bluuebunny/crossref_metadata_2025 huggingface dataset:
Topology Optimization for Elasticity Problem of Isotropic and Orthotropic Materials Based on the Complex Variable Element-Free Galerkin Method
Authors: Yang Yichen , Cheng Heng
Published: October 2024

By using the improved complex variable moving least squares (ICVMLS) approximation to construct the shape function, thus the improved complex variable element-free Galerkin (ICVEFG) method is established for analyzing two types of topology optimization problems including isotropic and orthotropic materials in this study. Solid isotropic microstructure with penalization (SIMP) is utilized with relative density of nodes selected as the design variable, volume fraction set as the constraint and structural flexibility selected as the objective function, thus a mathematical model for topology optimization is developed, and the formula of sensitivity is derived. Four optimization examples of isotropic and orthotropic materials are given, and the feasibility of the ICVEFG method for solving topology optimization problem is demonstrated, in addition, the checkerboard phenomenon can be avoided; it is also shown that the ICVEFG method is more advantageous than the EFG method in solving orthotropic beam as well as isotropic problem with two fixed ends.
Current AI: A Survey and Critique
Authors: Luger George F.
Published: October 2024

With the recent attention of the user community to the “successes” of large language models (LLMs), it is easy to overlook the extension and depth of AI research and practice over the past seventy years. Beginning with the 1956 Dartmouth summer workshop where the name artificial intelligence was first suggested, this new discipline branched out in multiple directions. In fact, many of these early AI research areas were to become the foundation for the later emergence of what we now call computer science. In this paper, we review the highlights of the major research and application areas of artificial intelligence including the symbol-based, genetic/emergent, probabilistic and neural network/deep learning. We conclude with several comments on the problems and promise of AI and the current generation of LLMs.
A mathematical study of the interaction between oxygen and lactate in an in vivo and in vitro tumor
Authors: Sadhu Gopinath , Dalal D. C.
Published: October 2024

Micro-environmental acidity is a common feature of the tumor. One of the causes behind tumor acidity is lactate production by hypoxic cells of the tumor. Hypoxia is a direct result of the establishment of oxygen gradients. It is commonly observed in the tumor in an in vitro experimental setup and also in vivo situation. Here, we propose a mathematical model to analyze the production of lactate by hypoxic cells, and it is used as an alternative fuel by normoxic cells in tumor tissue in vitro and in vivo conditions. Also, we study the effects of unequal oxygen concentrations at the tumor boundaries on lactate status in the tumor. The effects of necrotic core on lactate accumulation is examined. The results are in good agreement with experimental data and are in align with the theoretical findings of previous studies. The analytical results show that lactate levels are elevated in an in vivo tumor compared to that in an in vitro tumor. Also, during the onset of necrotic core formation, the effects of necrotic core on lactate levels are noticed. Knowledge of the lactate status in a patient’s tumor may be helpful in choosing the appropriate and effective medicines for cancer treatment.
Blockchain Scalability with Proof of Descriptor
Authors: Painter Zachary , Peterson Christina , Cook Victor , Dechev Damian
Published: October 2024

Blockchain networks use consensus mechanisms so that participants can exchange transactions without the need to rely on a trusted third party. Consensus mechanisms using Proof of Work burn significant energy to select a block miner, and this delay limits performance. Other consensus mechanisms such as Proof of Stake or Practical Byzantine Fault Tolerance still designate a single validator to append a block to the chain, preventing blocks from being built and published in parallel. In this paper we introduce a new consensus mechanism, Proof of Descriptor, enabling clients to work together to publish blockchain transactions using a
descriptor object
which stores information on the cooperative parallel execution of transactions. Proof of Descriptor consensus allows commutative transactions to be mined concurrently. It does not require a single leader to append transactions to the ledger, enabling clients to cooperate on publishing transactions. We also propose a novel graph-based ledger with multiple entry points to facilitate the scalability of Proof of Descriptor, as well as a secure hashing scheme to resist long-range-attacks. We demonstrate that our approach is as secure as related works with respect to a malicious leader, 51% attack, and other known blockchain vulnerabilities. Furthermore, our experimental evaluation shows that our approach scales with the size of the network, experiencing up to a 4x improvement in throughput over the fastest sequential blockchain,
Solana
.
Analysis of the Influence of Boundary Permeability Characteristics Under Fluid–Solid Coupling on Surface Subsidence in Deep Near‐Horizontal Coal Seam Mining
Authors: Sun Jie , Hao Zhe , Liu Le , Zhu Yanfei , Shen Cheng
Published: October 2024

The fluid–solid coupling effect is an important factor which cannot be ignored to study the surface subsidence of deep coal seam mining in the area with abundant underground water. To study the influence of boundary permeability characteristics on surface subsidence in deep near‐horizontal coal seam mining under the effect of fluid–solid coupling, the pore water pressure field, vertical stress field, surface subsidence, and vertical displacement of a rock seam during deep mining under different permeability boundary conditions were analyzed based on fluid–solid coupling theory, taking the 3−1501 working face of Erdos Hongqinghe coal mine as an example. The results revealed that the permeability characteristics of different hydraulic boundaries affected the pore water pressure, vertical stress in the rock layer, and surface subsidence during deep mining. Moreover, the trends of pore water pressure, vertical stress, and surface subsidence of a fixed‐head permeability boundary were largely the same as those under impermeable boundary conditions, but the calculated results of the fixed‐head permeability boundary were lower than those for the impermeable boundary at the same depth. The maximum surface subsidence for the fixed‐head permeable boundary condition and the impermeable boundary condition was 879 and 925 mm, respectively, which were 239 and 285 mm higher than those obtained when the fluid–solid coupling effect was neglected (an increase of 37.3% and 44.5%, respectively). The field monitoring trend for the subsidence basin aligns closely with the subsidence basin trend under the influence of fluid–solid coupling. Considering the constant head permeable boundary conditions in the context of fluid–solid coupling yields accurate surface subsidence results. The results have provided a theoretical basis for the analysis and prediction of coal mining surface subsidence considering the fluid–solid coupling effect.
Comparison of 3D Gradient‐Echo Versus 2D Sequences for Assessing Shoulder Joint Image Quality in MRI
Authors: Shirani Shapoor , Mousavi Najmeh-Sadat , Talib Milad Ali , Bagheri Mohammad Ali , Jazayeri Gharebagh Elahe , Hameed Qasim Abdulsahib Jaafar , Dehghani Sadegh
Published: October 2024

