bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure‐Based Evolution of G Protein‐Biased μ‐Opioid Receptor Agonists
Authors: Wang Haoqing , Hetzer Florian , Huang Weijiao , Qu Qianhui , Meyerowitz Justin , Kaindl Jonas , Hübner Harald , Skiniotis Georgios , Kobilka Brian K. , Gmeiner Peter
Published: April 2022

The μ‐opioid receptor (μOR) is the major target for opioid analgesics. Activation of μOR initiates signaling through G protein pathways as well as through β‐arrestin recruitment. μOR agonists that are biased towards G protein signaling pathways demonstrate diminished side effects. PZM21, discovered by computational docking, is a G protein biased μOR agonist. Here we report the cryoEM structure of PZM21 bound μOR in complex with Gi protein. Structure‐based evolution led to multiple PZM21 analogs with more pronounced Gi protein bias and increased lipophilicity to improve CNS penetration. Among them, FH210 shows extremely low potency and efficacy for arrestin recruitment. We further determined the cryoEM structure of FH210 bound to μOR in complex with Gi protein and confirmed its expected binding pose. The structural and pharmacological studies reveal a potential mechanism to reduce β‐arrestin recruitment by the μOR, and hold promise for developing next‐generation analgesics with fewer adverse effects.
An Activatable Polymeric Nanoprobe for Fluorescence and Photoacoustic Imaging of Tumor‐Associated Neutrophils in Cancer Immunotherapy
Authors: Zhang Yan , He Shasha , Xu Cheng , Jiang Yue , Miao Qingqing , Pu Kanyi
Published: April 2022

Imaging to evaluate tumor‐associated neutrophils (TANs) is imperative for cancer immunotherapy but remains challenging. We herein report an activatable semiconducting polymer nanoprobe (SPCy) for near‐infrared fluorescence (NIRF) and photoacoustic (PA) imaging of neutrophil elastase (NE), a biomarker of TANs. SPCy comprises a semiconducting polymer conjugated with a hemicyanine (hemi‐Cy) dye caged by a NE‐cleavable peptide as the side chain. After systemic administration, SPCy passively targets the tumor and reacts with NE to “uncage” the hemi‐Cy, leading to enhanced NIRF and PA signals of the hemi‐Cy but unchanged signals of the SP. Such NE‐activated ratiometric NIRF and enhanced PA signals of SPCy correlate with the intratumoral population of TANs. Thus, this study not only presents the first TAN‐specific PA probe, but also provides a general molecular design strategy for PA imaging of other immune‐related biomarkers to facilitate screening of cancer immunotherapeutics.
LiNbO3‐Type Polar Antiferromagnet InVO3 Synthesized under High‐Pressure Conditions
Authors: Tan Zhenhong , Lussier Joey A. , Yamada Takumi , Xu Yuanhui , Saito Takashi , Goto Masato , Kosugi Yoshihisa , Vrublevskiy Dmitry , Kanemitsu Yoshihiko , Bieringer Mario , Shimakawa Yuichi
Published: April 2022

The ambient pressure cation disordered InVO3 bixbyite has been predicted to form a GdFeO3‐type perovskite phase under high pressure and high temperature. Contrary to the expectation, InVO3 was found to crystallize in the polar LiNbO3‐type structure with a calculated spontaneous polarization as large as 74 μC cm−2. Antiferromagnetic coupling of V3+ magnetic moments and a cooperative magnetic ground state below about 10 K coupled with a polar structure suggest an intriguing ground state of the novel LiNbO3‐type high‐pressure InVO3 structure.
Bifunctionalized Metal–Organic Frameworks for Pore‐Size‐Dependent Enantioselective Sensing
Authors: Han Zongsu , Wang Kunyu , Min Hui , Xu Jun , Shi Wei , Cheng Peng
Published: April 2022

Porosity is a fundamental property of metal–organic frameworks (MOFs). However, the role of the pore size has always been underestimated in MOF‐based luminescent sensors for enantioselective sensing. The construction of isoreticular MOFs (IRMOFs) with variable pore sizes and the synergy between chirality and luminescence is challenging. Herein, a general strategy was developed to introduce chirality into two well‐known IRMOF‐74 analogs with nanochannels of identical shapes but different pore sizes by functionalizing the open metal site under mild conditions. To enhance the detection accuracy, a second luminescent center was introduced into the IRMOF‐74 system to achieve ratiometric sensing. The two bifunctionalized IRMOF‐74 compounds exhibited pore‐size‐dependent sensing performance for enantiomers. This study not only provides a convenient method to construct chiral MOFs as advanced sensing materials but also reveals the fundamental of the pores in MOF‐based luminescent sensors.
Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021)
Authors: Feng Lian‐Shun , Su Wen‐Qi , Cheng Jin‐Bo , Xiao Tao , Li Hong‐Ze , Chen De‐An , Zhang Zhi‐Liu
Published: April 2022

