bluuebunny/crossref_metadata_2025 huggingface dataset:
Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease
Authors: Luke Jason J , Davar Diwakar , Andtbacka Robert H , Bhardwaj Nina , Brody Joshua D , Chesney Jason , Coffin Robert , de Baere Thierry , de Gruijl Tanja D , Fury Matthew , Goldmacher Gregory , Harrington Kevin J , Kaufman Howard , Kelly Ciara M , Khilnani Anuradha D , Liu Ke , Loi Sherene , Long Georgina V , Melero Ignacio , Middleton Mark , Neyns Bart , Pinato David J , Sheth Rahul A , Solomon Stephen B , Szapary Philippe , Marabelle Aurelien
Published: April 2024

Background

Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis.

Methods

An Intratumoral Immunotherapy Clinical Trials Expert Panel composed of international key stakeholders from academia and industry was assembled. A multiple choice/free response survey was distributed to the panel, and the results of this survey were discussed during a half-day consensus meeting. Key discussion points are summarized in the following manuscript.

Results

The panel determined unique clinical trial designs tailored to different stages of cancer development—from premalignant to unresectable/metastatic—that can maximize the chance of capturing the effect of intratumoral immunotherapies. Design elements discussed included study type, patient stratification and exclusion criteria, indications of randomization, study arm determination, endpoints, biological sample collection, and response assessment with biomarkers and imaging. Populations to prioritize for the study of intratumoral immunotherapy, including stage, type of cancer and line of treatment, were also discussed along with common barriers to the development of these local treatments.

Conclusions

The SITC Intratumoral Immunotherapy Clinical Trials Expert Panel has identified key considerations for the design and implementation of studies that have the greatest potential to capture the effect of intratumorally delivered immunotherapies. With more effective and standardized trial designs, the potential of intratumoral immunotherapy can be realized and lead to regulatory approvals that will extend the benefit of these local treatments to the patients who need them the most.
Contribution of basal ganglia activity to REM sleep disorder in Parkinson’s disease
Authors: Yin Zixiao , Yuan Tianshuo , Yang Anchao , Xu Yichen , Zhu Guanyu , An Qi , Ma Ruoyu , Gan Yifei , Shi Lin , Bai Yutong , Zhang Ning , Wang Chunxue , Jiang Yin , Meng Fangang , Neumann Wolf-Julian , Tan Huiling , Zhang Jian-Guo
Published: April 2024

Background

Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson’s disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD.

Method

Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls.

Results

We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD.

Conclusions

These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD.
The journey from bench to bedside—it takes a science village
Authors: Mes-Masson Anne-Marie
Published: April 2024

I was fortunate enough to start my career at what was the dawn of modern-day molecular biology and to apply it to an important health problem. While my early work focused on fundamental science, the desire to understand human disease better and to find practical applications for research discoveries resulted, over the following decades, in creating a stream of translational research directed specifically toward epithelial cancers. This could only have been possible through multiple collaborations. This type of team science would eventually become a hallmark of my career. With the development of higher throughput molecular techniques, the pace of research and discovery has quickened, and the concept of personalized medicine based on genomics is now coming to fruition. I hope my legacy will not just reflect my published works, but will also include the impact I have had on the development of the next generation of scientists and clinician scientists who inspired me with their dedication, knowledge, and enthusiasm.
Tripartite quantum teleportation in de Sitter spacetime
Authors: Huang Zhiming , Zou Xiangfu , Situ Haozhen , He Zhimin , Zhao Lianghui , Ye Yiyong , Rong Zhenbang
Published: April 2024

In this paper, a tripartite quantum teleportation scheme in de Sitter vacuum is constructed. Then we investigate the influence of vacuum fluctuation, temperature and two-atom distance on performance of the tripartite quantum teleportation. It is found that fidelity drops fast with temperature and evolution time increasing. While temperature is low relatively, the influence of two-atom distance cannot be negligible, the change of fidelity is different with two-atom separation and time varying. The results may be helpful for dealing with quantum information tasks in curve spacetime and exploring the properties of curve spacetime through quantum information means.
Automated Test Case Generation for Path Coverage by Using Multi-Objective Particle Swarm Optimization Algorithm with Reinforcement Learning and Relationship Matrix Strategies
Authors: Liang Shuwen , He Zhitao
Published: April 2024

Software testing is an important phase in software life cycle, and test case generation occupies the main part of the testing workload. Path coverage is the most stringent and difficult coverage criteria, so automatic test case generation for path coverage (ATCG-PC) is an important task in software testing. ATCG-PC is usually abstracted as an optimization search problem, and the commonly used solution algorithm is swarm intelligence algorithm. This paper proposes a path coverage test case generation algorithm based on improved multi-objective particle swarm optimization (IMOPSO) algorithm. The algorithm uses the multi-objective strategy to generate test cases for a group of similar paths at a time, and is supplemented by the particle action selection strategy based on reinforcement learning and the secondary search algorithm based on relationship matrix, which makes use of the similarity information between paths to speed up the early convergence and help to quickly reach the optimal solution around the local optimal position. By grouping the paths according to the similarity, the algorithm reduces the test case consumption, and improves the efficiency of test case generation. Experimental results show that, compared with the existing methods, the proposed algorithm can achieve higher path coverage with less test case consumption and is also suitable for large-scale programs.
Search of effective interaction in dipole bands of an odd–odd trans-lead Nucleus: the case of 204At
Authors: Kanjilal Debasmita
Published: April 2024

