bluuebunny/crossref_metadata_2025 huggingface dataset:
Coal-Derived N-Doped Porous Carbon Accompanied with Fe2O3 for Oxygen Reduction Reaction
Authors: Chen Bo , Zhang Hui-Juan , Zhao Wenqing , Yuan Tao , Sun Liangliang , Xue Yuhua
Published: December 2022

In this study, a class of non-precious metal catalyst for oxygen reduction reaction (ORR), namely N-doped porous carbon accompanied with Fe2O3 (herein named as AC-4), is synthesized from one-step pyrolyzing the precursors of KOH, coal, Fe salt and melamine, followed by acid-leaching. Several catalysts, AC-1 from KOH + coal, AC-2 from KOH + coal + melamine and AC-3 from KOH + coal + Fe salt, are also shown for comparison. As a result, AC-4 provides the best ORR catalytic activity with the ORR peak potential (Ep) of 818 mV, followed by the order of AC-2 (783 mV) > AC-3 (775 mV) > AC-1(771 mV), meaning that the N-doping strategy plays more effect than the Fe2O3-doping method, and AC-4 has the synergetic effect of these two ways. Furthermore, the ORR mechanism on AC-4 is near a four-electron transfer pathway with the electron transfer number around 3.7–3.9. It also has a good stability and methanol-resistance. Structure measurements display that introduction of N heteroatom and/or metal can increase the disorder degree of AC, and AC-4 has a structure of N-doped porous carbon (the special surface area of 1193 m2 g−1) accompanied with Fe2O3.
Dynamic Photocurrent Response of CuO-Nanoarray-Based Photoelectrodes: Heterostructure and Small Electric Field Effects
Authors: Liu Yaqi , Zhan Kaidong , Shi Zhili , Lv Wenjing , Cheng Pujia , Ren Xuecheng , Wu Fan
Published: December 2022

CuO nanoarrays were synthesized by using a hydrothermal method, and TiO2 nanocrystals were deposited on the surface of CuO nanoarrays to form bulk heterostructure photoelectrodes. The current-time curve revealed that TiO2 nanocrystals can enhance the photocurrent of CuO nanoarrays, resulting from the higher charge separation efficiency and transfer rate. In addition, the effects of small biases (–0.1 and 0.1 V) on the photocurrent and photogenerated charge dynamics in the aforementioned photoelectrodes were evaluated. A small bias was found to not influence the macroscopic dynamical process during charging and discharging of the CuO photoelectrode, but it was more correlated with the microscopic dynamics. Additionally, the built-in electric field in the CuO nanoarray/TiO2 heterojunction could be affected by a small external bias, thereby influencing the charge separation and charge diffusion concentration, which, subsequently, influenced the charge diffusion length, L. In contrast, L in the pristine CuO nanoarray was not improved under a small reverse bias, because the small reverse bias could not efficiently improve the diffusion concentration owing to the lack of a built-in electric field to dissociate electron-hole pairs. These kinetic mechanisms are helpful in understanding the photoelectric conversion process in heterogeneous photoelectrodes.
Role of Smart-Release Pigments in Preventing Corrosion Driven Cathodic Disbondment of Organically Coated Hot Dip Galvanised Steel
Authors: Ansell P. , Berry L. , McGettrick J. , Searle J. , Wint N. , McMurray H. N. , Williams G.
Published: December 2022

The role of smart-release corrosion inhibitive pigments in preventing cathodic delamination of organically coated hot-dip galvanized steel (HDG) is investigated. The pigments consisted of hydrotalcite (HT) exchanged with a range of inorganic and organic anionic species and were dispersed in a model PVB coating. A scanning Kelvin probe (SKP) technique was used to determine cathodic delamination rates, and the inhibition efficiencies obtained for inorganic ions increased in the order

CO

3

2
−

<

MoO

4

2
−

<

NO

3

−

<

VO

4

3
−

<

WO

4

2
−

<

PO

4

3
−

<

CrO

4

2
−

.

The inhibition efficiencies for organic-based pigments increased in the order triazole <phenylphosphonate <trans-cinnamate <benzoate <salicylate <benzotriazole. The inhibition efficiency afforded by the best performing organic inhibitor, benzotriazole (BTA), rivalled that of HT containing stored chromate anions. Findings are consistent with HT-BTA acting to sequester anions from the underfilm electrolyte, releasing BTA− which subsequently strongly adsorbs on the underfilm metal surface but can also form an insoluble Zn-BTA precipitate at the coating-defect boundary.
Partly-O-Diamond Solution-Gate Field-Effect Transistor as an Efficient Biosensor of Glucose
Authors: Zhang Qianwen , Du Yuxiang , Chang Xiaohui , Xu Bangqiang , Chen Genqiang , He Shi , Dan Zhang  , Li Qi , Wang Juan , Wang Ruozheng , Wang Hong-Xing
Published: December 2022