Cancer, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of cellular differentiation and uncontrolled cellular growth, remains a prominent cause of death across the world. Almost all currently available anticancer agents used in clinical practice have developed multidrug resistance, creating an urgent need to develop novel chemotherapeutics. Benzimidazole derivatives could exert anticancer properties through diverse mechanisms, inclusive of the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, antiangiogenesis, and blockage of glucose transport. Moreover, several benzimidazole‐based agents have already been approved for the treatment of cancers. Hence, benzimidazole derivatives are useful scaffolds for the development of novel anticancer agents. In particular, benzimidazole hybrids could exert dual or multiple antiproliferative activities and had the potential to overcome drug resistance, demonstrating the potential of benzimidazole hybrids as potential prototypes for clinical deployment in the control and eradication of cancers. The purpose of the present review article is to provide a comprehensive landscape of benzimidazole hybrids as potential anticancer agents, and the structure–activity relationship as well as mechanisms of action are also discussed to facilitate the further rational design of more effective candidates, covering articles published from 2019 to 2021.
A critical view on the suitability of machine learning techniques to downscale climate change projections: Illustration for temperature with a toy experiment
Authors: Hernanz Alfonso , García‐Valero Juan Andrés , Domínguez Marta , Rodríguez‐Camino Ernesto
Published: April 2022

Machine learning is a growing field of research with many applications. It provides a series of techniques able to solve complex nonlinear problems, and that has promoted their application for statistical downscaling. Intercomparison exercises with other classical methods have so far shown promising results. Nevertheless, many evaluation studies of statistical downscaling methods neglect the analysis of their extrapolation capability. In this study, we aim to make a wakeup call to the community about the potential risks of using machine learning for statistical downscaling of climate change projections. We present a set of three toy experiments, applying three commonly used machine learning algorithms, two different implementations of artificial neural networks and a support vector machine, to downscale daily maximum temperature, and comparing them with the classical multiple linear regression. We have tested the four methods in and out of their calibration range, and have found how the three machine learning techniques can perform poorly under extrapolation. Additionally, we have analysed the impact of this extrapolation issue depending on the degree of overlapping between the training and testing datasets, and we have found very different sensitivities for each method and specific implementation.
Impact of the matching algorithm on the treatment effect estimate: A neutral comparison study
Authors: Heinz Priska , Wendel‐Garcia Pedro David , Held Ulrike
Published: April 2022

Propensity score matching is increasingly being used in the medical literature. Choice of matching algorithms, reporting quality, and estimands are oftentimes not discussed. We evaluated the impact of propensity score matching algorithms, based on a recent clinical dataset, with three commonly used outcomes. The resulting estimands for different strengths of treatment effects were compared in a neutral comparison study and based on a thoroughly designed simulation study. Different algorithms yielded different levels of balance after matching. Along with full matching and genetic matching with replacement, good balance was achieved with nearest neighbor matching with caliper but thereby more than one fifth of the treated units were discarded. Average marginal treatment effect estimates were least biased with genetic or nearest neighbor matching, both with replacement and full matching. Double adjustment yielded conditional treatment effects that were closer to the true values, throughout. The choice of the matching algorithm had an impact on covariate balance after matching as well as treatment effect estimates. In comparison, genetic matching with replacement yielded better covariate balance than all other matching algorithms. A literature review in the British Medical Journal including its subjournals revealed frequent use of propensity score matching; however, the use of different matching algorithms before treatment effect estimation was only reported in one out of 21 studies. Propensity score matching is a methodology for causal treatment effect estimation from observational data; however, the methodological difficulties and low reporting quality in applied medical research need to be addressed.
Anatomical variants identified on chest computed tomography of 1000+ COVID‐19 patients from an open‐access dataset
Authors: Yurasakpong Laphatrada , Asuvapongpatana Somluk , Weerachatyanukul Wattana , Meemon Krai , Jongkamonwiwat Nopporn , Kruepunga Nutmethee , Chaiyamoon Arada , Sudsang Thanwa , Iwanaga Joe , Tubbs R. Shane , Suwannakhan Athikhun
Published: April 2022

Chest computed tomography (CT) has been the preferred imaging modality during the pandemic owing to its sensitivity in detecting COVID‐19 infections. Recently, a large number of COVID‐19 imaging datasets have been deposited in public databases, leading to rapid advances in COVID‐19 research. However, the application of these datasets beyond COVID‐19‐related research has been little explored. The authors believe that they could be used in anatomical research to elucidate the link between anatomy and disease and to study disease‐related alterations to normal anatomy. Therefore, the present study was designed to investigate the prevalence of six well‐known anatomical variants in the thorax using open‐access CT images obtained from over 1000 Iranian COVID‐19 patients aged between 6 and 89 years (60.9% male and 39.1% female). In brief, we found that the azygos lobe, tracheal bronchus, and cardiac bronchus were present in 0.8%, 0.2%, and 0% of the patients, respectively. Variations of the sternum, including sternal foramen, episternal ossicles, and sternalis muscle, were observed in 9.6%, 2.9%, and 1.5%, respectively. We believe anatomists could benefit from using open‐access datasets as raw materials for research because these datasets are freely accessible and are abundant, though further research is needed to evaluate the uses of other datasets from different body regions and imaging modalities. Radiologists should also be aware of these common anatomical variants when examining lung CTs, especially since the use of this imaging modality has increased during the pandemic.
Storage Control Philosophies for Gas Filling Stations at Biogas Plants
Authors: Kube Jürgen , Gökgöz Fatih , Liebetrau Jan , Nelles Michael
Published: April 2022

