bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Capacity O2-Type Layered Oxide Cathode Materials for Lithium-Ion Batteries: Ion-Exchange Synthesis and Electrochemistry
Authors: Wang Zhaoshun , Wang Yong , Meng Dechao , Zheng Qinfeng , Zhang Yixiao , Cai Feipeng , Zhu Di , Liu Jiabing , He Yushi , Chen Liwei , Ma Zi-Feng , Li Linsen
Published: January 2022

The O2-type layered oxide cathode materials have attracted strong research interest recently because of their high specific capacity and their unique lattice structure that may help suppress the detrimental layer-to-spinel phase transition. These materials are metastable and commonly prepared through Li-Na exchange methods from the Na-containing P2-type oxides. Here we investigated the structural, chemical, and morphological changes during the ion-exchange processes in both the LiBr/hexanol solution and the LiNO3/LiCl molten salts. The solution method was more favorable in preparing high-capacity O2-type cathode materials, even though the structural reorganization was slower compared with the molten-salt method. The as-made O2-type cathode materials, contrary to the previous belief, were actually Li-deficient at their pristine states, but could accept more Li ions than that it was extracted during the first charge/discharge cycle. The O2-type cathode materials exhibited high capacities (up to 266 mAh g−1) but the cycle performance requires further improvements. XRD and Raman spectroscopy studies indicated that the structural changes in the bulk were quite reversible. Using a fluorinated electrolyte to address the interface instability improved the cycle performance. Our results provide a more complete understanding of the O2-type cathode materials and useful guidance in the design of low-cost, high-energy cathode materials for LIBs.
Effect of the Slurry Mixing Process on the Structural Properties of the Anode and the Resulting Fast-Charging Performance of the Lithium-Ion Battery Cell
Authors: Grießl Desiree , Adam Alexander , Huber Korbinian , Kwade Arno
Published: January 2022

Besides the performance of a lithium-ion battery cell, the manufacturing costs are crucial for the success of battery electric vehicles. To enable cost efficient yet well performing battery cells, an optimization of the manufacturing steps with respect to the cell properties is necessary. The slurry mixing process, being the initial step of the lithium-ion battery cell manufacturing process, is well known to affect the structure of the electrode coating (e.g. porosity, tortuosity or the distribution of the binder and conductive additive), which is further connected to its electrical and ionic resistances. Therefore, a variation of the formulation strategy or mixing device can affect the performance of the lithium-ion battery cell. In this study, several variations of the slurry mixing process are investigated with respect to its effect on the fast-charge capability of the lithium-ion battery cell. Properties of the slurry, the electrode and the resulting lithium-ion battery cell are characterized for each variation to detect interdependencies and derive process-structure-property relations.
Transition-Metal Single Atom Catalysts for Highly Efficient Artificial Photosynthesis
Authors: Wang Haotian
Published: January 2022

Utilizing solar energy to fix CO2 with water into chemical fuels and oxygen, a mimic process of photosynthesis in nature, is becoming increasingly important but still challenged by low selectivity and activity, especially in CO2 electrocatalytic reduction. Here, we report transition-metal atoms coordinated in a graphene shell as active centers for aqueous CO2 reduction to CO with high Faradaic efficiencies over 90% under significant currents up to ∼60 mA/mg 1 or a CO evolution rate of 3.81 mmol/h.2 We employed three-dimensional atom probe tomography to directly identify the single Ni atomic sites in graphene vacancies. Theoretical simulations suggest that compared with metallic Ni, the Ni atomic sites present different electronic structures that facilitate CO2-to-CO conversion and suppress the competing hydrogen evolution reaction dramatically. Coupled with Li+-tuned Co3O4 oxygen evolution catalyst and powered by a triple-junction solar cell, our artificial photosynthesis system achieves a peak solar-to-CO efficiency of 12.7% by using earth-abundant transition-metal electrocatalysts in a pH-equal system.

References

(1) Jiang, K.; Siahrostami, S.; Akey, A.J.; Li, Y.; Lu, Z.; Lattimer, J; Hu, Y.; Stokes, C.; Gangishetty, M.; Chen, G.; Zhou, Y.; Hill, W.; Cai, W.B.; Bell, D.C.; Chan, K.; Nørskov, J.K.; Cui, Y.; Wang, H. Chem
2017 https://doi.org/10.1016/j.chempr.2017.09.014.

(2) Jiang, K.; Siahrostami, S.; Zheng, T.; Hu, Y.; Hwang, S.; Stavitski, E.; Peng, Y; Dynes, J.; Gangishetty, M.; Su, D.; Attenkofer, K.; Wang, H. submitted.
Neurologically Relevant Enzyme Expression and Engineering for D-Amino Acid Enzymatic Electrochemical Biosensor Development
Authors: Mauzeroll Janine
Published: January 2022

Our interest lies in using enzymes to develop biosensors to be employed in studying neurochemical processes occurring in the brain. We will discuss expression and characterization of three different wild type enzymes and their mutants (Glycine oxidase, D-aspartate oxidase, D-amino acid oxidase). Enzyme expression and purification will be completed through standard biochemistry techniques while activity characterization will be assessed using spectrophotometric assays. Upon expression and characterization, these enzymes will then be used to develop enzymatic bioelectrochemical sensors which will be employed for in vitro single cell and in-vivo animal model studies of neurochemical processes.
A Recommendation Method of National Fitness Items Based on Neural Network Algorithm
Authors: Li Liangming , Yang Aihua
Published: January 2022

