bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet Activating Factor (PAF): A Mediator of Inflammation
Authors: Upton Julia E. M. , Grunebaum Eyal , Sussman Gordon , Vadas Peter
Published: August 2022

Platelet‐activating factor (PAF) is a phospholipid‐derived mediator with an established role in multiple inflammatory states. PAF is synthesized and secreted by multiple cell types and is then rapidly hydrolyzed and degraded to an inactive metabolite, lyso‐PAF, by the enzyme PAF acetylhydrolase. In addition to its role in platelet aggregation and activation, PAF contributes to allergic and nonallergic inflammatory diseases such as anaphylaxis, sepsis, cardiovascular disease, neurological disease, and malignancy as demonstrated in multiple animal models and, increasingly, in human disease states. Recent research has demonstrated the importance of the PAF pathway in multiple conditions including the prediction of severe pediatric anaphylaxis, effects on blood–brain barrier permeability, effects on reproduction, ocular diseases, and further understanding of its role in cardiovascular risk. Investigation of PAF as both a biomarker and a therapeutic target continues because of the need for directed management of inflammation. Collectively, studies have shown that therapies focused on the PAF pathway have the potential to provide targeted and effective treatments for multiple inflammatory conditions.
Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy
Authors: Feng Hao , Qiu Ling , Shi Zixiao , Sheng Yao , Zhao Peipei , Zhou Di , Li Fei , Yu Hailin , You Yanan , Wang Hui , Li Ming , Zhu Shurong , Du Yan , Cui Jun , Sun Jingwei , Liu Yarong , Jiang Hua , Wu Xin
Published: August 2022

Introduction

Adoptive cellular therapy with tumor‐infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the “prone‐to‐exhaustion” phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti‐tumor function and memory phenotype. Previous studies showed that the PI3K‐AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation.

Method

We modulated the PI3K‐AKT pathway in TIL isolated from cervical and ovarian cancer by application of AKT or PI3K inhibitors or CRISPR knockout of AKT1 and/or AKT2, and characterized their effects on TIL phenotype and effector function. Mechanistic study was further performed with RNA‐seq analysis of AKT1/2 KO TIL in comparison to control TIL.

Result

The inhibition of either PI3K or AKT led to an increase in the population of effector CD8+ T cells with upregulation of activation markers, elevated CD39−CD69− memory T cells, and significantly enhanced cytotoxicity when cocultured with tumor cell lines and patient‐derived tumor samples. Moreover, dual knockout of AKT1 and AKT2 largely phenocopies the functional impact of AKT or PI3K inhibition on TIL. This result was further validated by RNA‐seq analysis indicating that AKT1/2 ablation primarily regulates T cell differentiation and function‐related programs.

Conclusion

Modulation of PI3K‐AKT signaling represents a promising strategy to enhance TIL stemness and cytotoxicity and improve the clinical outcome of current TIL‐based therapy to treat solid tumors.
Prediction of presurgical metabolic syndrome for gastric cancer‐specific mortality is more evident in smokers: The FIESTA study
Authors: Zhang Xinran , Hu Dan , Deng Xiangling , Lin Jinxiu , Zheng Xiongwei , Peng Feng , Meng Fanqiang , Niu Wenquan
Published: August 2022

Backgrounds

We aimed to test whether the prediction of presurgical metabolic syndrome for postsurgical survival outcomes of gastric cancer hinges upon cigarette smoking status.

Methods

This study is a part of the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients with gastric cancer received radical resection of primary gastric cancer between January 2000 and December 2010, with the latest follow‐up ended in December 2015. The 1:1 propensity score matching analysis was adopted to balance confounders between smokers and never‐smokers. Effect‐size estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). Model performance was evaluated using the Hosmer and Lemeshow test and 10‐fold cross‐validated area under the receiver operating characteristic curve (AUROC). Statistical analyses were completed with SAS software (v9.4).

Results

Total 2779 patients with gastric cancer were analyzed, including 2223 smokers and 556 never‐smokers. Median follow‐up time was 45.6 months. Cigarette smoking was not associated with postsurgical survival differences. Presurgical metabolic syndrome complication was significantly associated with increased gastric cancer‐specific mortality in smokers (HR [95% CI]: 2.73 [1.53–4.89], p < 0.001), but not in never‐smokers. Relative excess risk due to interaction was estimated to be 2.43 (95% CI: 0.40–4.45). After constructing a risk assessment score, one unit increment was associated with 10% reduced risk of gastric cancer‐specific mortality (HR [95% CI]: 0.90 [0.88–0.91], p < 0.001), with 10‐fold cross‐validated AUROC being 0.82 (95% CI: 0.74–0.92).

Conclusions

Our findings showed that the prediction of presurgical metabolic syndrome for gastric cancer‐specific mortality was more evident in smokers. Practically, this study provides evidence base for future personalized prediction and helped risk‐stratify gastric cancer patients who might experience serious postsurgical consequences.
Suicide risk following a new cancer diagnosis among Veterans in Veterans Health Administration care
Authors: Dent Kallisse R. , Szymanski Benjamin R. , Kelley Michael J. , Katz Ira R. , McCarthy John F.
Published: August 2022

Background

Cancer diagnoses are associated with an increased risk for suicide. The aim of this study was to evaluate this association among Veterans receiving Veterans Health Administration (VHA) care, a population that has an especially high suicide risk.