The production of biomethane as a fuel is an opportunity for existing combined heat and power biogas plants. These plants are not necessarily located near access points to the natural gas grid and will need to store the produced biomethane on site. Fuel demand is not constant, and the anaerobic digestion plant can vary its production, ramp up compression, and store gas pre‐compression near ambient pressure or post‐compression in high‐pressure storage tanks. Compression is an energy‐intensive process, and some of the energy is lost when a storage tank compressed to 250 bar is connected to an empty fuel tank of a vehicle (30 bar). The aim of this work was to develop a method to identify reasonable and optimal tank sizes, volume splits, and starting pressures and provide two control philosophies for the filling station.
Integrating Photocatalysis and Microfiltration for Methylene Blue Degradation: Kinetics and Cost Estimation
Authors: Pham Duc Chinh , Cao Thi Mai Duyen , Nguyen Manh Cuong , Nguyen Thanh Dong , Nguyen Viet Hoang , Bui Van Hoi , Nguyen Thi Thu Trang
Published: April 2022

Methylene blue degradation by the UV/TiO2 and UV/TiO2/H2O2 photocatalysis in a suspended photocatalytic reactor coupled with a microfiltration (MF) module is described. The kinetics of methylene blue degradation, cake layer formation on the membrane surface, and the energy consumption of the system are evaluated and discussed. In addition, cost estimation of the treatment of methylene blue by different processes is implemented. The investment and operating costs of the photocatalytic membrane reactors are calculated and compared with the UV systems and UV/TiO2‐MF.
Development of an Automated Adsorbent Selection Strategy for Liquid–Phase Adsorption
Authors: Schreiber Mareike , Schembecker Gerhard
Published: April 2022

A systematic and automatic approach for adsorbent selection for liquid–phase adsorption is proposed. Based on physical properties like polarity, pore size, and specific surface, a screening strategy is developed and automated on a robotic platform. Key performance indicators are applied ensuring economically based decisions. The approach developed is verified by adsorption of caffeine out of an aqueous solution with vanillin, uracil, and α–ionon as impurities. The adsorbent selection strategy leads to the polymeric adsorbent SP207 and a specific surface of 15 m2mL−1 ending in a separation cost indicator of 16 € gCaffeine−1. This work proposes an opportunity for accelerated process design strengthened by the usage of robotic devices.
Construction of Core‐Shell Heterostructured Nanoarrays of Cu(OH)2@NiFe‐Layered Double Hydroxide through Facile Potentiostatic Electrodeposition for Highly Efficient Supercapacitors
Authors: Wang Zihao , Liu Zhiqiang , Wang Lei , Zhao Kai , Sun Xiaolin , Jia Dedong , Liu Jingquan
Published: April 2022

In this work, the densely distributed and core‐shell structured Cu(OH)2@NiFe‐LDH nanoarrays on copper foam (COH@NF‐LDH/CF) are constructed by a facile and feasible in situ oxidation method combined with potentiostatic electrodeposition. This distinct core‐shell structure as well as the synergetic effect between Cu(OH)2 and NiFe‐LDH provides a tremendous advantage, such as sufficient chemical active spots, the pathway for electron and ion transfer, to enhance the electrochemical performance of COH@NF‐LDH/CF. In particular, the area capacitance of synthesized COH@NF‐LDH/CF can reach 4.139 F cm−2 at 5 mA cm−2, which remarkably precede the single bare Cu(OH)2 (198 mF cm−2) or NiFe‐LDH/CF (71 mF cm−2) electrode materials at the same current density. Furthermore, the sample COH@NF‐LDH/CF is investigated and found to have excellent cycle stability (maintained 86.47 % after 5000 cycles). More importantly, the COH@NF‐LDH/CF electrode also can be utilized directly as the positive electrode and activated carbon (AC) as the negative electrode to assemble a facile asymmetric supercapacitor, which achieves a voltage window of up to 1.5 V and demonstrate up 65.56 Wh kg−1 brilliant energy density under 750 W kg−1. Therefore, their results indicate that COH@NF‐LDH/CF core‐shell structure nanocomposites may have a great prospect of application in energy storage.
Oxygen Vacancy‐Enhanced Ternary Nickel‐Tungsten‐Cerium Metal Alloy‐Oxides for Efficient Alkaline Electrochemical Full Cell Water Splitting Using Anion Exchange Membrane
Authors: Chen Kai , Rajendiran Rajmohan , Deviprasath Chinnadurai , Mathew Sobin , Cho Young‐Rae , Prabakar Kandasamy , Lun Li Oi
Published: April 2022

Alkaline water electrolysis is an attractive hydrogen generation technology with ultra‐high purity products and zero carbon emissions. However, the sluggish kinetics of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in both electrodes highly limits their applications. Benefiting from the abundant accessible active sites of the ternary alloy‐oxide structure formed on Ni foam directly, NiCeWOx shows superior HER and OER catalytic performances. The NiCeWOx‐2 (Ce/W ratio with 5/95) displays enhanced OER activity with an overpotential of 263 mV, while the NiCeWOx‐1 (Ce/W ratio with 79.8/21.2) shows better performance for alkaline HER with an overpotential of 130 mV at the current density of 10 mA cm−2. The catalysts show significant enhancement in terms of electrochemical reaction kinetics and conductivity compared to its original NiCeOx and NiWOx alloy phase. The efficient HER‐OER electrocatalytic performance is attributed to its unique alloyed oxygen vacancy structure‐property, which facilitates the diffusion of protons/OH− ions and significantly improves the electron conductivity for catalytic reactions. A low cell potential of 1.65 V is obtained at 10 mA cm−2 for NiCeWOx‐1||NiCeWOx‐2 in a full water‐splitting device in 1 M KOH electrolyzer with an anion exchange membrane. Also, NiCeWOx‐1||NiCeWOx‐2 exhibits extreme high stability after 24 h operation. This novel design utilizes low‐cost and robust electrocatalysts and will be useful for large‐scale alkaline water electrolysis.
Experimental Characterization of 3D Printed Structured Metal Packing with an Enclosed Column Wall
Authors: Riese Julia , Reitze Arnulf , Grünewald Marcus
Published: April 2022