Background: Three‐dimensional gradient‐echo (3D‐GRE) sequences provide isotropic or nearly isotropic 3D images, leading to better visualization of smaller structures, compared to two‐dimensional (2D) sequences. The aim of this study was to prospectively compare 2D and 3D‐GRE sequences in terms of key imaging metrics, including signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR), glenohumeral joint space, image quality, artifacts, and acquisition time in shoulder joint images, using 1.5‐T MRI scanner.

Methods: Thirty‐five normal volunteers with no history of shoulder disorders prospectively underwent a shoulder MRI examination with conventional 2D sequences, including T1‐ and T2‐weighted fast spin echo (T1/T2w FSE) as well as proton density‐weighted FSE with fat saturation (PD‐FS) followed by 3D‐GRE sequences including VIBE, TRUEFISP, DESS, and MEDIC techniques. Two independent reviewers assessed all images of the shoulder joints. Pearson correlation coefficient and intra‐RR were used for reliability test.

Results: Among 3D‐GRE sequences, TRUEFISP showed significantly the best CNR between cartilage‐bone (31.37 ± 2.57, p < 0.05) and cartilage‐muscle (13.51 ± 1.14, p < 0.05). TRUEFISP also showed the highest SNR for cartilage (41.65 ± 2.19, p < 0.01) and muscle (26.71 ± 0.79, p < 0.05). Furthermore, 3D‐GRE sequences showed significantly higher image quality, compared to 2D sequences (p < 0.001). Moreover, the acquisition time of the 3D‐GRE sequences was considerably shorter than the total acquisition time of PD‐FS sequences in three orientations (p < 0.01).

Conclusions: 3D‐GRE sequences provide superior image quality and efficiency for evaluating articular joints, particularly in shoulder imaging. The TRUEFISP technique offers the best contrast and signal quality, making it a valuable tool in clinical practice.
Development of a Symptom Self‐Management Guide for Older Chinese Americans Kidney Receiving Replacement Therapy
Authors: Sun Carolyn , Cheung Wing , Corpuz Kathryn , Shang Jingjing , Stone Patricia W.
Published: October 2024

Aim. To assess the acceptability of a symptom self‐management booklet among older Chinese Americans receiving kidney replacement therapy. Background. In previous work, we identified commonly occurring, bothersome symptoms and strategies used in this population to ameliorate symptoms. We used these data to develop a symptom self‐management booklet in English, traditional, and simplified Chinese. Introduction. In the United States, the prevalence of kidney disease is 1.5 times higher in Asians compared to whites. With the many symptoms associated with this disease, self‐management of symptoms would be particularly helpful. Methods. Seven older Chinese Americans receiving kidney replacement therapy and their caregivers were interviewed to assess the acceptability of the booklets. We reviewed participant feedback on content, graphics, and design, reading experience, suggestions for improvement, and health information sources using the inductive thematic method. Results. Overall, patients confirmed acceptability of these self‐management booklets across all domains. Discussion. This study validated the booklet as a source of health information for older Chinese American patients with kidney disease, which some studies suggest are preferred to electronic materials or methods in this population. Health care providers can use the resultant booklets when caring for these patients to provide culturally sensitive information on self‐management of symptoms. Conclusion and Implications for Nursing. These booklets provide a free resource tailored to an underserved population and may help nurses and nurse practitioners provide care with cultural humility. Implications for Health Policy. Embracing community‐based participatory research, as was done in this study, can help create culturally appropriate patient education materials that empower patient symptom self‐management and promote informative and culturally sensitive conversations between patients, families, and providers.
Multistep Wind Speed Prediction Based on the Fractional‐Order Longicorn Swarm Algorithm and the Two‐Stage Modal Decomposition Strategy
Authors: Pu Shuren , Gao Yuanchen , Sun Yifeng , Liu Chang , He Siyu , Wu Fengjiao , Zhu Delan , Wang Bin
Published: October 2024

Least squares support vector machine (LSSVM) and variational mode decomposition are common research methods for wind speed time series prediction. Addressing the challenge of selecting relevant parameters of LSSVM and VMD, a fractional‐order Beetle swarm optimization algorithm is proposed to optimize the relevant parameters. To weaken the negative impact of wind speed volatility on the accuracy of the prediction model, a two‐stage modal decomposition strategy based on extreme‐point symmetric mode decomposition, FO‐BSO algorithm, and VMD is proposed. ESMD is used to decompose the original wind speed time series. The diversity entropy is introduced as the criterion, and the FO‐BSO‐VMD secondary decomposition is applied for the high‐entropy modal components to further weaken the volatility of wind speed. Simulation results show that compared with the original LSSVM model, the ESMD‐FO‐BSO‐VMD‐LSSVM model presented in this study exhibits an average 44.10% increase in the fitting degree of wind speed prediction over three steps, which verifies the superior performance of the model in short‐term multistep wind speed prediction.
Research on Meso‐Damage Experiment and Simulation in the Anchorage Bonding Interface Between Rock Bolt and Rock Mass
Authors: Liu Yaxin , Xing Minglu , Zhao Tongbin , Yu Fenghai , Li Longfei , Chen Shiwei , Wang Xiaohao
Published: October 2024