Methods

Among 4,926,373 Veterans with VHA use in 2011 and in 2012 or 2013, and without VHA cancer diagnoses in 2011, we assessed suicide risk following incident cancer diagnoses. Risk time was from initial VHA use in 2012–2013 to 12/31/2018 or death, whichever came first. Cox proportional hazards regression models evaluated associations between new cancer diagnoses and suicide risk, adjusting for age, sex, VHA regional network, and mental health comorbidities. Suicide rates were calculated among Veterans with new cancer diagnoses through 84 months following diagnosis.

Results

A new cancer diagnosis corresponded to a 47% higher suicide risk (Adjusted Hazard Ratio [aHR] = 1.47, 95% CI: 1.33–1.63). The cancer subtype associated with the highest suicide risk was esophageal cancer (aHR = 6.01, 95% CI: 3.73–9.68), and other significant subtypes included head and neck (aHR = 3.55, 95% CI: 2.74–4.62) and lung cancer (aHR = 2.35, 95% CI: 1.85–3.00). Cancer stages 3 (aHR = 2.36, 95% CI: 1.80–3.11) and 4 (aHR = 3.53, 95% CI: 2.81–4.43) at diagnosis were positively associated with suicide risk. Suicide rates were highest within 3 months following diagnosis and remained elevated in the 3–6‐ and 6–12‐month periods following diagnosis.

Conclusion

Among Veteran VHA users, suicide risk was elevated following new cancer diagnoses. Risk was particularly high in the first 3 months. Additional screening and suicide prevention efforts may be warranted for VHA Veterans newly diagnosed with cancer.
Pylorus‐preserving versus Pylorus‐resecting: Impact on dynamic changes of nutrition and body composition in pancreatic cancer patients before and after pancreatoduodenectomy
Authors: Jin Qianna , Ren Qianqian , Chang Xiaona , Lu Xiaoming , Wang Guobin , He Nan
Published: August 2022

Objectives

To investigate if different methods of pancreatoduodenectomy (with or without pyloric preservation) would have different impacts on postoperative nutrition and body composition changes among pancreatic cancer patients.

Methods

Demographic and clinicopathological data, perioperative data were collected, body composition (e.g. skeletal muscle cross‐sectional area [CSA], visceral fat area [VFA]) were evaluated with abdominal CT before and after surgery. Sarcopenia patients' proportion changes were also recorded.

Results

The hospital stay in the PRPD group was significantly less than that in the PPPD group (p < 0.05). A significant difference was found in CSA, skeletal muscle index (SMI), VFA, VFA/CSA and albumin (ALB) in both groups between preoperative, 3, and 12 months after surgery. The loss of visceral fat in the PRPD group was more prominent than that in the PPPD group at 3 months and 12 months after surgery (p < 0.05). VFA/CSA was higher in the PPPD group than in the PRPD group (3 months: p < 0.05, 12 months: p < 0.001). The proportion of sarcopenic patients increased significantly over time in the PPPD and PRPD groups (p < 0.001).

Conclusions

Postoperative CSA and VFA continued to significantly decrease in both PPPD and PRPD groups, while the incidence of sarcopenia continued to increase. Compared with PRPD, PPPD has a protective effect on visceral fat. PPPD may contribute to better maintaining visceral fat mass and blood ALB levels. CT quantification can be an objective and effective method to evaluate the nutritional status of pancreatic cancer patients during the pre‐ and postoperative period and can provide a useful objective basis for guiding clinical treatment.
Coumarins from Sarcandra glabra (Thunb.) Nakai and Acetylcholinesterase Inhibiting Activity
Authors: Du Ning‐Ning , Bai Ming , Zhang Xin , Zhou Le , Huang Xiao‐Xiao , Song Shao‐Jiang
Published: August 2022

Nine coumarins including a pair of new enantiomers (1a/1b) and seven known compounds (2–8) were isolated from Sarcandra glabra (Thunb.) Nakai. Among them, compounds 1a and 1b were naturally occurring coumarin‐phenylpropanoid conjugate enantiomers. Their structures were identified by NMR and ECD calculations. Compounds 1–8 were tested for acetylcholinesterase (AchE) inhibiting activity. The results of the enzymology experiment showed that compound 3 demonstrated obvious AchE inhibitory activity which showed the IC50 value of 1.982±0.003 μM, and the binding sites were predicted by molecular docking.
3D‐atlas of the brain of the cockroach Rhyparobia maderae
Authors: Althaus Vanessa , Jahn Stefanie , Massah Azar , Stengl Monika , Homberg Uwe
Published: August 2022