Additive manufacturing is a promising tool for tailored solutions in chemical engineering. This applies in particular to the design of lab‐scale packed bed columns. We present experimental results to characterize a lab‐scale 3D printed structured metal packing and compare it to a conventional counterpart. The results indicate that necessary adjustments for the manufacturing process of the metal material have an influence on important operating parameters, resulting in higher specific pressure drop, slightly higher liquid holdup and lower mass transfer efficiency.
High cyclin E1 protein, but not gene amplification, is prognostic for basal‐like breast cancer
Authors: Aziz Diar , Lee Christine , Chin Venessa , Fernandez Kristine J , Phan Zoe ,   kConFab Investigators,   AOCS Study Group, Waring Paul , Caldon C Elizabeth
Published: April 2022

Basal‐like breast cancer (BLBC) has a greater overlap in molecular features with high‐grade serous ovarian cancer (HGSOC) than with other breast cancer subtypes. Similarities include BRCA1 mutation, high frequency of TP53 mutation, and amplification of CCNE1 (encoding the cyclin E1 protein) in 6–34% of cases, and these features can be used to group patients for targeted therapies in clinical trials. In HGSOC, we previously reported two subsets with high levels of cyclin E1: those in which CCNE1 is amplified, have intact homologous recombination (HR), and very poor prognosis; and a CCNE1 non‐amplified subset, with more prevalent HR defects. Here, we investigate whether similar subsets are identifiable in BLBC that may allow alignment of patient grouping in clinical trials of agents targeting cyclin E1 overexpression. We examined cyclin E1 protein and CCNE1 amplification in a cohort of 76 BLBCs and validated the findings in additional breast cancer datasets. Compared to HGSOC, CCNE1 amplified BLBC had a lower level of amplification (3.5 versus 5.2 copies) and lower relative cyclin E1 protein, a lack of correlation of amplification with expression, and no association with polyploidy. BLBC with elevated cyclin E1 protein also had prevalent HR defects, and high‐level expression of the cyclin E1 deubiquitinase ubiquitin‐specific protease 28 (USP28). Using a meta‐analysis across multiple studies, we determined that cyclin E1 protein overexpression but not amplification is prognostic in BLBC, while both cyclin E1 overexpression and amplification are prognostic in HGSOC. Overall CCNE1 gene amplification is not equivalent between BLBC and HGSOC. However, high cyclin E1 protein expression can co‐occur with HR defects in both BLBC and HGSOC, and is associated with poor prognosis in BLBC.
Mindfulness‐based stress reduction and cognitive function among breast cancer survivors: A randomized controlled trial
Authors: Duval Alicia , Davis Christopher G. , Khoo Eve‐Ling , Romanow Heather , Shergill Yaadwinder , Rice Danielle , Smith Andra M. , Poulin Patricia A. , Collins Barbara
Published: April 2022

Background

Breast cancer (BC) survivors frequently report changes in cognition after chemotherapy. Mindfulness may benefit survivors by mitigating cancer‐related cognitive impairment. As part of a larger study investigating the effects of mindfulness‐based stress reduction (MBSR) for BC survivors living with neuropathic pain, the authors assessed whether MBSR would have an effect on cognitive outcomes.

Methods

Participants were randomized to an MBSR intervention group (n = 30) or a waitlist control group (n = 30). Cognitive assessments were administered at 3 time points: at baseline, 2 weeks, and 3 months post‐MBSR in the intervention group and at equivalent time intervals for the control group. Multilevel models were used to assess whether MBSR significantly improved task performance at each time point.

Results

MBSR participants showed a significantly greater reduction in prospective and retrospective memory failures at 2 weeks postintervention. No effects of MBSR were noted for objective assessments.

Conclusions

These results suggest that MBSR training reduces subjective (but not objective) memory‐related impairments in BC survivors who receive treatment with chemotherapy. This study provides insight into a noninvasive intervention to ameliorate memory difficulties in BC survivors.
Secretory carcinoma of the salivary gland, a rare entity: An international multi‐institutional study
Authors: Wiles Austin B. , Gabrielson Matthew , Baloch Zubair W. , Faquin William C. , Jo Vickie Y. , Callegari Fabiano , Kholova Ivana , Song Sharon , Centeno Barbara A. , Ali Syed Z. , Tommola Satu , Fadda Guido , Petrone Gianluigi , Wang He , Rossi Esther D. , Pantanowitz Liron , Maleki Zahra
Published: April 2022

BACKGROUND

Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine‐needle aspiration (FNA) cases.

METHODS

FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles.

