bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Modelling of Valuation Adjustments for Comprehensive Financial Risk Management
Authors:   , van der Zwaard Thomas
Published: October 2024

The 2007-2008 global financial crisis provided a wake-up call for the financial industry that some assumptions underlying the classical risk-neutral valuation framework for financial derivatives are violated. Especially the assumption related to the absence of Counterparty Credit Risk, i.e., the risk that a counterparty goes in default. This gave rise to various Valuation Adjustments (xVAs) to account for aspects of trading financial derivatives which are not part of the risk-neutral framework. Appropriate assumptions and modelling choices must be made when developing an xVA model, such that the computed values are fit for purpose while keeping the computations practically feasible.

This thesis proposes refined xVA modelling techniques that enhance risk prediction accuracy for financial derivatives, addressing gaps in traditional Valuation Adjustment methodologies. We challenge assumptions related to Wrong-Way Risk (WWR) and the volatility smile, while guaranteeing the efficient computation of exposures, metrics and associated risks.

Chapter 2 explores dynamic Credit Valuation Adjustment (CVA) hedging, starting in a Black-Scholes setting, followed by a Merton jump-diffusion model to incorporate volatility smile. Chapters 3 and 4 focus on the relevance and efficient computation of WWR in Funding Valuation Adjustment (FVA) on linear interest rate and foreign exchange derivatives. We propose a method to split exposures into independent and WWR components and approximate the latter. Chapter 5 introduces a novel model for smile-aware xVA for linear and early-exercise IR derivatives.

These enhancements of the xVA modelling landscape give rise to interesting mathematical research at the cross-section of practically motivated work and academically relevant research.
Gambaran Tingkat Stres dan Pola Makan pada Penderitagastritis di Puskesmas Tanjung Paku Kota Solok Tahun 2024
Authors: Mirawati Anita , Apriliani Indah , Zulharmaswita Zulharmaswita , Deswita Desi
Published: October 2024

Gastritis adalah peradangan pada mukosa lambung yang disertai kerusakan atau erosi pada mukosa, berdasarkan data angka kejadian gastritis di seluruh puskesmas di Kota Solok selama setahun adalah 538 penderita, Puskesmas dengan penderita yang paling tinggi adalah Puskesmas Tanjung Paku dengan jumlah penderita yaitu sebanyak 222 penderita. Tujuan penelitian ini untuk mendeskripsikan bagaimana gambaran tingkat stres dan pola makan penderita gastritis di Puskesmas Tanjung Paku Kota Solok Tahun 2023. Desain penelitian ini adalah deskriptif yang bertujuan untuk mengetahui gambaran tingkat stres dan pola makan yang berperan dalam mempengaruhi kejadian gastritis di Puskesmas Tanjung Paku Kota Solok Tahun. Tempat penelitian di Puskesmas Tanjung Paku Kota Solok. Subjeknya yaitu pasien yang telah di diagnosa Gastritis sebanyak 40 orang. Waktu penelitian selama 14 hari dimulai tanggal 15-26 April 2024.Hasil penelitian ini menunjukkan bahwa penderita gastritis memiliki tingkat stres ringan sebagian kecil (45,0%) dan pola makan yang kurang baik sebagian besar (57,5%). Penderita Gastritis biasanya dianjurkan untuk menerapkan diet lambung/gastritis. Tujuan diberikannya diet lambung diantarannya menetralkan kelebihan asam lambung dengan memberikan makanan yang adekuat dan tidak merangsang. Penelitian ini diharapkan dapat bermanfaat sebagai bahan informasi dan pengetahuan mengenai stres dan pola makan yang dapat menyebabkan gastritis, sehingga dapat digunakan untuk referensi dalam mengembangkan ilmu pengetahuan dan acuan pengembangan penelitian dalam praktik keperawatan medikal bedah.
Penerapan Terapi Murottal dan Bermain Terapeutik dalam Asuhan keperawatan pada Pasien Anak Leukemia Limfoblastik akut (ALL) dengan Ansietas di Ruangan Kronis Irna Anak RSUP Dr. M. Djamil Padang
Authors: Pangesti Nindika Ario , Ilda Zolla Amely
Published: October 2024

Leukemia is the most common type of cancer in children. Long and repeated treatment periods cause children to experience hospitalization which has a psychological impact. One of the psychological impacts that children most often experience is anxiety. Anxiety needs to be anticipated, controlled and overcome so that the patient's quality of life remains optimal. One way is murottal therapy and therapeutic coloring play. Dr. Dr. Hospital's medical record data. M. Djamil Padang, recorded 169 cases of leukemia in 2022. The research aims to apply murottal therapy and therapeutic play (coloring) in the care of pediatric patients with Acute Lymphoblastic Leukemia (ALL) with anxiety in the chronic room of IRNA Children's Hospital Dr. M. Djamil Padang. Descriptive research design with a case study approach in the pediatric IRNA chronic room from 15 May - 3 June 2023. The research population was all 8 pediatric patients with ALL. The sample was 2 participants with ALL who met the criteria. The results of the research on the second participant showed a difference in anxiety levels before and after murottal therapy and therapeutic play (coloring) from anxiety level 5 (very anxious) to 2 (happy). Advice to nurses in the children's room to carry out Murottal therapy and therapeutic play for leukemia children who experience anxiety due to hospitalization.
CONTRAS OS MONOPÓLIOS E O IMPERIALISMO NORTE-AMERICANO: O PROGRAMA CULTURAL DA UNIDADE POPULAR
Authors: Paladino Luiza
Published: October 2024

