bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ivabradine for congenital ectopic tachycardia in newborn
Authors: Pamukcu Ozge , Citli Rümeysa 
Published: December 2023

AbstractIntroduction:Congenital junctional ectopic tachycardia is a rare arrhythmia that occurs in patients without previous cardiac surgery. In this report, we wanted to present a 6-hour-old newborn with congenital junctional ectopic tachycardia resistant to conventional anti-arrhythmic medications, who was successfully treated with ivabradine and amiadarone combination.Case:A six-hour-old newborn girl was hospitalised in neonatal ICU because transient tachypnoea of the newborn. She was tachycardic, and supraventricular tachycardia was noticed. There was no answer to the adenosine esmolol treatment; even synchronised direct cardioversion intravenous amiodarone was started. Junctional ectopic tachycardia was diagnosed. We have added propranolol to the treatment and followed patient for 2 days. On the fourth day, junctional ectopic tachycardia rhythm still persisted; therefore, ivabradine treatment was added to the treatment. On the following day, the heart rhythm was slowed to 110/min, and propranolol was stopped; intravenous amiodarone treatment was changed to the oral form. The rhythm turned into sinus; two days after starting ivabradine and oral amiodarone.Conclusion:Tachyarrhythmia originating in the atrioventricular node and atrioventricular junction including the bundle of His complex are junctional ectopic tachycardia. Congenital junctional ectopic tachycardia is rare, and it is mostly resistant to the conventional treatment.Ivabradine is a new anti-arrhythmic agent, used extensively to decrease sinus rate in the treatment of cardiac failure. Ivabradine may be an option for the resistant congenital ectopic tachycardia
People, Paper and Power: The Birth of the Passport in International Law
Authors: SOOMRO Anam 
Published: December 2023

AbstractThis paper presents a genealogy of the passport in international law. For the most part, the origins of our contemporary mobility order are narrated from the vantage point of the grand principles of sovereignty, hospitality, and liberty. The nuts and bolts through which people access mobility – passports and visas – are generally understood to be the natural, inevitable, and fair by-products of these principles. This paper contributes to existing debates on the coloniality of international migration law by examining the universalization of the passport under the League of Nations. I argue that the universalization of the passport meant abandoning the old idea that the rights of free movement belonged to everyone and, instead, instituted a system that ranks human mobility based on national origins. Theoretically, it is proposed that attention to these “lowly” practices of mobility governance allows us to track the afterlives of race in the international order.
Comparison of Continuously Recorded Seismic Wavefields in Tectonic and Volcanic Environments Based on the Network Covariance Matrix
Authors: Barajas Andrés , Journeau Cyril , Obara Kazushige , Shapiro Nikolai M. 
Published: December 2023

AbstractExtended and sufficiently dense seismic networks capture spatiotemporal properties of the continuously recorded wavefields and can be used to compute the level of their coherence at different frequencies via the analysis of the network covariance matrix, which has been successfully used to study volcanic seismicity. Here, we present an application of the covariance matrix method in a subduction zone environment. We show that most coherent signals identified through the covariance matrix analysis are related to regional earthquakes with the wavefield properties affected by the scattering, which depends on the source location. Tectonic tremors, on the other hand, are not characterized by a high level of coherence. We compare real data results with a set of synthetic tests aimed at mimicking the properties of seismic sources and the main features of wave propagation. We conclude that highly coherent volcanic tremor wavefields could be produced in two ways: by a spatially localized group of monochromatic seismic sources or by a single source located in a highly heterogeneous medium. In both cases, the stability of the source position is a necessary condition to reproduce the observations in volcanoes. On the other hand, the low coherence of tectonic tremor wavefields can be explained by a spatially extended distribution of sources, in agreement with large portions of the subduction interface being nearly simultaneously involved in the episodes of slow deformation.
Three‐Dimensional Global Hybrid Simulations of Mercury's Disappearing Dayside Magnetosphere
Authors: Guo Jin , Lu San , Lu Quanming , Slavin James A. , Sun Weijie , Ren Junyi , Wang Xueyi , Lin Yu , Hajra Rajkumar , Wang Rongsheng 
Published: December 2023

