bluuebunny/crossref_metadata_2025 huggingface dataset:
Room‐Temperature Reversible σ‐Dimerization of a Phenalenyl Radical
Authors: Dong Xue , Sun Quanchun , Feng Zhongtao , Ruan Huapeng , Tang Shuxuan , Liu Min , Zhao Yue , Su Yuanting , Wang Xinping
Published: April 2022

Comprehensive Summary

Phenalenyl derivatives have been of tremendous interest due to their reversible dimerization in response to the external stimuli such as temperature. However, most of PLY derivatives only show the reversibility dependent on temperature. Herein, we report a unique PLY‐based radical anionic salt with reversible σ‐dimerization controlled by solvent rather than temperature. The structure and reversibility of this PLY anion system have been spectroscopically, crystallographically, and theoretically investigated. The molecule exists mainly as the σ‐dimer form of K2[σ‐12] in toluene, while it can be broken into the monomeric radical anion 1•– by re‐dissolving in THF. Moreover, when THF is replaced with toluene, radical 1•– could be σ‐dimerized back again. Theoretical calculations reveal that the potassium ions are necessary for the formation of the σ‐dimer and the solvent polarity controls the σ‐dimerization by regulating the presence of K+.
Engineering Reversible Hydrogels for 3D Cell Culture and Release Using Diselenide Catalyzed Fast Disulfide Formation
Authors: Han Yueying , Liu Cheng , Xu Huaping , Cao Yi
Published: April 2022

Comprehensive Summary

Hydrogels crosslinked by dynamic covalent bonds can effectively mimic the viscoelastic properties of native extracellular matrix and have been widely explored for 3D cell culture. Disulfide is one of the most common dynamic bonds in biological systems whose formation and cleavage are catalyzed by a set of dedicated enzymes. However, in vitro formation of disulfide bonds is a slow process and requires harsh catalysts. Therefore, it is difficult to use disulfide crosslinked hydrogels for cell culture. In this work, we show that disulfide bonds can be formed by thiol‐diselenide (DiSe) exchange under blue light illumination. This reaction is fast, reversible, and biocompatible. Moreover, residual diselenide in the hydrogel network can also accelerate thiol–disulfide exchange reactions leading to faster cell release from the hydrogels upon the addition of thiol‐containing agents. We anticipate that disulfide crosslinked hydrogels catalyzed by diselenide can find broad biomedical applications, such as cell culture, cell delivery, and drug‐controlled release.
Using Two Ecological Engineering Technologies to Treat River Pollution in Changhua County, Taiwan
Authors: Chen Wei‐Ting , Chen Hua‐Wei , Chou Chen‐Chiang , Tsai Yung‐Pin
Published: April 2022

Polluted rivers are a primary concern in Changhua County, Taiwan, due to the rapid development and expansion of agriculture and industry. A water purification system is tested on samples from the Yangzi‐Cuo River, Ci‐Tong Jiao, Changhua County. Two ecological engineering technologies (a gravel contact oxidation and a surface flow constructed wetland treatment) are investigated separately and in combination. The river pollution index (RPI) is measured before and after treatment and used to quantify the results. The inflow volume is 1534–2261 m3 day−1. Pollution elimination efficiencies are 62.83–95.83% for suspended soils, 55.02–86.02% for biochemical oxygen demand, 52.43–88.43% for total nitrogen, 11.95–82.43% for total phosphate, and 40.43–100.00% for ammoniacal nitrogen after using the combined methods. The inflow water is classified as highly polluted with an RPI > 6 mg L–1, whereas the post‐treatment outflow has medium or low pollution with RPIs of 3–6 or 2–3 mg L–1, respectively. The combination of both methods effectively purified Yangzi‐Cuo River water.
Carbon Dots as Drug Delivery Vehicles for Antimicrobial Applications: A Minireview
Authors: Wang Zi‐Xi , Wang Zihao , Wu Fu‐Gen
Published: April 2022

Carbon dots are small carbon nanoparticles with intrinsic photoluminescence. Because of the advantages such as good biocompatibility and water dispersity, many researchers have applied carbon dots as delivery platforms of antimicrobial agents. Compared with the free small‐molecule antimicrobial agents alone, the carbon dot‐based systems may exhibit enhanced antimicrobial activity, increased stability, improved cellular uptake, and reduced side effects. This review will mainly discuss the antimicrobial agent‐loaded carbon dots for various antibacterial, antifungal, and antiviral applications. The current limitations and future research directions in the related field are also proposed. It is hoped that this review will have implications for the future development of functional carbon dots for various practical antimicrobial uses.
Isotropic‐Nematic Phase Transition and Liquid Crystal Droplets
Authors: Lin Fanghua , Wang Changyou
Published: April 2022