In order to improve the effectiveness of national fitness programs, this article analyzes the method of national fitness items recommendation based on a neural network algorithm. By using the time and space characteristics of fitness users’ sign-in, a novel POI recommendation model is proposed, and a novel fusion method is proposed to combine similarity and spatial similarity to achieve the final similarity calculation based on fitness users’ temporal and spatial preferences. In addition, in order to model the spatial similarity of fitness users, the Voronoi diagram is constructed by using the geographic locations of all POIs. Finally, this paper constructs a recommendation system for national fitness items based on a neural network algorithm. The experimental research results show that the national fitness program recommendation system proposed in this article basically meets the expected demand.
Dynamic Response Simulation of the Slope Triggered by Fluctuating Pressure during High Dam Flood Discharge
Authors: Zhang Hao-Hao , Wang Jun-Xing , Du Shuai-Qun , Chen Li , Da Jin-Rong
Published: January 2022

The problem of slope vibration induced by flood discharge of high dams cannot be ignored. In this paper, this problem is simplified to be the relationship among the fluctuating pressures, the inherent properties of the slope system, and its dynamic responses. The characteristics of fluctuating pressures in the plunge pool during flood discharge are analyzed by the hydraulic model test. And a numerical slope model consisting of the finite element domain and the PML domain is established to study the inherent characteristics and vibration responses by numerical simulation. The results show that the flow fluctuation in plunge pool is a continuous and stable random vibration process. And the fluctuating pressures on the bottom area of the plunge pool are greater than that of the sidewall, but the fluctuation phenomenon at the sidewall is more intense. In addition, the slope displacement vibration intensity caused by fluctuating pressures is small, only at the micron level. The fluctuating pressures on the bottom area of the plunge pool are the dominant factor affecting the kinetic energy density distribution of the slope. This work provides a simple and efficient method for the study of slope vibration induced by high dam flood discharge.
Differential Congestion Pricing Strategies for Heterogeneous Users in the Mixed Traffic Condition
Authors: Chen Yifan , Zhang Yuliang , Gu Ziyuan
Published: January 2022

Congestion pricing is one effective demand management strategy to alleviate traffic congestion. This work investigates pricing schemes for mixed traffic flow systems where the human-driven vehicles (HVs) and autonomous vehicles (AVs) coexist. The emerging and integration of autonomous vehicles can help improve the overall transportation efficiency and safety. Given the coexistence of HVs and AVs in the near future, there is need to adjust the existing traffic management strategies to adapt to the mixed traffic conditions. In this study, congestion pricing is imposed on the HVs and the AVs differently, that is, a distance-based toll to the HVs while a delay-based toll to the AVs. We consider six user groups based on the value of time (VOT) and the vehicle types. Compared with the unified distance-based toll, the advantage of delay-based toll is demonstrated first. Then, a surrogate-based optimization framework, namely the regressing Kriging (RK) model, is formulated. Three pricing schemes are investigated and compared: equity-oriented (EQ), environment friendliness-oriented (EN), and revenue-oriented (RE) schemes. Results show that the RE scheme collects the highest revenues; however, its cost-efficiency is weakened. The EQ scheme reduces the variance in the average travel costs among user groups, thus solving the equity issue.
Protective Effect of Trimetazidine on Potassium Ion Homeostasis in Myocardial Tissue in Mice with Heart Failure
Authors: Yang Kaijing , Xue Yitao , Yu Miao , Jiao Huachen , Li Yan , Wei Xijin , Liu Wenwen , Sun Yang , Chen Nannan , Song Linlin , Yu Ting , Chen Kaiming , Guo Dadong
Published: January 2022

The occurrence of heart failure (HF) is closely correlated with the disturbance of mitochondrial energy metabolism, and trimetazidine (TMZ) has been regarded as an effective agent in treating HF. Intracellular potassium ion (K+) homeostasis, which is modulated by K+ channels and transporters, is crucial for maintaining normal myocardial function and can be disrupted by HF. This study is aimed at exploring the protective effect of TMZ on K+ homeostasis within myocardial tissue in mice with HF. We observed the pathological changes of myocardial tissue under microscopes and further measured the content of adenosine triphosphate (ATP), the activity of Na+‐K+ ATPase, and the expression of ATP1α1 at the mRNA and protein levels. Moreover, we also analyzed the changes in K+ flux across the myocardial tissue in mice. As a result, we found that there was a large amount of myocardial fiber lysis and fracture in HF myocardial tissue. Meanwhile, the potassium flux of mice with HF was reduced, and the expression of ATP1α1, the activity of Na+‐K+ ATPase, and the supply and delivery of ATP were also decreased. In contrast, TMZ can effectively treat HF by restoring K+ homeostasis in the local microenvironment of myocardial tissues.
Applicable Formulas for Shear and Thermal Buckling of Perforated Rectangular Panels
Authors: Al Qablan Husam
Published: January 2022