The Madeira cockroach Rhyparobia maderae is a nocturnal insect and a prominent model organism for the study of circadian rhythms. Its master circadian clock, controlling circadian locomotor activity and sleep–wake cycles, is located in the accessory medulla of the optic lobe. For a better understanding of brain regions controlled by the circadian clock and brain organization of this insect in general, we created a three‐dimensional (3D) reconstruction of all neuropils of the cerebral ganglia based on anti‐synapsin and anti‐γ‐aminobutyric acid immunolabeling of whole mount brains. Forty‐nine major neuropils were identified and three‐dimensionally reconstructed. Single‐cell dye fills complement the data and provide evidence for distinct subdivisions of certain brain areas. Most neuropils defined in the fruit fly Drosophila melanogaster could be distinguished in the cockroach as well. However, some neuropils identified in the fruit fly do not exist as distinct entities in the cockroach while others are lacking in the fruit fly. In addition to neuropils, major fiber systems, tracts, and commissures were reconstructed and served as important landmarks separating brain areas. Being a nocturnal insect, R. maderae is an important new species to the growing collection of 3D insect brain atlases and only the second hemimetabolous insect, for which a detailed 3D brain atlas is available. This atlas will be highly valuable for an evolutionary comparison of insect brain organization and will greatly facilitate addressing brain areas that are supervised by the circadian clock.
Application of cellulose‐based hydrogel electrolytes in flexible batteries
Authors: Liu Zixiang , Wang Rui , Ma Quanwei , Kang Hongwei , Zhang Longhai , Zhou Tengfei , Zhang Chaofeng
Published: August 2022

Flexible energy storage devices have the advantages of portability and safety, and have great potential for developing electronic materials in the future. In flexible batteries, the electrolyte presents an essential role in the electrochemical performance and safety of the batteries. Hydrogel electrolyte materials are considered to be one of the ideal electrolyte materials due to their environmental friendliness, high safety, maneuverability, and innocuity. However, ordinary hydrogels often suffer some defects, such as insufficient ductility and poor water retention. Currently, many researchers report cellulose materials as reinforcing agents to improve the performance of hydrogels. In this paper, we review the recent application of cellulose in hydrogel‐based materials for energy storage technology and summarize the functions and properties of cellulose. In addition, we analyze the shortcomings of cellulose used in hydrogels and briefly describe the prospects of cellulose materials, hoping to contribute to the research in this field.
Advances in cutting‐edge electrode engineering toward CO2 electrolysis at high current density and selectivity: A mini‐review
Authors: Tang Jiayi , Weiss Ellen , Shao Zongping
Published: August 2022

Electrochemical CO2 conversion has been raised as a promising solution for building a carbon‐neutral economy under today's circumstances of increasing energy shortages and air pollution from human activities. Research on electrochemical CO2 reduction reaction (CO2RR) is gradually entering a pilot‐scale stage. The use of device‐level CO2 electrolysis in the production of value‐added chemicals and fuels at a high production rate and selectivity is highly required to make the technology economical and sustainable. With more exploration toward device‐level performance optimization, it gradually becomes clear that electrode engineering on structures, surface properties, active site distribution, and density, as well as the electrode–electrolyte interface, is more critical than the intrinsic activity of catalytic sites. Taking this into account, this review focuses on interpreting the design principles in aspects with the aim of enhancing the CO2RR toward a specific product yield and production rate. This mini‐review summarizes the advances in this dynamic field in the most recent 5 years, including the fabrication of porous gas diffusion electrodes, and self‐supporting electrodes, establishment of tandem or cascade electrode function, as well as tuning of interfacial cation buffering and wettability, and analyze the trends in the future scientific and technological development of device‐level CO2 electrolysis. Hopefully, this mini‐review could provide some insights into the opportunities in the next‐generation electrode design for the industrial carbon cycle.
Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton‐Pump Inhibitors
Authors: Sharma Shringi , Pepin Xavier , Burri Harini , Zheng Lianqing , Kuptsova‐Clarkson Nataliya , de Jong Anouk , Yu Ting , MacArthur Holly L. , Majewski Michal , Byrd John C. , Furman Richard R. , Ware Joseph A. , Mann James , Ramies David , Munugalavadla Veerendra , Sheridan Louise , Tomkinson Helen
Published: August 2022

Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or previously treated mantle cell lymphoma. As the bioavailability of the acalabrutinib capsule (AC) depends on gastric pH for solubility and is impaired by acid‐suppressing therapies, coadministration with proton‐pump inhibitors (PPIs) is not recommended. Three studies in healthy subjects (N = 30, N = 66, N = 20) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of acalabrutinib maleate tablet (AT) formulated with pH‐independent release. Subjects were administered AT or AC (orally, fasted state), AT in a fed state, or AT in the presence of a PPI, and AT or AC via nasogastric (NG) route. Acalabrutinib exposures (geometric mean [% coefficient of variation, CV]) were comparable for AT versus AC (AUCinf 567.8 ng h/mL [36.9] vs 572.2 ng h/mL [38.2], Cmax 537.2 ng/mL [42.6] vs 535.7 ng/mL [58.4], respectively); similar results were observed for acalabrutinib's active metabolite (ACP‐5862) and for AT‐NG versus AC‐NG. The geometric mean Cmax for acalabrutinib was lower when AT was administered in the fed versus the fasted state (Cmax 255.6 ng/mL [%CV, 46.5] vs 504.9 ng/mL [49.9]); AUCs were similar. For AT + PPI, geometric mean Cmax was lower (371.9 ng/mL [%CV, 81.4] vs 504.9 ng/mL [49.9]) and AUCinf was higher (AUCinf 694.1 ng h/mL [39.7] vs 559.5 ng h/mL [34.6]) than AT alone. AT and AC were similar in BTK occupancy. Most adverse events were mild with no new safety concerns. Acalabrutinib formulations were comparable and AT could be coadministered with PPIs, food, or via NG tube without affecting the PKs or PDs.
Hitting the Bull's Eye: Stable HeBeOH+Complex
Authors: Yun Gai‐ru , Li Hai‐xia , Cabellos Jose Luis , Tiznado William , Cui Zhong‐hua , Pan Sudip
Published: August 2022