Este artigo parte de um registro feito pelo fotógrafo português Armindo Cardoso na ocasião das comemorações do Dia Internacional do Trabalhador, em maio de 1971, em Santiago do Chile. Trata-se de uma imagem em que Salvador Allende aparece centralizado atrás de um púlpito discursando para apoiadores e, em segundo plano, um painel de grandes dimensões, no qual é possível observar algumas bandeiras políticas da Unidade Popular: “unidade para nacionalizar o cobre, para estatizar o setor bancário, pela reforma agrária, contra os monopólios, contra o imperialismo norte-americano e pela solidariedade internacional”. A análise apresentada tem como objetivo vincular essas diretrizes às principais inciativas culturais fomentadas ao longo dos mil dias do governo popular, tendo como referência a contribuição de Mário Pedrosa durante o exílio do crítico no país andino, de 1970 a 1973.
EL OTRO LADO DE LAS CORPORACIONES.
Authors: Casablanca Cecilia
Published: October 2024

A partir del análisis del ensayo fotográfico mapuche, El regreso de las voces antiguas del fotógrafo argentino Pablo E. Piovano, el artículo se organiza en torno al de los grandes ejes: las continuidades en las disputas por la tierra patagónica y el cuidado de los aguas sagradas de las mujeres en medicina de la comunidad contra la empresa estatal noruega de energías renovables Statkraft. El problema de investigación se centra en las formas de representación de los problemas ambientales actuales y las dificultades que existen a la hora de visualizar los daños generados por las prácticas extractivistas llevadas a cabo por las corporaciones transnacionales en los territorios del sur global. Metodológicamente se parte de las imágenes fotográficas para ponerlas en diálogo con procesos históricos, políticos y culturales de un largo período de tiempo que enriquecen sus sentidos. Este trabajo forma parte de la investigación que conduce a mi tesis doctoral, y se completa con entrevistas a los artistas, a los protagonistas de las imágenes y a los equipos implicados en la producción y circulación de las imágenes. El artículo aspira a resaltar las continuidades históricas de los despojos inaugurados por la conformación de los Estados-Nación argentino y chileno a fines del siglo XIX, a partir del saqueo y apropiación de cuerpos y tierras indígenas. Asimismo, busca dar cuenta de la enorme capacidad de resistencia por parte de las comunidades originarias al momento de transitar los complejos procesos de recuperación cultural, espiritual, territorial y política vigentes. En el contexto actual de emergencia climática global y exacerbación del extractivismo regional, conocer estas historias indígenas en defensa de los ecosistemas naturales y espirituales, son fundamentales sobre el terreno para seguir construyendo amplias trayectorias de resistencia en nuestro continente, pero también para proponer otras formas de vinculación. nosotros con nuestros bienes naturales.
QUE SAUDADES DO VAMPETA...
Authors: Longo Bahia Dora
Published: October 2024

Este texto é uma adaptação de uma aula ministrada na disciplina Entre Olympia e Bartleby, no Programa de Pós-Graduação em Artes Visuais da Universidade de São Paulo (PPGAV-USP), em 2023. A aula terminou com um trabalho realizado coletivamente, a partir de uma proposta para a refilmagem de I miss Sonja Henie, do diretor iugoslavo Karpo Godina, sob o título Que saudades do Vampeta. A filmagem foi realizada durante uma aula noturna, numa sala do Departamento de Artes Visuais da Escola de Comunicações e Artes da USP, com figurinos e objetos trazidos pelos alunos, a partir de roteiros desenvolvidos por eles de acordo com regras estabelecidas por Godina. Com as mesmas imagens, o grupo realizou quatro montagens, que podem ser acessadas aqui.
Unlocking the potential of simulated hyperspectral imaging in agro environmental analysis: a comprehensive study of algorithmic approaches
Authors: Khan Shafaq , Majdalawieh Munir , Boufama Boubakeur , Sharma Yajan , Basani Ashwitha
Published: October 2024

This study focuses on identifying and evaluating the severity of powdery mildew disease in tomato plants. The uniqueness of this work lies in combining the imaging and advanced deep learning methods to develop a technique that transforms Red Green Blue (RGB) images into Simulated Hyperspectral Images (SHSI) to perform spectral and spatial analysis for precise detection and assessment of powdery mildew severity, thereby enhancing disease management. Furthermore, this research evaluates three advanced pre-trained VGG16 models, ResNet50 and EfficientNet-B7 algorithms for image preprocessing and feature extraction. Extracted features are passed to a neural network generator model to convert RGB image features into SHSIs, providing insights into the spectrum. This method enables the image analysis to perform assessments from SHSIs for health classification using Normalized Difference Vegetation Index (NDVI) values, which are meticulously compared with accurate hyperspectral data using metrics like mean absolute error (MAE) and root mean squared error (RMSE). This strategy enhances precision farming, environmental monitoring, and remote sensing accuracy. Results show that ResNet50’s architecture offers a robust framework for this study’s spectral and spatial analysis, making it a suitable choice over VGG16 and EfficientNet-B7 for transforming RGB images into SHSI. These simulated hyperspectral images offer a scalable and affordable approach for precise assessment of crop disease severity.
Apoptosis, inflammatory and innate immune responses induced by infection with a novel goose astrovirus in goose embryonic kidney cells
Authors: Hou Zhanpeng , Jin Shaobing , Liang Yu , Wang Haiyue , Jiang Danli , Cao Nan , Sun Minhua , Tian Yunbo , Liu Wenjun , Xu Danning , Fu Xinliang
Published: October 2024