Liquid crystal droplets are of great interest from physics and applications. Rigorous mathematical analysis is challenging as the problem involves harmonic maps (or Oseen‐Frank energy minimizers in general), free interfaces, and topological defects which could be either inside the droplet or on its surface along with some intriguing boundary anchoring conditions for the orientation configurations. In this paper, through a study of the phase transition between the isotropic and nematic states of liquid crystal based on the Ericksen model, we can show, when the size of a droplet is much larger in comparison with the ratio of the Frank constants to the surface tension, a Γ‐convergence theorem for minimizers. This Γ‐limit is in fact the sharp interface limit for the phase transition between the isotropic and nematic regions when the small parameter ε, corresponding to the transition layer width, goes to 0. This limiting process not only provides a geometric description of the shape of the droplet as one would expect, and surprisingly it also gives the anchoring conditions for the orientations of liquid crystals on the surface of the droplet depending on material constants. In particular, homeotropic, tangential, and even free boundary conditions as assumed in earlier phenomenological modelings arise naturally, provided the surface tension, Frank‐Ericksen constants are in suitable ranges. © 2022 Wiley Periodicals LLC.
Multi‐level learning based on3D CTimage integrated medical clinic information for accurate diagnosis of pulmonary nodules
Authors: Zhang Yanan , Zhao Juanjuan , Wu Wei , Qiang Yan , Jia Liye
Published: April 2022

The diagnosis of pulmonary nodules by clinicians depends not only on radiological imaging but also on the patient's own clinical record information and other factors. However, exploring the guiding role of clinical information is a major challenge. In this article, an intelligent personalized diagnosis decision‐making model is proposed, which combines radiology images with patient information. First, the 3D image cube of the pulmonary nodule is constructed. Then, a 3D multi‐level fusion ResNet is designed to extract the features of the nodule by making full use of the spatial context information. Finally, a kind of classification model based on feature‐related analysis was proposed, which fused clinical information features and image features and realized a nonlinear radial basis feature mapping. We tested this method on the public dataset and a cooperation hospital dataset. Experiments show that this method can effectively improve the classification accuracy of unstable nodules at the classification boundary. Our model showed significant improvements in sensitivity, specificity, and accuracy. Meanwhile, compared with other deep learning diagnosis methods, our method achieves better discriminative results and is highly suited to be used for pulmonary nodule diagnosis.
An effective chronic lymphocytic leukemia detection method using hybrid optimization aware random multimodal deep learning
Authors: Sivalingam Nithya Priya , Chinnasamy Sundar , Suruli Muniyandi Thanabal
Published: April 2022

The leukemia represents a blood cancer that begins from bone marrow and spread to bloodstream and other limbs. The leukocytes pose various morphologies and size that makes it complex to detect and segment exactly. To consider this issue, this article develops a novel and efficient method for chronic lymphocytic leukemia (CLL) detection with blood smear images. Here, the preprocessing is done with Type 2 fuzzy and cuckoo search‐based filter for discarding artifacts and noise contained in the images. The cell segmentation is done with deep fuzzy clustering for producing the segments from the preprocessed blood smear images. The discovery of CLL is done with random multimodal deep learning (RMDL). The RMDL training is done with proposed Jaya‐competitive swarm optimization (Jaya‐CSO) algorithm. The developed Jaya‐CSO is devised by combining Jaya optimization and competitive swarm optimizer (CSO). Hence, the proposed Jaya‐CSO‐based RMDL is employed for discovering lymphocytic leukemia. The proposed Jaya‐CSO‐based RMDL offered improved performance with highest accuracy of 95.1%, highest true negative rate of 95.4% and highest true positive rate of 95.2%.
Impact of the ABCD‐GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi‐Site, Real‐World Investigation
Authors: Thomas Cameron D. , Franchi Francesco , Keeley Ellen C. , Rossi Joseph S. , Winget Marshall , David Anderson R. , Dempsey Alyssa L. , Gong Yan , Gower Megan N. , Kerensky Richard A. , Kulick Natasha , Malave Jean G. , McDonough Caitrin W. , Mulrenin Ian R. , Starostik Petr , Beitelshees Amber L. , Johnson Julie A. , Stouffer George A. , Winterstein Almut G. , Angiolillo Dominick J. , Lee Craig R. , Cavallari Larisa H.
Published: April 2022

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD‐GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD‐GENE score to predict the risk for atherothrombotic events in a diverse, real‐world population of clopidogrel‐treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all‐cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD‐GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD‐GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient‐years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23–2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient‐years, adjusted HR 1.59, 95% CI 1.11–2.30, P = 0.013). Our diverse, real‐world data demonstrate diminished clopidogrel effectiveness in post‐PCI patients with an ABCD‐GENE score ≥ 10.
The Effect of Ibuprofen Exposure and Patient Characteristics on the Closure of the Patent Ductus Arteriosus in Preterm Infants
Authors: Engbers Aline G. J. , Völler Swantje , Flint Robert B. , Goulooze Sebastiaan C. , de Klerk Johan , Krekels Elke H. J. , van Dijk Monique , Willemsen Sten P. , Reiss Irwin K. M. , Knibbe Catherijne A. J. , Simons Sinno H. P.
Published: April 2022