Role of effective interaction potential in shears band structure in [Formula: see text]At has been investigated in more detail than in previous studies. A semi-classical geometric model is used to obtain the interaction strengths between valence protons and neutron holes constituting the shears blades. The value produces overall good agreement with this region’s nuclei. Band crossing is observed in the spin-parity range [Formula: see text] – [Formula: see text]. Configurations of the Magnetic Rotational (MR) band are assigned in the light of the Shears mechanism with the Principal Axis Cranking (SPAC) model. Experimental rotational frequencies and the deduced ratio of [Formula: see text] are well reproduced by SPAC calculations, suggesting the dipole band in [Formula: see text]At can undoubtedly be interpreted as the MR band resulting from the effective interaction of repulsive potential.
Effect of mass ratio on rGO/TiO2 composite as catalyst for methylene blue degradation under UV irradiation
Authors: Junita Tri Komala , Michele Natan Cecilia , Aurellia Jedija Manondang , Khanifah Nur , Syakir Norman , Faizal Ferry , Hidayat Rahmat , Fitrilawati Fitri
Published: April 2024

Adsorption and photocatalytic are commonly used methods for the removal of dye contained in industrial wastewater. Therefore, this study aimed to combine reduced Graphene Oxide (rGO) with Titanium Oxide (TiO2) through various compositions using the hydrothermal method to obtain a catalyst of rGO/TiO2 nanocomposites for the removal of contaminants from wastewater. The synthesized rGO/TiO2 nanocomposites were mixed with methylene blue (MB) to reduce their content in water under dark conditions and UV light irradiation. The change of the optical properties of MB under both conditions was also examined, where a decrease in absorbance was observed. Under UV light irradiation, the maximum wavelength [Formula: see text] of MB shifted from 664[Formula: see text]nm to 649[Formula: see text]nm but remained constant at 664[Formula: see text]nm in dark conditions. The results of optical characterizations confirmed that the adsorption of MB by rGO/TiO2 nanocomposites under dark conditions did not change the MB structure. However, a significant degradation was observed with photocatalytic process under UV light irradiation. Nanocomposites rGO/TiO2 with rGO 60% and TiO2 40% (GT40) have better performance in reducing MB under UV light irradiation.
EFFECT OF CUPPING THERAPY ON PAIN, CARDIORESPIRATORY PARAMETERS, AND LUNG FUNCTION IN PATIENTS WITH FIBROMYALGIA SYNDROME
Authors: Khandelwal Muskan , Kalra Sheetal , Ajmera Puneeta , Hirendra Rai Richa
Published: April 2024

Background: The rheumatic condition fibromyalgia syndrome (FMS) is marked by extensive pain, and tender points, with accompanying complaints such as stiffened muscles, depression, anxiety, sleep disturbance, along with dyspnea, exhaustion, and other cardio-respiratory related dysfunction. This study’s goal was to determine the effect of dry cupping intervention on pain, cardiorespiratory parameters as well as lung function in patients with FMS.

Methods: Thirty females with FMS (40–60 years old) were enlisted and subsequently divided into two distinct groups: conventional treatment with ([Formula: see text] = 15) and without ([Formula: see text] = 15) cupping therapy i.e. experimental and control groups respectively. All participants received therapies 3 days a week during this study. Visual Analogue Scale (VAS), digital pressure pain threshold (PPT), cardiac parameters including blood pressure using a sphygmomanometer, O2 saturation and pulse rate using a pulse oximeter, respiratory parameters including chest expansion using a measuring tape, lung functions including FVC and FEV1/FVC using a spirometer were used to assess participants on baseline, last day of 2nd and 4th week of treatment.

Results: Improvements in pain, PPT, oxygen saturation, pulse rate, and chest expansion, FVC and FEV1/FVC were higher in the group who got cupping therapy including conventional treatment against the group who just received conventional treatment ([Formula: see text] 0.05). At the end of the 4th week, there was no appreciable change in blood pressure levels between the groups ([Formula: see text] 0.05).