The goal of this study is to create semiempirical formulations for predicting thermal and shear buckling loads of perforated rectangular isotropic panels for eight combinations of boundary conditions. The finite element method (FEM) was used to develop and evaluate empirical formulations. In this study, the influences of plate aspect ratios, boundary conditions, and perforation sizes on the buckling strength of perforated panels subjected to shear and thermal loads are investigated. The proposed formulas will enable consistent and reliable computation of the buckling loads for perforated rectangular panels without the need for complex calculations. The results of the empirical equations were found to be reasonably consistent with the outcomes of finite element analysis (FE) and findings from the literature. Various perforation patterns are investigated, ranging from a single circular hole up to 441 circular holes distributed across the plate. The results show that plates with a single central cutout have lower shear buckling loads than plates with multiple holes and an equal total cutout area.
Switching from Insulin Degludec plus Dipeptidyl Peptidase-4 Inhibitor to Insulin Degludec/Liraglutide Improves Glycemic Variability in Patients with Type 2 Diabetes: A Preliminary Prospective Observation Study
Authors: Oe Yuki , Nomoto Hiroshi , Nakamura Akinobu , Kuwabara Saki , Takahashi Yuka , Yasui Ayano , Izumihara Rimi , Miya Aika , Kameda Hiraku , Cho Kyu Yong , Atsumi Tatsuya , Miyoshi Hideaki
Published: January 2022

Incretins reduce glycemic variability (GV) in patients with type 2 diabetes, but it is unknown whether switching from a combination of basal insulin and a DPP-4 inhibitor to insulin degludec/liraglutide (IDegLira) improves GV. We performed an exploratory prospective observational study to compare the effect of IDegLira and the combination on GV. We recruited hospitalized patients with type 2 diabetes who had stable glycemic control with insulin degludec (≤16 units/day) and taking a DPP-4 inhibitor. GV was analyzed using continuous glucose monitoring (CGM) before and after switching the medication to IDegLira. The principal endpoint was the change in mean amplitude of glycemic excursions (MAGE). Other indices of GV and CGM parameters were analyzed as the secondary endpoints. Fifteen participants were enrolled and 12 completed the study. In these participants, the DPP-4 inhibitor and insulin degludec were discontinued, and the equivalent dose of IDegLira was commenced. Switching to IDegLira significantly improved MAGE from 74.9 (60.3, 97.7) mg/dL to 64.8 (52.0, 78.2) mg/dL (

P
<
0.05

), as well as other indices of GV and 24-hour mean blood glucose concentration. Analysis of the ambulatory glucose profile showed marked reductions in postprandial glucose concentration. Nocturnal glucose concentration was similar under the two treatment regimens. IDegLira improved GV as well as the mean and the postprandial glucose concentration by switching from insulin degludec plus DPP-4 inhibitor combination. IDegLira might be beneficial for patients being treated with low-dose basal insulin.
Deep Learning-Based Solutions for 5G Network and 5G-Enabled Internet of Vehicles: Advances, Meta-Data Analysis, and Future Direction
Authors: Almutairi Mubarak S.
Published: January 2022

The advent of the 5G mobile network has brought a lot of benefits. However, it prompted new challenges on the 5G network cybersecurity defense system, resource management, energy, cache, and mobile network, therefore making the existing approaches obsolete to tackle the new challenges. As a result of that, research studies were conducted to investigate deep learning approaches in solving problems in 5G network and 5G powered Internet of Vehicles (IoVs). In this article, we present a survey on the applications of deep learning algorithms for solving problems in 5G mobile network and 5G powered IoV. The survey pointed out the recent advances on the adoption of deep learning variants in solving the challenges of 5G mobile network and 5G powered IoV. The deep learning algorithm solutions for security, energy, resource management, 5G-enabled IoV, and mobile network in 5G communication systems were presented including several other applications. New comprehensive taxonomies were created, and new comprehensive taxonomies were suggested, analysed, and presented. The challenges of the approaches are already discussed in the literature, and new perspective for solving the challenges was outlined and discussed. We believed that this article can stimulate new interest in practical applications of deep learning in 5G network and provide clear direction for novel approaches to expert researchers.
Exploiting Machine Learning to Detect Malicious Nodes in Intelligent Sensor-Based Systems Using Blockchain
Authors: Sajid Maimoona Bint E. , Ullah Sameeh , Javaid Nadeem , Ullah Ibrar , Qamar Ali Mustafa , Zaman Fawad
Published: January 2022

In this paper, a blockchain-based secure routing model is proposed for the Internet of Sensor Things (IoST). The blockchain is used to register the nodes and store the data packets’ transactions. Moreover, the Proof of Authority (PoA) consensus mechanism is used in the model to avoid the extra overhead incurred due to the use of Proof of Work (PoW) consensus mechanism. Furthermore, during routing of data packets, malicious nodes can exist in the IoST network, which eavesdrop the communication. Therefore, the Genetic Algorithm-based Support Vector Machine (GA-SVM) and Genetic Algorithm-based Decision Tree (GA-DT) models are proposed for malicious node detection. After the malicious node detection, the Dijkstra algorithm is used to find the optimal routing path in the network. The simulation results show the effectiveness of the proposed model. PoA is compared with PoW in terms of the transaction cost in which PoA has consumed 30% less cost than PoW. Furthermore, without Man In The Middle (MITM) attack, GA-SVM consumes 10% less energy than with MITM attack. Moreover, without any attack, GA-SVM consumes 30% less than grayhole attack and 60% less energy than mistreatment. The results of Decision Tree (DT), Support Vector Machine (SVM), GA-DT, and GA-SVM are compared in terms of accuracy and precision. The accuracy of DT, SVM, GA-DT, and GA-SVM is 88%, 93%, 96%, and 98%, respectively. The precision of DT, SVM, GA-DT, and GA-SVM is 100%, 92%, 94%, and 96%, respectively. In addition, the Dijkstra algorithm is compared with Bellman Ford algorithm. The shortest distances calculated by Dijkstra and Bellman are 8 and 11 hops long, respectively. Also, security analysis is performed to check the smart contract’s effectiveness against attacks. Moreover, we induced three attacks: grayhole attack, mistreatment attack, and MITM attack to check the resilience of our proposed system model.
Comparative Effects of Sulforaphane and Allyl Isothiocyanate on 3T3-L1 Adipogenesis
Authors: Sakuma Satoru , Yasuda Kana , Kitahara Risa , Tsujimoto Kaho , Yamashita Kishiko , Hoshino Naohiro , Fujimoto Yohko , Okuhira Keiichiro
Published: January 2022