Spontaneous closure of the ductus arteriosus depends on gestational age (GA) and might be delayed in preterm infants, resulting in patent ductus arteriosus (PDA). Ibuprofen can be administered to enhance closure, but the exposure‐response relationship between ibuprofen and the closure of PDA remains uncertain. We investigated the influence of patient characteristics and ibuprofen exposure on ductus closure. A cohort of preterm infants with PDA and treated with ibuprofen was analyzed. Ibuprofen exposure was based on a previously developed population pharmacokinetic study that was in part based on the same study population. Logistic regression analyses were performed with ductus closure (yes/no) as outcome, to analyze the contribution of ibuprofen exposure and patient characteristics. In our cohort of 263 preterm infants (median GA 26.1 (range: 23.7–30.0) weeks, birthweight 840 (365–1,470) g) receiving ibuprofen treatment consisting of 3 doses that was initiated at a median postnatal age (PNAstart) of 5 (1–32) days, PDA was closed in 55 (21%) patients. Exposure to ibuprofen strongly decreased with PNAstart. Overall, the probability of ductus closure decreased with PNAstart (odds ratio (OR): 0.7, 95% CI: 0.6–0.8) and Z‐score for birthweight (ZBirthweight‐for‐GA; OR: 0.8, 95% CI: 0.6‐1.0), and increased with GA (OR: 1.5, 95% CI: 1.1–1.9). For patients with PNAstart < 1 week, concentrations of ibuprofen, GA, and ZBirthweight‐for‐GA predicted probability of ductus closure. During a window of opportunity for ductus closure within the first days of life, probability of closure depends on GA, ZBirthweight‐for‐GA, and ibuprofen exposure. Increased, yet unstudied dosages might increase the effectivity of ibuprofen beyond the first week of life.
Cytologic and histologic features of pigmented pleomorphic xanthoastrocytoma: A case report and literature review
Authors: Lee Yueh , Chang Min‐Hsiang , Chou Yueh‐Hung
Published: April 2022

In the central nervous system, the presence of pigment in astrocytic tumors is rare. Only nine cases were reported in the English literature: one ganglioglioma, one pilocytic astrocytoma, and seven cases of pleomorphic xanthoastrocytoma (PXA). Though squash cytology is a common and useful tool for intraoperative diagnosis during brain tumor surgeries, the cytologic findings of pigmented PXA have not been recorded previously. We present a 32‐year‐old woman with a mass in her medial right temporal lobe. Intraoperative squash cytology examination demonstrated pleomorphic tumor cells containing cytoplasmic pigment granules. The subsequent tissue section and additional workup revealed a PXA with melanosomal melanin pigment deposits. While conventional PXA has to be differentiated from high‐grade tumors such as glioblastoma, in the pigmented variant the presence of pigment can cause further diagnostic confusion with other pigmented tumors, in particular melanoma. It should be added into the differential diagnoses when a brain tumor smear shows nuclear pleomorphism and intracytoplasmic pigment particles.
Aboveground carbon responses to experimental and natural hurricane impacts in a subtropical wet forest in Puerto Rico
Authors: Chevalier Hervé , Brokaw Nicholas V. L. , Ward Sheila E. , Zimmerman Jess K. , Shiels Aaron B. , Bithorn John , Matta Carmona Samuel
Published: April 2022

Climate change and disturbance make it difficult to project long‐term patterns of carbon sequestration in tropical forests, but large ecosystem experiments in these forests can inform predictions. The Canopy Trimming Experiment (CTE) manipulates two key components of hurricane disturbance, canopy openness and detritus deposition, in a tropical forest in Puerto Rico. We documented how the CTE and a real hurricane affected tree recruitment, biomass, and aboveground carbon storage over 15 years. In the CTE treatments, we trimmed branches, but we did not fell trees. We expected that during the 14‐year period after initial canopy trimming, regrowth of branches and stems and stem recruitment stimulated by increased light and trimmed debris would help restore biomass and carbon loss due to trimming. Compared to control plots, in the trimmed plots recruitment of palms and dicot trees increased markedly after trimming, and stem diameters of standing trees increased. Data showed that recruitment of small trees adds little to aboveground carbon, compared to the amount in large trees. Nevertheless, this response restored pretreatment biomass and carbon in the experimental period. In particular, the experimental additions of trimmed debris on the forest floor seemed to stimulate increase in aboveground carbon. Toward the end of the experimental period, Hurricane Maria (Category 4 hurricane) trimmed and felled some trees but reduced aboveground carbon less in the plots (including untrimmed plots) than experimental trimming had. Thus, it appears that the amount of regrowth recorded after experimental trimming could also restore aboveground carbon in the forest after a severe hurricane in the same time span. However, Hurricane Maria, unlike the trimming treatments, felled large trees, and it may be that with predicted, more frequent severe hurricanes, that the continued loss of large trees would over the long term decrease aboveground carbon stored in this Puerto Rican forest and likewise in other tropical forests affected by cyclonic storms.
Anti‐Corrosion and Reconstruction of Surface Crystal Plane for Zn Anodes by an Advanced Metal Passivation Technique
Authors: Liu Si , Lin Hongxin , Song Qianqian , Zhu Jian , Zhu Changbao
Published: April 2022