It is now known that the heavier noble gases (Ng=Ar‐Rn) show some varying degrees of reactivity with a gradual increase in reactivity along Ar−Rn. However, because of their very small size and very high ionization potential, helium and neon are the hardest targets to crack. Although few neon complexes are isolated at very low temperatures, helium needs very extreme situations like very high pressure. Here, we find that protonated BeO, BeOH+can bind helium and neon spontaneously at room temperature. Therefore, extreme conditions like very low temperature and/or high pressure will not be required for their experimental isolation. The Ng−Be bond strength is very high for their heavier homologs and the bond strength shows a gradual increase from He to Rn. Moreover, the Ng−Be attractive energy is almost exclusively originated from the orbital interaction which is composed of one Ng(s/pσ)→BeOH+σ‐donation and two weaker Ng(pπ)→BeOH+π‐donations, except for helium. Helium uses its low‐lying vacant 2p orbitals to accept π‐electron density from BeOH+. Previously, such electron‐accepting ability of helium was used to explain a somewhat stronger helium bond than neon for neutral complexes. However, the present results indicate that such π‐back donations are too weak in nature to decide any energetic trend between helium and neon.
Assessment and aesthetic impact of a long‐term vertical discrepancy between the single anterior maxillary implant‐supported crown and adjacent teeth: A retrospective cross‐sectional study
Authors: Sauvin Grégoire , Nurdin Nathalie , Bischof Mark , Kiliaridis Stavros
Published: August 2022

Objectives

To assess the vertical discrepancy between implant‐supported crowns and adjacent teeth in the maxillary anterior region at least 8 years after implant placement and to evaluate the influence of this discrepancy on the level of aesthetic awareness of patients.

Material and Methods

The sample consisted of 23 adult individuals evaluated at least 8 years after placement of an implant‐supported central or lateral single tooth‐fixed partial denture. Patients had their crowns delivered at a mean age of 47.8 years (range: 18.9–65.8). The vertical discrepancy was measured by comparing initial and follow‐up periapical radiographs using the implant as a stable structure. The patients' satisfaction with their anterior teeth condition and awareness of the possible vertical problem were evaluated using a questionnaire. The aesthetic outcome and patient awareness were related to the objective measurement of the vertical discrepancy.

Results

The implant showed a mean infraocclusion of 0.62 mm (range: 0.15–1.63 mm). The vertical discrepancy was not associated with the patient's gender, age at implant placement, and duration between initial and recall radiograph. Patients were generally satisfied with the long‐term aesthetic outcome of their smile (mean: 3.9 on a 1–5 scale, 1 unsatisfied, and 5 completely satisfied). Out of 23 patients, 8 noticed the implant infraocclusion and 4 of them found the problem severe enough to be willing to improve the situation. The amount of vertical discrepancy was not associated with the patient's perception of the discrepancy and the pink aesthetic score.

Conclusion

Implant‐supported crowns in the anterior region may suffer infraocclusion over the long term. The amount of vertical discrepancy was not dependent on the gender and age of the patient. Patients were generally satisfied with the aesthetic result of the restoration. The amount of vertical discrepancy, at least in the range we have measured, was not perceived by the patients as a complication.
Sustainable business models of small and medium‐sized enterprises and the relationships to be established within the supply chain to support these models
Authors: Macchion Laura , Toscani Antonio Cavallin , Vinelli Andrea
Published: August 2022

Nowadays sustainability plays a crucial role in both academia and industry, and new insights are required to answer many open questions on the topic. This study focuses on sustainable business models (SBMs) by adopting a supply chain perspective to identify the value of sustainability practices along the supply chain for different SBMs. In particular, the research investigates four small and medium‐sized enterprises (SME) case studies that have been able to implement new SBMs wisely integrating the concept of sustainability with their supply chain partners. First, the results confirm that SBMs need to be supported by strong alignment with sustainability practices within the entire supply chain to be successfully implemented. Secondly, the application of the proper practices of selection, monitoring, collaboration, and integration among supply chain partners within various SBMs is the key to achieving sustainability objectives. The paper, therefore, contributes to the debate by bringing new evidence to the SBMs topic, investigating how the success of these models is possible only through a precise definition of the relationships to be established in the supply chain.
Fine needle aspiration cytology of the primitive myxoid mesenchymal tumor of infancy
Authors: Rajasekaran Sangamitra , Kundu Reetu , Dey Pranab
Published: August 2022

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a recently described entity, previously included under the umbrella of undifferentiated sarcomas. These tumors are notorious for recurrence, chemoresistance and may even metastasize. We describe here, for the first time, the cytomorphology of PMMTI. Further, we discuss the morphological differentials and relevant immunocytochemical markers to reach a correct diagnosis. Knowledge about the distinctive cytomorphological features with characteristic immunocytochemistry is the key to the challenging diagnosis of PMMTI. Establishing the diagnosis on cytology is not difficult in cases of recurrence when such a history is forthcoming. These tumors are a rarity, and awareness of cytomorphology and employment of ancillary techniques is diagnostic, guiding the appropriate therapeutic management.
Cystic hepatic metastases in treatment naïve neuroendocrine tumor: Cytomorphology clubbed with cell block immunocytochemistry clinches the diagnosis
Authors: Shastri Malvika , Kundu Reetu , Krishnaraju Venkata Subramanian , Bhujade Harish , Bhandari Rajan Mani , Sood Ashwani
Published: August 2022