Anchorage failure occurs mostly at the anchorage interface, and the mechanical mechanism of the anchorage interface is the key point and difficulty in the analysis and research of anchorage. In order to study the mechanics and failure mechanism of the anchorage interface, the shear failure characteristics of the anchorage interface and the deformation rule of the anchored rock under different rib spacings were analyzed through the indoor plane anchorage pull‐out test. Reasonable rib spacing can significantly improve the shear strength of the anchored solid. Finite element software ABAQUS was used to create an axisymmetric plane model of rock bolt pull‐out under different rib conditions to simulate the whole process of rock bolt pull‐out and anchorage interface failure. The results show that during the pull‐out process of anchorage rock mass, stress concentration zones occur at rib corners, and peak shear stress moves to the depths of the anchorage section. As the load increases, cracks emerge from the top of the rib and the edge of the rib angle of the rock bolt and propagate to the deep anchorage along the edge of the costal angle, resulting in damage at the rock mass interface. Load–displacement curves of different transverse rib shapes, heights, widths, and spacings indicate that rib changes affect the anchor‐bearing limit. The anchoring failure mode changes from rib wear and spreading slip, rib shear convex body propagation to interfacial crack propagation, and rib causes varying degrees of damage to the surrounding rock mass. Therefore, reasonable rib parameter improvements can enhance anchoring force performance.
A Comprehensive Review on Traditional Medicinal Plants in Ethiopia and Their Application for Treatment of Different Diseases
Authors: Gedlu Misganaw , Bizuayehu Tadesse , Melese Aklilu , Sewnet Agidew
Published: October 2024

Traditional medicine encompasses knowledge, skills, and practices derived from indigenous cultures, used to maintain health, prevent, diagnose, improve, or treat various diseases. In Ethiopia, up to 80% of the population uses traditional medicine due to the cultural acceptability of healers, local pharmacopeias, the relatively low cost of traditional medicine, and the difficulty of accessing modern health facilities. Traditional healthcare services are also sought in urban areas of Ethiopia, where allopathic services are more readily available and make a significant contribution to the country’s public health care system. Consequently, the objective of this article was to gather comprehensive information on medicinal plants used by Ethiopians in traditional medicine, to highlight the description of medicinal plants including local names, parts used, preparation methods, and traditional uses. Traditional medicines were prepared and applied in several methods; orally drinking or taking with food, directly applied on the affected area either through fresh leaf, latex, powder, or oil; rubbing (with fresh leaf, powder, latex, or ash of the burned part), squeezed on the affected area or paint applied on the affected area of herbal preparations. Approximately 206 species of medicinal plants grown in Ethiopia have been reported here to treat various diseases. Traditional Ethiopian knowledge applies to the treatment of different viral infections. Therefore, it is crucial for researchers in the field to conduct a study of the safety and effectiveness of traditionally claimed therapeutic herbs.
A Step Forward in Identifying Socially Desirable Respondents: An Integrated Machine Learning Model Considering T‐Scores, Response Time, Kinematic Indicators, and Eye Movements
Authors: Mazza Cristina , Ceccato Irene , Cannito Loreta , Monaro Merylin , Ricci Eleonora , Bartolini Emanuela , Cardinale Alessandra , Di Crosta Adolfo , Cardaioli Matteo , La Malva Pasquale , Colasanti Marco , Tambelli Renata , Giromini Luciano , Palumbo Rocco , Palumbo Riccardo , Di Domenico Alberto , Roma Paolo
Published: October 2024

Context: In high‐stakes assessments, such as court cases or managerial evaluations, decision‐makers heavily rely on psychological testing. These assessments often play a crucial role in determining important decisions that affect a person’s life and have a significant impact on society.

Problem Statement: Research indicates that many psychological assessments are compromised by respondents’ deliberate distortions and inaccurate self‐presentations. Among these sources of bias, socially desirable responding (SDR) describes the tendency to provide overly positive self‐descriptions. This positive response bias can invalidate test results and lead to inaccurate assessments.

Objectives: The present study is aimed at investigating the utility of mouse‐ and eye‐tracking technologies for detecting SDR in psychological assessments. By integrating these technologies, the study sought to develop more effective methods for identifying when respondents are presenting themselves in a favorable light.

Methods: Eighty‐five participants completed the Lie (L) and Correction (K) scales of the Minnesota Multiphasic Personality Inventory‐2 (MMPI‐2) twice: once answering honestly and once presenting themselves in a favorable light, with the order of conditions balanced. Repeated measures univariate analyses were conducted on L and K scale T‐scores, as well as on mouse‐ and eye‐tracking features, to compare the honest and instructed SDR conditions. Additionally, machine learning models were developed to integrate T‐scores, kinematic indicators, and eye movements for predicting SDR.