For the aqueous Zn‐ion battery, dendrite formation, corrosion, and interfacial parasitic reactions are major issues, which greatly inhibits their practical application. How to develop a method of Zn construction or treatment to solve these issues for Zn anodes are still great challenges. Herein, a simple and cheap metal passivation technique is proposed for Zn anodes from a corrosion science perspective. Similar to the metal anti‐corrosion engineering, the formed interfacial protective layer in a chemical way can sufficiently solve the corrosion issues. Furthermore, the proposed passivity approach can reconstruct Zn surface‐preferred crystal planes, exposing more (002) planes and improving surface hydrophilicity, which inhibits the formation of Zn dendrites and hydrogen evolution effectively. As expected, the passivated Zn achieves outstanding cycling life (1914 h) with low voltage polarization (<40 mV). Even at 6 mA cm−2 and 3 mA h cm−2, it can achieve stable Zn deposition over 460 h. The treated Zn anode coupled with MnO2 cathode shows prominently reinforced full batteries service life, making it a potential Zn anode candidate for excellent performance aqueous Zn‐ion batteries. The proposed passivation approach provides a guideline for other metal electrodes preparation in various batteries and establishes the connections between corrosion science and batteries.
Two β‐Diketiminate Zinc Complexes with 1‐D Chain and Dinuclear Topologies: Synthesis, Structures, and Catalytic Behavior
Authors: Zhang Liang , Li Yafei , Wang Li , Cao Zhu , Zhang Qian , Li Yahong
Published: April 2022

Two zinc complexes, [L1Zn2Et2]n (1) and [L2Zn2Et2] (2), were synthesized by reacting bis(β‐diketiminate) ligands H2L1 and H2L2 with ZnEt2. X‐ray single‐crystal diffraction analysis indicated that compound 1 displays a novel one‐dimensional chain structure. Compound 2 is dinuclear. The two compounds were employed to catalyze the coupling reaction of aryl iodides with B2Pin2. They were both catalytically active toward this transformation. Compound 1 exhibited higher catalytic activity than that of complex 2. The borylation reactions catalyzed by 1 possess the features of milder conditions, high functional group tolerance and wide range of substrate scopes.
Near‐wall velocities of particles suspended in shear flow and a streamwise electric field
Authors: Yee Andrew J. , Yoda Minami
Published: April 2022

Particles with a diameter of ∼0.5 µm in a dilute (volume fractions φ∞ < 4 × 10−3) suspension assemble into highly elongated structures called “bands” under certain conditions in combined Poiseuille and electroosmotic flows in opposite directions through microchannels at particle‐based Reynolds numbers Rep < < 1. The particles are first concentrated near, then form “bands” within ∼6 µm of, the channel wall. The experiments described here examine the near‐wall dynamics of individual “tracer” particles during the initial concentration, or accumulation, of particles, and the steady‐state stage when the particles have formed relatively stable bands at different near‐wall shear rates and electric field magnitudes. Surprisingly, the near‐wall upstream particle velocities are found to be consistently greater in magnitude than the expected values based on the particles being convected by the superposition of both flows and subject to electrophoresis, which is in the same direction as the Poiseuille flow. However, the particle velocities scale linearly with the change in electric field magnitude, suggesting that the particle dynamics are dominated by linear electrokinetic phenomena. If this discrepancy with theory is only due to changes in particle electrophoresis, electrophoresis is significantly reduced to values as small as 20%–50% of the Smoluchowski relation, or well below previous model predictions, even for high particle potentials.
Mitigating spatial confounding by explicitly correlating Gaussian random fields
Authors: Marques Isa , Kneib Thomas , Klein Nadja
Published: April 2022

Spatial models are used in a variety of research areas, such as environmental sciences, epidemiology, or physics. A common phenomenon in such spatial regression models is spatial confounding. This phenomenon is observed when spatially indexed covariates modeling the mean of the response are correlated with a spatial random effect included in the model, for example, as a proxy of unobserved spatial confounders. As a result, estimates for regression coefficients of the covariates can be severely biased and interpretation of these is no longer valid. Recent literature has shown that typical solutions for reducing spatial confounding can lead to misleading and counterintuitive results. In this article, we develop a computationally efficient spatial model that explicitly correlates a Gaussian random field for the covariate of interest with the Gaussian random field in the main model equation and integrates novel prior structures to reduce spatial confounding. Starting from the univariate case, we extend our prior structure also to the case of multiple spatially confounded covariates. In simulation studies, we show that our novel model flexibly detects and reduces spatial confounding in spatial datasets, and it performs better than typically used methods such as restricted spatial regression. These results are promising for any applied researcher who wishes to interpret covariate effects in spatial regression models. As a real data illustration, we study the effect of elevation and temperature on the mean of monthly precipitation in Germany.
Noncredit Career and Technical Community College Programs as a Bridge to Employers: Report on NYC Region Study
Authors: Haviland Sara , Robbins Steve , Kirova Dessi , Bochenek Jennifer , Fishtein Dan
Published: April 2022

Noncredit community college programs provide an important route for workforce development. They offer affordable and accessible short‐term training options for individuals seeking access to middle‐skills jobs. Absent the burdens of accreditation standards, they can respond nimbly to local labor market needs. However, they can also be varied and confusing, and despite the high volume of students that they serve, they are an underexamined area in higher education. This study examines noncredit programs in the New York City labor market to determine how schools align noncredit offerings to the labor market, focusing on credential design, competencies, and market processes. It pursues a push–pull design through a combination of document review and interviews with school leaders and employers and introduces quality taxonomy for understanding employer engagement in individual programs. Implications for students, programs, schools, and employers are explored.

