bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-industry contagion of systemic financial risks from the perspective of dynamic tail risk network: Evidence from China
Authors: Chang Dongfeng , Fu Tong , Zhang Weiping
Published: March 2024

Fluctuations in interconnectedness within different industrial sectors are hence critical not only for financial market stability but also for the development of real economy. Thus, this paper contractures the varying network structure and estimates the tail risk spillover linkages at the industry level by applying the TENET (Tail-Event driven NETwork) framework on China’s 24 sectors from 2007 to 2018. There is a higher level of risk spillovers and spatial linkages between sectors during turmoil periods, and the centrality indicators can effectively identify the systemically important industries. Notably, it is more comprehensive and accurate to judge the systemic importance node by considering its location and connection in the network rather than just its internal attributes. Furthermore, the high-order polynomial regressions show that degree and eigenvector centrality have a significantly positive effect on risk contagion, while closeness centrality has a two-regime (“both robust and fragile”) contagion mechanism. From a policy point of view, regulators could formulate early-warning measures based on the impact mechanism and spread paths of systemic risk, especially in financial turmoil periods. Meanwhile, they should pay more attention to preventing the aggregate risks of the most influential sectors.
Smooth Time-Varying Feedback Control of Nonholonomic Systems with Applications to the Attitude Control of Underactuated Spacecraft
Authors: Zhou Bin , Zhang Kang-Kang
Published: March 2024

This paper studies the control of chained nonholonomic systems by using smooth time-varying feedback. First, by using a time-varying state transformation, the chained nonholonomic system is transformed into a linear time-varying system. Second, with the aid of some properties of a class of parametric Lyapunov equations and time-varying systems theory, smooth time-varying state feedback controller is developed to ensure the exponential convergence of both the system states and controls. Different from existing results, the design parameters in the proposed control strategy are independent of the initial conditions of the system. Third, as an application of the proposed smooth time-varying feedback, the attitude control problem for underactuated axisymmetric spacecraft is addressed. Finally, a numerical simulation is presented to validate the effectiveness of the proposed method.
Implementing Privacy Homomorphism with Random Encoding and Computation Controlled by a Remote Secure Server
Authors: Hutto Kevin , Mooney Vincent
Published: March 2024

Remote IoT devices face significant security risks due to their inherent physical vulnerability. An adversarial actor with sufficient capability can monitor the devices or exfiltrate data to access sensitive information. Remotely deployed devices such as sensors need enhanced resilience against memory leakage if performing privileged tasks. To increase the security and trust of these devices we present a novel framework implementing a privacy homomorphism which creates sensor data directly in an encoded format. The sensor data is permuted at the time of creation in a manner which appears random to an observer. A separate secure server in communication with the device provides necessary information which allows the device to perform processing on the encoded data but does not allow decoding of the result. The device transmits the encoded results to the secure server which maintains the ability to interpret the results. In this article, we show how this framework works for an image sensor calculating differences between a stream of images, with initial results showing an overhead as low as only 266% in terms of throughput when compared to computing on standard unencoded numbers such as two’s complement. We further show 5,000× speedup over a recent homomorphic encryption ASIC.
An Explainable Stacked Ensemble Model for Static Route‐Free Estimation of Time of Arrival
Authors: Schleibaum Sören , Müller Jörg P. , Sester Monika
Published: March 2024