Introduction

Since 2016, a highly lethal visceral gout induced by infection with the novel goose astrovirus (GoAstV) resulted in an ongoing outbreak in goslings in China, with a mortality rate ranging from 10% to 50%, and causing considerable economic losses in the goose industry. However, the pathogenesis of GoAstV and the molecular mechanism by which kidney lesions are induced by GoAstV infection are unclear.

Methods

In the present study, a GEK cell infection model for GoAstV was established, and the apoptosis, inflammatory and innate immune responses induced by GoAstV were investigated in GEK cells.

Results

The results shown that the expression of proapoptotic proteins, including Bax, caspase-3, caspase-9 and cytochrome c, increased in the infection group; however, the expression of the antiapoptotic protein Bcl-2 decreased, indicating that apoptosis was induced by GoAstV infection in GEK cells. Besides, the activation of the RIG-I/MDA5 pathway and the downstream upregulation of proinflammatory cytokines, including the adapter proteins MAVS, IRF7 and NF-κB and the proinflammatory cytokines IL-6, IL-8 and TNF-α, were detected in GEK cells infected with GoAstV. In addition, GoAstV infection induces the activation of the NLPR3 pathway and further stimulates the increased production of IL-1β. In summary, the present study revealed that GoAstV infection could induce apoptosis and the activation of the RIG-I/MDA5 and NLRP3 pathways in GEK cells, as well as the massive release of proinflammatory cytokines.

Discussion

These results are helpful for elucidating the molecular mechanism of pathological lesions in the kidney in gout goslings infected with GoAstV and the interaction between GoAstV and the innate immune system of the host.
Genomic epidemiology and evolutionary dynamics of the Omicron variant of SARS-CoV-2 during the fifth wave of COVID-19 in Pakistan
Authors: Razzaq Aroona , Disoma Cyrollah , Iqbal Sonia , Nisar Ayesha , Hameed Muddassar , Qadeer Abdul , Waqar Muhammad , Mehmood Sardar Azhar , Gao Lidong , Khan Sawar , Xia Zanxian
Published: October 2024

Introduction

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed extraordinary challenges to global health systems and economies. The virus’s rapid evolution has resulted in several variants of concern (VOCs), including the highly transmissible Omicron variant, characterized by extensive mutations. In this study, we investigated the genetic diversity, population differentiation, and evolutionary dynamics of the Omicron VOC during the fifth wave of COVID-19 in Pakistan.

Methods

A total of 954 Omicron genomes sequenced during the fifth wave of COVID-19 in Pakistan were analyzed. A Bayesian framework was employed for phylogenetic reconstructions, molecular dating, and population dynamics analysis.

Results

Using a population genomics approach, we analyzed Pakistani Omicron samples, revealing low within-population genetic diversity and significant structural variation in the spike (S) protein. Phylogenetic analysis showed that the Omicron variant in Pakistan originated from two distinct lineages, BA.1 and BA.2, which were introduced from South Africa, Thailand, Spain, and Belgium. Omicron-specific mutations, including those in the receptor-binding domain, were identified. The estimated molecular evolutionary rate was 2.562E-3 mutations per site per year (95% HPD interval: 8.8067E-4 to 4.1462E-3). Bayesian skyline plot analysis indicated a significant population expansion at the end of 2021, coinciding with the global Omicron outbreak. Comparative analysis with other VOCs showed Omicron as a highly divergent, monophyletic group, suggesting a unique evolutionary pathway.

Conclusions

This study provides a comprehensive overview of Omicron’s genetic diversity, genomic epidemiology, and evolutionary dynamics in Pakistan, emphasizing the need for global collaboration in monitoring variants and enhancing pandemic preparedness.
The role of circulating cytokines in heart failure: a bidirectional, two-sample Mendelian randomization study
Authors: Zheng Haoran , Mao Xinxin , Fu Zhenyue , Chen Chunmei , Lv Jiayu , Wang Yajiao , Wang Yuxin , Wu Huaqin , Li Yvmeng , Tan Yong , Gao Xiya , Zhao Lu , Xu Xia , Zhang Bingxuan , Song Qingqiao
Published: October 2024

Background

Cytokines play a pivotal role in the progression of heart failure (HF) by modulating inflammatory responses, promoting vasoconstriction, and facilitating endothelial injury. However, it is now difficult to distinguish the causal relationship between HF and cytokines in observational studies. Mendelian randomization (MR) analyses of cytokines probably could enhance our comprehension to the underlying biological processes of HF.

Methods

This study was to explore the correlation between 41 cytokines with HF at the genetic level by MR analysis. We selected a HF dataset from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) 2018 and a cytokine dataset from a meta-analysis of cytokine levels in Finns. Two-sample, bidirectional MR analyses were performed using Inverse Variance Weighted (IVW), Weighted Median and MR- egger, and the results were tested for heterogeneity and pleiotropy, followed by sensitivity analysis.