The executive summary for this report can be downloaded at
https://www.ets.org/Media/Research/pdf/Executive_Summary_RR‐22‐09.pdf
Milk composition, traditional processing, marketing, and consumption among smallholder dairy farmers in selected towns of Jimma Zone, Oromia Regional State, Ethiopia
Authors: Duguma Belay
Published: April 2022

In Ethiopia, dairy products remain the most important animal source of foods including in the current study area. However, poor milk quality is frequently told constraint, and this affects smallholder dairy development. This study aimed to assess raw cow milk composition, processing, consumption, and marketing among smallholder dairy producers in selected towns of Jimma Zone, Ethiopia. Primary data were collected by surveying 52 randomly selected dairy cattle keeping households using a structured questionnaire and analysis of raw milk chemical composition. The results revealed that the average milk production was 5.98 ± 1.01 liters/household/day, of which the majority (62.9%) was marketed. About 22.7% of households reported processing milk into butter, cottage cheese, ghee, and fermented milk at household level mainly for domestic use. A combination of fresh whole milk, fermented milk, butter, cottage cheese, and ghee (51.7%) were the main dairy products consumed by respondents. About 72.2% and 6.1% of households consumed boiled and raw milk, respectively, while 100% respondents reported consuming raw fermented whole milk. Milk was channeled to consumers and retailers through informal marketing system (100%). The awareness of respondents about zoonotic diseases was found to be very low. The mean fat, lactose, and protein content of raw cow milk were significantly (p < .05) affected by breed. It is recommended that consumption of raw milk and fermented milk could pose a public health risk to consumers, implying the need for urgent farmers’ awareness creation to boil milk before consumption for prevention and control of zoonotic diseases.
Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States
Authors: Ahn Joseph C. , Lauzon Marie , Luu Michael , Noureddin Mazen , Ayoub Walid , Kuo Alexander , Sundaram Vinay , Kosari Kambiz , Nissen Nicholas , Gong Jun , Hendifar Andrew , Roberts Lewis R. , Abou‐Alfa Ghassan K. , Singal Amit G. , Yang Ju Dong
Published: April 2022

Background and Aims

Immunotherapy has emerged as an effective treatment for patients with advanced‐stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy.

Approach and Results

We used the US National Cancer Database to identify patients with tumor‐node‐metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first‐line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65–0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46–0.83) and Black patients (aOR: 0.71, 95% CI: 0.54–0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race‐ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004).

Conclusions

Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial‐ethnic disparities in the management of advanced HCC is urgently needed.
Proteomics‐based identification of the role of osteosarcoma amplified‐9 in hepatocellular carcinoma recurrence
Authors: Wei Xuyong , Yang Mengfan , Pan Binhua , Zhang Xiaobing , Lin Hanchao , Li Wangyao , Shu Wenzhi , Wang Kun , Khan Abdul Rehman , Zhang Xuanyu , Cen Beini , Xu Xiao
Published: April 2022

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies; its recurrence is associated with high mortality and poor recurrence‐free survival and is affected by multisystem and multilevel pathological changes. To identify the key proteins associated with tumor recurrence and the underlying mechanisms, proteomic profiling of tumor specimens from early recurrence and nonrecurrence patients was performed in this study. Proteomics was applied to identify differentially expressed proteins during the early recurrence of HCC after surgery. Osteosarcoma amplified‐9 (OS‐9) was discovered, and the correlation between OS‐9 expression and the clinicopathological characteristics of patients was analyzed. Invasion and migration were examined in SMMC‐7721 cells with and without OS‐9 overexpression. Proteomics was performed once again using SMMC‐7721 cells with OS‐9 overexpression to further analyze the proteins with altered expression. OS‐9 was overexpressed in the early recurrence group, and OS‐9 overexpression was associated with high serum alpha‐fetoprotein levels and poor recurrence‐free survival in 196 patients with HCC. The invasion and migration abilities of SMMC‐7721 cells were enhanced in the OS‐9 overexpression group. Bioinformatic functional enrichment methods, including Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis, revealed that the hypoxia‐inducible factor 1 (HIF‐1) and tumor necrosis factor (TNF) signaling pathways were activated in the OS‐9 overexpression group. The migration and invasion capacities of OS‐9 overexpressed HCC cell line were weakened while treated with HIF‐1α or TNF‐α inhibitors. Conclusion: Our results suggest that the overexpression of OS‐9 is related to HCC recurrence, thereby contributing to the migration and invasion capacities of HCC cell line by regulating the HIF‐1 and TNF pathways.
Ecosystem services at risk in Italy from coastal inundation under extreme sea level scenarios up to 2050: A spatially resolved approach supporting climate change adaptation
Authors: Furlan Elisa , Derepasko Diana , Torresan Silvia , Pham Hung V. , Fogarin Stefano , Critto Andrea
Published: April 2022