Conclusion: The FMS treatment plan should include cupping therapy in addition to conventional treatment to help patients improve their cardio-respiratory fitness and overall quality of life.
Multifractal Analysis of International Energy and Agricultural Markets Under the Influence of Russia–Ukraine Conflict
Authors: Wei Jing-Wen , Wang Hong-Yong , Cao Guang-Xi
Published: April 2024

Taking six representative futures in the international energy and agricultural markets as the research objects, we use multifractal analysis methods to study the fluctuation characteristics, market risks and cross-correlations within and between these markets before and after the outbreak of the Russia–Ukraine conflict in this paper. The empirical results show that both the auto-correlations and cross-correlations have obvious multifractal features. It is confirmed that the multifractal strength and market risks of the international energy markets have weakened, while those of the international agricultural markets have enhanced after the Russia–Ukraine conflict broke out. In addition, the Russia–Ukraine conflict has intensified the strength of the multifractality and the degree of fluctuation complexity between these two classes of international markets. Further, the intrinsic multifractal natures of cross-correlations are tested, and the apparent and intrinsic multifractality before and after the conflict are revealed. Finally, some policy suggestions are put forward based on the empirical results.
ASSESSMENT OF GROWTH AND RUPTURE OF CAROTID ATHEROSCLEROSIS AND PLAQUE WITH DIFFERENT DEGREES OF STENOSIS
Authors: HU MENGCHAO , JIAO SHUPING , WU JIANJIN , QU LEFENG , CHEN HONGXUN , DAICHIN
Published: April 2024

In this study, the growth and rupture of plaque were investigated to predict the development of carotid atherosclerosis and plaque. Realistic 3D models of multi-component plaque and carotid artery were established in healthy, mild, moderate, and severe stenosis. Fluid–structure interaction (FSI) simulations were performed on these models, and the wall shear stress (WSS), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and wall tensile stress (WTS) in a natural cardiac cycle were analyzed to assess the epidermal rupture, growth tendency, and internal rupture of plaques in a natural state. Results show that in severe stenosis, the WSS at the stenosis sites exceeds the threshold of rupture during almost the entire cardiac cycle, thus causing an epidermal injury, bringing about plaque detachment and thrombosis. TAWSS decreased and OSI and RRT increased in the bifurcation region and the downstream region of the plaque. The deposition is more likely to occur in these regions. A higher degree of stenosis will increase the OSI and RRT in the downstream region of the plaque, leading to continuous deterioration of the plaque, while the degree of stenosis has little effect on the upstream region of the plaque. The fibrous cap is the starting point for rupture within the plaque, and calcification increases the stress on the fibrous cap, thereby increasing the risk of rupture.
Uncertain Leaky Integrate-and-Fire Neuron Equation
Authors: Qiu Xiaoyue , Zhu Jiaxuan , Liu Liying
Published: April 2024

The Leaky Integrate-and-Fire (LIF) neuron model is a simplified neuronal model commonly used to describe voltage changes on the cell membrane. Considering the influence of real-world environmental factors on the total input current received by neurons, we propose an uncertain LIF neuron equation driven by the Liu process, which belongs to a class of uncertain differential equations. Furthermore, analytical solutions for the uncertain LIF neuron equation are derived. To explore the sensitivity of the uncertain LIF neuron equation to initial state perturbations, we discuss many kinds of stability of the uncertain LIF neuron equation, including stability in measure, stability in distribution and stability in mean. Additionally, a paradox for the stochastic LIF neuron equation is identified.
Nonlinear Analysis of Electric Potential in a Piezoelectric Thin Plate as Pressure Sensor
Authors: Zhao Minghao , Zhan Xiaohan , Lian Mengmeng , Fan Cuiying , Qin Guoshuai , Lu Chunsheng
Published: April 2024

Piezoelectric materials are widely applied in electronic components due to their ability to couple electric and mechanical fields. For the piezoelectric thin plate as a pressure sensor, we extend the modified first-order piezoelectric plate theory to explore the nonlinear solution of electric potential and discuss the relevant regulation mechanisms. Based on the piezoelectric effect, the electric potential generated by deformation is not linear with thickness. A quadratic function of electric potential across thickness is introduced. However, the electric potential on upper and lower electrodes is an unknown constant, which can be determined by the nonlinear complementary equation based on the Gauss theorem. It is shown that the nonlinear results of electric potential are consistent with outcomes by the three-dimensional finite element method. Furthermore, relevant regulation mechanisms are discussed on electric potential, including supported conditions, plate thickness, and load area. In addition, the influence of load locations on the electric potential response is analyzed. It is expected that these findings will be instructive to the structural design of piezoelectric pressure sensors.
CdS@CS/PVA inverse opal films as photocatalyst
Authors: Huang Jiani , Chu Zhaoran , Li Junling , Shao Wenting , Tang Wenwei , Ning Xuanjun , Chen Cheng
Published: April 2024