Results

Genetic prediction of high levels of circulating Macrophage inflammatory pro-tein-1β(MIP-1β) (P = 0.0389), Interferon gamma induced protein 10(IP-10) (P = 0.0029), and Regu-lated on activation, normal T cell expressed and secreted(RANTES) (P = 0.0120) expression was associated with an elevated risk of HF. HF was associated with the increased levels of circulating Interleukin-2 receptor, alpha subunit(IL-2ra) (P = 0.0296), Beta nerve growth fac-tor(β-NGF) (P = 0.0446), Interleukin-17(IL-17) (P = 0.0360), Basic fibroblast growth factor(FGF-basic) (P = 0.0220), Platelet derived growth factor BB(PDGF-BB) (P = 0.0466), and Interferon-gamma(IFN-γ) (P = 0.0222); and with decreased levels of Eotaxin (P = 0.0133). The heterogeneity and pleiotropy of the cytokines were acceptable, except for minor heterogeneity of FGF-basic and IL-17.

Conclusion

These findings provide compelling evidence for a genetically predictive relationship between cytokines and HF, emphasizing a great potential of targeted modulation of cytokines in slowing the progression of HF. This study draws further conclusions at the genetic level, providing a basis for future large-scale clinical trials.
Safety and efficacy of DEB-TACE in combination with lenvatinib and camrelizumab for the treatment of unresectable hepatocellular carcinoma (uHCC): a two-centre retrospective study
Authors: Xuexian Zhang , Ruidong Wang , Yuhan Ding , Qingwei Li , Feng Xiong , Hong Ren , Jun Zhang , Wei Li
Published: October 2024

Objectives

The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC).

Methods

This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People’s Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed.

Results

The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, P = 0.005; DCR: 88.1% vs. 67.8%, P = 0.039; PFS: 10 months vs. 6 months, P <0.0001; OS: 24 months vs. 16 months, P = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (P > 0.05).

Conclusion

Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients.
Acute-phase innate immune responses in SIVmac239-infected Mamu-B*08+ Indian rhesus macaques may contribute to the establishment of elite control
Authors: Rosen Brandon C. , Sawatzki Kaitlin , Ricciardi Michael J. , Smith Elise , Golez Inah , Mauter Jack T. , Pedreño-López Núria , Yrizarry-Medina Aaron , Weisgrau Kim L. , Vosler Logan J. , Voigt Thomas B. , Louw Johan J. , Tisoncik-Go Jennifer , Whitmore Leanne S. , Panayiotou Christakis , Ghosh Noor , Furlott Jessica R. , Parks Christopher L. , Desrosiers Ronald C. , Lifson Jeffrey D. , Rakasz Eva G. , Watkins David I. , Gale Michael
Published: October 2024

Introduction

Spontaneous control of chronic-phase HIV/SIV viremia is often associated with the expression of specific MHC class I allotypes. HIV/SIV-specific CD8+ cytotoxic T lymphocytes (CTLs) restricted by these MHC class I allotypes appear to be critical for viremic control. Establishment of the elite controller (EC) phenotype is predictable in SIVmac239-infected Indian rhesus macaques (RMs), with approximately 50% of Mamu-B*08+ RMs and 20% of Mamu-B*17+ RMs becoming ECs. Despite extensive characterization of EC-associated CTLs in HIV/SIV-infected individuals, the precise mechanistic basis of elite control remains unknown. Because EC and non-EC viral load trajectories begin diverging by day 14 post-infection, we hypothesized that hyperacute innate immune responses may contribute to viremic control.

Methods

To gain insight into the immunological factors involved in the determination of EC status, we vaccinated 16 Mamu-B*08+ RMs with Vif and Nef to elicit EC-associated CTLs, then subjected these 16 vaccinees and an additional 16 unvaccinated Mamu-B*08+ controls to repeated intrarectal SIVmac239 challenges. We then performed whole-blood transcriptomic analysis of all 32 SIVmac239-infected Mamu-B*08+ RMs and eight SIVmac239-infected Mamu-B*08– RMs during the first 14 days of infection.

Results

Vaccination did not provide protection against acquisition, but peak and setpoint viremia were significantly lower in vaccinees relative to controls. We did not identify any meaningful correlations between vaccine-induced CTL parameters and SIVmac239 acquisition rate or chronic-phase viral loads. Ultimately, 13 of 16 vaccinees (81%) and 7 of 16 controls (44%) became ECs (viremia ≤ 10,000 vRNA copies/mL plasma for ≥ 4 weeks). We identified subsets of immunomodulatory genes differentially expressed (DE) between RM groupings based on vaccination status, EC status, and MHC class I genotype. These DE genes function in multiple innate immune processes, including the complement system, cytokine/chemokine signaling, pattern recognition receptors, and interferon-mediated responses.