According to the latest projections of the Intergovernmental Panel on Climate Change, at the end of the century, coastal zones and low-lying ecosystems will be increasingly threatened by rising global mean sea levels. In order to support integrated coastal zone management and advance the basic “source–pathway–receptor–consequence” approach focused on traditional receptors (e.g., population, infrastructure, and economy), a novel risk framework is proposed able to evaluate potential risks of loss or degradation of ecosystem services (ESs) due to projected extreme sea level scenarios in the Italian coast. Three risk scenarios for the reference period (1969–2010) and future time frame up to 2050 under RCP4.5 and RCP8.5 are developed by integrating extreme water-level projections related to changing climate conditions, with vulnerability information about the topography, distance from coastlines, and presence of artificial protections. A risk assessment is then performed considering the potential effects of the spatial-temporal variability of inundations and land use on the supply level and spatial distribution of ESs. The results of the analysis are summarized into a spatially explicit risk index, useful to rank coastal areas more prone to ESs losses or degradation due to coastal inundation at the national scale. Overall, the Northern Adriatic coast is scored at high risk of ESs loss or degradation in the future scenario. Other small coastal strips with medium risk scores are the Eastern Puglia coast, Western Sardinia, and Tuscany's coast. The ESs Coastal Risk Index provides an easy-to-understand screening assessment that could support the prioritization of areas for coastal adaptation at the national scale. Moreover, this index allows the direct evaluation of the public value of ecosystems and supports more effective territorial planning and environmental management decisions. In particular, it could support the mainstreaming of ecosystem-based approaches (e.g., ecological engineering and green infrastructures) to mitigate the risks of climate change and extreme events while protecting ecosystems and biodiversity. Integr Environ Assess Manag 2022;18:1564–1577. © 2021 SETAC

KEY POINTS

The loss of coastal ecosystem services to extreme sea level scenarios is evaluated. The index integrates climatic, physical, and environmental indicators. About 8% of the Italian shoreline is subjected to potential ecosystem services loss. Ecosystem services at greatest risk are mainly located on the North Adriatic coast. Results can inform ecosystem-based coastal zone management and climate adaptation.
Higher genetically predicted low‐density lipoprotein levels increase the renal cancer risk independent of triglycerides and high‐density lipoprotein levels: A Mendelian randomization study
Authors: Ma Yucheng , Jian Zhongyu , Xiang Liyuan , Jin Xi
Published: April 2022

The causation between lipids and renal cancer remains inconclusive. Our purpose is to explore the causal relationships between the three primary lipid metabolism‐related substances, namely triglycerides (TG), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) with the risk of renal cancer using Mendelian randomization (MR) methods. Genetic instruments for lipids were acquired from the UK Biobank. Outcome data were from the FinnGen study (1397 renal cancer cases and 204 070). Single‐variable MR (SVMR) and multi‐variable MR (MVMR) analyses were conducted with TwoSampleMR package based on R 4.0.3. The random‐effect inverse‐variance weighted (IVW), MR‐Egger, weighted‐median method, and weighted mode were the four main computing methods. We found that per 1 SD elevated LDL level was causally associated with renal cancer occurrence based on SVMR (OR, 1.31, 95% CI: 1.05‐1.64, P = .016). Similar significant associations were found in other methods. However, the results of SVMR did not support significant associations between TG, and HDL with renal cancer risk in all methods. The association between LDL and renal cancer was still significant in MVMR analysis (OR for IVW method: 1.22 per 1 SD higher trait (SD, 95% CI: 1.11‐1.34, P < .001; OR for MR‐Egger: 1.22 per 1 SD higher trait, 95% CI: 1.01‐1.47, P = .042) when taking TG and HDL into consideration. Our study supported that elevated serum LDL levels is causally associated with an increased risk of renal cancer independent of TG and HDL.
Gut microbiota correlates with antitumor activity in patients with mCRC and NSCLC treated with cetuximab plus avelumab
Authors: Martini Giulia , Ciardiello Davide , Dallio Marcello , Famiglietti Vincenzo , Esposito Lucia , Corte Carminia Maria Della , Napolitano Stefania , Fasano Morena , Gravina Antonietta Gerarda , Romano Marco , Loguercio Carmelina , Federico Alessandro , Maiello Evaristo , Tuccillo Concetta , Morgillo Floriana , Troiani Teresa , Di Maio Massimo , Martinelli Erika , Ciardiello Fortunato
Published: April 2022