AbstractAn important discovery of MESSENGER is the occurrence of dayside disappearing magnetosphere (DDM) events that occur when the solar wind dynamic pressure is extremely high and the interplanetary magnetic field (IMF) is both intense and southward. In this study, we investigate the DDM events at Mercury under extreme solar wind conditions using a three‐dimensional (3‐D) global hybrid simulation model. Our results show that when the solar wind dynamic pressure is 107 nPa and the magnitude of the purely southward IMF is 50 nT, most of the dayside magnetosphere disappears within 10 s after the interaction between the solar wind and the planetary magnetic field starts. During the DDM event, the ion flux is significantly enhanced at most of the planetary dayside surface and reaches its maximum value of about 1010 cm−2 s−1 at the low‐latitude surface, which is much larger than that under normal solar wind conditions. During the DDM events, the dayside bow shock mostly disappears for about 9 s and then reappears. Moreover, the time evolution of magnetopause standoff distance under different solar wind conditions is also studied. When the solar wind dynamic pressure exceeds 25 nPa and the IMF is purely southward, a part of the dayside magnetosphere disappears. Under the same IMF, the higher the solar wind dynamic pressure, the faster the magnetopause standoff distance reaches the planetary surface. When the solar wind conditions are normal (with a dynamic pressure of 8 nPa) or the IMF is purely northward, the dayside magnetosphere does not disappear. The results provide a clear physical image of DDM events from a 3‐D perspective.
Enhancing Biopsychosocial Care for Disorders of Gut–Brain Interaction: 10-Year Growth of an Integrated Pediatric Gastroenterology Psychology Program
Authors: Turner Elizabeth , Rodriguez Kelly O’Neil , Holbein Christina , Fussner Lauren , Wilkes Caroline , Szabo Margo , Baber Kari , Piccoli David 
Published: December 2023

Objective: Effective treatment for disorders of gut–brain interaction (DGBIs) is furthered by integrated interdisciplinary care. Initial efforts at psychology integration in pediatric gastroenterology (GI) clinics may encounter physician referral variability and low patient utilization as barriers to patient access and program growth. Method: In this brief report, clinical service approaches and educational efforts to address these barriers and enhance biopsychosocial care for pediatric patients with DGBIs are described, including program structure and growth considerations, levels of outpatient care (e.g., group interventions, specialized interdisciplinary clinics) for patients with DGBIs, and innovative physician and patient/family education on biopsychosocial treatment for DGBIs. Results: Over a decade, our established GI Psychology program has grown both in terms of service providers and visit volume to achieve increased access to psychological services and biopsychosocial care for patients with DGBIs and other GI conditions. Conclusions: Recommendations for GI Psychology program growth with financial sustainability are discussed. Implications for Impact Statement Gastroenterology (GI) Psychology programs can utilize clinical service expansion and educational efforts to enhance biopsychosocial care for pediatric patients with disorders of gut–brain interaction (DGBIs). A strong partnership between GI Psychology and GI leadership is essential to successful program growth and sustainability. Specific strategies that may reduce barriers to biopsychosocial care for patients with GI conditions include distinct levels of outpatient GI Psychology care, Health and Behavior Assessment and Intervention codes for billing, provision of telehealth services, scheduling access via multiple avenues, and departmental efforts to improve health care equity.
Innovations in the Psychological Care of Pediatric Disorders of Gut–Brain Interaction
Authors: Essner Bonnie S. , Boyle Shana L. 
Published: December 2023

Objective: Disorders of gut–brain interaction (DGBI, formerly known as functional gastrointestinal disorders [FGIDs]) are highly prevalent in the pediatric population. DGBIs in youth are often associated with academic, physical, and psychosocial impairments. Assessment and treatment of DGBIs are best conceptualized using a biopsychosocial approach. The inclusion of psychological therapies as part of integrated care for pediatric DGBIs is well supported. The purpose of this special issue is to present innovations in the psychological treatment of pediatric DGBIs. Method: Articles inclusive of topics on novel assessment and treatment approaches, quality improvement work, program development, case examples, and commentaries addressing pediatric DGBIs were considered for this special issue. Results: This special issue includes eight articles that highlight innovations in the psychological treatment of pediatric DGBIs. Articles cover a wide range of conditions, treatment delivery models, and intervention modalities. Future directions for areas of study, as well as discussion of clinical challenges, disparities in care, program development initiatives, and dissemination opportunities within pediatric psychogastroenterology are also offered. Conclusions: The articles included in this issue are expected to guide future evidence-based assessment and treatment of pediatric DGBIs across various settings. Implications for Impact Statement This special issue seeks to expand the current research base on psychological assessment and intervention for pediatric disorders of gut-brain interaction. Guidance regarding ethical, logistical, financial, and other potential barriers to expansion and delivery of psychological DGBI-related care are embedded throughout the special issue.
Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery
Authors: Blackwell James E. M. , Gharahdaghi Nima , Deane Colleen S. , Brook Matthew S. , Williams John P. , Lund Jonathan N. , Atherton Philip J. , Smith Ken , Wilkinson Daniel J. , Phillips Bethan E. 
Published: December 2023