Discussion

A striking difference in the kinetics of differential gene expression among our RM groups suggests that Mamu-B*08-associated elite control is characterized by a robust, rapid innate immune response that quickly resolves. These findings indicate that, despite the association between MHC class I genotype and elite control, innate immune factors in hyperacute SIV infection preceding CTL response development may facilitate the establishment of the EC phenotype.
Comprehensive evaluation of clinical outcomes in hepatic epithelioid hemangioendothelioma subsets: insights from SEER Database and departmental cohort analysis
Authors: Wang Bingchen , Chen Xiao , Li Rongxuan , Ai Bolun , Ye Feng , Zhao Jianjun , Zhang Yefan , Huang Zhen , Li Zhiyu , Bi Xinyu , Zhao Hong , Cao Dayong , Cai Jianqiang , Zhou Jianguo , Yan Tao
Published: October 2024

Background

Epithelioid hemangioendothelioma (EHE), is an uncommon, intermediate-grade malignant vascular tumor that can manifest in diverse organs, including the liver, lungs, and bones. Given its unique malignancy profile and rarity, there lacks a consensus on a standardized treatment protocol for EHE, particularly for hepatic epithelioid hemangioendothelioma (HEHE). This study aims to elucidate factors influencing the clinical prognosis of EHE by analyzing data from the SEER database, complemented with insights from a departmental cohort of 9 HEHE cases. Through this, we hope to shed light on potential clinical outcomes and therapeutic strategies for HEHE.

Methods

Using SEER data from 22 registries, we analyzed 313 liver cancer patients with ICD-O-3 9130 and 9133 histology. Twelve variables were examined using Cox regression and mlr3 machine learning. Significant variables were identified and compared. Clinical data, imaging characteristics, and treatment methods of nine patients from our cohort were also presented.

Result

In univariate and multivariate Cox regression analyses, Age, Sex, Year of diagnosis, Surgery of primary site, Chemotherapy, and Median household income were closely related to survival outcomes. Among the ten survival-related machine learning models, CoxPH, Flexible, Mboost, and Gamboost stood out based on Area Under the Curve(AUC), Decision Curve Analysis(DCA), and Calibration Curve Metrics. In the feature importance analysis of these four selected models, Age and Surgery of primary site were consistently identified as the most critical factors influencing prognosis. Additionally, the clinical data of nine patients from our cohort not only demonstrated unique imaging characteristics of HEHE but also underscored the importance of surgical intervention.

Conclusion

For patients with resectable HEHE, surgical treatment is currently a highly important therapeutic approach.
A new prognostic scoring system for newly diagnosed multiple myeloma in the era of new drugs
Authors: Li Ye , Liu Junru , Deng Jingjing , Jian Yuan , Zhang Zhiyao , Zhou Huixing , Li Juan , Chen Wenming
Published: October 2024

Background

We developed a new predictive staging system to explore the heterogeneity of survival in newly diagnosed multiple myeloma (NDMM) patients in the real world.

Methods

In this retrospective study, we evaluated the predictive value of cytogenetic abnormal and clinical data in 375 patients with NDMM at our center. Established a weighted MM prognostic scoring system risk model and validated its predicted PFS and OS by external cohort.

Results

Elevated lactate dehydrogenase levels (1 point), international staging system stage II/III (1 point), 1q21+ ≥ 52.75% (0.5 point), del (17p) ≥ 3.5% (0.5 point), and t (14;16) ≥ 35.25% (1 point) had independent prognostic significance. Patients were further divided into three risk groups: low (I) (score 0–0.5, 16.5%), intermediate (II) (score 1, 46.7%), and high (III) (score 1.5–3, 36.8%). In the training cohort, the 3-year PFS was 79.5% vs. 65.3% vs. 40.3% (p < 0.001), and the 3-year OS was 87.7% vs.70.1% vs. 55% (p < 0.001) for the three risk groups. In the external validation cohort, the 3-year PFS was 85.5% vs.61.2% vs. 43.1% (p < 0.001) and the 3-year OS was 91.4% vs.83.5% vs. 56.9% (p < 0.001) for the three risk groups.

Conclusion

The risk stratification of this model shows good discrimination and calibration, and its application in clinical practice can improve the risk assessment of patients with NDMM and guide personalized treatment strategies.
Soft-sensor model development for CHO growth/production, intracellular metabolite, and glycan predictions
Authors: Liang George , Sha Sha , Wang Zhao , Liu Huolong , Yoon Seongkyu
Published: October 2024

Efficaciously assessing product quality remains time- and resource-intensive. Online Process Analytical Technologies (PATs), encompassing real-time monitoring tools and soft-sensor models, are indispensable for understanding process effects and real-time product quality. This research study evaluated three modeling approaches for predicting CHO cell growth and production, metabolites (extracellular, nucleotide sugar donors (NSD) and glycan profiles): Mechanistic based on first principle Michaelis-Menten kinetics (MMK), data-driven orthogonal partial least square (OPLS) and neural network machine learning (NN). Our experimental design involved galactose-fed batch cultures. MMK excelled in predicting growth and production, demonstrating its reliability in these aspects and reducing the data burden by requiring fewer inputs. However, it was less precise in simulating glycan profiles and intracellular metabolite trends. In contrast, NN and OPLS performed better for predicting precise glycan compositions but displayed shortcomings in accurately predicting growth and production. We utilized time in the training set to address NN and OPLS extrapolation challenges. OPLS and NN models demanded more extensive inputs with similar intracellular metabolite trend prediction. However, there was a significant reduction in time required to develop these two models. The guidance presented here can provide valuable insight into rapid development and application of soft-sensor models with PATs for ipurposes. Therefore, we examined three model typesmproving real-time product CHO therapeutic product quality. Coupled with emerging -omics technologies, NN and OPLS will benefit from massive data availability, and we foresee more robust prediction models that can be advantageous to kinetic or partial-kinetic (hybrid) models.
Desidustat: a novel PHD inhibitor for the treatment of CKD-induced anemia
Authors: Joharapurkar Amit , Pandya Vrajesh , Patel Harilal , Jain Mukul , Desai Ranjit
Published: October 2024