Cystic hepatic lesions encompass a vast spectrum of infectious, non‐neoplastic, and neoplastic entities. Most hepatic cysts are benign and asymptomatic, requiring no active intervention. However, symptomatic and malignant cysts need proper evaluation and specific treatment. An accurate preoperative diagnosis is pivotal for patient management. At times, these lesions may mimic, especially symptomatology and radiology, leading to a diagnostic ordeal. We herein present a case of a patient with cystic liver lesions in a treatment naïve neuroendocrine tumor that was a diagnostic dilemma on radiology. Low cellularity of cytology smears made the diagnosis challenging, and cell block immunocytochemistry finally clinched the diagnosis. A timely diagnosis provided on cytology fuelled further work‐up, the discovery of primary tumor, and initiation of appropriate therapy.
Eating Disorder Examination–Questionnaire and Clinical Impairment Assessment norms for intersectional identities using an MTurk sample
Authors: Kambanis P. Evelyna , Bottera Angeline R. , Mancuso Christopher J. , Spoor Samantha P. , Anderson Lisa M. , Burke Natasha L. , Eddy Kamryn T. , Forbush Kelsie T. , Keith Jill F. , Lavender Jason M. , Mensinger Janell L. , Mujica Christin , Nagata Jason M. , Perez Marisol , De Young Kyle P.
Published: August 2022

Objective

There are limited data to guide the interpretation of scores on measures of eating‐disorder psychopathology among underrepresented individuals. We aimed to provide norms for the Eating Disorder Examination–Questionnaire (EDE‐Q) and Clinical Impairment Assessment (CIA) across racial/ethnic, gender, and sexual identities, and sexual orientations and their intersections by recruiting a diverse sample of Amazon MTurk workers (MTurkers; N = 1782).

Method

We created a comprehensive, quantitative assessment of racial/ethnic identification, gender identification, sex assigned at birth, current sexual identification, and sexual orientation called the Demographic Assessment of Racial, Sexual, and Gender Identities (DARSGI). We calculated normative data for each demographic category response option.

Results

Our sample was comprised of 68% underrepresented racial/ethnic identities, 42% underrepresented gender identities, 13% underrepresented sexes, and 49% underrepresented sexual orientations. We reported means and standard deviations for each demographic category response option and, where possible, mean estimates by percentile across intersectional groups. EDE‐Q Global Score for a subset of identities and intersections in the current study were higher than previously reported norms for those identities/intersections.

Discussion

This is the most thorough reporting of norms for the EDE‐Q and CIA among racial/ethnic, sexual, and gender identities, and sexual orientations and the first reporting on multiple intersections, filling some of the gaps for commonly used measures of eating‐disorder psychopathology. These norms may be used to contextualize eating‐disorder psychopathology reported by underrepresented individuals. The data from the current study may help inform research on the prevention and treatment of eating‐disorder psychopathology in underrepresented groups.

Public Significance

We provide the most thorough reporting on racial/ethnic, sexual, and gender identities, and sexual orientations for the Eating Disorder Examination – Questionnaire and Clinical Impairment Assessment, and the first reporting on intersections, which fills some of the gaps for commonly used measures of eating‐disorder psychopathology. These norms help inform research on the prevention and treatment of eating‐disorder psychopathology in underrepresented groups.
Boosting High‐Voltage Dynamics Towards High‐Energy‐Density Lithium‐Ion Capacitors
Authors: Huang Junfeng , Lu Xin , Sun Teng , Yu Daiyao , Xu Zhong , Xie Yanting , Jiang Xinglin , Wang Yongbin , Wang Shenglong , Zhang Xiong , Yang Weiqing , Zhang Haitao
Published: August 2022

Lithium‐ion capacitors (LICs) are becoming important electrochemical energy storage systems due to their great potential to bridge the gap between supercapacitors and lithium‐ion batteries. However, capacity lopsidedness and low output voltage greatly hinder the realization of high‐energy‐density LICs. Herein, a strategy of balancing capacity towards fastest dynamics is proposed to enable high‐voltage LICs. Through electrochemical prelithiation of Nb2C to be 1.1 V with 165 mAh g−1, Nb2C // LiFePO4 LICs show a broadened potential window from 3.0 to 4.2 V and an according high energy density of 420 Wh kg−1. Moreover, the underlying mechanism between prelithiation and high voltage is disclosed by electrochemical dynamic analysis. Prelithiation declines the Nb2C anode potential that facilitates electron transmission in the interlayer of two‐dimensional Nb2C MXene. This effect induces small drive force for Li+ ions deposition and hence weakens the repulsive force from adsorbed ions on the electrode surface. Benefiting from even more Li+ ions deposition, a higher voltage is eventually delivered. In addition, prelithiation significantly increases Coulomb efficiency of the 1st cycle from 74% to 90%, which is crucial to commercial application of LICs.
Performance evaluation of a new prognostic‐efficacy‐combination design in the context of telemedical interventions
Authors: Pigorsch Mareen , Möckel Martin , Gehrig Stefan , Wiemer Jan C. , Koehler Friedrich , Rauch Geraldine
Published: August 2022