Assessment of glucose concentration is vital for diagnosis and treatment of diabetes mellitus. Since the electrochemical advantages of diamond for biosensing, we introduced partly-oxygen-diamond solution-gate field-effect transistor (SGFET) to detect glucose. Partly-O-diamond was obtained from H-diamond by ultraviolet ozone treatment. Then, 1-pyrenebutyric acid–N-hydroxy succinimide ester and glucose oxidase were modified on diamond surface. At last, shifts of transfer characteristics were applied to determine glucose concentration. The as-prepared biosensor exhibited a wide linear response from 10−5 to 10−1 M with high sensitivity of −53 mV/log10 [glucose concentration]. Furthermore, this biosensor showed good repeatability and stability in multiple detections.
Bimetallic Coreshell-Hemoglobin Complex Immobilized MXene Based Voltammetric Biosensor for the Electrochemical Detection of Acrylamide
Authors: Divya Karutha Pandian , Keerthana Shanmuganathan , Viswanathan Chinnuswamy , Ponpandian Nagamony
Published: December 2022

The gold electrode was modified with MXene nanosheets followed by Au@Ag coreshell and Hb complex (Au@Ag CS-Hb/MXene/AuE) for the detection of acrylamide. The prepared MXene was delaminated followed by the etching process and well characterized using X-ray powder diffraction (XRD), Raman spectroscopy, field emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). The constructed biosensor showed electrochemical signal for acrylamide in the cyclic voltammetric method. The biosensor was tested in different pH and scan rate variations. The biosensor exhibited a limit of detection of 3.46μM with two linear curves in higher and lower concentration ranges. The stability, reproducibility and repeatability studies of Au@Ag CS/Hb/MXene/AuE biosensor showed results emphasizing the good analytical performance of the biosensor. For practical applications, acrylamide was tested in spiked real samples and a good recovery rate was obtained. The proposed biosensor could further be converted to a rapid, portable sensor for acrylamide sensing.
Diamond Shaped Compact Split Ring Resonator Array Antenna with defected ground plane for 5-6-GHz
Authors: Alvi Talha Shahid , Ali Muhammad
Published: December 2022

This article introduces a fractal antenna inspired by diamond shaped split-ring resonators for 5 and 6-GHz 5G applications. The antenna geometry is accomplished on a low-cost lead glass substrate and consists of a mixture of diamond-shaped split-ring resonators organized in a fractal layout. The proposed antenna's total dimensions are 56*56 mm2 (lowest frequency). With a peak gain of 3.14 and 1.91 dBi at respective resonant peaks, the antenna resonates at a dual-frequency bands of 5.4 GHz and 6.1 GHz, and these values sufficiently agree with the measured data. With a nearly omnidirectional radiation pattern, Sierpinski fractal geometry on top, a partial ground plane at the bottom, and an efficiency of about 80%, the suggested antenna is commercially suitable for 5 and 6-GHz 5G communication applications.
Influence the Graphene Filler Addition on the Tensile Behavior of Natural Kenaf Fiber‐Based Hybrid Nanocomposites
Authors: Natrayan L. , Kaliappan S. , Hatti Gururaj , Patil Pravin P. , Gaur Piyush , Manikandan T. , Murugan P.
Published: December 2022

In current centuries, emphasis has moved from previous resources and compounds to lightweight substances to generate softer, most effective components for particular needs. Using organic kenaf fibers with nanoreinforced epoxy polymers in a blended microbially nanocomposite can improve properties and be environmentally friendly. Adding graphene powder to the epoxy resin increases barrier and mechanical properties while maintaining rigidity without compromising toughness. To explore the impression of such parameters on the materials’ properties of the construction, a mechanical test on nanocomposite features, such as size, filler content, and treatment effect, may be utilized. The elastic behavior, tension characteristics, and stress at vintage for three types of nanobased materials were calculated using the test results: graphite raw kenaf, nanosheets and sun‐bleached kenaf fibers, salinized graphene oxide, and epoxy reinforced with salinized kenaf fibers. The impact of nanocomposite magnitude, filler concentration, and filler processing on mechanical properties is carefully investigated. According to the findings, the three‐weight proportion of 75 nm‐sized particles with salinized filler and kenaf fiber produces the maximum mechanical performance. Compared to other combinations, these combinations increase tensile strength by 16%. However, it appears to be beneficial when it comes to strength properties and deflection. Because of flaws and cavities at the micrometer level, the framework was less robust and distorted quickly after including a nanoparticle filler.
Multifocal Multisystem Langerhans Cell Histiocytosis Involving Pituitary Masquerading as Crohn’s Disease: A Case Report and Review of the Literature
Authors: Ganie Mohd. Ashraf , Malhotra Bhanu , Saini Manpreet , Dutta Arshiya , Sharma Atul , Vaiphie Kim , Dutta Pinaki
Published: December 2022