We prepared CdS@CS/PVA inverse opal (IO) films by the colloidal photonic crystal (CPC) template method. The photonic structure of the CdS@CS/PVA IO films consists of three-dimensional periodic macropores interconnected by CS/PVA polymers. The as-prepared CdS@CS/PVA IO films were utilized as photocatalysts for the degradation of methylene blue dyes. The degradation rate of methylene blue by the CdS@CS/PVA IO film catalyst was 92%, while that of the CdS@CS/PVA film catalyst was 55% for 6 h. The photocatalytic degradation effect of the CdS@CS/PVA IO film catalyst on methylene blue is [Formula: see text]1.7 times higher than that of the CdS@CS/PVA film catalyst, which proves that the introduction of the inverse opal structure into the photocatalyst is beneficial to improve the efficiency of the photocatalyst for degrading dyes.
HETEROGENEOUS RESPONSES OF COMMERCIAL BANKS TO VARIOUS CLIMATE RISKS: EVIDENCE FROM 42 A-SHARE LISTED BANKS IN CHINA
Authors: FAN WENNA , WANG FENG , ZHANG HAO , LING RUI , JIANG HONGFEI
Published: April 2024

Financial supervisors across the world recognize the threats posed by climate change. This research aims to examine the immediate impact of climate risks on bank returns using an event study methodology, with data from 42 A-share listed banks in China spanning the years 2012–2022. The findings reveal a delayed effect of climate risks on commercial banks. Hydrological disasters such as floods significantly reduce the returns of large state-owned, national joint-stock, and city commercial banks. Additionally, the launch of China’s carbon emissions trading market leads to a short-term decline in returns for national joint-stock banks, while rising loan exposure and weakening market sensitivity (MS), induced by climate change, reduce the returns of commercial banks. However, bolstering credit risk management proves effective in enhancing profitability. This study provides insights at the market level into the financial implications of climate change for banking institutions, supplementing existing evidence.
Foot-End Global Trajectory Planning via GCN-Based Heuristic Tree Search for Crossing Obstacles
Authors: Xue Junfeng , Wang Shoukun , Si Jinge , Wang Junzheng
Published: April 2024

Achieving smooth motion for multi-legged robots on complex terrains is a significant focus of research. When encountering high obstacles, robots often need to alter their motion direction to avoid them, increasing redundancy in their motion trajectories. To address this challenge, this paper proposes a method for planning the foot-end trajectory during the swing phase while considering obstacle avoidance without modifying the fuselage trajectory. The method combines the Global Optimal Path Search Tree (GOPST) algorithm and a prior path estimation method utilizing Graph Convolutional Network (GCN). The GOPST explores multiple global paths by conducting local path tree searches in each step, guided by an objective function. To enhance efficiency, redundant search branches with high intensity or high possibility of collision with obstacles or other feet, etc. are eliminated using an event-triggering mechanism based on expert constraints. Another objective function is also formulated to obtain an optimal path that offers a larger safety space and a shorter path length. The optimal path nodes and their environmental features are integrated into a GCN for training. Before the operation of the GOPST, the GCN network provides a preliminary path with fast estimation speed. If the estimated path falls outside the safety margin, the GOPST is reactivated to explore a reliable path. Numerical simulation results validate that the GOPST–GCN approach can rapidly generate a smooth trajectory within the safety space of the foot-end workspace. Furthermore, the search time for finding the optimal path in an untrained environment decreases as the number of tests increases. Experimental verification confirms that robots successfully avoid obstacles by employing foot-end swinging without altering the initial motion direction of the fuselage. The GOPST–GCN algorithm is publicly available at https://github.com/bjmyX/GOPST-GCN-a-foot-end-path-planning-method- .
U–Pb zircon ages from tuffaceous beds in the Terreneuvian to Cambrian Series 2 sections of Avalonian southern New Brunswick, Canada: new constraints on chronostratigraphic correlations and the Cambrian time scale
Authors: Hamilton Michael A. , Álvaro J. Javier , Barr Sandra M. , Jensen Sören , Johnson Susan C. , Palacios Teodoro , van Rooyen Deanne , White Chris E.
Published: April 2024

Avalonian sections in the Saint John area, southern New Brunswick, have long contributed to global understanding of Cambrian chronostratigraphy. A tuffaceous bed in the Ratcliffe Brook Formation (RBF) in the Somerset Street section dated at
c.
531 Ma has traditionally been considered to post-date small shelly fossils attributed to the
Watsonella crosbyi
Zone in the Hanford Brook section. A fine-grained tuffaceous bed approximately 8 m stratigraphically lower in the Somerset Street section yields a chemical abrasion isotope dilution–thermal ionization mass spectrometry zircon age of 532.3 ± 0.3 Ma; a tuffaceous carbonate unit in the lower RBF in Hanford Brook gives an age of 531.5 ± 0.3 Ma. Crystal and crystal-lithic tuff beds near the top of the RBF yield ages of 520.3 ± 0.3 Ma (in Hanford Brook) and 519.1 ± 0.3 Ma (in Ratcliffe Brook). The new ages confirm the correlation between the Somerset Street and Hanford Brook sections based on acritarchs and make the association of small shelly fossils in the Hanford Brook section younger than 531 Ma. This result is relevant to ongoing discussions on the age of the base of undefined Cambrian Stage 2. The radiometric ages also support a young age for the upper part of the RBF, perhaps extending into Epoch 2.
The late Neogene distribution of C
3
–C
4
plants in the Himalayan Foreland Basin: insight from the δ
13
C values and sedimentological architecture of the Siwaliks
Authors: Ghosh S. , Roy B. , Sanyal P.
Published: April 2024