Sulforaphane and allyl isothiocyanate, naturally occurring isothiocyanates, have been reported to inhibit adipocyte differentiation, but little is known about how they compare in terms of their potency and mechanism of action. In the present study, we compared the effects of sulforaphane and allyl isothiocyanate on the differentiation of 3T3-L1 preadipocytes. A mixture of insulin, dexamethasone, and 3-isobutyl-1-methylxanthine was used to establish a differentiation medium. We found that, at a concentration as low as one-tenth that of allyl isothiocyanate, sulforaphane reduced triacylglycerol levels, lipid-filled adipocyte quantity, and mRNA and protein levels of CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). These results suggested that sulforaphane may be a more potent adipocyte differentiation inhibitor than allyl isothiocyanate. Our results may provide insight into possible strategies for the prevention of obesity and related conditions.
Study on Occupancy Behaviors of Passengers in the Subway Cabin: An Observation in Chengdu, China
Authors: He Si-Jun , Zhi Jin-Yi
Published: January 2022

Insufficient attention has been paid to how subway cabins are used by passengers and especially the distribution of passengers and occupancy of facilities. In this study, passengers were observed in 133 sections from the beginning to the end of the early peak of Chengdu Metro in the working days. The differences in occupancy behaviors of passengers to different areas, seats, and standing auxiliary facilities in the cabin were analyzed by the nonparametric test. The occupancy curve was fitted by the least square method from the minimum to the maximum load factor, and the prediction and explanatory model for the use of cabin was established. As expected, the distribution of passengers in the cabin is uneven. The highest occupancy rate has been maintained at the cabin end. Female passengers accounted for the largest proportion in the door area, while male passengers accounted for a larger proportion at the end of the cabin. There is no difference in the use of different seat types by passengers. There are more seats in female passengers, and females are more likely to get the remaining seats when the seat load is nearly saturated. For the auxiliary standing facilities, there are always passengers who do not use the facilities and the proportion is increasing. The facilities that can be relied on account for a greater median proportion of the passengers with facilities, but service capacity is limited. In response to these conclusions, measures to improve the design of the cabin are proposed.
[Retracted] Research on Intelligent Function Design of Vocational Education System under Mobile Learning Mode
Authors: Qing Li
Published: January 2022

Because the traditional vocational education system has intelligent functions, long running time, and low recommendation accuracy of vocational education resources, the vocational education system under mobile learning mode is designed. The system is designed through the registration and login function module, course learning function module, examination and evaluation function module, communication and interaction function module, mobile learning function module, and personalized recommendation function module. In the personalized recommendation function module, the user’s preference for vocational education resources is obtained by calculating the user’s interest weight, as well as personalized recommendation of vocational education resources. The simulation results show that the intelligent function of vocational education system can operate normally under the designed mobile learning mode, the operation efficiency is high, and the effect of Vocational Education Resource Recommendation is good.
Antidiarrheal Effect of 80% Methanol Extract and Fractions of the Roasted Seed of Coffea arabica Linn (Rubiaceae) in Swiss Albino Mice
Authors: Alemu Muluken Adela , Birhanu Wubneh Zewdu , Adugna Ayanaw Meaza
Published: January 2022

Background. Globally in 2019, diarrhea was the second leading cause of mortality in children, accounting for more than half a million under-five deaths yearly. Several societies use Coffea arabica Linn for the treatment of diarrhea. However, its use is not scientifically validated. Objective. The study was conducted to evaluate antidiarrheal activity of 80% methanol extract and solvent fractions of roasted seed of Coffea arabica Linn in mice. Methods. Coffea arabica Linn seed was roasted, milled, extracted, and fractionated using hexane, ethyl acetate, and distilled water. Castor oil-induced diarrhea, enteropooling, and motility tests were conducted. Effects on onset, number of feces, weight of feces, fluid content, volume and weight of intestinal content, and motility were evaluated by administering 100 mg/kg, 200 mg/kg, and 400 mg/kg of each extract. Negative controls received 10 ml/kg of the vehicle, and positive controls received either loperamide (3 mg/kg) or atropine (1 mg/kg). Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Results. Ethyl acetate fraction at all tested doses significantly prolonged (p<0.05) onset of diarrhea. The number and weight of feces were also reduced significantly by crude extract and ethyl acetate fraction. Reduction in fluid content was observed at 200 mg/kg and 400 mg/kg of the crude extract (p<0.01) and aqueous fraction (p<0.001) as well as all tested doses of ethyl acetate fraction (p<0.001). Similarly, the crude extract, ethyl acetate fraction, and aqueous fraction showed a significant reduction in the volume and weight of intestinal content. At 400 mg/kg, the crude extract, hexane fraction, aqueous fraction, and all doses of ethyl acetate fraction showed significant antimotility activity. Conclusion. The results of this study revealed that the roasted seed of Coffea arabica Linn has antidiarrheal activity.
Apolipoprotein (a)/Lipoprotein(a)-Induced Oxidative-Inflammatory α7-nAChR/p38 MAPK/IL-6/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm
Authors: Lin Yen-Kuang , Yeh Chi-Tai , Kuo Kuang-Tai , Fong Iat-Hang , Yadav Vijesh Kumar , Kounis Nicholas G. , Hu Patrick , Hung Ming-Yow
Published: January 2022