Sustainable concepts for on‐demand transportation, such as ridesharing or ridehailing, require advanced technologies and novel dynamic planning and prediction methods. In this paper, we consider the prediction of taxi trip durations, focusing on the problem of the estimated time of arrival (ETA). ETA can be used to compute and compare alternative taxi schedules and to provide information to drivers and passengers. To solve the underlying hard computational problem with high precision, machine learning (ML) models for ETA are the state of the art. However, these models are mostly black box neural networks. Hence, the resulting predictions are difficult to explain to users. To address this problem, the contributions of this paper are threefold. First, we propose a novel stacked two-level ensemble model combining multiple ETA models; we show that the stacked model outperforms state‐of‐the‐art ML models. However, the complex ensemble architecture makes the resulting predictions less transparent. To alleviate this, we investigate explainable artificial intelligence (XAI) methods for explaining the first‐ and second‐level models of the ensemble. Third, we consider and compare different ways of combining first‐level and second‐level explanations. This novel concept enables us to explain stacked ensembles for regression tasks. The experimental evaluation indicates that the considered ETA models correctly learn the importance of those input features driving the prediction.
Figure 4 from The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance
Authors: Lawson Mandy , Cureton Natalie , Ros Susana , Cheraghchi-Bashi Azadeh , Urosevic Jelena , D'Arcy Sophie , Delpuech Oona , DuPont Michelle , Fisher David I. , Gangl Eric T. , Lewis Hilary , Trueman Dawn , Wali Neha , Williamson Stuart C. , Moss Jennifer , Montaudon Elodie , Derrien Heloise , Marangoni Elisabetta , Miragaia Ricardo J. , Gagrica Sladjana , Morentin-Gutierrez Pablo , Moss Thomas A. , Maglennon Gareth , Sutton Daniel , Polanski Radoslaw , Rosen Alan , Cairns Jonathan , Zhang Pei , Sánchez-Guixé Mònica , Serra Violeta , Critchlow Susan E. , Scott James S. , Lindemann Justin P.O. , Barry Simon T. , Klinowska Teresa , Morrow Christopher J. , Carnevalli Larissa S.
Published: March 2024

Camizestrant has superior in vivo activity to fulvestrant in ESR1wt and ESR1m PDX models (2). A, Characteristics of ER+ breast cancer models used. B, Change in ER pathway gene activation after treatment, expressed as change in ER pathway gene score and in cell-cycle G1–S checkpoint genes. See Supplementary Methods for details. Statistical analysis comparing fulvestrant and camizestrant was done using one-way analysis of covariance (n ≥ 4 animals per group). Models shown in bold (x-axis) are fulvestrant sensitive; those in regular type are fulvestrant resistant. ***, P < 0.001; ****, P < 0.0001. Amp, amplification; CCND1, cyclin D1; Del, deletion; MET, metastasis; Mut, mutation; PIK3CA, phosphatidylinositol 3-kinase subunit α; PR, progesterone receptor; PRIM, primary; RESIST, resistant; RB1, retinoblastoma gene; SENS, sensitive. Patient treatment reported: Be, bevacizumab; Ch, chemotherapy; E, exemestane; Ev, everolimus; F, fulvestrant; I, investigational; L, letrozole, T, tamoxifen; X, radiotherapy.
Figure 1 from The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance
Authors: Lawson Mandy , Cureton Natalie , Ros Susana , Cheraghchi-Bashi Azadeh , Urosevic Jelena , D'Arcy Sophie , Delpuech Oona , DuPont Michelle , Fisher David I. , Gangl Eric T. , Lewis Hilary , Trueman Dawn , Wali Neha , Williamson Stuart C. , Moss Jennifer , Montaudon Elodie , Derrien Heloise , Marangoni Elisabetta , Miragaia Ricardo J. , Gagrica Sladjana , Morentin-Gutierrez Pablo , Moss Thomas A. , Maglennon Gareth , Sutton Daniel , Polanski Radoslaw , Rosen Alan , Cairns Jonathan , Zhang Pei , Sánchez-Guixé Mònica , Serra Violeta , Critchlow Susan E. , Scott James S. , Lindemann Justin P.O. , Barry Simon T. , Klinowska Teresa , Morrow Christopher J. , Carnevalli Larissa S.
Published: March 2024