Recent studies emphasize that, in addition to climate-driven forces, sediment grain size and depositional setting with respect to the mountain front significantly influenced the abundance of late Neogene C
3
–C
4
plants in the Himalayan Foreland Basin (HFB). The contrasting depositional settings of the Siwalik Group exposed across the western, central and eastern HFB therefore provide an ideal opportunity to understand the influence of sedimentary architecture on the distribution of C
3
–C
4
plants in palaeolandscapes. To this end, we generate new δ
13
C
soil carbonate
data from the Siwaliks of the Katilukhad region (12 Ma to 6 Ma) of the Kangra sub-basin and synthesize these data with compiled sedimentological data and δ
13
C values of organic matter, soil carbonate and
n
-alkane data from the western to eastern HFB Siwalik Group. Our comparison suggests that the rate and magnitude of the positive shift in the
13
C/
12
C ratios were higher in the floodplain-dominated Siwaliks. Despite an existing conducive climate for the growth of C
4
plants in the late Neogene, the channel-fill-dominated Siwaliks favoured C
3
plants over C
4
plants in the eastern HFB.
JavaScript Language Design and Implementation in Tandem
Authors: Ryu Sukyoung , Park Jihyeok
Published: April 2024

Proposing a new approach to programming language development.
A Physical Insight of Phase-Dependent Electron Transfer Kinetic Behaviors and Electrocatalytic Activity of an Iron Oxide-Based Sensing Nanoplatform Towards Chloramphenicol
Authors: Ngo Xuan Dinh , Phung Thi Lan Huong , Nguyen Ngoc Huyen , Nguyen Tuan Anh , Vinh Nguyen Thanh , Quy Nguyen Van , Le Anh-Tuan
Published: April 2024

Insight into the phase-dependent electron transfer kinetics and electrocatalytic activity of metal oxide nanostructures is important in the rational design of functional nanostructures for realizing high-performance electrochemical sensors. This study focuses on elucidating the effect of the crystalline phase on the electron transfer kinetics and electrocatalytic activity of iron(III) oxide. The α-FeOOH, γ-Fe2O3, and α-Fe2O3 nanorods were designed by using a simple chemical method and calcining process. The phase-dependent difference in the electron transfer kinetics and electrocatalytic activity toward the sensitive response of chloramphenicol (CAP) is observed by the transformation from α-FeOOH to γ-Fe2O3, and from α-FeOOH to α-Fe2O3 nanorods. We found that the oxygen vacancies formed in phase transformation from α-FeOOH to α-Fe2O3 is a key factor in promoting the electrochemical reduction of chloramphenicol. The α-Fe2O3 nanorods-based electrochemical sensors showed a linear response in the CAP concentration range from 0.1 to 75 μM with a limit of detection of 60 nM and an electrochemical sensitivity of 2.86 μA μM−1 cm−2. This work further provides valuable physical insight into the phase-dependent electron transfer kinetics and electrocatalytic activity of metal oxide nanostructures for the rational design of sensing interface.
Exploring the Dynamics of Sleep Deprivation: Insights into Complete Blood Count and Coagulation Parameters in a Case‐Control Study
Authors: Agena Abd Elhadi , Mirghani Leena , Ali Mude Abdirasak
Published: April 2024

Background. The lack of preceding research in Sudan emphasizes the importance of this study, which contributes critical data to the global understanding of sleep‐related health effects. This study investigates the complex relationship between sleep deprivation and blood‐related factors, particularly focusing on full blood count and coagulation parameters. Methods. From January to March 2022, a case‐control study was conducted in Kosti, Sudan. A control group of 11 healthy 23–33‐year‐olds (6 men and 5 women) had regular sleep patterns. Six men and five women ages 23–33 were chosen for this sleep‐deprived case study. The case group was deprived of sleep from 7:00 p.m. to 7:00 a.m. for three days and allowed to sleep normally during the day. Daily at 7:00 a.m., antecubital vein blood was drawn. The ACL 7000 coagulation analyzer and Sysmex fully automated hematology analyzers were used for coagulation and whole blood count analysis. Data analysis included descriptive and inferential approaches like the Mann–Whitney U test for group comparisons. Results. The study found no significant differences in total white blood cell counts reported between case and control groups (p = 0.898). The case group had a substantial drop in lymphocyte counts on day 3 (p = 0.016). The third day showed significant differences in neutrophil and eosinophil levels (p = 0.003 and 0.000, respectively). The difference in hemoglobin and hematocrit on day 3 was statistically significant (p = 0.023). Platelet counts were stable. Both groups’ prothrombin times were unaffected. On all three days, groups had significant differences in activated partial thromboplastin time (APTT) (p = 0.004). Therefore, the intrinsic coagulation system may have changed. Conclusion. This study demonstrates the complex link between sleep deprivation, coagulation indicators, and complete blood count. Monitoring blood indicators in poor sleep helps explain fundamental mechanisms and medicinal implications.
Stability Analysis of Retaining Wall in Backfilled Stope Based on Catastrophe Theory and Numerical Analysis
Authors: Liu Chang , Zhao Kui , Zeng Peng , Gong Cong , Xiong Liangfeng , Xiong Jinbo , Pan Rongsen
Published: April 2024