Background/Objective. We present a case of Langerhans cell histiocytosis (LCH) with gastrointestinal involvement masquerading as inflammatory bowel disease (IBD) in a patient who initially had features of central diabetes insipidus (CDI). Case Report. A 19-year-old male presented at 14 years of age with central diabetes insipidus. He subsequently developed panhypopituitarism and sellar-suprasellar mass, the biopsy of which was inconclusive. Secondary causes for hypophysitis were ruled out. Five years later, he developed perianal pus discharging sinuses, positive ASCA, and sacroiliitis. Rectal ulcer biopsy showed nonspecific inflammation and necrosis. Hence, he was managed as inflammatory bowel disease (IBD). Due to nonresponsiveness of symptoms, doubt about diagnosis was invoked and rectal ulcer biopsy was repeated, which then showed infiltration by Langerhans cells. Hence, he was diagnosed with LCH and showed resolution of symptoms on initiating steroids and vinblastine. Discussion. Gastrointestinal involvement by LCH is unusual and only rarely has represented a prominent clinical manifestation. In most cases, such involvement suggests widespread multisystem disease. Its distinctive morphologic and immunohistochemical features allow LCH to be distinguished from other inflammatory infiltrations found in mucosal biopsy specimens. Conclusion. Preceding CDI and hypopituitarism may predict LCH in patients with IBD-like diseases.
MicroRNA-101-3p Suppresses mTOR and Causes Mitochondrial Fragmentation and Cell Degeneration in COPD
Authors: Fang Lei , Wang Xinggang , Zhang Ming , Khan Petra , Tamm Michael , Roth Michael
Published: December 2022

Background. Cigarette smoke is assumed to cause the loss of airway wall structure in chronic obstructive pulmonary disease (COPD) by reducing airway smooth muscle cell (ASMC) function. It also modifies mTOR activity, microRNA (miR)-101-3p expression, and mitochondria function. Here, the link between miR-101-3p and mTOR-regulated mitochondria integrity and ASMC deterioration was assessed. Methods. Disease-specific miR-101-3p expression was determined by RT-PCR in primary ASMC (non-COPD smokers: n = 6; COPD: n = 8; healthy: n = 6). The regulatory effect of miR-101-3p modification on mTOR expression, mitochondrial fragmentation, and remodeling properties (α-SMA, fibronectin, MTCO2, and p70S6 kinase) was assessed in ASMC (healthy nonsmokers: n = 3; COPD: n = 3) by Western blotting and immunofluorescence microscopy. MiR-101-3p was modified by specific mimics or inhibitors, in ASMC stimulated with TNF-α (10 ng/ml) or cigarette smoke extract (CSE). Results. MiR-101-3p expression was significantly higher in ASMC of COPD patients, compared to ASMC of healthy or active smokers. MiR-101-3p expression was increased by TNF-α or CSE. TNF-α or miR-101-3p deteriorated ASMC and mitochondria, while decreasing mTOR signaling, α-SMA, fibronectin, and MTCO2. MiR-101-3p inhibition reduced ASMC deterioration and mitochondrial fragmentation. Conclusion. Constitutive high miR-101-3p expression characterizes COPD-ASMC, causing increased mitochondrial fragmentation and ASMC deterioration. Thus, reactivation mTOR or blocking miR-101-3p presents a potential new strategy for COPD therapy.
A Three-Phase Reduced Switch Count Multilevel Inverter Topology
Authors: Sivamani S. , Mohan V.
Published: December 2022

Multilevel inverters play a vital role in the industrial and renewable energy sectors due to their flexibility in synthesizing sinusoidal waveforms using a low-pass filter with a medium voltage range. It has several drawbacks, such as a higher number of power component requirements and voltage balancing problems. In this study, a new structure for multilevel inverters has been developed to offer good power quality with minimum number of switching devices and gate driver circuits. The proposed structure is configured to operate in symmetrical and asymmetrical configurations for single/three-phase versions. A simulation study using MATLAB/Simulink has been utilized to study the operating characteristics under both configurations. A laboratory prototype has been built to check the feasibility of the proposed structure for real-time applications.
Dynamic Evaluation of Flow Unit Based on Reservoir Evolution: A Case Study of Neogene Guantao Ng3 Formation in M Area, Gudao, Bohai Bay Basin
Authors: Liu Ruhao , Sun Yu , Yao Xiutian , Yan Baiquan , Ma Jun , Guo Changchun , Wang Xinrui
Published: December 2022

To clarify the dynamic evolution characteristics of reservoir flow units during water injection development, the upper member of the Neogene Guantao formation in Block M of Gudao Oilfield is taken as a case study. Based on logging data, water injection profile test data, subwell data, and production performance data, among others, the flow zone index (FZI static) was proposed as the static evaluation parameter of the flow unit. The relationship between cumulative water injection (WT) and FZI change (

△
FZI

) was fitted. Hence, the

△
FZI

caused by water injection is combined with the static parameter of flow unit evaluation (FZI static) as the dynamic parameter of flow unit evaluation (FZI dynamic). The comprehensively evaluated reality of flow units in different periods is characterized by formula

FZI
 
static

+

△
FZI

=

FZI
 
dynamic

. The study shows that as the division standard of the flow unit, the FZI has a good correlation with the test results of the water absorption profile, such as water absorption intensity and relative water injection volume. Using the FZI as the static parameter of flow unit evaluation, four types of flow units were divided as follows: type I flow unit,