Camizestrant (AZD9833) is a selective ER degrader and pure antagonist. A, Chemical structure of camizestrant. B, The indicated cell lines were treated with 100 nmol/L of the indicated compound for 48 hours. Levels of ERα were assessed by Western blotting and normalized to an untreated control and fulvestrant. Each point represents an independent experiment. C, MCF7 or CAMA-1 cells were treated with DMSO, 1 nmol/L estradiol, or 100 nmol/L of the indicated compound + 1 nmol/L estradiol for 24 hours. RNA expression was assessed by RNA sequencing. Data represent z-scores of normalized gene expression for genes in an ER activity signature. D, MCF7 and CAMA-1 cells were treated with the indicated concentration of the indicated compound for 7 days. Cell number was estimated with a Sytox Green assay normalized to an untreated control on the day of treatment (0.0) and an untreated control on day 7 after treatment (1.0). Data points represent the mean from three independent experiments performed in triplicate ± SD. E, Ishikawa cells were treated with the indicated concentration of fulvestrant or camizestrant, or 100 nmol/L AZD9496 for 24 hours, and ERα and PgR expressions were determined by Western blot. DMSO, dimethyl sulfoxide; PR, progesterone receptor.
Supplementary Table 6 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

CRISPR-Cas9 oligonucleotides
Supplementary Table 3 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Exon 8 SNP in primary vs recurrence/metastasis
Supplementary Table 2 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Exon 8 SNP frequency in normal vs tumors
Supplementary Table 1 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

GAN gene exon primers
Supplementary Figure Legends from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Supplementary figure legends
Supplementary Figure 8 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Map of lentiviral cloning vector
Supplementary Figure 7 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

ME180 and CRISPR-Cas9 clones
Supplementary Figure 6 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Incucyte live cell assay of cisplatin treated ME180 cells
Supplementary Figure 4 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

MTT and sift agar assay and Snapshot view of exon 8 of C33A and HT3 cell lines
Supplementary Figure 2 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Morphology of fibroblast and cancer cell lines
Supplementary Figure 15 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Invasion and migration of control and GAN siRNA treated ME180 cells
Supplementary Figure 10 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Synonymous exome SNP and Indel sequences in ME180 and GAN edited cell lines
FIGURE 6 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Inhibition of mouse lung metastasis with re-expression of gigaxonin. A, Table shows xenograft tumors formation by ME180 cells and lung metastasis by GAN edited clones. ME180 did not form lung metastasis. Greater than 50% reduced metastasis was seen in GAN lentiviral transfected cells compared with untransfected and control lentiviral transfected cells. B, H&E staining shows absence of tumor cells in the lung of parental ME180 cells after tail vein injection indicating absence of lung metastasis. While high metastasis (tumor cells infiltrating >50% of the lung, cells, bracketed and circled areas) is seen with GAN edited and control lentiviral transfected cells, a 50% reduction in metastasis (black circles) compared with the control virus transfected cells is observed in GAN lentiviral transfected cells. C and D, Statistically significant expression (3+, >90%, P < 0.01) of e-cadherin is seen in the epithelium of normal lung tissue after ME180 tail vein injection. GAN edited cells and control lentiviral transfected cells show low level expression (1+, 40%) in the lung metastatic tumor cells. GAN lentiviral transfected cells have higher expression (3+, >80%) in tumor cells (P < 0.01). E and F, The pneumocytes of normal lung tissue of ME180 injected mice shows nuclear Snail expression serving as an internal positive control. Lung tumors of GAN edited, and control lentiviral cell injected mice show higher nuclear expression. However, there is statistically significant reduced nuclear expression (P < 0.01) in GAN lentiviral injected lung tumor cells. The non-tumor cells of this sample (indicated by arrows) have weak cytoplasmic expression. Thus, an inverse relationship in the expression of e-cadherin and Snail is seen in gigaxonin overexpressing cells versus the GAN edited cells indicating a reduction in metastasis related to higher gigaxonin expression. Thicker arrows point to non-tumor cells and the thinner arrow points to tumor cells.
Data from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Abstract
Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C>T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial–mesenchymal transition through inhibition of Snail.
Significance:
Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer.
Adherence to Treatment Guidelines in Ambulatory Heart Failure Patients with Reduced Ejection Fraction in a Latin-American Country: Observational Study of the Colombian Heart Failure Registry (RECOLFACA)
Authors: Rivera-Toquica Alex , Echeverría Luis Eduardo , Arias-Barrera Carlos Andrés , Mendoza-Beltrán Fernán , Hoyos-Ballesteros Diego Hernán , Plata-Mosquera Carlos Andrés , Ortega-Madariaga Juan Carlos , Carvajal-Estupiñán Juan Fernando , Quintero-Yepes Viviana , Zárate-Correa Luz Clemencia , García-Peña Ángel Alberto , Velásquez-López Nelly , Anchique Claudia Victoria , Saldarriaga Clara Ines , Gómez-Mesa Juan Esteban
Published: March 2024