Results: The results showed that participants in the SDR condition recorded significantly higher T‐scores, longer response times, wider mouse trajectories, and avoided looking at the answers they intended to fake, compared to participants in the honest condition. Machine learning algorithms predicted SDR with 70%–78% accuracy.

Conclusion: New assessment strategies using mouse‐ and eye‐tracking can help practitioners identify whether data is genuine or fabricated, potentially enhancing decision‐making accuracy.

Implications: Combining self‐report measures with implicit data can improve SDR detection, particularly in managerial, organizational, and forensic contexts where precise assessments are crucial.
The Role of CXCR3 in Nervous System‐Related Diseases
Authors: Wang Fangyuan , Guo Bing , Jia Ziyang , Jing Zhou , Wang Qingyi , Li Minghe , Lu Bingqi , Liang Wulong , Hu Weihua , Fu Xudong
Published: October 2024

Inflammatory chemokines are a group of G‐protein receptor ligands characterized by conserved cysteine residues, which can be divided into four main subfamilies: CC, CXC, XC, and CX3C. The C‐X‐C chemokine receptor (CXCR) 3 and its ligands, C‐X‐C chemokine ligands (CXCLs), are widely expressed in both the peripheral nervous system (PNS) and central nervous system (CNS). This comprehensive literature review aims to examine the functions and pathways of CXCR3 and its ligands in nervous system‐related diseases. In summary, while the related pathways and the expression levels of CXCR3 and its ligands are varied among different cells in PNS and CNS, the MPAK pathway is the core via which CXCR3 exerts physiological functions. It is not only the core pathway of CXCR3 after activation but also participates in the expression of CXCR3 ligands in the nervous system. In addition, despite CXCR3 being a common inflammatory chemokine receptor, there is no consensus on its precise roles in various diseases. This uncertainty may be attributable to distinct inflammatory characteristics, that inflammation simultaneously possesses the dual properties of damage induction and repair facilitation.
Supplementary Table S2 from Kidney Function and Risk of Renal Cell Carcinoma
Authors: Alcala Karine , Zahed Hana , Cortez Cardoso Penha Ricardo , Alcala Nicolas , Robbins Hilary A. , Smith-Byrne Karl , Martin Richard M. , Muller David C. , Brennan Paul , Johansson Mattias
Published: October 2024

Supplemental table 2 shows the betas estimates and standard errors from the original risk model, the recalibrated model without and with CRP, and the updated model with eGFR.
Supplementary Figure 5 from Kidney Function and Risk of Renal Cell Carcinoma
Authors: Alcala Karine , Zahed Hana , Cortez Cardoso Penha Ricardo , Alcala Nicolas , Robbins Hilary A. , Smith-Byrne Karl , Martin Richard M. , Muller David C. , Brennan Paul , Johansson Mattias
Published: October 2024

Supplemental figure 5 shows the comparison of the original and updated 1-year and 5-years risk of RCC for the participants with and without RCC diagnosis in the training and testing set of UKB.
Supplementary Figure 3 from Kidney Function and Risk of Renal Cell Carcinoma
Authors: Alcala Karine , Zahed Hana , Cortez Cardoso Penha Ricardo , Alcala Nicolas , Robbins Hilary A. , Smith-Byrne Karl , Martin Richard M. , Muller David C. , Brennan Paul , Johansson Mattias
Published: October 2024

Supplemental figure 3 shows the estimated 1-year and 5-years risk of RCC with eGFRcreat_cystC by common RCC risk factors across ages for females.
Data from Kidney Function and Risk of Renal Cell Carcinoma
Authors: Alcala Karine , Zahed Hana , Cortez Cardoso Penha Ricardo , Alcala Nicolas , Robbins Hilary A. , Smith-Byrne Karl , Martin Richard M. , Muller David C. , Brennan Paul , Johansson Mattias
Published: October 2024

AbstractBackground:
We evaluated the temporal association between kidney function, assessed by estimated glomerular filtration rate (eGFR), and the risk of incident renal cell carcinoma (RCC). We also evaluated whether eGFR could improve RCC risk discrimination beyond established risk factors.
Methods:
We analyzed the UK Biobank cohort, including 463,178 participants of whom 1,447 were diagnosed with RCC during 5,696,963 person-years of follow-up. We evaluated the temporal association between eGFR and RCC risk using flexible parametric survival models, adjusted for C-reactive protein and RCC risk factors. eGFR was calculated from creatinine and cystatin C levels.
Results:
Lower eGFR, an indication of poor kidney function, was associated with higher RCC risk when measured up to 5 years prior to diagnosis. The RCC HR per SD decrease in eGFR when measured 1 year before diagnosis was 1.26 [95% confidence interval (95% CI), 1.16–1.37], and 1.11 (95% CI, 1.05–1.17) when measured 5 years before diagnosis. Adding eGFR to the RCC risk model provided a small improvement in risk discrimination 1 year before diagnosis with an AUC of 0.73 (95% CI, 0.67–0.84) compared with the published model (0.69; 95% CI, 0.63–0.79).
Conclusions:
This study demonstrated that kidney function markers are associated with RCC risk, but the nature of these associations are consistent with reversed causality. Markers of kidney function provided limited improvements in RCC risk discrimination beyond established risk factors.
Impact:
eGFR may be of potential use to identify individuals in the extremes of the risk distribution.
Supplementary Figure 2 from Preclinical Evaluation of STI-8811, a Novel Antibody–Drug Conjugate Targeting BCMA for the Treatment of Multiple Myeloma
Authors: Springer Aaron D. , Wang Rengang , Wang Jiawei , Du Qinyi , Pi Willie , Nguyen Austin Q. , Li Xiaoqing , Khasanov Alisher , Zhu Tong , Yan Zheng , Hong Yufeng , Zhou Heyue , Zhang Yanliang , Kerwin Lisa , Li Lingna , Ji Henry , Zhang Hong
Published: October 2024