FZI
≥
4.1

; type II flow unit,

4.1
>
FZI
≥
2.4

; type III flow unit,

2.4
>
FZI
≥
1.7

; type IV flow unit,

1.7
>
FZI

. The reservoir porosity and permeability characteristics of different flow units are highly correlated. Moreover, the relative permeability curve confirms that different flow units have different seepage capacities. Though, comparing characteristic reservoir parameters in different periods, the reservoir’s physical parameters became more conducive to fluid flow with the water injection development. The increase in the same water injection rate for type I and II flow units was greater than that for type III and IV flow units. Furthermore, when type I flow units were continuously distributed in a large area, high water consumption bands were formed, absorbing most of the water injection in the water injection wells. Hence, the waterflood efficiency was low. The change in different flow units was mainly controlled by the injection production well pattern and WT. Combined with the relative change characteristics of interlayer flow units, the changes can be divided into increasing type change and decreasing type changes. Finally, according to the distribution characteristics of different flow units, oil saturation, and water flooding results, strategies for tapping the potential of the remaining oil from three aspects (plane, interlayer, and inner layer) were formulated.
Mitigation of Social Impacts of Alternative Road Development Plans Based on Local Wisdom in West Sumatra, Indonesia
Authors: Priyambodo  , Buditiawan Kristian , Irawan Agung Budi , Setyawan Dendy , Rinawati Herrukmi Septa , Afriyanni  , Momon  , Yolarita Elsa , Khasanah Masbiran Vivi Ukhwatul , Dananjaya Imbang
Published: December 2022

Infrastructure development, especially roads, is hampered by the fact of rejection based on urgency and attachment to the Ulayat land of the local community. Therefore, further models are needed in the form of mitigation based on culture and local wisdom to avoid conflicts and land disputes and changes in their use. This study aims to identify the social impacts of the bypass Amor Road construction and its mitigation strategies based on the perceptions of the community and stakeholders. This research study uses a descriptive qualitative research method. Data collection techniques were carried out through documentation studies, observation, and in-depth interviews. The data analysis technique was carried out using SIA (social impact analysis). SIA helps the community, government, and private sector to better understand and anticipate possible social problems and the changes they bring about as a result of the construction of the bypass Amor road. The results of the study conclude that the success of road construction depends on the government’s mitigation strategy in adopting local values that live in the community which is then followed by the existence of a foundation and expansion of the fulfilment of community interests. This study recommends three things, namely, (1) conduct intensive and responsive socialization and approach; (2) approach community involvement through a community-based approach and traditional leaders; and (3) prepare alternative livelihoods based on community interest, local potential, market opportunities, and financial feasibility as well as providing capital for businesses.
Valorization of Seaweed Wracks: Inclusion as Additive in Diets for Grass Carp (Ctenopharyngodon idella)
Authors: Galindo Ana , Rodríguez Covadonga , Reis Diana B. , Marrero Manuel , Acosta Nieves G. , Barreto Maria Carmo , Jiménez Ignacio A. , de Urioste Jaime , Venuleo Marianna , Pérez José A.
Published: December 2022

Macroalgae have been recently described as a potential ingredient for aquafeeds, exerting several physiological benefits. Grass carp (Ctenopharyngodon idella) is a freshwater species, which has been the major fish species produced in the world in the last years. In order to determine the potential use of macroalgal wracks in fish feeding, C. idella juveniles were fed with an extruded commercial diet (CD) or the CD supplemented with 7% of a wind dried-powder (1 mm) from either a multispecific macroalgal wrack (CD + MU7) or a monospecific macroalgal wrack (CD + MO7) obtained from Gran Canaria island (Spain) coasts. After 100 days of feeding, survival, fish weight, and body indexes were determined, and muscle, liver, and digestive tract samples were collected. The total antioxidant capacity of macroalgal wracks was analyzed by assesing the antioxidant defense response and digestive enzymes activity in fish. Finally, muscle proximate composition, lipid classes (LC), and fatty acid (FA) profiles were also studied. Our results suggest that dietary inclusion of macroalgal wracks does not have negative effects on growth, proximate, and lipid composition, antioxidative status, or digestive capacity of C. idella. In fact, both macroalgal wracks caused a general lower fat deposition, and the multispecific wrack enhanced catalase activity in the liver.
Research on Fatigue Performance of the Rib Beam Bridge Carriageway Slab Based on Cumulative Damage Theory
Authors: Chen Binglin , Yu Tianlai , Zhang Linlin , Wu Yuxuan , Wang Yifan
Published: December 2022

The purpose of this paper is to study the development law of fatigue damage of the carriageway slab of reinforced concrete ribbed girder bridge and to provide theoretical support for carriageway slab design. The fatigue test of reinforced concrete rib beam bridge carriageway slabs was conducted. Based on the material fatigue damage theory, the fatigue damage model was established by ABAQUS software. The fatigue performance, failure mechanism, and the effect of fatigue level on the fatigue performance of the carriageway slab were studied. The experimental research results show that when the slab of the rib beam bridge was fatigued, and the radial crack appeared at the bottom of the slab, which belonged to punching shear failure. The fatigue failure process was divided into three stages as follows: in the initial stage of fatigue, the deflection and reinforcement strain increased linearly with fatigue times, and in the stable development stage, the bottom deflection and reinforcement strain increased steady progression. With the increase in fatigue cycles, the fatigue accumulation damage was gradually accumulated, and the stiffness of the carriageway slab gradually decreases. In the rapid development stage, the deflection, reinforcement strain, and crack growth speed were significantly increased. According to the fatigue damage model, the simulation analysis results show that the accumulated damage to the bridge carriageway was more serious with the increase in fatigue load level. The fatigue damage degree was lower when the design fatigue load level is not greater than 0.55.
Certificateless Cross-Domain Group Authentication Key Agreement Scheme Based on ECC
Authors: Cao Liling , Liang Mei , Zhang Zheng , Cao Shouqi
Published: December 2022