Introduction: Although several guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) be treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aimed to describe the use patterns of HFrEF treatments in the Colombian Heart Failure Registry (RECOLFACA). Methods: Patients with HFrEF enrolled in RECOLFACA during 2017–2019 were included. Heart failure (HF) medication prescription and daily dose were assessed using absolute numbers and proportions. Therapeutic schemes of patients treated by internal medicine specialists were compared with those treated by cardiologists. Results: Out of 2,528 patients in the registry, 1,384 (54.7%) had HFrEF. Among those individuals, 88.9% were prescribed beta-blockers, 72.3% with ACEI/ARBs, 67.9% with MRAs, and 13.1% with ARNIs. Moreover, less than a third of the total patients reached the target doses recommended by the European HF guidelines. No significant differences in the therapeutic schemes or target doses were observed between patients treated by internal medicine specialists or cardiologists. Conclusion: Prescription rates and target dose achievement are suboptimal in Colombia. Nevertheless, RECOLFACA had one of the highest prescription rates of beta-blockers and MRAs compared to some of the most recent HF registries. However, ARNIs remain underprescribed. Continuous registry updates can improve the identification of patients suitable for ARNI and SGLT2i therapy to promote their use in clinical practice.
Treatment of Gastrointestinal Bleeding in the Biliopancreatic Limb with Embolization in a Patient with Duodenal Switch Anatomy
Authors: Pang Alice S. , Adamo Robert , Coben Robert
Published: March 2024

Introduction: Biliopancreatic diversion with duodenal switch (BPD/DS) is an uncommon type of bariatric surgery that can rarely lead to bleeding in the biliopancreatic limb. The altered anatomy poses significant diagnostic and therapeutic challenges. Case Presentation: We present an unusual case of a woman status post-BPD/DS nearly a decade ago who presented with gastrointestinal bleeding in the duodenum of the biliopancreatic limb, a rare phenomenon given the unique surgery. Conclusion: We illustrate a promising minimally invasive option of successfully treating the bleeding by interventional radiology (IR) embolization as an alternative to more invasive and challenging options of balloon-assisted enteroscopy, lumen-apposing metal stent placement and surgical intraoperative enteroscopy.
Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry
Authors: Guerra Iván , Barros Francisco , Chaparro María , Benítez José M. , Martín-Arranz María Dolores , de Francisco Ruth , Piqueras Marta , de Castro Luisa , Carbajo Ana Y. , Bermejo Fernando , Mínguez Miguel , Gutiérrez Ana , Mesonero Francisco , Cañete Fiorella , González-Muñoza Carlos , Calvo Marta , Sicilia Beatriz , Alfambra Erika , Rivero Montserrat , Lucendo Alfredo J. , Tardillo Carlos A. , Almela Pedro , Bujanda Luis , van Domselaar Manuel , Ramos Laura , Fernández Sánchez María , Hinojosa Esther , Verdejo Cristina , Gimenez Anna , Rodríguez-Lago Iago , Manceñido Noemí , Pérez Calle José L. , Moreno Mónica del Pilar , Delgado-Guillena Pedro Genaro , Antolín Beatriz , Ramírez de la Piscina Patricia , Casanova María José , Soto Escribano Pilar , Martín Arranz Eduardo , Pérez-Martínez Isabel , Mena Raquel , García Morales Natalia , Granja Alicia , Boscá Watts Marta Maia , Francés Rubén , Fernández Cristina , Calafat Margalida , Roig-Ramos Cristina , Vera María Isabel , Carracedo Ángel , Domènech Eugeni , Gisbert Javier P. ,   ENEIDA Project of GETECCU
Published: March 2024