Figure S2. Long-term tumor suppression study of repeat dosing of STI-8811 in NCI-H929 s.c. xenograft model. SCID-Beige (n = 7) mice were treated i.v. with 4 doses of indicated molecules at biweekly regimen. Data represent mean ± SD
Figure 6 from Preclinical Evaluation of STI-8811, a Novel Antibody–Drug Conjugate Targeting BCMA for the Treatment of Multiple Myeloma
Authors: Springer Aaron D. , Wang Rengang , Wang Jiawei , Du Qinyi , Pi Willie , Nguyen Austin Q. , Li Xiaoqing , Khasanov Alisher , Zhu Tong , Yan Zheng , Hong Yufeng , Zhou Heyue , Zhang Yanliang , Kerwin Lisa , Li Lingna , Ji Henry , Zhang Hong
Published: October 2024

Serum stability and PK studies. A, PK curves of STI-8811 and STI-1260 in SCID beige mice following single-dose 8 mg/kg i.v. administration. B, PK curves of STI-8811 and STI-1260 in cynomolgus monkeys with single-dose i.v. administration. C, Serum concentration vs. TV change of STI-8811 in a NCI-H929 xenograft model in SCID beige mice over 14 days (n = 3). Data are represented as the mean ± SD.
Data from Preclinical Evaluation of STI-8811, a Novel Antibody–Drug Conjugate Targeting BCMA for the Treatment of Multiple Myeloma
Authors: Springer Aaron D. , Wang Rengang , Wang Jiawei , Du Qinyi , Pi Willie , Nguyen Austin Q. , Li Xiaoqing , Khasanov Alisher , Zhu Tong , Yan Zheng , Hong Yufeng , Zhou Heyue , Zhang Yanliang , Kerwin Lisa , Li Lingna , Ji Henry , Zhang Hong
Published: October 2024

Abstract
Treatment for patients with multiple myeloma has experienced rapid development and improvement in recent years; however, patients continue to experience relapse, and multiple myeloma remains largely incurable. B-cell maturation antigen (BCMA) has been widely recognized as a promising target for treatment of multiple myeloma due to its exclusive expression in B-cell linage cells and its critical role in the growth and survival of malignant plasma cells. Here, we introduce STI-8811, a BCMA-targeting antibody–drug conjugate (ADC) linked to an auristatin-derived duostatin payload via an enzymatically cleavable peptide linker, using our proprietary C-lock technology. STI-8811 exhibits target-specific binding activity and rapid internalization, leading to G2/M cell-cycle arrest, caspase 3/7 activation, and apoptosis in BCMA-expressing tumor cells in vitro. Soluble BCMA (sBCMA) is shed by multiple myeloma cells into the blood and increases with disease progression, competing for ADC binding and reducing its efficacy. We report enhanced cytotoxic activity in the presence of high levels of sBCMA compared with a belantamab mafodotin biosimilar (J6M0-mcMMAF). STI-8811 demonstrated greater in vivo activity than J6M0-mcMMAF in solid and disseminated multiple myeloma models, including tumor models with low BCMA expression and/or in large solid tumors representing soft-tissue plasmacytomas. In cynomolgus monkeys, STI-8811 was well tolerated, with toxicities consistent with other BCMA-targeting ADCs with auristatin payloads in clinical studies. STI-8811 has the potential to outperform current clinical candidates with lower toxicity and higher activity under conditions found in patients with advanced disease.

Significance: STI-8811 is a BCMA-targeting ADC carrying a potent auristatin derivative. We report unique binding properties which maintain potent cytotoxic activity under sBCMA-high conditions that hinder the clinical efficacy of current BCMA-targeting ADC candidates. Beyond disseminated models of multiple myeloma, we observed efficacy in solid tumor models of plasmacytomas with low and heterogenous BCMA expressions at a magnitude and duration of response exceeding that of clinical comparators.
Detection of MUC1+/MUC2 and MUC5AC− Membrane-Associated Mucins in the Intraepithelial Surface Mucous Cells of the Developing Rabbit Esophagus
Authors: Mohamedien Dalia , Gaber Wafaa , Hirayama Makoto , Awad Mahmoud
Published: October 2024

Introduction: Mucins are polydisperse molecules created to perform a variety of functions at the mucosal surface of the adult gastrointestinal tract. Two main groups of mucins could be identified: the membrane-associated mucins (MUC1, MUC4, MUC13, and MUC16), those bound to the apical plasma membrane of epithelial cells, and the secreted mucins (MUC2, MUC5AC, MUC5B, and MUC6), those secreted from the goblet cells. Little is known about the types and distribution patterns of mucins in prenatal life. Methods: We detected mucin-secreting cells in the developing rabbit esophagus though these cells are absent in the adult one. In order to identify the content and possible functions of these cells, we investigated the histochemical and immunohistochemical characteristics of their mucins. Results: Starting at 16th day of pregnancy, periodic acid Schiff (PAS), alcian blue (AB) pH (2.5), and PAS-AB combination intensely stained the mucous content, demonstrating both acidic and neutral mucopolysaccharides. Some blebs could be recognized on the free surface of the esophageal epithelium. Also, the mucous cells and some basal cells strongly immunoreacted with MUC1, but not MUC2, nor MUC5AC antibodies. Conclusion: Collectively, these data suggest that surface mucous cells are modified epithelial cells, not goblet cells, and may originate from the basal layer of the epithelial cells. A possible regulatory role for these MUC1-positive mucins in esophageal epithelial and mesenchymal cell differentiation and late organogenesis is suggested. However, future functional studies are recommended.
Obinutuzumab May Be an Effective and Safe Option for Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis Patients after Multitarget Therapy Including Rituximab
Authors: Lin Yuxin , Pan Yixuan , Han Quan , Xu Jianhang , Wang Junni , Lei Xin , Chen Liangliang , Wang Yaomin , Ren Pingping , Lan Lan , Chen Jianghua , Han Fei
Published: October 2024