Gut microbiota is involved in immune modulation and immune checkpoint inhibitors (ICIs) efficacy. Single‐arm phase II CAVE‐mCRC and CAVE‐LUNG clinical trials investigated cetuximab + avelumab combination in RAS wild‐type (WT) metastatic colorectal cancer (mCRC) and chemo‐refractory nonsmall cell lung cancer (NSCLC) patients, respectively. A comprehensive gut microbiota genetic analysis was done in basal fecal samples of 14 patients from CAVE‐mCRC trial with circulating tumor DNA (ctDNA) RAS/BRAF WT and microsatellite stable (MSS) disease. Results were validated in a cohort of 10 patients from CAVE‐Lung trial. 16S rRNA sequencing revealed 23 027 bacteria species in basal fecal samples of 14 patients from CAVE‐mCRC trial. In five long‐term responding patients (progression‐free survival [PFS], 9‐24 months) significant increases in two butyrate‐producing bacteria, Agathobacter M104/1 (P = .018) and Blautia SR1/5 (P = .023) were found compared to nine patients with shorter PFS (2‐6 months). A significantly better PFS was also observed according to the presence or absence of these species in basal fecal samples. For Agathobacter M104/1, median PFS (mPFS) was 13.5 months (95% confidence interval [CI], 6.5‐20.5 months) vs 4.6 months (95% CI, 1.8‐7.4 months); P = .006. For Blautia SR1/5, mPFS was 5.9 months (95% CI, 2.2‐9.7 months) vs 3.6 months (95% CI, 3.3‐4.0 months); P = .021. Similarly, in CAVE‐Lung validation cohort, Agathobacter M104/1 and Blautia SR1/5 expression were associated with PFS according to their presence or absence in basal fecal samples. Agathobacter and Blautia species could be potential biomarkers of outcome in mCRC, and NSCLC patients treated with cetuximab + avelumab. These findings deserve further investigation.
Healthy lifestyle index and the risk of ductal carcinoma in situ of the breast in the Women's Health Initiative
Authors: Peila Rita , Lane Dorothy S. , Shadyab Aladdin H. , Saquib Nazmus , Strickler Howard D. , Manson JoAnn E. , Pan Kathy , Rohan Thomas E.
Published: April 2022

A relatively high healthy lifestyle index (HLI) score, representing a healthy diet, participation in moderate to vigorous physical exercise, no smoking, low to no alcohol intake and a normal body mass index, has been associated with a reduced risk of invasive breast cancer. However, no study has shown an association between the HLI and the risk of ductal carcinoma in situ of the breast (DCIS), which is considered to be a nonobligate precursor of invasive breast cancer. We evaluated this association in a prospective cohort of 132 230 postmenopausal women, aged 50 to 79 years, recruited between 1993 and 1998 across the United States and enrolled in the Women's Health Initiative study. The HLI score was created and categorized into quartiles. During an average follow‐up of 15.4 years, 2035 DCIS cases were ascertained. Multivariable‐adjusted Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of HLI with the risk of DCIS. Women in the highest HLI quartile had a lower DCIS risk than those in the lowest quartile (HR4thQT = 0.80, 95% CI, 0.70‐0.92) and this association was stronger in women with a family history of breast cancer (HR4thQT = 0.70, 95% CI, 0.52‐0.93), and for ER+/PR+ DCIS (HR4thQT = 0.66, 95% CI, 0.52‐0.83). These findings suggest that there is an inverse association between HLI and risk of DCIS, and suggest that the adoption of a healthy lifestyle might lower the risk of DCIS.
Direct retrieval bias for general and specific memories for negatively valenced cues in major depression
Authors: Hallford David John , Matsumoto Noboru
Published: April 2022

Major depressive disorder (MDD) is associated with reduced specificity in autobiographical memory. It has been argued that this tendency occurs through a failure of effortful generative retrieval, regardless of valence of cue word. However, we propose that in MDD general memories are likely to be recalled via direct retrieval, and direct retrieval is more likely for negatively valenced cues. To provide a preliminary test of this, a large sample with MDD (N = 298; M age = 47.2) completed the autobiographical memory test and indicated whether retrievals were generative or direct. Categoric and extended memories for negatively valenced cues were more often directly retrieved than generatively retrieved, and more often than direct retrieval for positively valenced cues. In contrast, categoric and extended memories for positively valenced cues were more often generatively retrieved relative to generative retrieval for negatively valenced cues. Relative to non‐clinical samples, direct retrieval for negatively valenced cues was high. Retrieval method and valence may be moderating processes in the type of memories recalled. This preliminary work presents the possibility of an extension of theory on retrieval tendencies in MDD.
Energy‐efficient DoS attack against remote state estimation
Authors: Gan Ruimeng , Wang Yangyang , Xiao Zhe , Zhang Heng , Wang Xin , Yang Ming
Published: April 2022

In this paper, the security issue in cyber‐physical system (CPS) is investigated. In order to maximize the attack effect and save the limited energy, the energy efficiency problem is investigated from the perspective of the jammer. This problem is established as a mixed‐integer programming problem firstly, and then a necessary condition is presented to explore the optimal energy for a given attack number. Moreover, an energy efficiency optimization (EEO) algorithm is proposed to derive the optimal attack schedule. Lastly, some numerical results are shown to validate the effectiveness of the proposed algorithm.
Identification of the optimal primary care clinical pharmacy comprehensive medication management practice in the veterans health administration
Authors: McFarland M. Shawn , Ourth Heather , Seckel Ellina , Gould Kyleigh , Ragan Addison , Morreale Anthony
Published: April 2022