Introduction: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. Methods: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. Results: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. Conclusion: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.
Mutations in STARD8 (DLC3) May Cause 46,XY Gonadal Dysgenesis
Authors: Sirokha Dmytro , Rayevsky Alexey , Gorodna Olexandra , Kalynovskyi Vitalii , Zelinska Nataliya , Samson Oksana , Kwiatkowska Krystyna , Nef Serge , Jaruzelska Jadwiga , Kusz-Zamelczyk Kamila , Livshits Ludmila
Published: March 2024

Introduction: 46,XY gonadal dysgenesis is a condition that is characterised by undeveloped testes in individuals with a male karyotype. Mutations in many genes that underlie this condition have been identified; however, there are still a considerable number of patients with an unknown genetic background. Recently, a mutation in the STARD8 X-linked gene in two sisters with 46,XY gonadal dysgenesis has been reported. It was localised within the START domain, whose homologue in Drosophila is responsible for maintaining testes integrity during their development. Methods: We analysed the potential pathogenicity of another STARD8 mutation, p.R887C, that was identified in a patient with 46,XY asymmetric gonadal dysgenesis. For this purpose, molecular dynamics simulations were performed. Results: These simulations revealed the full rearrangement of the helix containing the p.R887C substitution upstream from the START domain, which may cause STARD8 protein dysfunction and contribute to 46,XY gonadal dysgenesis. A comparison of the phenotypes of the three described 46,XY gonadal dysgenesis patients that harbour STARD8 mutations indicated that alterations of this gene can result in a partial or complete gonadal dysgenesis phenotype. Conclusion: Based on these and previous results, it is reasonable to include STARD8 in gene panels for 46,XY gonadal dysgenesis.
Helicobacter pylori Infection: A 40-Year Journey through Shifting the Paradigm to Transforming the Management
Authors: Malfertheiner Peter , Schulz Christian , Hunt Richard H.
Published: March 2024

Background: Helicobacter pylori (H. pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases. Summary: Over a period of 40 years following the discovery, more than 50,000 articles can be retrieved in PubMed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H. pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H. pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel Prize in Medicine awarded to Barry Marshall and Robin Warren. H. pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. Key Messages: H. pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today.
Tooth Brushing Learning Methods: Differential or Conventional? – A Randomized Controlled Clinical Trial
Authors: Leghrouz Loay , Khole Manasi R. , Splieth Christian H. , Schmoeckel Julian
Published: March 2024