Introduction: Rituximab has proven effective and safe in pediatric and adult minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients with frequently relapsing nephrotic syndrome. However, its efficacy diminishes in several patients who experience nephrotic syndrome relapsing in short durations or failing to achieve remission. We aimed to explore the efficacy and safety of obinutuzumab, a novel anti-CD20 antibody, in these patients. Methods: A retrospective case series study at our center included 11 adult MCD or FSGS patients who presented with nephrotic syndrome characterized by short-duration relapses or lack of remission after multitarget therapy, including rituximab. Primary outcomes included the first relapse-free time, relapse rate during follow-up, and the use of immunosuppressants after obinutuzumab. All adverse events were recorded. Results: Eleven adult patients (median age 26.0 years, 81.9% males) received an average obinutuzumab dose of 2.0 (1.0, 2.0) g during a median follow-up period of 17.0 (12.0, 22.0) months. The first relapse-free time was 12.1 (10.8, 18.9) months. Two patients with FSGS experienced relapses, while the remaining maintained remission by the end of follow-up. Six patients (54.5%) achieved cessation of corticosteroids and immunosuppressants within 3 months after obinutuzumab. Adverse events were mostly mild. Conclusion: Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic syndrome relapsing in short durations or failed to achieve remission after multitarget therapy, including rituximab. It was effective in maintaining remission in MCD patients, while its efficacy in maintaining remission in FSGS patients remained uncertain.
A Rare Noncoding Enhancer Variant in
SCN5A
Contributes to the High Prevalence of Brugada Syndrome in Thailand
Authors: Walsh Roddy , Mauleekoonphairoj John , Mengarelli Isabella , Bosada Fernanda M. , Verkerk Arie O. , van Duijvenboden Karel , Poovorawan Yong , Wongcharoen Wanwarang , Sutjaporn Boosamas , Wandee Pharawee , Chimparlee Nitinan , Chokesuwattanaskul Ronpichai , Vongpaisarnsin Kornkiat , Dangkao Piyawan , Wu Cheng-I , Tadros Rafik , Amin Ahmad S. , Lieve Krystien V.V. , Postema Pieter G. , Kooyman Maarten , Beekman Leander , Sahasatas Dujdao , Amnueypol Montawatt , Krittayaphong Rungroj , Prechawat Somchai , Anannab Alisara , Makarawate Pattarapong , Ngarmukos Tachapong , Phusanti Keerapa , Veerakul Gumpanart , Kingsbury Zoya , Newington Taksina , Maheswari Uma , Ross Mark T. , Grace Andrew , Lambiase Pier D. , Behr Elijah R. , Schott Jean-Jacques , Redon Richard , Barc Julien , Christoffels Vincent M. , Wilde Arthur A.M. , Nademanee Koonlawee , Bezzina Connie R. , Khongphatthanayothin Apichai
Published: October 2024

BACKGROUND:

Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the
SCN5A
gene encoding the Na
v
1.5 sodium channel and common noncoding variants at this locus are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown.

METHODS:

Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare noncoding variants at the
SCN5A-SCN10A
locus that were enriched in patients with BrS. A likely causal variant was prioritized by computational methods and introduced into human induced pluripotent stem cell (hiPSC) lines using CRISPR-Cas9. The effect of the variant on
SCN5A
expression and Na
v
1.5 sodium channel current was then assessed in hiPSC-derived cardiomyocytes (hiPSC-CMs).

RESULTS:

A rare noncoding variant in an
SCN5A
intronic enhancer region was highly enriched in patients with BrS (detected in 3.9% of cases with a case-control odds ratio of 45.2). The variant affects a nucleotide conserved across all mammalian species and predicted to disrupt a Mef2 transcription factor binding site. Heterozygous introduction of the enhancer variant in hiPSC-CMs caused significantly reduced
SCN5A
expression from the variant-containing allele and a 30% reduction in Na
v
1.5-mediated sodium current density compared with isogenic controls, confirming its pathogenicity. Patients with the variant had severe phenotypes, with 89% experiencing cardiac arrest.