Focusing on the problem that existing traditional cross-domain group authentication schemes have a high complexity, a certificateless cross-domain group authentication key agreement scheme based on ECC is proposed. The protocol provides scalability and can meet the requirements of cross-domain key negotiation by multiple participants in different domains. Security analysis shows that the proposed scheme is secure in the random oracle security model, it can resist some attacks under the extended Canetti-Krawczyk (eCK) security model. Performance analysis shows that the proposed scheme is of strong practical application value with high efficiency; it costs relatively low amount of calculation and communication.
A Prognostic Model of Seven Immune Genes to Predict Overall Survival in Childhood Acute Myeloid Leukemia
Authors: Luo Yan , Xu Yanpeng , Li Xue , Shi Xiaoqi , Huang Pei , Chen Yan , He Zhixu
Published: December 2022

Background. Acute myeloid leukemia (AML) is one of the most common hematological malignancies and accounts for about 20% of childhood leukemias. Currently, immunotherapy is one of the recommended treatment schemes for recurrent AML patients to improve their survival rates. Nonetheless, low remission and high mortality rates are observed in recurrent AML and challenge the prognosis of AML patients. To address this problem, we aimed to establish and verify a reliable prognostic risk model using immune‐related genes to improve the prognostic evaluation and recommendation for personalized treatment of AML. Methods. Transcriptome data and clinical data were acquired from the TARGET database while immune genes were sourced from InnateDB and ImmPort Shared databases. The mRNA expression profile matrix of immune genes from 62 normal samples and 1408 AML cases was extracted from the transcriptome data and subjected to differential expression (DE) analysis. The entire cohort of DE immune genes was randomly divided into the test group and training group. The prognostic model associated with immune genes was constructed using the training group. The test group and entire cohort were employed for model validation. Lastly, we analyzed the potential clinical application of the model and its association with immune cell infiltration. Results. In total, 751 DE immune genes were differentially regulated, including 552 upregulated and 199 downregulated. Based on these DE genes, we developed and validated a prognostic risk model composed of seven immune genes, GDF1, TPM2, IL1R1, PSMD4, IL5RA, DHCR24, and IL12RB2. This model is able to predict the 5‐year survival rate more accurately compared with age, gender, and risk stratification. Further analysis showed that CD8+ T‐cell contents and neutrophil infiltration decreased but macrophage infiltration increased as the risk score increased. Conclusions. A seven‐immune gene model of AML was developed and validated. We propose this model as an independent prognostic variable able to estimate the 5‐year survival rate. In addition, the model can also reflect the immune microenvironment of AML patients.
Mechanical and Microstructural Investigation on AZ91B Mg Alloys with Tool Tilt Variation by Friction Stir Welding
Authors: Yaknesh S. , Tharwan Mohammed , Saminathan Rajasekaran , Rajamurugu N. , Prakash K. B. , Ankit  , Pasupathi Manoj Kumar , Sarojwal Atul , Gebreyohannes Dawit Tafesse
Published: December 2022

By modifying the angle of tilt of 2 distinct tool pin shapes, both tapered with and without threaded structures, TPT tool pin with threads and TPNT tool pin with no threads, the mechanical behaviour and microstructural attributes were examined for the joints of AZ91B alloy formed by friction stir welding. Spindle torque and unique forces operating laterally and axially (referred to as Y-force and X-force, respectively) were created at the junction of the tool and plate, which were monitored and assessed in order to know the influence of degrees of tilt. When the tool’s angle of tilt advances, torque and forces of the spindle also show an increasing trend that is important to friction stir welding. The spindle torque and Y-force produced by the TPT tool are higher than those of the TPNT tool, whereas the X-force associated with the TPT tool is less. Discrepancies in forces grow along the concurrent increase in the angle of tilt for the TPNT as well as TPT tools, exhibiting opposite behaviour. The onion ring-type structure was visualized in the threaded tool pin structure TPT due to the high flow of plasticized metal compared to TPNT tool joints, for which the onion ring shape is not visible. With the TPT tool, the joint made at a 0° angle of tilt had a peak tensile strength of 232 MPa.
Effect of the Number and Distribution of Circular Holes on the Damage and Fracture of Limestone Using PFC2D
Authors: Liu Handong , Liu Shuai , Liu Haining , Fu Yunyou , Kang Minglei , Bai Zhe , Xu Jianglong , Zheng Chao
Published: December 2022