Introduction: Proper tooth brushing is a complicated process for children. Therefore, the aim of this study was to investigate the effect of differential learning to improve tooth brushing in children. Methods: In this prospective, controlled, single-blinded, randomized clinical trial, 58 children between 3 and 8 years of age (mean: 5.7 ± 1.5 years; 29 female) were randomly assigned to test or control group through the child’s self-drawing of an unlabeled envelope from a box. All children received oral hygiene instructions and information in these sealed envelopes and were asked to follow the corresponding instructions at home for 28 days. Children in the test group received instructions with exercises using the differential learning method, whereas the children in the control group received the usual tooth brushing instructions. Results: At baseline and planned follow-ups after 4 and 12 weeks, plaque and gingival indices (QHI, PBI) were recorded in both groups by 2 calibrated and blinded investigators. At baseline, there were no significant differences between the test and control groups regarding plaque and gingival indices (QHI: 4.1 ± 0.5 vs. 4.1 ± 0.4; p = 0.7; PBI: 0.6 ± 0.3 vs. 0.6 ± 0.3; p = 0.7). At the 1st and 2nd follow-up, both groups showed improved oral health indices, but there was an overall better improvement in the test group. While the difference in gingival indices was statistically significant in the 1st recall (PBI/test: 0.1 ± 0.2 vs. control: 0.3 ± 0.2; p < 0.001), the difference in plaque indices was not (QHI/test: 2.1 ± 0.9; control: 2.6 ± 0.9; p = 0.07). At the 2nd recall (mean week = 19.5 weeks), the test group showed statistically significant and clinically relevant better oral health indices than the control group (2nd recall, QHI/test: 2.1 ± 0.9 vs. control: 3.2 ± 1; p < 0.001; PBI/test: 0.1 ± 0.2 vs. control: 0.5 ± 0.2; p < 0.001). Conclusion: In conclusion, differential learning leads to oral hygiene improvement in children with high caries risk and initially poor oral hygiene, which was superior to the conventional learning method through repetition in the medium term.
Global prevalence of pre-existing antibodies against human adenoviruses, surveyed from 1962-2021
Authors: Luo Hui , Zhou Qian , Feng Jinqi , Wu Yi , Chen Huangliang , Mao Meihan , Qi Rui
Published: March 2024

Background: Human Adenoviruses (HAdVs) are extensively used as vectors for vaccines development and cancer therapy. People who already have antibodies against HAdVs, on the other hand, would have an impact on the preventative or therapeutic effect. This review focuses primarily on the prevalence of pre-existing antibodies against HAdVs in distinct geographical populations.
Summary: After screening, 64 studies from 31 countries between 1962 and 2021 were selected, totaling 39,427 samples. The total prevalence of pre-existing antibodies to HAdVs varied by country or location, ranging from 2.00% to 95.70%. Southeast Asia had the highest prevalence (54.57%) while Europe had the lowest (18.17%). The prevalence in practically all developing nations was higher than in developed nations. Adults have a greater frequency than children and newborns in most nations. The primary HAdV antibody types varied by country. Adults in China, the United States, the United Kingdom, and Belgium had the lowest prevalence of pre-existing antibodies against HAdV55, HAdV37, HAdV8, and HAdV36, respectively. Children in the United States, China, the United Kingdom, and Japan had the lowest rates of HAdV48, HAdV11, HAdV8, and HAdV40. The frequency of antibodies differed significantly between military and civilian groups.
Key Messages: Pre-existing antibodies against various types of HAdVs differed greatly throughout worldwide populations. Future development of HAdV-vector vaccines and medicines should focus on pre-existing antibodies in target groups rather than a "one-size-fits-all" strategy. It might be advantageous in selecting HAdV vectors for studying the prevalence of pre-existing antibodies against HAdVs in different locations and people throughout the world.
Real-World Evidence of Tumor and Patient Characteristics and Survival with Avelumab Maintenance after Chemotherapy for Advanced and Metastatic Urothelial Carcinoma
Authors: Banek Séverine , Wenzel Mike , Lauer Benedikt , Le Quynh Chi , Hoeh Benedikt , Koll Florestan , Cano Garcia Cristina , Humke Clara , Köllermann Jens , Chun Felix K.H. , Kosiba Marina , Kluth Luis A.
Published: March 2024