RESULTS

In total, 40 SCs were identified (male‐to‐female ratio, 14:26) in patients with a mean age of 52 years (age range, 13‐80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round‐to‐oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA‐3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6‐NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next‐generation sequencing (n = 1).

CONCLUSIONS

Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.;
Nanozymes of Ni0.5Fe0.5S2 Mediated Synergetic Antitumor Treatment
Authors: Zeng Jia , Wang Yufeng , Wu Jingpeng , Wang Huiwen , Lu Junrong , Li Shijie , He Dongfeng
Published: April 2022

How to establish a multi‐modality oncotherapy method on the basis of single matter mediated utilization of tumor endogenous substances is very promising for efficient antitumor treatment. In this work, we have designed a metallic Ni0.5Fe0.5S2 nanosphere for synergetic chemodynamic/photodynamic/photothermal antitumor treatments. Under NIR excitation, a remarkable photothermal effect could be generated by Ni0.5Fe0.5S2 for realizing the photothermal therapy. Meanwhile, Ni0.5Fe0.5S2 could also trigger formation of reactive oxygen species (ROS) via transformation of tumor‐site oxygen for the further photodynamic therapy. Furthermore, peroxidase‐like property of Ni0.5Fe0.5S2 favors the catalysis of endogenous H2O2 into hydroxyl radical to achieve a chemodynamic therapy. As a result, the on‐site tumor hyperthermia, tumor‐site oxygen and H2O2 conversion are worked for the antitumor action. On the merits of above synergistic effect, a better antitumor outcome was confirmed as compared with any single antitumor action, and complete removal of solid tumor under a relative lower temperature has been accomplished.
Effects of Unsuppressed Endogenous Insulin on Pharmacokinetics and/or Pharmacodynamics of Study Insulin in the Healthy: A Retrospective Study
Authors: Liu Hui , Yu Hongling , Sun Lisi , Qiao Jingtao , Li Jiaqi , Tan Huiwen , Yu Yerong
Published: April 2022

C‐peptide, a marker of endogenous insulin, should be consistently inhibited during euglycemic clamping, while an elevated postdosing C‐peptide (CPpostdosing) is not an occasional phenomenon. This was a retrospective study that included 33 men who underwent a manual euglycemic clamp with a subcutaneous injection of insulin aspart (IAsp) aiming to describe the effects of insufficient suppression of endogenous insulin on estimates of the pharmacokinetics and pharmacodynamics of injected insulin. The time profiles of whole blood glucose, human insulin, glucose infusion rate (GIR), and C‐peptide were recorded. The subjects were divided into 2 groups at a ratio of 2:1: group A ([CPpostdosing]max>baseline CP [CPbaseline]), group B ([CPpostdosing]max ≤ CPbaseline). The endogenous insulin was approximately equal to the measured value of human insulin or calculated from the C‐peptide. The basal glucose, CPbaseline, basal human insulin, homeostatic model assessment of insulin resistance, IAsp dose, and demographic statistics were all comparable between the 2 groups except the “clamped” glucose. The average clamped glucose was 99.7% (group A) and 94.9% (group B) of baseline. After correction for clamped glucose, GIR area under the concentration‐time curve from time 0 to 8 hours was higher in group A (P < .05) under comparable IAsp exposure. Endogenous insulin area under the concentration‐time curve from time 0 to 8 hours calculated from C‐peptide was different from that measured from human insulin in group A (P < .05), whereas no statistical difference between these measures was observed in group B. Hence, blood glucose should be controlled below the baseline to ensure the inhibition of endogenous insulin. Unsuppressed endogenous insulin may contribute to observed GIR, and the endogenous insulin–corrected pharmacokinetics estimated by C‐peptide may be inaccurate with insufficient endogenous insulin suppression.
Using Fiber Bragg Grating Sensors to Quantify Temperature Non‐Uniformities in Plasmonic Catalyst Beds under Illumination
Authors: Xu Man , den Hartog Tim , Cheng Lun , Wolfs Marciano , Habets Roberto , Rohlfs Jelle , van den Ham Jonathan , Meulendijks Nicole , Sastre Francesc , Buskens Pascal
Published: April 2022

The front cover artwork is provided by TNO (The Netherlands). The image illustrates an optical temperature sensor based on fiber Bragg gratings which enables accurate temperature measurements at various positions inside an illuminated plasmonic catalyst powder bed. Read the full text of the Research Article at 10.1002/cptc.202100289.
Effects of ginger (Zingiber officinale) on gingival fibroblasts: An in vitro study
Authors: Al‐Shibani Nouf , Al‐Kattan Reem , Alssum Lamees , Allam Eman
Published: April 2022

Objectives

Ginger, the powdered rhizome of the herb Zingiber officinale, is commonly used as a traditional medicine in many areas around the world. Anti‐inflammatory actions of its extract have been previously reported. The aim of this study was to investigate the effect of ginger extract on matrix metalloproteinase (MMP) and interleukin (IL) expression from human gingival fibroblasts (HGFs) in vitro.