CONCLUSIONS:

This is the first example of a functionally validated rare noncoding variant at the
SCN5A
locus and highlights how genome sequencing in understudied populations can identify novel disease mechanisms. The variant partly explains the increased prevalence of BrS in this region and enables the identification of at-risk variant carriers to reduce the burden of sudden cardiac death in Thailand.
Prayer in Crisis
Authors: Adams Scott Lewis
Published: October 2024

This article examines the topics of prayer and the Spirit (Paraclete) that appear in textual sequence in Lk. 11.9–13 and Jn 14.13–17 but are absent from Mark and Matthew. While much attention has been devoted to the Lukan sequence, scholars have failed to offer a detailed analysis concerning the Johannine sequence and how it contributes to the author’s rhetorical and missiological agendas. Therefore, this article seeks to contribute to the scholarly discussion by examining both the Lukan and Johannine sequences on their own terms and in light of one another in order to elucidate how they function within the crises that are unique to each Gospel tradition. In the final analysis, this article will demonstrate that both Luke and John establish a relationship between prayer and the promise of pneumatic assistance that is not attested by Mark or Matthew.
Livres polémiques imprimés en arabe, en Moldavie et en Valachie, au milieu du XVIIIe siècle
Authors: Chițulescu Policarp
Published: October 2024

Les livres arabes imprimés dans les Principautés roumaines au milieu du XVIIIe siècle par le patriarche Sylvestre d’Antioche, avec l’aide généreuse des princes Ioan et Constantin Mavrocordat et de nombreux partisans locaux, étaient très recherchés dans les provinces arabophones de l’Empire ottoman. Ainsi, les copies ont presque entièrement disparu, détruites par un usage intense ou le passage du temps, ou pour des raisons confessionnelles. Par conséquent, les livres arabes du patriarche Sylvestre sont extrêmement rares de nos jours, leur contenu restant peu connu et peu étudié, une circonstance qui est révélée par leur absence dans les bibliographies et les études scientifiques du monde entier. Il est donc impératif de faire des recherches approfondies sur les livres arabes de Iași et de Bucarest imprimés en soutien aux chrétiens orthodoxes arabophones, de découvrir le contexte historique qui a généré un besoin d’œuvres polémiques imprimées en arabe, et les efforts du clergé orthodoxe et des princes roumains pour la consolidation de l’orthodoxie au Levant. Cette étude démontre que des projets véritablement missionnaires tels que celui du patriarche Sylvestre ont placé les sociétés roumaine, grecque, arabe et ottomane dans une interdépendance fascinante. L’article présente les résultats de nos recherches consacrées à l’imprimerie arabe en Moldavie et en Valachie à l’époque du patriarche Sylvestre d’Antioche en soutien à ses ouailles orthodoxes arabophones.
Analysing the Legal Development of the Case Management System in the High Court of Tanzania
Authors: Siyani Mustapher M. , Marwa Ryoba
Published: October 2024

This article traces the legal development of case management as applied in the High Court of Tanzania for the timely justice dispensation. To make it easier for the readers, the authors of this article employed a doctrinal approach by carrying out a systematic documentary review, including the constitution, legislation, reports, and case laws. This review aimed to provide a thorough historical perspective of the development of the case management system in the High Court of Tanzania. The findings reveal that Tanzania introduced a case management system to address the inefficiency of justice in the court system. Furthermore, timely dispensation of justice is the constitutional essence of the existence of the Judiciary of Tanzania. However, even with the introduction of the case management system, the need for the timely justice dispensation in the court of law has not been satisfactorily achieved.
Quantitative risk assessment for aflatoxins in beans from northern Tanzania
Authors: Nyangi C. , Runyogote J. , Mng’ong’o M.
Published: October 2024

The study focussed on quantitative risk assessment for population exposure to aflatoxins by consuming beans from bean farmers in three villages; Long, Sabilo and Seloto in Babati District, Northern Tanzania. Aflatoxin levels were determined in a total of 144 bean samples; a total of 38 samples were collected from harvesting beans, while 106 samples were collected from stored beans. This kind of assessment allows modelling bean consumption data (kg/kg body weight (bw)/day) using an estimated average weight of an adult of 60 kg with previously collected data for total aflatoxin (AF) contamination (μg/kg) beans samples from the 2013/14 survey. Consumption was estimated by using the minimum annual per capita consumption of beans in Tanzania of 13.02 kg (which is equivalent to 35.67 g/day) and the exposure assessment was performed with the @RISK analysis software. Results from the assessment showed exposure for lower bound (LB) having a mean value of 1.06, 0.79 and 0.95 ng/kg bw/day in Long, Sabilo and Seloto villages, respectively, while for the medium bound (MB) the mean values were 1.33, 1.07 and 1.26 ng/kg bw/day, respectively, and for the upper bound (UB) the values were 1.65, 1.38 and 1.58 ng/kg bw/day, respectively. The margins of exposure (MoE) from this study were below 10,000 for all scenarios and this is of public health concern. Even though all samples had aflatoxin contamination below the maximum tolerable limit (MTL) of 4, 10 and 20 μg/kg for aflatoxins in cereals and pulses in the EU, the East African Community (EAC) and the USA, there is still a serious long-term health implication. Meeting MTL will not by itself guarantee food safety, but using the data collected and available on various health effects from aflatoxin and other mycotoxins, it is important to incorporate them into a risk assessment and show how excessive consumption of foods meets MTLs can still carry significant public health risks.
Introduction
Authors: Stead Evanghelia
Published: October 2024

Close reading of “A New Poster” by Evelyn Sharp, a Yellow-Book story after Beardsley's dismissal from the periodical, stresses the importance of indirect strategies, hidden references and messages, details and oblique treatment in the British fin de siècle and in Beardsley's work. The introduction argues that Beardsley's art is not to be taken at face value. It underscores his rapid ascent thanks to the media, occasioning exceptional artistic influence in five short creative years and remarkable fame both in bohemian and bourgeois contexts. It calls attention to Beardsley's renewal of the grotesque, revitalisation of marginalia, performance, witty use of monstrous self-portraits and masterly command in Britain and beyond through the burgeoning network of periodicals. It approaches the subject through an interdisciplinary methodology bringing together art, literature, differential comparative studies, print culture and periodical studies.
2. A Foetal Laboratory and Its Influence
Authors: Stead Evanghelia
Published: October 2024