Introduction: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AEs), and survival of avelumab maintenance (AVM)-treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). Methods: We relied on our institutional database to identify mUC patients who received AVM between January, 2021 and December, 2023. The main outcomes consisted of overall survival (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to programmed death ligand 1 (PD-L1) status. Results: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67–76) years, of which 67% were males. Of these, 63%, 21%, and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients; however, they were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4–20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (confidence interval [CI]: 3.2–18.2). Median OS was 13.4 (CI: 6.9 – not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1-positive patients, median PFS and OS were 6.4 (CI: 2.7 – NR) months and 13.4 (CI: 7.7 months – NR), respectively. Conclusion: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in real-world setting.
Evaluation of the Vestibulo-Ocular Reflex Using the Video Head Impulse Test in Patients with Unilateral Chronic Otitis Media
Authors: Nam Gi-Sung , Han Seunghyun , Cho Sung Il
Published: March 2024

Introduction: The aim of the study was to evaluate the vestibulo-ocular reflex (VOR) using the video head impulse test (vHIT) as a vestibular function assessment method in patients with unilateral chronic otitis media (COM). Methods: Twenty-eight patients with unilateral COM scheduled for middle ear surgery, including 12 males and 16 females with a mean age of 54.5 years, successfully underwent preoperative vHIT. vHIT variables, including VOR gain, VOR gain asymmetry, and the incidence of corrective saccades, were compared between the ipsilesional and contralesional ears. Results: Ten (35.7%) patients reported varying degrees of disequilibrium or lightheadedness. The VOR gain in the ipsilesional and contralesional ears was 1.01 ± 0.10 and 1.04 ± 0.11, 0.97 ± 0.12 and 0.94 ± 0.13, and 0.97 ± 0.13 and 1.04 ± 0.15 in the horizontal canal (HC), anterior canal, and posterior canal (PC), respectively. The average VOR gains in the ipsilesional ears were within the predefined range of normal values; however, the gains in HC and PC significantly decreased compared with those in contralesional ears (p = 0.038 in HC and p = 0.015 in PC). The prevalence of corrective saccades, including overt and/or covert saccades, did not differ significantly between the two ears. Conclusion: This study assessed the pathophysiology of the inner ear affected by chronic middle ear infection by quantitatively comparing the VOR using vHIT. It demonstrated that vHIT can be a practical assessment of vestibular function in patients with COM.
Intravenous Thrombolysis Before Thrombectomy Improves Functional Outcome After Stroke Independent of Reperfusion Grade
Authors: Sedghi Annahita , Kaiser Daniel P. O. , Cuberi Ani , Schreckenbauer Sonja , Wojciechowski Claudia , Friehs Ingeborg , Reichmann Heinz , Barlinn Jessica , Barlinn Kristian , Puetz Volker , Siepmann Timo
Published: March 2024

Background

We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large‐vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration.

Methods and Results

We included consecutive patients with anterior circulation large‐vessel occlusion from our prospective registry of thrombectomy‐eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset‐to‐recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy‐eligible patients (513 women; median age, 77 years [interquartile range, 67–84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0–2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32–0.75];
P
=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31–0.74];
P
=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35‐point decrease in 90‐day modified Rankin Scale score (ß=–0.35 [95 CI%, −0.68 to 0.01];
P
=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=–1.79 [95% CI, −3.43 to –0.15];
P
=0.03) and distal thrombus migration (ß=–0.41 [95% CI, −0.69 to –0.13];
P
=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=–0.46 [95% CI, −0.74 to –0.17];
P
=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=–0.47 [95% CI, −0.96 to 0.01];
P
=0.05).