Aims

Telemedical interventions in heart failure patients intend to avoid unfavourable, indication‐related events by an early, individualized care, which reacts to the current patients need. However, telemedical support is an expensive intervention, and usually only patients with high risk for unfavourable follow‐up events will be able to profit from it. Möckel et al. therefore adapted a new design which we call ‘prognostic‐efficacy‐combination design’. This design allows to define a biomarker cut‐off and to perform a randomized controlled trial (RCT) in a biomarker‐selected population within a single study. However, so far, it has not been evaluated if this double use of the control group for biomarker cut‐off definition and efficacy assessment within the RCT leads to a bias in treatment effect estimation. In this methodological research work, we therefore want to evaluate whether the ‘prognostic‐efficacy‐combination design’ leads to biased treatment effect estimates and also compare it to alternative designs. If there is a bias, we further want to analyse its magnitude under different parameter settings.

Methods

We perform a systematic Monte Carlo simulation study to investigate among others potential bias, root mean square error and sensitivity, and specificity as well as the total treatment effect estimate in various realistic trial scenarios that mimic and vary the true data characteristics of the published TIM‐HF2 Trial. In particular, we vary the event proportion, the sample size, the biomarker distribution, and the lower bound for the sensitivity.

Results

The results show that indeed the proposed design leads to some bias in the effect estimators, indicating an overestimation of the effect. However, this bias is relatively small in most scenarios.

Conclusions

The ‘prognostic‐efficacy‐combination design’ can generally be recommended for clinical applications due to its efficiency compared to two separate trials. We recommend a sufficiently large sample size depending on the trial scenario. Our simulation code can be adapted to explore suitable sample sizes for other settings.
Evaluation of In Vitro Skin Permeation of Enzymatically Synthesized Phloridzin Acetates from Emulsions and Liposomes Dispersed in Gel
Authors: Milivojević Ana , Ćorović Marija , Simović Milica , Banjanac Katarina , Pjanović Rada , Bezbradica Dejan
Published: August 2022

This work aims to evaluate the effect of cosmetic formulations on the skin permeation of phloridzin acetates, therefore in vitro transdermal delivery of these bioactive compounds across Strat‐M membrane is investigated. The formulations tested are gel emulsion, oil in water emulsion (O/W emulsion), gel in oil emulsion, liquid crystal emulsion, and liposomes dispersed in gel. The release of esters from the O/W emulsion is diffusion‐controlled (n = 0.5), while release kinetics from gel‐based formulations depends on coupled diffusion and polymer relaxations effect (0.5 < n < 1). The highest values of effective diffusion coefficient are obtained after release from O/W emulsion (24.64 × 10−10 m2 min−1 for phloridzin acetate and 6.55 × 10−10 m2 min−1 for phloridzin diacetate). The lag phase lasting from 1 h (gel emulsion) to 5 h (liquid crystal emulsion) indicates that esters permeation is significantly affected by the formulation used. Formulations in which the water is continuous phase are the most appropriate carrier system for transdermal delivery of phloridzin esters. Additionally, liposomes are successfully applied as carrier systems for the controlled release of esters, although it should be noted that liposomes without cholesterol show remarkable stability (ζ = −43 mV) and homogeneity (polydispersity index = 0.198).

Practical application: Phloridzin is a flavonoid glycoside that possesses many beneficial activities such as antioxidant, UV‐protecting, and anti‐inflammatory activity, so the use of this flavonoid and its derivatives in numerous cosmetic and pharmaceutical formulations seems very attractive. Results obtained in this study give a comprehensive insight into the release mechanism of phloridzin acetates from emulsions and liposomes, enable the selection of optimum cosmetic formulations depending on the application, and provide significant scientific contribution in the field of topical administration of bioactive flavonoid derivatives.
Achieving High‐Performance Oxygen Reduction Catalyst and Zn–Air Battery through a Synergistic Nitrogen Doping Strategy
Authors: Zhu Xiaoran , Zhang Jianze , Wang Yan , Yang Mingsheng , Yu Haiping , Li Tengfei , Hu Mingjun , Yang Jun
Published: August 2022

It remains a challenge to achieve high‐performance, low‐cost, and robustly durable Fe, N co‐doped carbon‐based oxygen reduction reaction (ORR) catalysts with abundantly accessible Fe–NX sites. Herein, a novel scheme is designed to enrich the pore structure, increase the specific surface area, and generate spatially isolated Fe–NX sites of the ORR catalyst, in which pyridine nitrogen‐rich lamellar metal–organic complex (Fe–tetrapyridophenazine) is employed as the precursor and 2D graphitic carbon nitride (g‐C3N4) as additional nitrogen source for achieving synergistic nitrogen‐doping effect. The introduction of g‐C3N4 not only ameliorates the nitrogen coordination environment of metal active centers of the composite, but also increases the specific surface area and improves the pore structure. The resultant Fe–NC&CN composite has abundant active sites as well as remarkable electrical conductivity and suitable pore size for electron transfer and reactant diffusion. As expected, the catalyst exhibits excellent ORR activity, driving the reaction with low overpotential (E1/2 = 0.879 V) and remaining stable over a long reaction time (93% for 60 000 s), better than commercial Pt/C (20%) in all aspects. The assembled Zn–air battery exhibits high open‐circuit voltage of 1.566 V and high specific capacity of 815 mAh gZn−1, as well as stable and persistent discharge performance.
Seismic evaluation of friction spring‐based self‐centering braced frames based on life‐cycle cost
Authors: Zhang Ruibin , Wang Wei , Alam M. Shahria
Published: August 2022