Retaining wall is essential for stopes mining in two steps, for it can prevent the instability and collapse of backfill. In this study, taking the retaining wall of backfilled stope as the research object, a stability analysis method of retaining wall based on the close coupling of catastrophe theory and numerical analysis was proposed. First, by extracting the unit failure rate of the retaining wall from the numerical simulation results and fitting it with the mining depth, the functional expression between them was established. Second, the function relation was transformed into the normal form according to catastrophe theory, and the instability criterion of retaining wall was deduced. Furthermore, an effort was made to analyze the changing law of the state of retaining wall and calculate the critical span of stope, under different thickness conditions. On this basis, the application test of retaining wall was carried out by using this method. The results show that with the thickness decreasing, the values of splitting variables a and b show a reverse trend, which leads to the discriminant of instability criterion decreasing and turning from positive to negative, resulting in the collapse. Meanwhile, in order to ensure the stability, the wider the span of the stope, the thicker the retaining wall is required, and conversely, the thicker the retaining wall, the higher the adaptability to the span of stope. In addition, it can be found from the application test that instability was bound to occur with a thickness of 3 m, but the retaining wall with a thickness of 4 m maintained stable, which tended to be consistent with the analysis. Therefore, the stability analysis method proposed in this study provides a way to accurately evaluate the stability of the retaining wall and calculate the critical thickness of that, and its application value is expected to be further explored.
Does Neighborhood Socioeconomic Status Alter Memory Change Associated with a Cancer Diagnosis? Preliminary Evidence from the US Health and Retirement Study
Authors: Westrick Ashly C. , Ospina-Romero Monica , Clarke Philippa , Langa Kenneth M. , Kobayashi Lindsay C.
Published: April 2024

Background:

Neighborhood disadvantage has been linked to cognitive impairment, but little is known about the effect of neighborhood disadvantage on long-term cancer-related memory decline.

Methods:

Incident cancer diagnosis and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial interviews in the US Health and Retirement Study (N = 13,293, 1998–2016). Neighborhood disadvantage was measured using the National Neighborhood Data Archive disadvantage index, categorized into tertiles (T1: least disadvantaged–T3: most disadvantaged). Linear mixed-effects models estimated the standardized memory trajectories in participants with or without cancer, by neighborhood disadvantage.

Results:

Living in more disadvantaged neighborhoods was associated with worse mean memory function and steeper memory declines, regardless of cancer status. An incident cancer diagnosis was associated with an acute memory drop for those living in least disadvantaged neighborhoods but not more disadvantaged neighborhoods [T1: −0.05, 95% confidence interval (CI): −0.08, −0.01; T3: −0.13, 95% CI: −0.06, 0.03]. Cancer survivors in the least disadvantaged neighborhoods had a slight memory advantage in the years prior to diagnosis (T1: 0.09, 95% CI: 0.04, 0.13) and after diagnosis (T1: 0.07, 95% CI: 0.01, 0.13).

Conclusions:

An incident cancer diagnosis among those living in the least disadvantaged neighborhoods was associated with an acute memory drop at the time of diagnosis and a long-term memory advantage before and after diagnosis compared with cancer-free individuals in similar neighborhoods.

Impact:

These findings could inform interventions to promote cancer survivor’s long-term aging. Future studies should investigate the social and biological pathways through which neighborhood socioeconomic status could influence cancer-related memory changes.
Synergy of EGFR and AURKA Inhibitors in KRAS-mutated Non–small Cell Lung Cancers
Authors: Bagnyukova Tetyana , Egleston Brian L. , Pavlov Valerii A. , Serebriiskii Ilya G. , Golemis Erica A. , Borghaei Hossein
Published: April 2024

The most common oncogenic driver mutations for non–small cell lung cancer (NSCLC) activate EGFR or KRAS. Clinical trials exploring treatments for EGFR- or KRAS-mutated (EGFRmut or KRASmut) cancers have focused on small-molecule inhibitors targeting the driver mutations. Typically, these inhibitors perform more effectively based on combination with either chemotherapies, or other targeted therapies. For EGFRmut NSCLC, a combination of inhibitors of EGFR and Aurora-A kinase (AURKA), an oncogene commonly overexpressed in solid tumors, has shown promising activity in clinical trials. Interestingly, a number of recent studies have indicated that EGFR activity supports overall viability of tumors lacking EGFR mutations, and AURKA expression is abundant in KRASmut cell lines. In this study, we have evaluated dual inhibition of EGFR and AURKA in KRASmut NSCLC models. These data demonstrate synergy between the EGFR inhibitor erlotinib and the AURKA inhibitor alisertib in reducing cell viability and clonogenic capacity in vitro, associated with reduced activity of EGFR pathway effectors, accumulation of enhanced aneuploid cell populations, and elevated cell death. Importantly, the erlotinib-alisertib combination also synergistically reduces xenograft growth in vivo. Analysis of signaling pathways demonstrated that the combination of erlotinib and alisertib was more effective than single-agent treatments at reducing activity of EGFR and pathway effectors following either brief or extended administration of the drugs. In sum, this study indicates value of inhibiting EGFR in KRASmut NSCLC, and suggests the specific value of dual inhibition of AURKA and EGFR in these tumors.