Desidustat is a small molecule inhibitor of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) discovered and developed by Zydus Lifesciences for the treatment of anemia associated with chronic kidney disease (CKD). This review summarizes the preclinical and clinical profile of desidustat which led to its approval and clinical use in India.
Reinventing gut health: leveraging dietary bioactive compounds for the prevention and treatment of diseases
Authors: Wang Qiurong , Huang Hui , Yang Ying , Yang Xianglan , Li Xuemei , Zhong Wei , Wen Biao , He Feng , Li Jun
Published: October 2024

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.
Very early symptomatic metastasis pseudoprogression after stereotactic brain radiosurgery in a melanoma patient treated with BRAF/MEK inhibitors: a case report and review of the literature
Authors: Romano Edouard , Tran Sebastien , Ben Aissa Assma , Carvalho Goncalves Miguel , Durham André , Tsoutsou Pelagia
Published: October 2024

Introduction

Significant therapeutic changes have recently occurred in the management of melanoma brain metastases (BMs), both in the field of local treatments, with the rise of stereotactic radiotherapy (RT), as well as in systemic ones, with the advent of immunotherapy and targeted therapies (TT). These advances have brought about new challenges, particularly regarding the potential interactions between new TT (notably BRAF/MEK inhibitors) and irradiation. Through a clinical case, we will discuss a side effect not previously described in the literature: ultra-early pseudoprogression (PP) following brain stereotactic radiosurgery (SRS), in a patient treated with dabrafenib-trametinib.

Case presentation

A 61-year-old patient with BRAFV600E-mutated melanoma, receiving second-line dabrafenib-trametinib therapy, was referred for SRS on three progressing meningeal implants, without evidence of systemic progression. Four days after the first RT session (1x6 Gy on a fronto-orbital lesion prescribed 5x6 Gy, and 1x20 Gy single fraction on the other lesions), the patient presented with an epileptic seizure. An MRI, compared to the planning MRI ten days earlier, revealed significant progression of the irradiated lesions. The patient’s condition improved with dexamethasone and levetiracetam, and RT was halted out of caution. A follow-up MRI at one month demonstrated a size reduction of all treated lesions. Subsequent imaging at five months revealed further shrinking of the two lesions treated with an ablative dose of 20 Gy, while the under-treated fronto-orbital lesion progressed. These dynamics suggest an initial PP in the three irradiated lesions, followed by good response in the ablatively treated lesions and progression in the partially treated lesion.

Conclusion

To our knowledge, this represents the first documented case of ultra-early PP following brain SRS in a patient receiving concomitant dabrafenib-trametinib. It highlights the need for particular vigilance when using tyrosine kinase inhibitors (TKIs) with SRS, and warrants further research into potential treatment interactions between RT and novel systemic agents, as well as the optimal treatment sequence of melanoma BMs.
Cellular therapy in older adults with relapsed/refractory diffuse large B-cell lymphoma
Authors: Esteghamat Naseem , Tsumura Aaron , Marquez-Arreguin Gabriel , Tuscano Joseph
Published: October 2024

Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with poor prognosis and limited therapeutic options. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (autoHCT) was historically the curative-intent treatment for patients who demonstrated chemosensitivity to salvage therapy. However, a significant portion of patients do not make it autoHCT due to disease progression or overall fitness and eligibility. This is of particular concern in the older adult population. In recent years, significant advances in cellular therapies including chimeric antigen receptor (CAR) T-cells and bispecific antibodies, in addition to improvement in autoHCT tolerability, have allowed for additional treatment options for patients with R/R DLBCL. These novel therapies offer the potential for durable remissions and cure, and should be considered in older patients. We present a review focused on the safety and efficacy of cellular therapies in the older adult population with R/R DLBCL.
Benefits of laparoscopic liver resection for liver tumors in obese patients: a meta-analysis
Authors: Zhang Jie , Zeng Cuifang , Chen Rui , Tang Gang , Zhou Rongxing
Published: October 2024

Objective

The superiority of laparoscopic liver resection (LLR) and open liver resection (OLR) in obese patients remains controversial. The study aims to assess the available literature and compare the perioperative outcomes of LLR and OLR for liver tumors in obese patients.

Methods

We searched PubMed, Cochrane Library, Embase, and Web of Science databases for studies comparing LLR and OLR. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated.

Results

Nine studies were included, with a total of 1116 patients (LLR group: 482 patients; OLR group: 634 patients). Compared with OLR, LLR has lower overall morbidity (OR 0.47, 95% CI 0.34, 0.64), major complications (OR 0.45, 95% CI 0.25, 0.82), surgical site infection (OR 0.18, 95% CI 0.07, 0.48), bile leak (OR 0.45, 95% CI 0.22, 0.95), less blood loss (MD, -329.12 mL; 95% CI, -623.35, -34.88), and shorter length of stay (MD, -5.20 days; 95% CI, -7.43, -2.97). There were no significant differences in mortality, operation time, liver failure, and blood transfusion between the two groups.