In recent decades, a variety of self‐centering braces (SCBs) have been developed to address the limitations of conventional frames by decreasing residual drift due to earthquakes. However, the initial construction cost of self‐centering (SC) structures is expected to be higher and the study about its cost‐effectiveness over the life‐cycle span is limited. This paper presents a seismic life‐cycle cost evaluation of emerging friction spring‐based self‐centering braced frames (SCB‐Fs) compared with traditional buckling restrained braced frames (BRB‐Fs) when an existing structure is upgraded. Particular focus is on the effect of residual deformation, initial construction cost, and high fatigue performance of the SCB. Following the performance‐based design of the SCB‐F and BRB‐F, system‐level analyses are conducted. Numerical results of case‐study buildings indicate that the total expected annual loss (EAL) of the BRB‐F increases by approximately three times when the effect of residual deformation is considered, while its effect on the total EAL of the SCB‐F is negligible. Besides, the superior performance of the SCB‐F compared to BRB‐F is highlighted by a substantial reduction in EAL induced by earthquakes. In addition, the acceleration‐related seismic losses of SCB‐F constitute approximately 44% of the total EAL. Its contribution is significantly larger in the case of the SCB‐F compared to the BRB‐F. From the perspective of economic benefit, increasing the structural life‐cycle span is beneficial to the SCB‐F compared to the BRB‐F. The high fatigue performance of the SCB is favorable to increase the economic benefit of the SCB‐F, especially when the reduction of repair time is considered. The economic benefit of the SCB‐F compared to the BRB‐F is highly related to the initial construction cost. Taking the 100 years as an expected life‐cycle span, the high initial construction cost of the SCB‐F would not be paid off when the unit cost of the SCB is about 2.1 times that of the BRB.
A cost‐aware approach for cloud federation formation
Authors: Dinachali Bijan Pourghorbani , Jabbehdari Sam , Javadi Hamid Haj Seyyed
Published: August 2022

The number of computing resources required for high‐volume applications is ever‐increasing. As far as the users' requests generate workload variations over time and the resources of cloud servers that respond to the requests are limited, the quality of services (QoS) of the cloud server is experiencing fluctuations. The cloud federation is a place where the cloud service providers work together to overcome the problem of resource scarcity and poor service quality. As a result, the main aim of forming a cloud federation is to create an optimal one in a way that provides the required resources and QoS for customers and maximum profit for the providers. Since the service providers play a key role in cloud federation formation, and their absence deteriorates the QoS of the federation, it is required to form an optimal cloud federation that provides the best profit for service providers to encourage them to remain in the federation. In the present paper, first, a model will be introduced for evaluating the cloud service providers, inspired by the concepts of macroeconomics. Then a greedy algorithm will be presented for forming an optimal federation. The proposed algorithm uses the evaluation results to rank the service providers and selects the best federation based on this ranking. In addition, the reputation of providers is evaluated based on the proposed method, which is a criterion for introducing the best providers. Furthermore, the surplus shared resources of the providers will be determined using the evaluation results and its optimal value will be proposed to cloud service providers using the proposed method. Finally, a set of tests will be performed on the introduced system.
Immunomodulatory activity of mannosylglycerate and two unnatural mannosyl‐oligosaccharides obtained from microbial fermentation on RAW264.7 macrophages
Authors: Liu Juanjuan , Yang Jiangang , Zeng Yan , Tian Chaoyu , Men Yan , Sun Yuanxia
Published: August 2022

Mannosyl compounds have been widely used in nutrition, fodder, and vaccine adjuvant industries. In our previous study, the engineered strains for the biosynthesis of three mannosyl compounds including β‐1,2‐mannobiose (M2‐β‐1,2), β‐1,2‐mannotriose (M3‐β‐1,2), and mannosylglycerate (MG) have been developed. However, their biological activities have not been reported. Here, those three compounds were successfully purified after fermentation of the engineered strains, and their potential immunomodulatory activities on RAW264.7 macrophages were investigated with commercialized β‐1,4‐mannotriose (M3‐β‐1,4) as control. Our results showed that M3‐β‐1,2 and MG promoted the viability and phagocytic function of RAW264.7. Meanwhile, the cytokine TNF‐α and interleukin‐6 (IL‐6) level of RAW264.7 macrophages were significantly enhanced upon the stimulation of M3‐β‐1,2 and MG compared with M3‐β‐1,4. Moreover, MG significantly stimulated macrophages to secrete IL‐10 compared with other mannan oligosaccharides. Finally, this study proved that the immunomodulatory activity of M3‐β‐1,2 and MG on RAW 264.7 cells was mainly through mitogen‐activated protein kinases and myeloid differentiation protein 88 (MyD88)‐dependent signaling pathways. All these findings suggested that M3‐β‐1,2 and MG exhibited immunomodulatory activities in the innate and adaptive immune systems, thus facilitating the application potential in developing of mannosyl compounds as an immunomodulator available for food and pharmaceutical area.
Loss of ALK hotspot mutations in relapsed neuroblastoma
Authors: Allinson Lisa M. , Potts Aaron , Goodman Angharad , Bown Nick , Bashton Matthew , Thompson Dean , Basta Nermine O. , Gabriel Alem S. , McCorkindale Michael , Ng Antony , McNally Richard J. Q. , Tweddle Deborah A.
Published: August 2022