Objective. Apolipoprotein (a)/lipoprotein(a) (Lp(a)), a major carrier of oxidized phospholipids, and α7-nicotinic acetylcholine receptor (α7-nAChR) may play an important role in the development of coronary artery spasm (CAS). In CAS, the association between Lp(a) and the α7-nAChR-modulated inflammatory macrophage polarization and activation and smooth muscle cell dysfunction remains unknown. Methods. We investigated the relevance of Lp(a)/α7-nAChR signaling in patient monocyte-derived macrophages and human coronary artery smooth muscle cells (HCASMCs) using expression profile correlation analyses, fluorescence-assisted cell sorting flow cytometry, immunoblotting, quantitative real-time polymerase chain reaction, and clinicopathological analyses. Results. There are increased serum Lp(a) levels (3.98-fold,

p
=
0.011

) and macrophage population (3.30-fold,

p
=
0.013

) in patients with CAS compared with patients without CAS. Serum Lp(a) level was positively correlated with high-sensitivity C-reactive protein (

r

2

=
0.48

,

p
<
0.01

), IL-6 (

r

2

=
0.38

,

p
=
0.03

), and α7-nAChR (

r

2

=
0.45

,

p
<
0.01

) in patients with CAS, but not in patients without CAS. Compared with untreated or low-density lipoprotein- (LDL-) treated macrophages, Lp(a)-treated macrophages exhibited markedly enhanced α7-nAChR mRNA expression (

p
<
0.01

) and activity (

p
<
0.01

), in vitro and ex vivo. Lp(a) but not LDL preferentially induced CD80+ macrophage (M1) polarization and reduced the inducible nitric oxide synthase expression and the subsequent NO production. While shRNA-mediated loss of α7-nAChR function reduced the Lp(a)-induced CD80+ macrophage pool, both shRNA and anti-IL-6 receptor tocilizumab suppressed Lp(a)-upregulated α7-nAChR, p-p38 MAPK, IL-6, and RhoA-GTP protein expression levels in cultures of patient monocyte-derived macrophages and HCASMCs. Conclusions. Elevated Lp(a) levels upregulate α7-nAChR/IL-6/p38 MAPK signaling in macrophages of CAS patients and HCASMC, suggesting that Lp(a)-triggered inflammation mediates CAS through α7-nAChR/p38 MAPK/IL-6/RhoA-GTP signaling induction, macrophage M1 polarization, and HCASMC activation.
Identification of Active Bronchioalveolar Stem Cells as the Cell of Origin in Lung Adenocarcinoma
Authors: Yin Huijing , Jing Bo , Xu Dongliang , Guo Wenzheng , Sun Beibei , Zhang Jie , Liao Yueling , Song Hongyong , Wang Tong , Liu Shuli , Kuang Yanbin , Hu Min , Li Kaimi , Zhang Siwei , Zhang Hongjia , Xu Jianhua , Li Xue , Du Jing , Wu Yadi , Wu Yingli , Wang Qi , Yao Feng , Chin Yueh Eugene , Zhou Binhua P. , Deng Jiong
Published: January 2022

While initiation is established as a critical step in tumorigenesis, the identity of the cell of origin for lung adenocarcinoma and the mechanism controlling susceptibility to initiation remain elusive. Here we show that lung tumor suppressor Gprc5a-knockout (KO) mice are susceptible to initiation of lung tumorigenesis. Bronchioalveolar stem cells (BASC) and alveolar type 2 (AT2) cells were aberrantly expanded in Gprc5a-KO mouse lungs compared with those in wild-type (WT) mice, suggesting that Gprc5a-KO might confer susceptibility to initiation by increasing the cell of origin in mouse lungs. BASCs from Gprc5a-KO mice (KO-BASC) exhibited significantly increased stemness and self-renewal potential and reduced differentiation capacity compared with BASCs from WT mice (WT-BASC). AT2 cells did not possess self-renewal potential regardless of Gprc5a status. KO-BASCs expressed a stem-like gene profile with upregulated Abcg2, EGFR, and NF-κB signaling compared with WT-BASCs. Blockade of EGFR and NF-κB signaling inhibited both expansion of BASC and AT2 cells and lung tumorigenesis. Abcg2 was expressed in active KO-BASCs as well as in lung tumor cells but not in quiescent WT-BASCs or AT2 cells, supporting that lung adenocarcinoma cells are derived from Abcg2-positive KO-BASCs (active). Taken together, Gprc5a deletion leads to expansion of active BASCs via dysregulated EGFR and NF-κB signaling that confers susceptibility to initiation of lung tumorigenesis, marking Abcg2-positive BASCs as candidate cell of origin for lung adenocarcinoma.