Conclusions

LLR for obese patients is safe and feasible. Compared to OLR, it offers better short-term outcomes. Further randomized controlled trials to verify the potential advantages of LLR over OLR are warranted.
Key data elements for a successful pediatric rheumatology virtual visit: a survey within the PR-COIN network
Authors: Goh Y. Ingrid , Ryan Meghan E. , Akoghlanian Shoghik , Pooni Rajdeep , Harris Julia G. , Bullock Danielle R. , Vora Sheetal S. , Lee Tzielan C. , Tse Shirley M.L. , Barbar-Smiley Fatima
Published: October 2024

Introduction

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease which is commonly monitored by a combination of history, physical examination, bloodwork, and imaging. The COVID-19 pandemic prompted a rapid shift to telemedicine to ensure that patients continued to receive healthcare. The shift to telemedicine changed the methodology and ability of healthcare providers to monitor their patients' progress, as they were unable to perform direct hands-on assessments. The following survey sought to understand the impact of switching pediatric rheumatology healthcare delivery from in-person to telemedicine modality. Specifically, it sought to examine the rate of collection of critical data elements (CDE) for monitoring JIA disease activity and outcomes, barriers and facilitators to its collection, opinions on difficulty and importance of collecting CDE over telemedicine, tools and electronic medical record modifications that facilitated CDE collection, and other data elements that were important to collect during telemedicine visits.

Methods

A cross-sectional survey was sent to healthcare providers at all PR-COIN centers who saw patients using telemedicine. Qualitative data was analyzed using descriptive statistics and qualitative data was analyzed using an inductive approach.

Results

Survey respondents reported that they documented the CDE at least 75% of the time. Barriers to assessing and documenting critical data elements included (1) the inability to palpate or visualize all joints over telemedicine, (2) connectivity issues, and (3) forgetfulness with collecting all CDE. Respondents suggested using reminders within the electronic medical record to prompt documentation completeness and improve reliability. They also suggested including medication adherence, quality of life, and patient/caregiver satisfaction with their telemedicine experience as part of their documentation. A few centers reported that they had established processes to assist with data collection in advance of the telemedicine visit; however, the variation in responses reflects the need to standardize the process of providing care over telemedicine.

Discussion

Multiple barriers and facilitators to collecting CDE during telemedicine visits exist. Given that a proportion of the population will continue to be seen over telemedicine, teams need to adapt their practices to consistently provide high-quality care over virtual platforms, ensuring that patients at any institution receive a standardized level of service.
Blestriarene C exerts an inhibitory effect on triple-negative breast cancer through multiple signaling pathways
Authors: An Junsha , Han Mingyu , Tang Hailin , Peng Cheng , Huang Wei , Peng Fu
Published: October 2024

Introduction

Breast cancer is the most common cancer worldwide, the leading cause of cancer death in women, and the fifth leading cause of cancer death. Triple negative breast cancer (TNBC), with high metastasis and mortality rates, is the most challenging subtype in breast cancer treatment. There is an urgent need to develop anti-TNBC drugs with significant efficacy, low side effects and good availability. In early drug screening, blestriarene C was found to have inhibitory effects on TNBC cells. In this article, we further explore the mechanisms associated with blestriarene C for breast cancer.

Methods

In this article, we take the approach of network pharmacology combined with in vivo and in vitro experiments. Network pharmacology analysis was used to predict the active components in Baiji, and to investigate the hub targets and related mechanisms of BC in TNBC treatment. The mechanism of anti-TNBC in vitro was evaluated by CCK-8 assay, cell apoptosis and cell cycle assays, wound healing assay, WB assay, and molecular docking analysis. The inhibition effect in vivo was test in subcutaneous tumor models established in mice.

Results

Through network pharmacology analysis and experiments, we screened out BC as the main active ingredient, and found that BC could inhibit the Ras/ERK/c-Fos signaling pathway while downregulating the expression of HSP90AA1 and upregulating the expression of PTGS2, thereby promoting apoptosis, causing S-phase cycle arrest, and inhibiting the proliferation and migration of BT549 cells. The in vivo results illustrated that BC inhibited the growth of TNBC tumors and has a high safety profile. By integrating network pharmacology with in vitro and in vivo experiments, this study demonstrated that BC inhibited the proliferation and migration of TNBC cells by inhibiting the Ras/ERK/c-Fos signaling pathway, promoting apoptosis, and causing S-phase cycle arrest.

Discussion

This study provides new evidence for the use of BC as a novel drug for TNBC treatment.
Sphagnum cuspidatulum extract prevents acute kidney injury induced by high-fat diet and streptozotocin via alleviation of oxidative stress and apoptosis in pre-diabetic rats
Authors: Laorodphun Pongrapee , Chaisen Sutheera , Amattat Sarocha , Maphet Pornchita , Printrakul Narin , Pandith Hataichanok , Panya Aussara , Kongmali Burit , Swe Myat Theingi , Arjinajarn Phatchawan
Published: October 2024

Context

Obesity and pre-diabetes are associated with renal dysfunction via elevated oxidative stress. Peat moss, or Sphagnum cuspidatulum Müll. Hal., Sphagnaceae (SC), are rich in phenolic compounds that enhance antioxidant activity.

Objective

SC might show beneficial effects in pre-diabetes-associated renal dysfunction.