Material and Methods

HGFs were obtained from subcultures of biopsies from clinically healthy gingival tissues of 10 patients. Ginger extract was prepared from commercial powder of rhizome of Z. officinale (GZO) and its effect on cell viability was assessed using the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide cytotoxicity assay. Cells were then incubated and treated (except for the control samples) with either GZO, lipopolysaccharides (LPS), and GZO before or after LPS stimulation. Culture supernatants of all five samples were collected for the Milliplex analysis to measure MMP‐1, MMP‐2, MMP‐8, MMP‐9, IL‐1β, and IL‐8. One‐way analysis of variance and Duncan multiple range tests were used to compare the mean values of all groups.

Results

The gingerextract showed minimal cytotoxicity to HGFs even with the maximum tested concentration. Compared to the control group, GZO treatment alone caused little or no effect on the levels of expression of MMP‐1, MMP‐2, MMP‐8, MMP‐9, IL‐1β, and IL‐8. While GZO treatment after LPS stimulation significantly reduced the expression of MMP‐1, MMP‐2, MMP‐8, MMP‐9, and IL‐8 when compared to LPS alone. Comparing the control to LPS stimulation after GZO treatment, significant differences were detected for all tested MMPs and cytokines.

Conclusions

These findings suggest a potential role for ginger extract in inhibiting MMP and IL HGFs' expression in inflamed gingival tissues.
Practice does not make perfect: Juvenile object play does not improve the predation skills of adult mink in “simulated prey” tests
Authors: Dawson Lauren C. , Meagher Rebecca , Ahloy‐Dallaire Jamie , Mason Georgia
Published: April 2022

In carnivores, juvenile object play is hypothesized to improve the development of adult predation ability. We tested this hypothesis in a model carnivore, the American mink (Neovison vison). Play was induced via the provision of diverse “enrichment” objects to 32 litters from 4 to 15 weeks of age on a rotating schedule; control mink (32 litters) were instead provided with one static object. Behavioral observations confirmed that enriched juveniles engaged in more object play than control juveniles (p < .01). Tenacity, strength, and chasing motivations were assessed in 52 mink at 27–29 weeks of age using five “simulated prey” tests. These tests showed internal consistency, with measures from the same test being weakly to very strongly correlated (r or ρ: |.33–.95|). Across tests assessing similar skills, some measures of tenacity and strength were also moderately correlated. Treatment had little effect, however, other than on maximum force during vertical pulling, in which control mink unexpectedly scored higher (1.01 ± 0.06 kg vs. 0.84 ± 0.06 kg, p = .0458). Although we did not find evidence to support the hypothesis that object play leads to improved predatory skills, the tests developed have the potential to be used in humane, prey‐free future investigations of predation abilities.
Spatial Control of Lithium Deposition by Controlling the Lithiophilicity with Copper(I) Oxide Boundaries
Authors: Kim Ju Ye , Chae Oh B. , Kim Gukbo , Jung Woo‐Bin , Choi Sungho , Kim Do Youb , Moon San , Suk Jungdon , Kang Yongku , Wu Mihye , Jung Hee‐Tae
Published: April 2022

Spatial control of lithium deposition is the most important issue in lithium‐metal batteries because of the considerable control of lithium dendrite suppression via the uniform distribution of Li+ flux. Although seed materials are crucial for the behavior of lithium deposition, in‐depth studies on their physical and chemical control have not been conducted. Here, we describe a new design of seed structure comprising a wrinkled Cu/graphene substrate surrounded by copper(I) oxide (Cu2O) on a graphene grain boundary over a large area, which is fabricated by the oxidation of the Cu surface via graphene boundary defects by using chemical vapor deposition (CVD). Scanning and transmission electron microscopy results reveal that Cu2O on the graphene boundary can render a preferential reaction with lithium during the first deposition and assist in the uniform deposition of lithium by preventing the agglomeration of lithium clusters during the second deposition. This two‐step process is attributed to the degree of selectivity due to the difference in lithium affinity, which allows long‐term electrochemical stability and a high rate capability via boundary effects. This study highlights the significance of the boundary effect, which can open new avenues for the formation of a large family of seed structures in lithium‐metal batteries.
Formation of Iron (III) Trimesate Xerogel by Ultrasonic Irradiation
Authors: Ennas Guido , Gedanken Aharon , Mannias Giada , Kumar Vijay B. , Scano Alessandra , Porat Ze'ev , Pilloni Martina
Published: April 2022

Fe−BTC materials have attracted vast attention owing to their high chemical stability, adaptable synthesis, and potential applications. Herein, we describe, for the first time, the preparation of iron trimesate gels by ultrasonic (US) irradiation of an aqueous solution of Iron (III) nitrate and trimesic acid. Two different procedures were used: (1) sonication for 10 or 20 minutes, (2) 3 minutes sonication under controlled pH (pH 3–5). After drying, stable Fe−BTC xerogels were obtained from both procedures. The xerogels consisted of interconnected spherical nanoparticles with similar microstructure when analyzed by FT‐IR and PXRD and similar thermal behavior under oxygen in the range of 25–900 °C. When analyzed by Nitrogen adsorption‐desorption at 77 K, all samples showed a permanent porosity with a narrow micropore distribution below 10 Å. Different textural properties were found among samples obtained with the same procedure. The product of 10 minutes sonication had a specific surface area (SSA) of 1042 m2/g.
The 2021–2022 European Natural Gas Disaster: Was Reagan Right and Thatcher Wrong?
Authors: Makholm Jeff D.
Published: April 2022