Significance:

Identification of active bronchioalveolar stem cells as lung adenocarcinoma cells of origin provides insights into mechanisms of lung tumorigenesis and could facilitate development of effective strategies for cancer prevention and therapy.

See related commentary by Osborne and Minna, p. 972
Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis
Authors: Kao Hsiang-Fong , Liao Bin-Chi , Huang Yen-Lin , Huang Huai-Cheng , Chen Chun-Nan , Chen Tseng-Cheng , Hong Yuan-Jing , Chan Ching-Yi , Chia Jean-San , Hong Ruey-Long
Published: January 2022

Purpose:

EGFR pathway inhibition may promote anti–programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen presentation during anti–PD-1 monotherapy in humans remain unknown. We hypothesized that afatinib, an irreversible EGFR tyrosine kinase inhibitor, would improve outcomes in patients treated with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by promoting antigen presentation and immune activation in the tumor microenvironment.

Patients and Methods:

The ALPHA study (NCT03695510) was a single-arm, Phase II study with Simon's 2-stage design. Afatinib and pembrolizumab were administered to patients with platinum-refractory, recurrent, or metastatic HNSCC. The primary endpoint was the objective response rate (ORR). The study applied gene expression analysis using a NanoString PanCancer Immune Profiling Panel and next-generation sequencing using FoundationOne CDx.

Results:

From January 2019 to March 2020, the study enrolled 29 eligible patients. Common treatment-related adverse events were skin rash (75.9%), diarrhea (58.6%), and paronychia (44.8%). Twelve patients (41.4%) had an objective partial response to treatment. The median progression-free survival was 4.1 months, and the median overall survival was 8.9 months. In a paired tissue analysis, afatinib–pembrolizumab were found to upregulate genes involved in antigen presentation, immune activation, and natural killer cell–mediated cytotoxicity. Unaltered methylthioadenosine phosphorylase and EGFR amplification may predict the clinical response to the therapy.

Conclusions:

Afatinib may augment pembrolizumab therapy and improve the ORR in patients with HNSCC. Bioinformatics analysis suggested the enhancement of antigen presentation machinery in the tumor microenvironment.
Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity
Authors: Tokatlian Talar , Asuelime Grace E. , Naradikian Martin S. , Mock Jee-Young , Daris Mark E. , Martin Aaron D. , Toledo Warshaviak Dora , Kamb Alexander , Hamburger Agnes E.
Published: January 2022

Neoantigens are among the most intriguing potential immuno-oncology targets because, unlike many cancer targets that are expressed on normal tissues, they are by definition restricted to cancer cells. Medicines directed at common neoantigens such as mutant KRAS are especially interesting because they may offer the convenience and cost of an off-the-shelf therapy. However, all common KRAS mutations produce proteins that differ from the wild type at a single amino acid, creating challenges for molecular discrimination. We have undertaken an effort to optimize single-chain variable fragments (scFv) against peptide/major histocompatibility antigen complexes composed of HLA-A*11 and either G12V- or G12D-mutant KRAS peptides. These scFvs could in principle be used in chimeric antigen receptor (CAR) T-cell therapies for selected patients whose tumors bear either of these mutations. Here we show that optimization of such CARs involves a trade-off between potency and selectivity. We further show that targeting this family without high selectivity engenders risks of cross-reactivity against other members of the G-protein family to which KRAS belongs.

Significance:

We report an effort to generate high potency, selective CARs directed at mutant KRAS peptides. Although the heavily optimized CARs maintain high selectivity against wild-type KRAS, they lose selectivity against other KRAS-related peptides derived from human proteins. To our knowledge, this work is the first to examine the trade-off between potency and selectivity with regard to KRAS pMHC-directed CARs, illustrating the challenge to achieve both sufficient potency and high selectivity.
Percutaneous Nephrolithotomy in Patients with Chronic Kidney Disease: A Systematic Review
Authors: Mehra Ketan , Satpathy Parameshwar , Joshi Ankur , Manikandan Ramanitharan
Published: January 2022

Background: Renal calculi in chronic kidney disease (CKD) are not uncommon. Percutaneous nephrolithotomy (PCNL) is a standard treatment for large renal calculi. PCNL in CKD has been a subject of debate as it may improve the renal function with stone clearance but may be associated with an increased complication rate. Studying the impact of PCNL in CKD patients is of utmost significance. Objective: The aim of the study was to evaluate the efficacy and safety of PCNL in patients with renal insufficiency in order to provide clinicians expected outcomes to effectively counsel patients. Methods: We performed a systematic review of clinical trials reporting the outcomes of PCNL in CKD patients. The search was performed in MEDLINE, EMBASE, Cochrane Library, CINAHL, Google Scholar, and Web of Science. All studies with a minimum of 15 patients carried out in the last 20 years were selected. A total of 13 studies involving 2,192 patients were included for final analysis. The pre-operative and post-operative renal function was compared. Post-procedure complications were analysed. Evidence Analysis: The majority of patients in all studies except one had either improvement or stabilization in renal function. The complication rate was 31.9%, which was more than that in patients with normal renal function. Conclusion: Our review suggested that the majority of the patients of renal calculus with renal insufficiency are benefitted with PCNL in improving or preserving the renal function. But the post-operative complications are more in CKD and increases as the severity of renal insufficiency increases.
A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis
Authors: Mazen Inas , Kamel Alaa , McElreavey Kenneth , Bashamboo Anu , Elaidy Aya , Abdel-Hamid Mohamed S.
Published: January 2022