ALK is the most commonly mutated oncogene in neuroblastoma with increased mutation frequency reported at relapse. Here we report the loss of an ALK mutation in two patients at relapse and a paired neuroblastoma cell line at relapse. ALK detection methods including Sanger sequencing, targeted next‐generation sequencing and a new ALK Agena MassARRAY technique were used to detect common hotspot ALK variants in tumors at diagnosis and relapse from two high‐risk neuroblastoma patients. Copy number analysis including single nucleotide polymorphism array and array comparative genomic hybridization confirmed adequate tumor cell content in DNA used for mutation testing. Case 1 presented with an ALK F1174L mutation at diagnosis with a variant allele frequency (VAF) ranging between 23.5% and 28.5%, but the mutation was undetectable at relapse. Case 2 presented with an ALK R1257Q mutation at diagnosis (VAF = 39%–47.4%) which decreased to <0.01% at relapse. Segmental chromosomal aberrations were maintained between diagnosis and relapse confirming sufficient tumor cell content for mutation detection. The diagnostic SKNBE1n cell line harbors an ALK F1174S mutation, which was lost in the relapsed SKNBE2c cell line. To our knowledge, these are the first reported cases of loss of ALK mutations at relapse in neuroblastoma in the absence of ALK inhibitor therapy, reflecting intra‐tumoral spatial and temporal heterogeneity. As ALK inhibitors are increasingly used in the treatment of refractory/relapsed neuroblastoma, our study highlights the importance of confirming whether an ALK mutation detected at diagnosis is still present in clones leading to relapse.
Bird species potentially exposed to pesticide-treated corn seeds in the continental United States
Authors: Sullivan Joseph P. , Wisk Joseph D.
Published: August 2022

In the United States, the use of pesticide-coated seeds in agriculture is a widely adopted practice. Consumption of treated crop seeds is a possible route of exposure of birds to pesticides. A combination of agronomic and bird life history information is used to identify those species most likely to consume freshly planted corn seeds. Species listed as threatened or endangered by the US Fish and Wildlife Service that could consume treated seeds are also identified. Corn-growing counties in the continental United States were compiled for the years 2017–2020. Seven hundred and eight bird species occur in corn-growing counties. Feeding habits and habitats of North American bird species that occur in corn-growing counties indicate that 107 species could feed on the ground in or adjacent to freshly planted corn fields and consume seeds. Of these, 21 species show a high tendency to feed in or around freshly planted corn fields and could consume a large quantity of corn seeds. Of the 107 species with the potential to consume freshly planted corn, only two full species (as opposed to subspecies), the Gunnison sage-grouse and whooping crane, are listed as threatened or endangered under the US Endangered Species Act. Additionally, two subspecies, Mississippi sandhill crane and masked bobwhite, are listed as endangered. The streaked horned lark is listed as threatened. Of the 21 species, including subspecies, that have the greatest potential to consume a freshly planted treated corn seed, the Mississippi sandhill crane is the only listed species considered to have a high potential to consume treated corn seeds. Therefore, the potential exposure of federally listed threatened or endangered bird species to pesticides through the direct consumption of pesticide-treated corn seeds is low, with the possible exception of the Mississippi sandhill crane. Integr Environ Assess Manag 2023;19:461–473. © 2022 SETAC
Time intervals in the care pathway to cancer diagnosis during the COVID‐19 pandemic: A large retrospective study from a high‐volume center
Authors: Bosch Xavier , Montori‐Palacin Elisabet , Martínez‐Ferrer Rosa , Aldea Anna , Moreno Pedro , López‐Soto Alfonso
Published: August 2022

Despite extensive research on cancer care during the COVID‐19 pandemic, evidence on the impact on prediagnostic time intervals is lacking. To better understand how COVID‐19 changed the pathway to diagnosis of cancer, we examined the length of intervals from symptom onset to diagnosis for 13 common cancer types with known clinical stage over 1‐year nonpandemic period (March 2019 to March 2020; N = 844) and three biannual COVID periods (March 2020 to September 2021; N = 1172). We analyzed the patient interval (from first symptoms to presentation to a physician), the primary care/emergency department interval (from presentation with relevant symptoms to a primary care or emergency department physician to referral to a hospital‐based diagnosis center) and the hospital interval (from referral to diagnosis). Compared to nonpandemic data, there were significant changes across COVID periods. The pandemic mostly impacted patient intervals for cancers diagnosed over the first 6 months after onset in March 2020. Overall median patient intervals were longest in the early COVID period (39 [IQR 22‐64] days) and shortest in the nonpandemic period (20 [IQR 13‐30] days; Kruskal‐Wallis test [χ2], P < .0001). Differences in clinical stage between periods were relevant, with cancers from the mid‐period (September 2020 to March 2021) showing the most advanced stage. A shift to later stage was plausibly a result of delayed intervals in the early COVID period. Since intervals are eventually relevant to prognosis, our results provide a baseline against which the impact of improvement strategies to minimize the negative outcomes of COVID‐19‐associated cancer delays can be assessed and implemented.