The common occurrence of various number and distribution of hole flaws complicates the mechanical behavior and fracture mode of the rock masses that contain them. This study develops seven numerical models of limestone samples with different numbers and distributions of circular hole flaws using 2-D particle flow discrete element code (PFC2D) to investigate their impact on the mechanical properties of limestone while maintaining the same flaws area. In addition, it analyzes the effect of these factors on the mesomechanical features of each model, including the characteristic stress values (peak stress, crack initiation, and damage stress), crack evolution, stress, and displacement field. The results showed that the peak stress, crack initiation, and damage stress of the single-hole model are between those of multihole models. As the arrangement of dip angle increases, the peak stress, crack initiation, and damage stress of models with the same number of multihole flaws exhibit a V-shaped change. The characteristic stress values are the largest when the holes are vertically aligned. Model differences in crack development path, shape, and number, as well as stress concentration area and failure mode, are primarily due to the number and distribution of holes. The circular holes are arranged at approximately 45°, and the greater the number of defects, the more likely the model is to fail. The study’s findings can provide support and reference for the research system of deformation and failure of rock mass with hole flaws.
First-in-Maintenance Therapy for Localized High-Grade Osteosarcoma: An Open-Label Phase I/II Trial of the Anti–PD-L1 Antibody ZKAB001
Authors: Zhou Yan , Yang Qingcheng , Dong Yang , Ji Tong , Zhang Bing , Yang Cheng , Zheng Shuier , Tang Lina , Zhou Chenliang , Qian Guowei , Huang Yujing , Yu Wenxi , Li Hongtao , Wang Yonggang , He Aina , Shen Zan , Bao Qiyuan , Hua Yingqi , Bai Hongyu , Zhao Jiayi , Li Xiaoyi , Dai Xiangrong , Zhang Jianjun , Hu Haiyan , Yao Yang
Published: December 2022

Purpose:

We investigated the safety and preliminary efficacy of anti–PD-L1 antibody (ZKAB001) as maintenance therapy for localized patients with high-grade osteosarcoma to reduce the risk of recurrence and metastasis.

Patients and Methods:

This open-label Phase I/II study was divided into dose-escalation Phase I and expansion Phase II. Phase I used a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and Phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3.

Results:

Between October 2018 and 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase, and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The MTD was not defined in Phase I. All doses had a manageable safety profile. The recommended dose in Phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only 1 (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year event-free survival (EFS) and overall survival (OS) were not established; however, 24-month EFS was 71.4% (95% confidence interval, 47.2–86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population.

Conclusions:

Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized patients with osteosarcoma.
FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer
Authors: Fallah Jaleh , Agrawal Sundeep , Gittleman Haley , Fiero Mallorie H. , Subramaniam Sriram , John Christy , Chen Wei , Ricks Tiffany K. , Niu Gang , Fotenos Anthony , Wang Min , Chiang Kelly , Pierce William F. , Suzman Daniel L. , Tang Shenghui , Pazdur Richard , Amiri-Kordestani Laleh , Ibrahim Amna , Kluetz Paul G.
Published: December 2022

On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC; n = 551) or BSoC alone (n = 280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and one or two prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS), with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (HR: 0.62; 95% confidence interval: 0.52–0.74; P < 0.001). The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving 177Lu-PSMA-617 were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving 177Lu-PSMA-617 were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. This article summarizes the FDA review of data supporting traditional approval of 177Lu-PSMA-617 for this indication.
ATM Regulation of the Cohesin Complex Is Required for Repression of DNA Replication and Transcription in the Vicinity of DNA Double-Strand Breaks
Authors: Bass Thomas E. , Fleenor Donald E. , Burrell Paige E. , Kastan Michael B.
Published: December 2022

Ataxia-telangiectasia mutated (ATM) is an apical regulator of responses to DNA double-strand breaks (DSB). Using two complementary unbiased proteomic screens, we identified the cohesin complex proteins PDS5A, PDS5B, RAD21, NIPBL, and WAPL as apparent novel ATM interactors and substrates. ATM-dependent phosphorylation of PDS5A on Ser1278 following treatment with ionizing radiation is required for optimal cell survival, cell-cycle checkpoint activation, and chromosomal stability. Using a system that introduces site-specific DNA breaks, we found that ATM phosphorylation of cohesin proteins SMC1A, SMC3, and PDS5A are all required for repression of both RNA transcription and DNA replication within the vicinity of a DSB, the latter insight based on development of a novel localized S-phase cell-cycle checkpoint assay. These findings highlight the significance of interactions between ATM and cohesin in the regulation of DNA metabolic processes by altering the chromatin environment surrounding a DSB.

Implications:

Multiple members of the cohesin complex are involved in the regulation of DNA replication and transcription in the vicinity of DNA double-strand breaks and their role(s) are regulated by the ATM kinase.
In VivoModeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities
Authors: ten Hacken Elisa , Sewastianik Tomasz , Yin Shanye , Hoffmann Gabriela Brunsting , Gruber Michaela , Clement Kendell , Penter Livius , Redd Robert A. , Ruthen Neil , Hergalant Sébastien , Sholokhova Alanna , Fell Geoffrey , Parry Erin M. , Broséus Julien , Guieze Romain , Lucas Fabienne , Hernández-Sánchez María , Baranowski Kaitlyn , Southard Jackson , Joyal Heather , Billington Leah , Regis Fara Faye D. , Witten Elizabeth , Uduman Mohamed , Knisbacher Binyamin A. , Li Shuqiang , Lyu Haoxiang , Vaisitti Tiziana , Deaglio Silvia , Inghirami Giorgio , Feugier Pierre , Stilgenbauer Stephan , Tausch Eugen , Davids Matthew S. , Getz Gad , Livak Kenneth J. , Bozic Ivana , Neuberg Donna S. , Carrasco Ruben D. , Wu Catherine J.
Published: December 2022

Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing of recurrent CLL loss-of-function drivers in mice and recapitulated the process of transformation from indolent CLL into large cell lymphoma [i.e., Richter syndrome (RS)]. Evolutionary trajectories of 64 mice carrying diverse combinatorial gene assortments revealed coselection of mutations in Trp53, Mga, and Chd2 and the dual impact of clonal Mga/Chd2 mutations on E2F/MYC and interferon signaling dysregulation. Comparative human and murine RS analyses demonstrated tonic PI3K signaling as a key feature of transformed disease, with constitutive activation of the AKT and S6 kinases, downmodulation of the PTEN phosphatase, and convergent activation of MYC/PI3K transcriptional programs underlying enhanced sensitivity to MYC/mTOR/PI3K inhibition. This robust experimental system presents a unique framework to study lymphoid biology and therapy.