Significance:

The introduction of specific KRAS G12C inhibitors to the clinical practice in lung cancer has opened up opportunities that did not exist before. However, G12C alterations are only a subtype of all KRAS mutations observed. Given the high expression of AURKA in KRASmut NSCLC, our study could point to a potential therapeutic option for this subgroup of patients.
Validation of a Risk Prediction Equation for Incident Chronic Kidney Disease in a Hypertensive Non-Diabetes Cohort in Singapore Primary Care Patients
Authors: Weng Wanting , Wong Siow-Yi , Ang Gary Yee , Xian Ng Sheryl Hui , Lim Chee Kong , Yeo See Cheng
Published: April 2024

Background: Accurate identification of individuals at risk of developing chronic kidney disease (CKD) may improve clinical care. Nelson et al. developed prediction equations to estimate the risk of incident eGFR of less than 60 mL/min/1.73 m2 in diabetic and non-diabetes patients using data from 34 multinational cohorts. We aim to validate the non-diabetes equation in our local multi-ethnic cohort and develop further prediction models. Methods: Demographics, clinical and laboratory data of hypertensive non-diabetes patients with baseline eGFR ≥60 mL/min/1.73 m2 on follow-up with primary care clinics between 2010 and 2015 were collected. Follow-up was 5 years from entry to study. We validated Nelson’s equation and developed our own model which we subsequently validated. The developmental cohort included patients between 2010 and 2014 while the validation cohort included patients in 2015. Variables included age, sex, eGFR, history of cardiovascular disease, ever smoker, body mass index, albuminuria, cholesterol, and treatment. Primary outcome was incident eGFR <60/min/1.73 m2 within 5 years. Model performance was evaluated by C-statistics and calibration was assessed. Results: In the developmental cohort of 27,800 patients, 2823 (10.2%) developed the outcome during a mean follow-up of 4.4 years while 638 (12.8%) patients developed the outcome in the validation cohort of 4,994 patients. Applicability of Nelson’s equation was limited by missing albuminuria, absence of black race, and exclusion of non-hypertensive patients in our cohort. Nonetheless, the modified Nelson’s model demonstrated C-statistic of 0.85 (95% CI: 0.84–0.86). The C-statistic of our bespoke model was 0.85 (0.85–0.86) and 0.87 (0.85–0.88) for the developmental cohort and validation cohort, respectively. Calibration was suboptimal as the predicted risk exceeded the observed risk. Conclusions: The modified Nelson’s equation and our locally derived novel model demonstrated high discrimination. Both models may potentially be used in predicting risk of CKD in hypertensive patients who are managed in primary care, allowing for early interventions in high-risk population.
Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study
Authors: Wang Yi , Zheng Ying , Chen Lijia , Lin Lingjie , Chen Binwu , Lin Zhengfeng , Bao Shihui
Published: April 2024

Introduction: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. Methods: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. Results: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610–0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. Conclusion: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.
Genetic Susceptibility Variants of Vascular Dementia among Asians: A Systematic Review and Meta-Analysis
Authors: Vasudevan  , Nur Afiqah  , Mohd Nazil  , Wan Aliaa WS , Liyana Najwa IM , Mohd Hazmi  , Siew Mooi  , Abdul Hanif Khan YK , Hamidon  , Pannerselvam  , Suganthi  , Narenkumar
Published: April 2024