Chapter 2, A Foetal Laboratory and Its Influence, studies the foetus motif in Beardsley’s oeuvre from its earliest provocative advent in Incipit Vita Nova (1892) and among the Bon-Mots vignettes up to the untimely end of his career. I grant primacy not to biographical detail (as usual in prior scholarship) but to the motif’s creative and cultural bearings, and its challenging manifesto-like value as portrait of a generation. The chapter shows the foetus’s symbolic meaning for the decadent post-Darwinian zeitgeist and stresses its role as a plastic and morphing stimulus with immediate effect on fin-de-siècle graphic design. It analyses the motif's influence and spread in the work of German artist Marcus Behmer (foetal variations), Dutchman Karel de Nérée tot Babberich (mises en abyme), and French anarchist Jossot (defending caricature as a superior form of deforming art).
4. Beardsley Images and the “Europe of Reviews”
Authors: Stead Evanghelia
Published: October 2024

Chapter 4, Beardsley Images and the “Europe of Reviews,” stresses the exceptional amount of press articles devoted to Beardsley and how he worked them into shaping his image, having early grasped the importance of media in an artist’s career. The chapter shows the weight of the first Studio article on his art and fame to then take his images beyond the London scene and discuss his media performance in the Italian magazine Emporium, replaced within the framework of a “Europe of Reviews.” It places the Emporium articles in their generic category, the fine and applied arts journals aimed at the educated reader, and shows how self-modelling of images, borrowed from the Sketch, an English magazine of general circulation, echoes far-away journals transiting via French ones. Recourse to a yet different periodical type, the French avant-garde reviews, exemplifies how a poignant portrait of Beardsley comes to the fore, related to the artist’s early passing. The chapter concludes stressing the benefits of considering periodicals as a network.
5. Paris Performance Alive and Dead
Authors: Stead Evanghelia
Published: October 2024

Chapter 5, Paris Performance Alive and Dead, explores Beardsley's reception in periodicals and the press in France with new first-hand evidence. It highlights the reproduction and diffusion of Beardsley's images beyond textual comments favoured by previous studies, and shows their flexibility and sway. Recalling Beardsley’s multiple connections to France, it follows his performance though the Montmartre journal Le Courrier français, his deliberate choice of images that had shocked the English public, his adaptability, and influence on French artists. It highlights the paradox in the relations between Le Courrier français and the Savoy instead of the expected Parisian aesthete reviews. It shows how tribute to the deceased artist mingles with chauvinistic anecdotes borrowed from the English press and how, adding to his gallery, the French reviews stage-manage dramatized images of Beardsley against his wish.
Conclusion and Aftermath
Authors: Stead Evanghelia
Published: October 2024

Conclusion and Aftermath. The book posits Beardsley as a central figure in sophisticated creation, the interrelation of the arts, and intertwining of modes of expression. He reverted customary relations between art and literature, and fostered innovating tactics through which Decadence paved the way to the historical avant-garde. The conclusion makes explicit five principles used in this book and applicable beyond Beardsley's case: a motif's aesthetic evolution (beyond biography); the reversal of conventional standards of “major” and “minor;”comparison within a wider context (in contrast to monographs); the weight of media-driven modernity and burgeoning print culture; and the power of widely circulating images in disseminating an artist’s work. It shows how Beardsley's oeuvre was furthered in three-dimensional stage and screen performances. It ends with a call to reassess his legacy in a rich wake of related artists’ production.
Co-occurring mental and substance use disorders in Australia 2020–2022: Prevalence, patterns, conditional probabilities and correlates in the general population
Authors: Sunderland Matthew , Vescovi Joshua , Chapman Cath , Arya Vikas , Harris Meredith , Burgess Philip , Marel Christina , Mills Katherine , Baillie Andrew , Teesson Maree , Slade Tim
Published: October 2024

Background:

Previous estimates from 2007 found that co-occurring mental and/or substance use disorders were a pervasive feature of Australia’s mental health. Since that time there have been shifts and improvements in the conceptualisation and incorporation of co-occurring disorders in research and treatment settings. The current study provides up-to-date estimates on the prevalence of co-occurring mental and/or substance use disorders, highlights common patterns of co-occurrence, identifies significant correlates and examines any changes in the extent of co-occurring disorders since 2007.

Methods:

Data were from the two Australian National Surveys of Mental Health and Wellbeing conducted in 2020–2022 ( N = 15,893) and 2007 ( N = 8841). Descriptive statistics were estimated for the number of co-occurring conditions, correlations and pairwise conditional probabilities. Multinomial logistic and robust Poisson regressions were used to identify significant correlates and compare changes in co-occurring conditions across surveys.

Results:

Approximately 46% of people with a mental or substance use disorder in the past 12 months experienced two or more diagnosable conditions. There was little evidence to suggest that the prevalence of co-occurring disorders has changed since 2007 (Prevalence Ratio (PR) = 1.08, 95% CI = 0.98–1.18). Subgroup analysis indicated that those aged 16–24 years were significantly more likely to experience any co-occurrence in 2020–2022 compared with those aged 16–24 years in 2007 (PR = 1.44, 95% CI = 1.17–1.77).

Conclusions:

Co-occurring mental and substance use disorders remain endemic in Australia. Indeed, they appear to be increasingly problematic in younger, more recent cohorts. The results suggest that continued effort is needed to develop and implement transdiagnostic interventions that target broad contextual and/or societal factors.