Significance:

Mouse models reflective of the genetic complexity and heterogeneity of human tumors remain few, including those able to recapitulate transformation to aggressive disease histologies. Herein, we model CLL transformation into RS through multiplexed in vivo gene editing, providing key insight into the pathophysiology and therapeutic vulnerabilities of transformed disease.

This article is highlighted in the In This Issue feature, p. 101
Effects of Sprayable, Highly Adhesive Hydrophobized Gelatin Microparticles on Endoscopic Submucosal Dissection: A Swine Model
Authors: Kabayama Masayuki , Sasaki Fumisato , Hidehito Maeda , Fujino Yusuke , Yano Hiroki , Tanaka Akihito , Arima Shiho , Tanoue Shiroh , Hashimoto Shinichi , Kanmura Shuji , Hirade Hiromi , Nishiguchi Akihiro , Taguchi Tetsushi , Ido Akio
Published: December 2022

Introduction: Sprayable wound dressings containing hydrophobized microparticles (hMPs) are characterized by strong adhesiveness. We examined the effect of hMPs derived from Alaska pollock gelatin on endoscopic submucosal dissection (ESD) ulcers. Methods: (1) In an in vivo model of miniature swine gastric ESD, gastric ulcers were created by ESD and then sprayed with hMPs or untreated followed by microscopic examination. (2) In an ex vivo ESD model of resected stomach, a pinhole-shaped perforation was created on the ESD ulcer of resected stomach; hMPs were then sprayed on the perforation; and air leakage and intragastric pressure were measured. (3) In an in vivo duodenal ESD model of miniature swine, duodenal artificial ESD ulcers with pinhole-shaped perforation were examined; ulcers were classified into hMPs-sprayed and nonsprayed groups, and inflammation in the intrinsic muscle layer and serosa were compared between the groups. Results: (1) Histological observation of submucosal tissues showed a decreased number of invading inflammatory cells in hMP-sprayed tissues compared with the control in miniature swine gastric ESD (p < 0.05). In addition, the rates of anti-alpha smooth muscle actin and type I collagen positivity were significantly lower in the hMPs group than in the control group (p < 0.05). (2) Intragastric pressure could not be measured in the nonsprayed group, whereas no air leakage was observed in the sprayed group when pressurized up to 26 mm Hg in the resected stomach model. (3) The sprayed group showed suppressed inflammation of the intrinsic muscular layer and serosa in both cases compared with the nonsprayed group in miniature swine duodenal ESD (p < 0.05). Conclusions: Sprayable, tissue-adhesive hMPs are a promising medical material for intraoperative and postoperative treatment of ESD-induced wound via anti-inflammation and strong adhesiveness.
Neurochemical Correlates of Cue Reactivity in Individuals with Excessive Smartphone Use
Authors: Henemann Gudrun M. , Schmitgen Mike M. , Wolf Nadine D. , Hirjak Dusan , Kubera Katharina M. , Sambataro Fabio , Lemenager Tagrid , Koenig Julian , Wolf Robert Christian
Published: December 2022

Background: Excessive smartphone use (ESU), that is, a pattern of smartphone use that shows specific features of addictive behavior, has increasingly attracted societal and scientific interest in the past years. On the neurobiological level, ESU has recently been related to structural and functional variation in reward and salience processing networks, as shown by, for example, aberrant patterns of neural activity elicited by specific smartphone cues. Objectives: Expanding on these findings, using cross-modal correlations of magnetic resonance imaging (MRI)-based measures with nuclear imaging-derived estimates, we aimed at identifying neurochemical pathways that are related to ESU. Methods: Cross-modal correlations between functional MRI data derived from a cue-reactivity task administered in persons with and without ESU and specific PET/SPECT receptor probability maps. Results: The endogenous mu-opioid receptor (MOR) system was found to be significantly (FDR-corrected) correlated with fMRI data, and z-transformed correlation coefficients showed an association (albeit nonsignificant after FDR-correction) between MOR and the Smartphone Addiction Inventory “withdrawal” dimension. Conclusions: We could identify the MOR system as a neurochemical pathway associated with ESU. The MOR system is closely linked to the reward system, which has been recognized as a key player in addictive disorders. Together with its potential link to withdrawal, the MOR system hints toward a biologically highly relevant marker, which should be taken into consideration in the ongoing scientific discussion on technology-related addictive behaviors.
Demystifying the Mystery of Vitamin B12 Deficiency in an Infant with Developmental Delay
Authors: Aldarawsha Heba Ali , AlDoory Sura Ahmed , Saleh Shafiqa Mohamed , Chencheri Nidheesh Cheeyancheri
Published: December 2022