Introduction: Vascular dementia (VaD), a neurocognitive impairment directly related to vascular injury, is the second most common cause of age-related dementia. Although numerous studies have investigated candidate genetic polymorphisms associated with VaD in Asia, the genetics of VaD remains unclear. Methods: This review provides an updated meta-analysis of genetic polymorphisms associated with VaD in Asians, using the PRISMA guidelines. Published literature up to May 2021 was extracted from the PubMed, Scopus, Ovid, and EBSCOhost databases. Meta-analysis was conducted using the Open Meta analyst, Review Manager, and MedCalc® Statistical Software. Trial sequential analysis (TSA) was performed using TSA viewer software. Results: A total of 46 eligible studies, comprising 23 genes and 35 single nucleotide polymorphisms, were retrieved. The meta-analysis was conducted on the following genetic polymorphisms, APOE ε2/3/4, MTHFR rs1801131, ACE rs4340 (I/D) gene polymorphism, and a PSEN1 intron 8 variant. The pooled odds ratio (ORs) revealed a significant increase in the risk of VaD in the apolipoprotein E (APOE) ε4 allelic model (OR, 1.79, p < 0.001), and the methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism T allele in the allelic model (OR, 1.23, p = 0.013). Conclusion: Our findings provide evidence that genetic polymorphisms of the APOE ε4 allele and MTHFR rs1801133 T allele increase the risk of developing VaD in Asians. However, future large-scale investigations examining particularly on South-Eastern and West-Asian populations are highly recommended.
Analysis of the Characteristics of Coexisting Lesions in Colorectal Cancer Patients in an International Study: A Subgroup Analysis of the ATLAS Trial
Authors: Yoshida Naohisa , Suzuki Sho , Inoue Ken , Aniwan Satimai , Chiu Han-Mo , Laohavichitra Kannikar , Chirapongsathorn Sakkarin , Yamamura Takeshi , Kuo Chen-Ya , Ang Tiing Leong , Takezawa Takahito , Rerknimitr Rungsun , Ishikawa Hideki ,   ATLAS Trial Group
Published: April 2024

Introduction: We investigated coexisting lesion types in patients with invasive colorectal cancer (CRC) in a multinational study for comprehending the adenoma-carcinoma and serrated pathway about the development of CRC. Methods: We retrospectively reviewed 3,050 patients enrolled in the international randomized controlled trial (ATLAS study) to evaluate the colorectal polyp detection performance of image-enhanced endoscopy in 11 institutions in four Asian countries/regions. In the current study, as a subgroup analysis of the ATLAS study, 92 CRC patients were extracted and compared to 2,958 patients without CRC to examine the effects of age, sex, and coexisting lesion types (high-grade adenoma [HGA], low-grade adenoma with villous component [LGAV], 10 adenomas, adenoma ≥10 mm, sessile serrated lesions [SSLs], and SSLs with dysplasia [SSLD]). Additional analyses of coexisting lesion types were performed according to sex and location of CRC (right- or left-sided). Results: A multivariate analysis showed that HGA (odds ratio [95% confidence interval] 4.29 [2.16–8.18]; p < 0.01), LGAV (3.02 [1.16–7.83], p = 0.02), and age (1.04 [1.01–1.06], p = 0.01) were independently associated with CRC. According to sex, the coexisting lesion types significantly associated with CRC were LGAV (5.58 [1.94–16.0], p < 0.01) and HGA (4.46 [1.95–10.20], p < 0.01) in males and HGA (4.82 [1.47–15.80], p < 0.01) in females. Regarding the location of CRC, SSLD (21.9 [1.31–365.0], p = 0.03) was significant for right-sided CRC, and HGA (5.22 [2.39–11.4], p < 0.01) and LGAV (3.46 [1.13–10.6], p = 0.02) were significant for left-sided CRC. Conclusions: The significant coexisting lesions in CRC differed according to sex and location. These findings may contribute to comprehending the pathogenesis of CRC.
Indonesian and Korean teachers’ awareness of interculturality and world Englishes
Authors: Lestiono Riski , Setyaningrum Rina Wahyu , Gusdian Rosalin I. , Rifah Lailatul
Published: April 2024

English for young learners (EYL) teachers have practiced some creative activities to maintain their pupils’ learning with natural exposure to the target language amidst the pandemic. One activity practiced by Indonesian and Korean teachers was an international collaboration to perform a virtual drama of each country’s folktale. This phenomenological research aimed at tapping the teachers’ perceptions regarding interculturality and world Englishes (WE) in the virtual dramatic play collaboratively conducted and delving into their commitments in honing interculturality and WE. Two Indonesian and Korean teachers were involved in three sessions of in-depth interviews using pre-prepared interview questions. The trustworthiness of the data was achieved by the group discussions allowing the participants to comment on and revise the transcribed data, as well as triangulation by two international collaborators. Thematic analysis was performed to identify emerging themes and to provide novel insights into EYL teachers' encounters with interculturality and WE. The Indonesian and Korean teachers admitted the compatibility between language and culture, the urgency of introducing varieties of English, and the merits of conducting international collaboration to promote interculturality and WE. The teachers are committed to integrate interculturality and WE in their instructions despite some differences in the stipulated curricula.
Students’ writing test: an argumentative study of English as a foreign language learner
Authors: Masrul Masrul , Erliana Santi
Published: April 2024

Writing is hard for students who are learning English; they often find it challenging to transform what is on their mind in writing. Therefore, this study examined the relationship between the writing test and assessment writing through argumentative writing. Data was analyzed using the correlation test to determine the close relationship between independent and dependent variables. This study involved 100 students from the Department of English Education at the University of Riau, Indonesia. The results showed that the writing test and assessment writing was closely related, as evidenced by the influence and significance between the writing test and assessment writing, which was tested through argumentative writing. The results revealed that the writing test and assessment writing have similar results. Overall, both variables are equally important and related.