Introduction: Disorders of gonadal development represent a clinically and genetically heterogeneous group of DSD, and the etiology in many cases remains unknown, indicating that our knowledge of factors controlling sex determination is still limited. Methods: We describe a 46,XY DSD patient from Egypt. The patient was reared as female, born to consanguineous parents, and was referred to us at the age of 5 years because of ambiguous genitalia. On examination, the girl was microcephalic (head circumference –3 SD), but her height and weight were normal for her age and sex. Results: Exome sequencing identified a homozygous variant in the hedgehog acyltransferase (HHAT) gene, which encodes an enzyme that is required for multimerization and signaling potency of the hedgehog secreted proteins. The variant is a novel homozygous missense change c.1329C>A (p.N443K), located within transmembrane domain 9, which segregated with the phenotype in the family. Discussion/Conclusion: Our results expand the phenotypic spectrum associated with HHAT variants to include 46,XY gonadal dysgenesis and reinforce the role of exome sequencing in unraveling new genes that play a pivotal role in sexual development.
Role of Governance and Public Trust on Government Debt-Economic Growth Nexus (A Global Empirical Analysis)
Authors: Andar Ristabet Hesda  , Yuliani Efi
Published: January 2022

High government debts in several countries have the potential to trigger or exacerbate economic instability. These concerns are consistent with the results of this study, where countries that have a high debt ratio tend to have declining economic growth. To provide more understanding about this effect, this study tries to examine the effect of debt on economic growth by utilising the governance and public trust level as a contextual variable and mediator. Empirically, both variables have a prominent role in the debt and economic growth nexus. The debt threshold as a budgetary rule is necessary but might not be sufficient to validate the rationality of rising debt. The capability of government in providing public governance and the effect of additional debt on public trust is another crucial aspect that needs to be seriously scrutinised, or when the addition of debt becomes inevitable (such as in pandemic situation), the government should strengthen governance capability to ensure the productivity of debt and mitigate the decreased public trust. This finding implies that the debt policy should not only be based on budgetary rule but also the capacity of governance and the potential implication of the falling public trust.
Dampak Pembatasan Ekspor Hasil Tambang Terhadap Perekenomian Kalimantan Timur
Authors: Maulina Windi Agustin
Published: January 2022

Berbagai studi telah dilakukan untuk menganalisis dampak ekspor hasil tambang terhadap perekonomian Kalimantan Timur. Namun, studi-studi tersebut umumnya belum memperhitungkan dampak ekspor tambang Kalimantan terhadap provinsi lainnya. Padahal, perekonomian antar wilayah dapat saling bergantung melalui berbagai macam eksternalitas dan jaringan rantai suplai. Studi ini menganalisis perekonomian Kalimantan Timur dan dampak ketika adanya kebijakan pembatasan ekspor hasil tambang yang merupakan komoditi unggulan Kalimantan Timur berdasarkan Tabel Inter Regional Input Output (IRIO). Studi ini tidak hanya mempertimbangkan perekonomian Kalimantan Timur sendiri, namun juga mempertimbangkan hubungan ekonomi Kalimantan Timur dengan provinsi lainnya. Model yang digunakan adalah Inter Regional Input Output (IRIO) menggunakan Tabel IRIO berukuran 17 industri x 34 provinsi yang baru saja di rilis oleh Badan Pusat Statistik pada Mei 2021. Hasil analisis menunjukkan meskipun industri pertambangan memiliki kontribusi terbesar dalam perekonomian Kalimantan Timur, namun industri pertambangan dan penggalian bukanlah industri unggulan di Kalimantan Timur sehingga pembatasan ekspor produk pertambangan dan penggalian akan memberikan dampak internal dalam sektor jauh lebih besar dibanding sektor lain. Provinsi di Indonesia yang terkena dampak paling besar dari pembatasan ekspor tambang Kalimantan Timur adalah DKI Jakarta, Jawa Barat, dan Jawa Timur.
Potensi Hilirisasi Industri di Provinsi Riau (Perspektif Tabel Interregional Input Output)
Authors: Ronalia Pipit
Published: January 2022

Salah satu tujuan hilirisasi industri adalah untuk menggeser struktur ekonomi yang semula berbasis komoditas menjadi ekonomi berbasis investasi, produksi, dan memiliki nilai tambah tinggi. Provinsi Riau dikaruniai kekayaan sumber daya alam yang berpotensi dikembangkan untuk hilirisasi industri. Akan tetapi hilirisasi industri tanpa memperhatikan keterkaitan antar sektor ekonomi dan antarwilayah tentu tidak akan berjalan maksimal. Studi ini menganalisis perekonomian Riau tidak hanya berdasarkan keterkaitan antar sektor, tetapi juga mempertimbangkan keterkaitan antara Riau dengan provinsi lainnya. Model yang digunakan dalam penelitian ini adalah Tabel Inter Regional Input Output (IRIO) Indonesia dan Tabel Input Output (IO) Provinsi Riau tahun 2016 yang diperoleh dari Badan Pusat Statistik. Hasil penelitian menunjukkan bahwa industri unggulan di Provinsi Riau adalah Industri Pengolahan dan Pengadaan Listrik dan Gas. Hilirisasi industri di Riau sangat tepat dilakukan karena Industri Pengolahan yang merupakan industri unggulan juga akan dapat menarik dan mendorong pertumbuhan sektor lain. Analisis keterkaitan antar wilayah menunjukkan bahwa shock permintaan akhir di Provinsi Riau berdampak besar terhadap perekonomian di Provinsi DKI Jakarta. Di sisi lain, perekonomian Riau sangat dipengaruhi oleh shock permintaan akhir di Provinsi Aceh.
Dampak Kebijakan Moneter dan Makroprudensial terhadap Pembangunan Keuangan Studi Lintas Negara, 2000 – 2014
Authors: Sukowati Nisa Nurjannah , Falianty Telisa Aulia
Published: January 2022

