐step evaluation, only 21.4–38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB‐4 values followed by LSM in all subjects and using LSM after NFS or FIB‐4 determination only in subjects with indeterminate/high NFS or FIB‐4 values (two‐step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB‐4.

Conclusion

The two‐step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives.
A registry study of relapsed or refractory multiple myeloma pre‐exposed to three or more prior therapies including a proteasome inhibitor, an immunomodulatory agent and CD38‐targeted monoclonal antibody therapy in England
Authors: Elsada Ahmed , Zalin‐Miller Amy , Knott Craig , Caravotas Leonidas
Published: June 2021

Some patients with multiple myeloma are receiving treatment in clinical practice in England after prior exposure to a proteasome inhibitor, an immunomodulatory agent, and an anti‐CD38 monoclonal antibody. We investigated the characteristics of these patients, their outcomes, and the salvage therapies they received using the national cancer registry for England and linked healthcare data. After a median follow‐up time of 6.4 months from T0, median overall survival and time to next treatment were 8.2 and 5.3 months, respectively. This real‐world data provide useful clinical insight into a little‐studied patient population and highlight the poor outcomes in the UK setting.
Prospective multicenter evaluation of moving cell metallic stents in endoscopic multiple stent deployment for hepatic hilar obstruction
Authors: Kawai Junichi , Ogura Takeshi , Takenaka Mamoru , Shiomi Hideyuki , Ueshima Kazuya , Ueno Saori , Okuda Atsushi , Matsuno Jun , Minaga Kousuke , Omoto Shunsuke , Nakai Atsushi , Ikegawa Takuya , Hakoda Akitoshi , Higuchi Kazuhide
Published: June 2021

Background and Aim

Bilateral stent deployment for malignant biliary obstruction (MHBO) can be achieved using side‐by‐side (SBS) or stent‐in‐stent (SIS) procedures. Compared with SBS techniques, the procedural steps of SIS are technically complex due to the necessity of introducing the delivery system into a contralateral biliary tract through the mesh of the SEMS. To overcome this issue, a novel uncovered SEMS, the HILZO Moving Cell Stent (MCS) has been released. The present study examined the technical feasibility of treating MHBO using bilateral deployment of this novel stent without dilating the mesh of the first stent to achieve insertion of the second stent within a single session, using a prospective, multicenter setting.

Method

The primary outcome in the present study was the technical success rate. Technical success was defined as deployment of bilateral MCSs into two or more biliary tracts using SIS without a dilation device in a single‐session.

Results

A total of 27 patients with complications of MHBO were enrolled in this study. Bilateral SIS using two MCS was successfully performed in 23 patients without using dilation devices among 27 patients (initial technical success rate; 85.2%). Median time to recurrent biliary obstruction (TRBO) was 271 days. Stent dysfunction was observed in 12 patients (44.4%), and re‐intervention was successfully performed in all patients without one patient who instead received best supportive care.

Conclusions

The SIS technique using MCS without dilation of the mesh may be technically feasible and safe. In addition, this may be useful for re‐intervention. Further comparative randomized trials are needed.
Anatomical patterns of biliary atresia including hepatic radicles at the porta hepatis influence short‐ and long‐term prognoses
Authors: Sasaki Hideyuki , Nio Masaki , Ando Hisami , Kitagawa Hiroaki , Kubota Masayuki , Suzuki Tatsuya , Taguchi Tomoaki , Hashimoto Takashi ,   The Japanese Biliary Atresia Society
Published: June 2021

Background/Purpose

The biliary atresia (BA) inflammatory process leads to various obstructive patterns of extrahepatic biliary trees. The significance of the various BA obstructive patterns is unclear. This study aimed to determine the relationship between the anatomical patterns of the biliary tract and short‐ and long‐term prognoses in BA.

Methods

Between 1989 and 2018, 3483 patients were registered in the Japanese Biliary Atresia Registry. For this study, we selected 2649 patients who underwent Kasai portoenterostomy (KP) between the ages of 31 and 90 days to eliminate the influence of age at KP as much as possible.

Results

Regarding the main type, there were significant differences in the jaundice clearance rate (JCR; Type I: 67.9%, Type I‐cyst: 79.4%, Type II: 74.5%, Type III: 60.9%; P < .0001) and the native liver survival rate (NLSR; P < .0001). In subgroups with hepatic radicles in Types I, II, and I‐cyst, there was a significant difference in JCR (P = .0004) and NLSR (P = .0026). In subgroups with hepatic radicles in Type III, there was a significant difference in JCR (P = .0148) and NLSR (P = .0421).

Conclusions

Anatomical patterns of obstruction influenced short‐ and long‐term prognoses in BA. These patterns were suggested to be prognostic factors following KP.
A five biases, three layers graphene basedTHzabsorber: Exploiting dual bias periodic arrays of grapheme ribbons
Authors: Cyrus Sindokht , Ghahramany Masood
Published: June 2021

Wave absorbers are considered main operational block for light manipulation. Numerous optical and electromagnetic systems can be realized via wave absorbers such as wave modulators, filters, and detectors. Here in this work, a highly tunable wave absorber is proposed, which includes three layers of grapheme patterns on dielectric. While whole device is placed on top of a relatively thick metallic reflector. Leveraging dual bias scheme for periodic arrays of grapheme ribbons and exploiting impedance matching concept give the opportunity to adjust absorption response via external bias voltages. All consisting parts of the device are modeled by passive circuit elements include resistor, inductor, and capacitor. Compared to conventional methods of full wave numerical modeling like finite element methods, the presented design methodology requires less CPU time and occupied memory. According to the simulation results, proposed wave absorber shows a multi‐band absorption with four peaks, which make it perfect choice for several application from medical imaging to indoor communication.
Plasma high‐resolution metabolomic phenotyping of lean mass in a United States adult cohort
Authors: Bellissimo Moriah P. , Jones Dean P. , Martin Greg S. , Alvarez Jessica A. , Ziegler Thomas R.
Published: June 2021

Background

Rapid loss of lean mass during catabolic states is associated with impaired convalescence and increased mortality rates. An understanding of metabolic pathways related to lean mass is needed to enable future interventions designed to combat malnutrition. This study assessed the plasma metabolome in relation to lean mass in clinically stable working adults in a US cohort.

Methods

This cross‐sectional study included 180 adults (mean ± SD, aged 49.7 ± 10.0 years; body mass index, 27.3 ± 5.5 kg/m2; 64% female [n=116]). Fasting plasma was analyzed using high‐resolution metabolomics (HRM) via liquid chromatography/mass spectrometry. Lean mass was assessed by dual‐energy x‐ray absorptiometry and expressed as lean mass index (LMI, lean mass kg/height m2). Multiple linear regression, metabolic pathway enrichment, and module analyses were used to characterize systemic metabolism associated with LMI.

Results

Of 5360 metabolites used in analyses, 593 were related to LMI, either upregulated or downregulated (P< .05). These were enriched within 11 metabolic pathways, including branched‐chain amino acid degradation, metabolism of alanine and aspartate and other amino acids, butyrate, purines, and niacin metabolism. Module analysis revealed central associations between LMI and L‐glutamate, L‐leucine/L‐isoleucine, L‐valine, L‐phenylalanine, L‐methionine, and L‐aspartate, among other validated metabolites.

Conclusion

These novel plasma HRM data demonstrate the wide‐reaching associations of lean mass with systemic metabolism in a single snapshot. Such data may inform targeted nutrition support interventions designed to mitigate loss of lean mass and promote regaining skeletal muscle mass and function after illness or injury.