Conclusions

In thrombectomy‐eligible patients with anterior circulation large‐vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.
An Overview of the Free Energy Principle and Related Research
Authors: Zhang Zhengquan , Xu Feng
Published: March 2024

The free energy principle and its corollary, the active inference framework, serve as theoretical foundations in the domain of neuroscience, explaining the genesis of intelligent behavior. This principle states that the processes of perception, learning, and decision making—within an agent—are all driven by the objective of “minimizing free energy,” evincing the following behaviors: learning and employing a generative model of the environment to interpret observations, thereby achieving perception, and selecting actions to maintain a stable preferred state and minimize the uncertainty about the environment, thereby achieving decision making. This fundamental principle can be used to explain how the brain processes perceptual information, learns about the environment, and selects actions. Two pivotal tenets are that the agent employs a generative model for perception and planning and that interaction with the world (and other agents) enhances the performance of the generative model and augments perception. With the evolution of control theory and deep learning tools, agents based on the FEP have been instantiated in various ways across different domains, guiding the design of a multitude of generative models and decision-making algorithms. This letter first introduces the basic concepts of the FEP, followed by its historical development and connections with other theories of intelligence, and then delves into the specific application of the FEP to perception and decision making, encompassing both low-dimensional simple situations and high-dimensional complex situations. It compares the FEP with model-based reinforcement learning to show that the FEP provides a better objective function. We illustrate this using numerical studies of Dreamer3 by adding expected information gain into the standard objective function. In a complementary fashion, existing reinforcement learning, and deep learning algorithms can also help implement the FEP-based agents. Finally, we discuss the various capabilities that agents need to possess in complex environments and state that the FEP can aid agents in acquiring these capabilities.
Unraveling the Origins, Evolution, and Contemporary Applications of qili qiji 契理契机
Authors: Xuan Fang
Published: March 2024

This article presents a historical exploration of the concept of qili qiji 契理契机 (according with the [core] principles [of Buddhism] and the circumstances or capacities [of sentient beings]) in the context of Buddhist thought from the Eastern Jin era (317–420 CE) to contemporary times, examining its origins, development, and dissemination, and the progressive expansion of its definition. The study explores the significance of qili qiji in the writings and discussions of influential figures and organizations in the domain of “Buddhism for the Human Realm” (renjian fojiao 人间佛教), such as Taixu 太虚, Yin Shun 印顺, Sheng-yen 圣严, Hsing Yun 星云, Zhao Puchu 赵朴初, and the Buddhist Association of China. Lastly, the study investigates the adoption of this term beyond the Buddhist community, specifically its incorporation into the official discourse of governmental religious affairs departments and its usage within other religions such as Daoism.
The Invention and Vicissitudes of the “Three Great Marvelous Traditions” (san da youliang chuantong 三大优良传统) in Contemporary Chinese Buddhism
Authors: Krause Carsten
Published: March 2024

Religious life after the Cultural Revolution was more than just a revival of traditions. Much depended on the theoretical framing provided by Buddhist elites, the most prominent of whom became Zhao Puchu (1907–2000). As president of the Buddhist Association of China, he (re-)introduced the so-called renjian fojiao 人间佛教 (Buddhism for a Human Realm) as “guiding thought” and connected it with the “Three Great Marvelous Traditions,” which he identified as “equal weighting of agriculture and chan,” “strong concern for scientific research,” “friendly international exchange.” This article examines the trajectories of this construction and attempts to explore how it has been interpreted and used in official rhetoric and wider discourse over the past four decades, including possible reinterpretations after Zhao’s passing away. In a broader sense, this conceptual history may also raise the question of what the changing connotations of “tradition(s)”—old or new, dead or alive—have become in contemporary China.
Should We Confucians Be Liberals? Reflections on Roy Tseng’s Confucian Liberalism
Authors: Angle Stephen C.
Published: March 2024

Roy Tseng’s Confucian Liberalism: Mou Zongsan and Hegelian Liberalism is a tremendously significant work because of its improved understandings of some of Mou’s most central ideas and the opportunities it creates toward a full and appealing articulation of democratic, progressive Confucianism. After emphasizing some of Tseng’s key insights, I probe an ambiguity that might undercut Tseng’s contribution to progressive Confucianism. Is Mou’s view, or Tseng’s, a Confucian-flavored liberalism? While there are multiple, legitimate ways to draw on Tseng’s achievements, the one most apt for Confucians today is not best characterized as “Confucian liberalism.”