Europe's energy supply is in crisis this winter. Owing to the evident Russian manipulation of its natural gas exports to the European Union (EU) in advance of its invasion of Ukraine, prices have spiked wildly—24 times the prevailing EU natural gas price in the summer of 2020 and up to 10 times contemporaneous US natural gas prices in early 2022. Because natural gas prices often‐enough drive the EU's electricity market model prices, the resulting electricity prices at the time of writing throughout the EU were three to six times higher than their 2019 level. The result is a disaster for EU energy consumers in 2022. Russia's potential to hold hostage critical winter natural gas supplies to Europe's millions of natural gas consumers was not unforeseen. Lacking the means to protect against such energy hostage‐taking should call the EU's natural gas regulations into question. It is uncertain whether the EU can avoid such situations next winter and beyond without a fundamental political reexamination of how its regulatory methods led to the current crisis.
Lessons in Energy Policy from 2021–2022
Authors: Smead Richard G.
Published: April 2022

In world energy markets, the current chaos around uncertainty of supplies and price spikes highlights the critical need for a balanced energy policy, both in the United States and abroad. Of course, the most recent disruption is due primarily to the world and energy market's reaction to the Russian invasion of Ukraine and its consequences. One can only hope and pray that by the time this column is published, that crisis will have been peacefully resolved. However, embargoes on Russian oil and natural gas, with the associated stress they have placed on Europe and other countries who rely on these commodities, only exacerbated a situation that was already spiraling out of control. Many governments around the world, the United States included, announced major policy initiatives to move away from oil and natural gas, in favor of renewable energy resources, such as wind and solar. A great deal of that movement has already happened in Europe, leading to very tough energy choices in 2021 when wind as a resource option was diminished—it just wasn't windy enough. Some policies were a bit ambivalent about natural gas, recognizing its environmental advantages over other fossil fuels, but—at least in the United States—consistent, “cancel culture” hostility toward any development of drilled hydrocarbons pervaded environmental nongovernment organizations (NGOs) and many government agencies.
Does early disease progression predict survival after first line‐treatment of Waldenström macroglobulinemia?
Authors: Labreuche Julien , Assouan Deborah , Durot Eric , Tomowiak Cecile , Roos‐Weil Damien , Toussaint Elise , Bijou Fontanet , Lemal Richard , Brion Annie , Laribi Kamel , Ysebaert Loic , Duhamel Alain , Morel Pierre ,   for the French Innovative Leukaemia Organisation (FILO) Chronic Lymphocytic Leukaemia group
Published: April 2022

In symptomatic Waldenström macroglobulinemia (sWM) patients, prognosis is assessed with the international prognostic scoring system (IPSSWM). In follicular lymphoma and other B‐cell and T‐cell lymphomas, disease progression within 24 months (POD24) or (in patients without POD24) after 24 months has been proposed as the start date for stratifying subsequent survival. In the present report, we assessed in a large series of 472 sWM patients, the prognostic value of this new dynamic endpoint already reported in many other lymphomas subtypes. The 3 year subsequent survival for patients with POD24 was 75% and 93% for patients without POD24. In sWM patients, departure from the proportional hazards assumption complicated this analysis. In patients without POD24, the median subsequent progression‐free survival time of 43 months accounted for favorable outcome, whereas survival after progression was not influenced by the time to progression. In addition, sensitivity analysis showed that the baseline IPSSWM score also influenced survival after POD24. In sWM patients, we conclude that the apparent difference in survival after POD24 or the 24 months time‐point (in patients without POD24) is mainly explained by the prolonged subsequent progression free survival of latter patients. Indeed, the mortality after progression is not influenced by the time to this event.
The impact of aquaculture system on the microbiome and gut metabolome of juvenile Chinese softshell turtle (Pelodiscus sinensis)
Authors: Ding Xia , Jin Feng , Xu Jiawang , Zhang Shulei , Chen Dongxu , Hu Beijuan , Hong Yijiang
Published: April 2022

The commercial aquatic animal microbiome may markedly affect the successful host's farming in various aquaculture systems. However, very little was known about it. Here, two different aquaculture systems, the rice–fish culture (RFC) and intensive pond culture (IPC) systems, were compared to deconstruct the skin, oral, and gut microbiome, as well as the gut metabolome of juvenile Chinese softshell turtle (Pelodiscus sinensis). Higher alpha‐diversity and functional redundancy ofP. sinensismicrobial community were found in the RFC than those of the IPC. The aquaculture systems have the strongest influence on the gut microbiome, followed by the skin microbiome, and finally the oral microbiome. Source‐tracking analysis showed that the RFC's microbial community originated from more unknown sources than that of the IPC across all body regions. Strikingly, the RFC's oral and skin microbiome exhibited a significantly higher proportion of generalists and broader habitat niche breadth than those of the IPC, but not the gut. Null model analysis revealed that the RFC's oral and skin microbial community assembly was governed by a significantly greater proportion of deterministic processes than that of the IPC, but not the gut. We further identified the key gene and microbial contribution to five significantly changed gut metabolites, 2‐oxoglutarate,N‐acetyl‐d‐mannosamine,cis‐4‐hydroxy‐d‐proline, nicotinamide, andl‐alanine, which were significantly correlated with important categories of microbe‐mediated processes, including the amino acid metabolism, GABAergic synapse, ABC transporters, biosynthesis of unsaturated fatty acids, as well as citrate cycle. Moreover, different aquaculture systems have a significant impact on the hepatic lipid metabolism and body shape ofP. sinensis. Our results provide new insight into the influence of aquaculture systems on the microbial community structure feature and assembly mechanism in an aquatic animal, also highlighting the key microbiome and gene contributions to the metabolite variation in the gut microbiome‐metabolome association.
Cost analysis of coronavirus disease 2019 test strategies using pooled reverse transcriptase‐polymerase chain reaction technique
Authors: Kim Eun Young , Kim Juyoung , Sung Heungsup , Jo Min‐Woo
Published: April 2022

Background

This study aimed to compare the testing strategies for COVID‐19 (i.e., individual, simple pooling, and matrix pooling) in terms of cost.