Abstract
Background
Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer.

Methods
Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling.

Results
OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day−1, p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160Thr642 (p = 0.046) post-HIIT.

Conclusions
A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
Authors: Bahar Md Entaz , Kim Hyun Joon , Kim Deok Ryong 
Published: December 2023

AbstractMetastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS–RAF–MAPK kinase (MEK)–extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for the sequential activation of downstream targets, such as MEK and the transcription factor ERK, which control numerous cellular and physiological processes, including organism development, cell cycle control, cell proliferation and differentiation, cell survival, and death. Defects in this signaling cascade are associated with diseases such as cancer. RAF inhibitors (RAFi) combined with MEK blockers represent an FDA-approved therapeutic strategy for numerousRAF-mutant cancers, including melanoma, non-small cell lung carcinoma, and thyroid cancer. However, the development of therapy resistance by cancer cells remains an important barrier. Autophagy, an intracellular lysosome-dependent catabolic recycling process, plays a critical role in the development of RAFi resistance in cancer. Thus, targeting RAF and autophagy could be novel treatment strategies forRAF-mutant cancers. In this review, we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and RAFi-resistance. Furthermore, we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic profiles. Additionally, this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.
Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis
Authors: Teixeira Adilson Fonseca , Wang Yanhong , Iaria Josephine , ten Dijke Peter , Zhu Hong-Jian 
Published: December 2023

AbstractMetastasis is the leading cause of cancer-related deaths. Transforming growth factor beta (TGF-β) signaling drives metastasis and is strongly enhanced during cancer progression. Yet, the use of on-target TGF-β signaling inhibitors in the treatment of cancer patients remains unsuccessful, highlighting a gap in the understanding of TGF-β biology that limits the establishment of efficient anti-metastatic therapies. Here, we show that TGF-β signaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle (sEV) secretion. Demonstrating sEV’s unique role, TGF-β signaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β. Further, genetic disruption of sEV secretion in highly-metastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-β signaling to nearly-normal levels. Otherwise, TGF-β signaling activity in non-invasive breast cancer cells is inherently low, but can be amplified by sEVs, enabling invasion and metastasis of poorly-metastatic breast cancer cells. Underscoring the translational potential of inhibiting sEV trafficking in advanced breast cancers, treatment with dimethyl amiloride (DMA) decreases sEV secretion, TGF-β signaling activity, and breast cancer progression in vivo. Targeting both the sEV trafficking and TGF-β signaling by combining DMA and SB431542 at suboptimal doses potentiated this effect, normalizing the TGF-β signaling in primary tumors to potently reduce circulating tumor cells, metastasis, and tumor self-seeding. Collectively, this study establishes sEVs as critical elements in TGF-β biology, demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-β signaling levels in breast cancer cells.
Targeting S100A9 protein affects mTOR-ER stress signaling and increases venetoclax sensitivity in Acute Myeloid Leukemia
Authors: Fan Rong , Satilmis Hatice , Vandewalle Niels , Verheye Emma , De Bruyne Elke , Menu Eline , De Beule Nathan , De Becker Ann , Ates Gamze , Massie Ann , Kerre Tessa , Törngren Marie , Eriksson Helena , Vanderkerken Karin , Breckpot Karine , Maes Ken , De Veirman Kim 
Published: December 2023