Penelitian ini bertujuan untuk menginvestigasi dampak kebijakan moneter dan makroprudensial terhadap pembangunan keuangan, baik di negara maju dan berkembang. Dengan menggunakan regresi panel data dinamis metode GMM pada 43 negara, penelitian ini menunjukkan bahwa terdapat dampak negatif akibat pelonggaran kebijakan tersebut. Penurunan suku bunga kebijakan dan indeks makroprudensial terutama instrumen kredit dan likuiditas dapat meningkatkan rasio kredit privat terhadap PDB, yang berarti mendorong proses pembangunan keuangan. Selanjutnya, penurunan suku bunga kebijakan signifikan mendorong proses pembangunan keuangan negara maju, namun indeks makroprudensial tidak signifikan. Sebaliknya, penurunan suku bunga kebijakan dan indeks makroprudensial tidak signifikan berdampak pada proses pembangunan keuangan negara berkembang.
Pengembangan Kawasan Wisata pada Rest Area Boja dalam Mendukung Peningkatan Pedapatan Desa Melalui Perilaku Herding (Studi Kasus di Kawasan Wisata Rest Area Desa Boja, Kecamatan Boja, Kabupaten Kendal)
Authors: Ristianawati Yuyun , Nugroho Prihasantyo Siswo , Kiswoyo
Published: January 2022

The aims of this research is to study the mindset of Herding's behavior on the income level of tourism objects through the results of tourism development in the Rest Area of Boja Kendal Village. In this study, 95 people/MSMEs. In this study, the authors used a purposive random sampling technique.

The results of this study are herding behavior has a positive and significant effect on the income level of MSMEs in the Boja rest area tourist attraction. Herding behavior has no effect on tourism development decisions. The development of tourism objects has no effect on increasing income. Herding behavior has no significant effect on the income level of tourist objects through tourism area development decisions. So that the development of tourist areas is not able to mediate the influence of herding behavior on increasing MSME income in the Boja rest area tourist attraction.
Pengaruh Religiusitas, Love of Money, dan Status Sosial Ekonomi Terhadap Kecenderungan Perilaku Tax Evasion dalam Perspektif Ekonomi Islam
Authors: Oktaviana Riska , Fasa M Iqbal , Suharto Suharto
Published: January 2022

Tax is a mandatory expenditure imposed on taxpayers to assist the development of the country. However, taxpayers feel that taxes are a burden for them, because the distribution of development has not been maximized, causing the people to feel reluctant to pay their obligations. So in this case the taxpayer is trying to find a way to evade taxes. The purpose of this study was to determine the effect of religiosity, love of money, and socio-economic status on the tendency of tax evasion behavior in an Islamic economic perspective. This study used a literature study which refers to journals and books. The results of this study reveal that religiosity and love of money have an effect on tax evasion behavior. However, socioeconomic status has no effect on tax evasion behavior.
Carotid Atherosclerosis Predicts Blood Pressure Control in Patients With Hypertension: The Campania Salute Network Registry
Authors: Mancusi Costantino , Manzi Maria Virginia , de Simone Giovanni , Morisco Carmine , Lembo Maria , Pilato Emanuele , Izzo Raffaele , Trimarco Valentina , De Luca Nicola , Trimarco Bruno
Published: January 2022

Background

The 2018 European Society of Cardiology/European Society of Hypertension arterial hypertension guidelines do not recommend routine carotid ultrasound as a tool to identify hypertension‐mediated organ damage, unless clinically indicated. However, carotid plaque (CP) is a strong correlate of increased arterial stiffness, which influences blood pressure (BP) control over time. Thus, we assessed whether evidence of CP at first visit could predict BP control during follow‐up.

Methods and Results

From the CSN (Campania Salute Network) Registry, 6684 patients with hypertension had complete carotid ultrasound examination and were categorized by the presence of CP at baseline. Optimal BP control was defined as average BP <140/90 mm Hg and <135/85 during follow‐up for office and home BP, respectively. At baseline, participants with CP (n=3061) were more likely to be men, to be older, to have diabetes, and to exhibit higher systolic BP, lower diastolic BP, worse lipid profile, and higher prevalence of left ventricular hypertrophy (all
P
<0.0001) than patients without CP. Optimal office BP control was adjudicated in 54% with and 62% without CP (
P
<0.0001), and optimal home BP in 51% with and 58% without CP (
P
<0.01). Presence of CP was significantly associated with the reduced probability of controlled office BP during follow‐up (both
P
<0.0001), independently of significant effect of older age, male sex, higher baseline BP values, classes of medication, and presence of left ventricular hypertrophy, and only attenuated by duration of hypertension.

Conclusions

Presence of CP in treated patients with hypertension is associated with suboptimal BP control during follow‐up, independently of worse metabolic profile and presence of left ventricular hypertrophy.