Clinical pharmacists are well‐positioned as the medication experts on the health care team to work collaboratively with providers and patients to achieve optimal medication use in order to maximize patient benefit and outcome. Comprehensive medication management (CMM) is defined as a patient‐centered approach to optimizing medication use and improving patient health outcomes that is delivered by a clinical pharmacist working in collaboration with the patient and other health care providers. Lack of fidelity in practice model design and implementation make generalization of results of clinical pharmacy CMM practice difficult. There is currently no organization that evaluates standardized implementation of clinical pharmacists providing CMM in a Patient‐Centered Medical Home (PCMH) leading to wide variability of CMM implementation within the PCMH model. The Veterans Health Administration (VA) is the largest integrated health care system in the United States. Clinical pharmacy specialists (CPS) in the VA work autonomously but collaboratively under a practice area‐based scope of practice with prescriptive authority. The goal of the Clinical Pharmacy Practice Office Platinum Practice Designation was to develop a standardized review process to recognize sites that have achieved core elements of desired primary care pharmacy practice. In this paper, we describe the creation and implementation of this process. The submission process consisted of three rounds ranging from survey, data submission, data review and validation, and a facility interview. A total of 19 submissions were completed with two sites identified as achieving greater than 90% fidelity to the CMM model and were considered best practices. The creation of a rigorous set of implementation tools and measurement metrics creates the necessary fidelity to evaluate programs across different geographic areas. Identified sites provide examples for other facilities to emulate and creates momentum for pharmacy practice advancement throughout the nation.
Evaluating an interactive teaching approach with personal genotyping to provide pharmacy students with a knowledge base for clinical pharmacogenetics
Authors: Arwood Meghan J. , McDonough Caitrin W. , Cavallari Larisa H. , Elsey Amanda R. , Frye Reginald F. , Gong Yan , Langaee Taimour , Johnson Julie A. , Wiisanen Kristin
Published: April 2022

Introduction

Although the majority of pharmacy schools are teaching pharmacogenetics in their curricula, there is limited coverage of important clinical concepts and pharmacists report low comfortability in utilizing pharmacogenetic results.

Objectives

To compare the effectiveness of a combined didactic and patient case‐based, interactive teaching approach (including optional personal genotyping) with a traditional didactic teaching strategy on students' knowledge and confidence in their ability to use pharmacogenetic data in clinical decision‐making.

Methods

The University of Florida College of Pharmacy offered elective and required courses in personalized medicine from 2014 to 2016. The elective course, Clinical Applications of Personalized Medicine, emphasized interactive patient case‐based teaching and incorporated personal genotype results into learning activities, while the required course, Personalized Medicine, primarily used a didactic lecture‐based format. Students enrolled in both courses concurrently (intervention group) and the required course alone (control group) completed pre‐ and post‐course surveys with patient case‐based assessments to evaluate their knowledge and confidence in their ability to apply genotype data to drug therapy recommendations.

Results

Fifty‐two students (intervention: n = 21; control: n = 31) completed both surveys. Between the intervention and control groups respectively, there were no differences in mean pre‐course knowledge (43.1% vs 37.7% questions correct, P = .15) or median confidence scores (35 vs 40, P = .84). Mean post‐course knowledge (65.4% vs 46.9% questions correct, P < .001) and median confidence scores (97 vs 81, P = .0003) were significantly higher in the intervention vs control group, respectively. There was no correlation between students' knowledge and confidence for pre‐course assessment in either group. For the post‐course assessment, knowledge and confidence were positively correlated in the intervention group (adjusted r = .46, adjusted P = .04), but were not correlated in controls.

Conclusion

Our data suggest that a combined teaching strategy that employs didactic lecture plus patient‐centered, case‐based teaching and personal genotype application improves students' ability to accurately self‐assess their knowledge in pharmacogenetics.
Solving the toxicology mystery: An educational activity focused on team‐based problem‐solving
Authors: Blue Heather L. , Zaheer Sakina F.
Published: April 2022

Introduction

Toxicology is traditionally taught in a lecture‐based format. This type of instruction makes it difficult to assess clinical thinking skills. A team‐based learning activity utilizing puzzles was developed for third‐year pharmacy students at the University of Minnesota College of Pharmacy to practice both knowledge retention and clinical application skills.

Methods

The puzzles used in this activity addressed key concepts in toxicology on lower cognitive levels, such as identifying and naming the toxicity. Solving the puzzles revealed clues to a patient case. Students were then tasked with compiling and analyzing these clues to successfully identify the toxicity and recommend appropriate treatment. After finishing the activity, the students completed a short assessment to provide feedback on the program.

Results

In the allotted 90 minutes, all 20 groups of eight or nine students correctly completed the puzzles, analyzed the clues, identified the specific toxicity, and created an appropriate treatment regimen. Ninety percent of groups reported that the activity enhanced their learning of toxicology, noting that the activity was engaging, promoted teamwork, and allowed application of knowledge to practical settings. Groups were also asked how the program could be improved, and responses included incorporating more facilitators, making the puzzles more challenging, and to clarify a particular puzzle.

Conclusion

This team‐based escape room‐style activity successfully engaged teams of students in applying their clinical knowledge to solve key concept toxicology puzzles and also identify and treat a poisoned patient case. Feedback provided will be used to improve and expand future team‐based learning activities.