AbstractAcute Myeloid Leukemia (AML) is a heterogeneous disease with limited treatment options and a high demand for novel targeted therapies. Since myeloid-related protein S100A9 is abundantly expressed in AML, we aimed to unravel the therapeutic impact and underlying mechanisms of targeting both intracellular and extracellular S100A9 protein in AML cell lines and primary patient samples. S100A9 silencing in AML cell lines resulted in increased apoptosis and reduced AML cell viability and proliferation. These therapeutic effects were associated with a decrease in mTOR and endoplasmic reticulum stress signaling. Comparable results on AML cell proliferation and mTOR signaling could be observed using the clinically available S100A9 inhibitor tasquinimod. Interestingly, while siRNA-mediated targeting of S100A9 affected both extracellular acidification and mitochondrial metabolism, tasquinimod only affected the mitochondrial function of AML cells. Finally, we found that S100A9-targeting approaches could significantly increase venetoclax sensitivity in AML cells, which was associated with a downregulation of BCL-2 and c-MYC in the combination group compared to single agent therapy. This study identifies S100A9 as a novel molecular target to treat AML and supports the therapeutic evaluation of tasquinimod in venetoclax-based regimens for AML patients.
Combined absence of TRP53 target genes ZMAT3, PUMA and p21 cause a high incidence of cancer in mice
Authors: Brennan Margs S. , Brinkmann Kerstin , Romero Sola Gerard , Healey Geraldine , Gibson Leonie , Gangoda Lahiru , Potts Margaret A. , Lieschke Elizabeth , Wilcox Stephen , Strasser Andreas , Herold Marco J. , Janic Ana 
Published: December 2023

AbstractTranscriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of ZMAT3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the PUMA and p21, the critical effectors of TRP53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system. Therefore, we generated Zmat3 knockout and compound gene knockout mice, lacking Zmat3 and p21, Zmat3 and Puma or all three genes. Puma−/−p21−/−Zmat3−/− triple knockout mice developed tumours at a significantly higher frequency compared to wild-type, Puma−/−Zmat3−/− or p21−/−Zmat3−/−deficient mice. Interestingly, we observed that the triple knockout and Puma−/−Zmat3−/− double deficient animals succumbed to lymphoma, while p21−/−Zmat3−/− animals developed mainly solid cancers. This analysis suggests that in addition to ZMAT3 loss, additional TRP53-regulated processes must be disabled simultaneously for TRP53-mediated tumour suppression to fail. Our findings reveal that the absence of different TRP53 regulated tumour suppressive processes changes the tumour spectrum, indicating that different TRP53 tumour suppressive pathways are more critical in different tissues.
Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice
Authors: Bu Mengfei , Follett Jordan , Deng Isaac , Tatarnikov Igor , Wall Shannon , Guenther Dylan , Maczis Melissa , Wimsatt Genevieve , Milnerwood Austen , Moehle Mark S. , Khoshbouei Habibeh , Farrer Matthew J. 
Published: December 2023

AbstractDysregulation of dopamine neurotransmission profoundly affects motor, motivation and learning behaviors, and can be observed during the prodromal phase of Parkinson’s disease (PD). However, the mechanism underlying these pathophysiological changes remains to be elucidated. Mutations in vacuolar protein sorting 35 (VPS35) and leucine-rich repeat kinase 2 (LRRK2) both lead to autosomal dominant PD, and VPS35 and LRRK2 may physically interact to govern the trafficking of synaptic cargos within the endo-lysosomal network in a kinase-dependent manner. To better understand the functional role of VPS35 and LRRK2 on dopamine physiology, we examined Vps35 haploinsufficient (Haplo) and Vps35 p.D620N knock-in (VKI) mice and how their behavior, dopamine kinetics and biochemistry are influenced by LRRK2 kinase inhibitors. We found Vps35 p.D620N significantly elevates LRRK2-mediated phosphorylation of Rab10, Rab12 and Rab29. In contrast, Vps35 haploinsufficiency reduces phosphorylation of Rab12. While striatal dopamine transporter (DAT) expression and function is similarly impaired in both VKI and Haplo mice, that physiology is normalized in VKI by treatment with the LRRK2 kinase inhibitor, MLi-2. As a corollary, VKI animals show a significant increase in amphetamine induced hyperlocomotion, compared to Haplo mice, that is also abolished by MLi-2. Taken together, these data show Vps35 p.D620N confers a gain-of-function with respect to LRRK2 kinase activity, and that VPS35 and LRRK2 functionally interact to regulate DAT function and striatal dopamine transmission.