A 7-month-old boy presented to our hospital with complaints of epistaxis. Pancytopenia was found on a blood test, and physical examination was significant for hepatosplenomegaly, acral hyperpigmentation of hands and feet, and hypotonia, along with mild delayed milestones. The infant underwent extensive investigations including metabolic workup and bone marrow aspiration, which revealed abundant megalocytes. Vitamin B12 was deficient (result 82 pg/mL, reference range 187–883 pg/mL); therefore, vitamin B12 therapy was commenced. Following the initiation of vitamin B12 therapy, blood cell lines normalized, neurological symptoms improved, hepatosplenomegaly regressed, and milestones were achieved.
Mixed Neuroendocrine Non-Neuroendocrine Neoplasm Arising in the Ectopic Gastric Mucosa of Esophagus
Authors: Gushima Ryosuke , Miyamoto Hideaki , Imamura Miyuki , Sonoda Takayoshi , Matsuno Kenshi , Yamasaki Akira , Furuta Yoki , Hashigo Shunpei , Tateyama Masakuni , Naoe Hideaki , Tanaka Yasuhito
Published: December 2022

Esophageal neuroendocrine neoplasms are extremely rare, and their prognosis is poor. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are even more rare and are defined as tumors consisting of neuroendocrine carcinoma and either adenocarcinoma or squamous cell carcinoma. We report a rare case featuring endoscopic submucosal dissection (ESD) for an esophageal MiNEN, arising from the ectopic gastric mucosa in the lower thoracic esophagus. A 92-year-old male patient was referred to this hospital for investigation of an esophageal tumor. An endoscopic examination revealed a 10 mm elevated lesion, with 8 mm flat areas on the anal side, within the ectopic gastric mucosa located in the lower thoracic esophagus. ESD was carried out, and a histopathological examination revealed a tubular adenocarcinoma composed of differentiated neuroendocrine cells. Immunohistochemical staining was positive for synaptophysin and negative for chromogranin A. The labeling index of Ki-67 was more than 80%. Based on these results, we diagnosed the lesion as an esophageal MiNEN, arising in the ectopic gastric mucosa of the esophagus. The patient remains alive, without recurrence of cancer, 24 months after ESD.
A Novel Treatment Approach to Treatment-Resistant, Recurrent Clostridium difficile
Authors: Gangadhar Megha , Kottapalli Anita , Kottapalli Ven
Published: December 2022

A 36-year-old male with a previous medical history of persistent Clostridium difficile presented to clinic for evaluation of diarrheal symptoms intermittently for the last 2 years. He reported recurrent episodes of C. difficile that initially began after prophylactic antibiotic use prior to a tooth extraction. He underwent 12 unsuccessful treatment trials at a nearby clinic with courses of vancomycin, metronidazole, and fidaxomicin. His chronic diarrhea had caused him to endure significant lifestyle alterations over the years. After multiple episodes of incomplete bacterial clearance, he was referred to a university-based tertiary care facility but instead opted for care at a nearby clinic. Upon work-up, his serology was again positive for C. difficile, and he was initiated on a 14-day course of fidaxomicin 200 mg p.o. BID, along with yogurt and probiotic supplementation. Despite fidaxomicin treatment, subsequent serological PCR testing for C. difficile remained positive, consistent with CT abdomen and pelvis findings suspicious for enteritis. His recurrent resistance to standard therapy protocols inspired an unconventional treatment approach: another 14-day course of fidaxomicin 200 mg p.o. BID, followed by fidaxomicin 200 mg p.o. each morning and cholestyramine 4 g p.o. each evening for another 2 weeks, concluded by fecal microbial transplant. Two weeks following this antibiotic regimen and fecal transplant, serology was negative for C. difficile. Subsequent follow-up revealed no evidence of recurrence.
Multiple Intelligence and Career Preference: A Basis for Senior High School Career Guidance Orientation
Authors: Parojenog Robin C. , Parojenog Anna-Louise Precila R. , Atup Ma. Delilah C.
Published: December 2022

This study aimed to determine the multiple intelligence and career preferences of Grade XII students of Biabas Trade High School as the basis for career guidance orientation. The respondents of the study are the 179 grade 12 students from different tracks. A descriptive survey method type of research was used in conducting the research using an adapted multiple intelligence test survey, multiple intelligence checklist, and an adapted and modified inventory of occupational interest checklist from National Career Assessment Examination (NCAE). The results were analyzed using analysis of variance and Pearson r to determine the significant difference and significant correlation respectively. The results showed that there is no significant relationship between the multiple intelligence and career preferences of the students. This implies that students have different multiple intelligences without any regard to their career preference.  It was observed that among the nine multiple intelligences, the Existential and the Kinesthetic strength are most dominant among the Grade 12 Senior High School students. On the other hand, students who fall under the Logical strength are the least dominant. In terms of career preferences, the careers that fall under the Interpersonal strength are most dominant. The least dominant preferred careers are the ones that belongs to the Existential strength. Based on the given result, it is recommended that it must be disseminated to all senior high school teachers, career guidance advocates, and school heads through conference, in-service trainings, or during LAC sessions to communicate the importance of developing multiple intelligence and career guidance orientation among senior high school students.