Materials and methods

Male Wistar rats, after 4 weeks on a high-fat diet, received low-dose streptozotocin to induce pre-diabetes. Then, the pre-diabetic rats were randomly divided into 4 groups: untreated pre-diabetic rats (P-DM), pre-diabetic rats treated with SC 50 or 100 mg/kg/day (P-DM50 or P-DM100), and pre-diabetic rats treated with metformin 100 mg/kg/day (MET). The drugs were fed by gavage for 4 weeks.

Results

Treatment with SC100 dramatically lowered serum creatinine (S.Cr.), blood urea nitrogen (BUN), and augmented creatinine clearance in pre-diabetic rats. Additionally, SC100 significantly decreased the malondialdehyde level. Furthermore, pre-diabetic rats treated with SC100 significantly upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream mediators, with downregulated apoptotic markers.

Discussion and conclusion

Our findings provide a scientific basis for the clinical application of SC and a new strategy for the prevention of nephrotoxicity and other kidney disease in the future.
How parenting styles affect primary school students’ subjective well-being? The mediating role of self-concept and emotional intelligence
Authors: Gao Tiantian , Li Baoqian , Liang Shuxian , Zhou Wanmeng , Zhu Xinyi , Bai Lu , Li Guoqiang
Published: October 2024

Purpose

To explore the relationship between parenting styles and self-concept, emotional intelligence, and subjective well-being among primary school students.

Methods

In total, 1,683 students from 10 primary schools in Hangzhou, China, were surveyed using a simple random sampling method. Participants completed the Parenting Style Scale, the Self-Concept Scale, the Emotional Intelligence Scale, and the Subjective Well-Being Scale.

Results

(1) Father’s and mother’s emotional warmth was significantly positively correlated with students’ subjective well-being (r = 0.513, p < 0.01 and r = 0.478, p < 0.01, respectively). Father’s and mother’s rejection was significantly negatively correlated with students’ subjective well-being (r = −0.257, p < 0.01 and r = −0.285, p < 0.01, respectively). Father’s overprotection was significantly negatively correlated with students’ subjective well-being (r = −0.178, p < 0.01; r = −0.227, p < 0.01). (2) Self-concept and emotional intelligence acted as chain mediators between father’s and mother’s emotional warmth and students’ subjective well-being (0.337, 0.477 and 0.366, 0.520, respectively). Self-concept and emotional intelligence acted as chain mediators between father’s and mother’s rejection and students’ subjective well-being (−0.590, −0.377 and −0.693, −0.460, respectively). Self-concept chain-mediated between father’s and mother’s overprotection and students’ subjective well-being (−0.380, −0.224 and −0.413, −0.264 respectively).

Conclusion

Parenting styles can affect primary school student’s subjective well-being both directly and through mediating effects. Self-concept and emotional intelligence partially mediate the impact of emotional warmth and rejection parenting styles, and fully mediate the impact of father’s overprotective parenting on subjective well-being.
Listening comprehension in a home language: a case of Russian in Germany
Authors: Gacs Luca , Ritter Anna , Goltsev Evghenia
Published: October 2024

Listening comprehension is central to language learning, yet it remains the least understood and least researched skill. This statement is still relevant today, as there is insufficient research to explore listening comprehension from the perspective of family-related multilingualism and to consider the complete linguistic repertoire of multilingual speakers. Moreover, with regard to home language, listening comprehension is assumed to be a more developed language competence than reading or writing. Based on the mentioned research, the aim of the present study is to investigate listening comprehension and its influencing factors specifically in German-Russian simultaneous bilinguals aged 13–19 (n = 99) by considering the home- and majority language. The study uses quantitative data collection methods such as linguistic tests in Russian and German for the elicitation in different levels of listening and questionnaires for strategy use and background. The research questions are as follows: What does the language proficiency and input in Russian look like? (1) Regarding listening comprehension in Russian as a home language, are there differences between the speakers within comprehension on different levels, e.g., is sound decoding easier than sentence parsing? (2) If there are differences in Russian as a home language, which linguistic and background variables can correlate with the performance of listening comprehension on its different levels? Concerning the first research question, the results show relevant differences between four different levels of listening comprehension (phoneme, word, sentence, and text level), which strengthened the assumed complexity of listening comprehension in the home language. In addition, the results show different connections between the listening comprehension competence and the input from different family members, as well as exposure to film and television in the home and majority language.
The impact of Philosophy for Children (P4C) activities on enhancing the speaking skills of gifted students
Authors: Balcı Emine , Eryılmaz Ramazan
Published: October 2024

The aim of this study was to investigate the impact of Philosophy for Children (P4C) activities integrated into Turkish lessons on the speaking skills of gifted students. Both quantitative and qualitative data were collected through interviews and various scales, employing a mixed-method design. The results indicated that students had positive feelings about P4C, including appreciation, curiosity, surprise, excitement, self-confidence, and empathy. They believed that P4C enhanced their problem-solving, creativity, questioning, effective speaking, and collaboration skills. However, some students also expressed negative views, tough less frequently, citing issues such as nonsense, limited time, the necessity of prior knowledge, and lack of idea diversification. Quantitative data revealed that P4C activities significantly improved the speaking skills of gifted students and notably reduced their speaking anxiety. Additionally, sex and program variables showed no significant effect on speaking skills and speaking anxiety.