Methods

We simulated the total expenditures of each testing strategy for running 10,000 tests. Three parameters were used: positive rate (PR), pool size, and test cost. We compared the total testing costs under two hypothetical scenarios in South Korea. We also simulated country‐specific circumstances in India, South Africa, South Korea, the UK, and the USA.

Results

At extreme PRs of 0.01% and 10%, simple pooling was the most economic option and resulted in cost reductions of 98.0% (pool size ≥80) and 36.7% (pool size = 3), respectively. At moderate PRs of 0.1%, 1%, 2%, and 5%, the matrix pooling strategy was the most economic option and resulted in cost reductions of 97.0% (pool size ≥88), 86.1% (pool size = 22), 77.9% (pool size = 14), and 59.2% (pool size = 7), respectively. In both hypothetical scenarios of South Korea, simple pooling costs less than matrix pooling. However, the preferable options for achieving cost savings differed depending on each country's cost per test and PRs.

Conclusions

Both pooling strategies resulted in notable cost reductions compared with individual testing in most scenarios pertinent to real‐life situations. The appropriate type of testing strategy should be chosen by considering the PR of COVID‐19 in the community and the test cost while using an appropriate pooling size such as five specimens.
DNA damage response signaling pathways as important targets for combination therapy and chemotherapy sensitization in osteosarcoma
Authors: Alemi Forough , Malakoti Faezeh , Vaghari‐Tabari Mostafa , Soleimanpour Jafar , Shabestani Nazila , Sadigh Aydin R. , Khelghati Nafiseh , Asemi Zatollah , Ahmadi Yasin , Yousefi Bahman
Published: April 2022

Osteosarcoma (OS) is the most common bone malignancy that occurs most often in young adults, and adolescents with a survival rate of 20% in its advanced stages. Nowadays, increasing the effectiveness of common treatments used in OS has become one of the main problems for clinicians due to cancer cells becoming resistant to chemotherapy. One of the most important mechanisms of resistance to chemotherapy is through increasing the ability of DNA repair because most chemotherapy drugs damage the DNA of cancer cells. DNA damage response (DDR) is a signal transduction pathway involved in preserving the genome stability upon exposure to endogenous and exogenous DNA‐damaging factors such as chemotherapy agents. There is evidence that the suppression of DDR may reduce chemoresistance and increase the effectiveness of chemotherapy in OS. In this review, we aim to summarize these studies to better understand the role of DDR in OS chemoresistance in pursuit of overcoming the obstacles to the success of chemotherapy.
Understanding trust between pediatric hospitalists and outpatient clinicians during hospital admissions: A multisite qualitative analysis
Authors: McDaniel Corrie E. , Arthur Kimberly C. , Arakelyan Mary , Stevens Cathryn , Montalbano Amanda , Ojugbele Olutosin , Leyenaar JoAnna K.
Published: April 2022

Background

During transitions between sites of care, clinicians must build trust with colleagues to make decisions that ensure safe, high‐quality care.

Objectives

This study explored factors that could influence trust between outpatient clinicians and pediatric hospitalists when children are referred for hospital admission.

Design, Setting, and Participants

We conducted an analysis of 41 semistructured interviews with outpatient clinicians and pediatric hospitalists from May 2020 through October 2021 across three healthcare systems participating in a multisite comparative effectiveness study of pediatric direct and emergency department admissions.

Intervention, Main Outcomes, and Measures

Qualitative interviews. A conceptual model for trust between outpatient clinicians and pediatric hospitalists during hospital admission referral. Interviews were professionally transcribed, verified for accuracy, and analyzed using a combination of inductive and deductive.

Results

We identified two primary domains: (1) interpersonal trust and (2) trust‐by‐proxy. Interpersonal trust included five relational factors that influenced collaboration between clinicians: antecedent relationships, confidence in others clinical abilities, understanding others’ practice culture, recognition of available resources, and power dynamic. An individual clinicians’ assessment of risk and past clinical experiences also influenced trust during clinical decision‐making. Trust‐by‐proxy represented system‐level factors that could influence trust, independent of any pre‐existing relationships, including communication infrastructure, guidelines and protocols, the organizational culture, and professional courtesy.

Conclusion

Interpersonal and system‐level factors influence trust between outpatient clinicians and hospitalists during decision‐making encounters. System‐level factors may serve as a proxy for trust when clinicians do not have pre‐existing interpersonal relationships. These factors could be explored as an explicit target of interventions to improve interdisciplinary collaboration and decision‐making between hospitalists and primary care clinicians.