bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancient scars and rotating ribbons: Appalachian–Caledonian orogenic influence on the genesis of the Flemish Cap and the Porcupine Bank during Mesozoic North Atlantic rifting
Authors: Welford J. Kim , Brune Sascha , Neuharth Derek , King Michael T.
Published: December 2024

The Newfoundland–Irish Atlantic conjugate margin pair hosts more continental ribbons, failed rifts, and unusually sized and oriented sedimentary basins than anywhere else in the modern Atlantic Ocean. These margins also happen to have formed through rifting and break-up of the lithosphere that was involved in Appalachian–Caledonide orogenesis in the Paleozoic, with the Mesozoic propagating rift having impinged on the orogenic structures at an oblique angle. Here we combine results from 3D numerical modelling of oppositely propagating rifts, which are superimposed on deformable plate reconstructions of the southern North Atlantic. We propose that the rift oddities of the Newfoundland–Irish Atlantic conjugate margin pair resulted from the northward propagating rift responsible for the break-up of Pangaea reactivating Appalachian–Caledonide inherited structures under extension, effectively turning them into a southward propagating rift. The interaction of the two rifts caused the formation and clockwise rotation of a large continental microplate, which was ultimately split by a transform fault into two smaller clockwise-rotated mirrored continental ribbons, namely the Flemish Cap and the Porcupine Bank. The rotations of these continental microplates, which created the Orphan and Porcupine sedimentary basins and failed rifts therein, show the influence of inherited orogenic structures on subsequent rifting.
A Survey on WiFi-based Human Identification: Scenarios, Challenges, and Current Solutions
Authors: Wei Zhongcheng , Chen Wei , Ning Shuli , Lin Weidong , Li Nan , Lian Bin , Sun Xiang , Zhao Jijun
Published: December 2024

With the evolution of wireless sensing technology, WiFi-based human identification has demonstrated tremendous potential in human-computer interaction and home security. However, most existing research operates in controlled environments, overlooking the complexities of real-world scenarios, such as signal fading, signal interference and uncertainty, and the diversity of application requirements. This article presents a comprehensive analysis of a series of representative research articles on WiFi-based human identification and summarizes five major challenges in achieving high-precision identification in complex application scenarios. Non-line-of-sight (NLOS) user sensing, coexistence user sensing, dynamic group user sensing, cross-domain user sensing, and multi-task sensing. Additionally, this article proposes a series of current solutions, including improving the signal-to-noise ratio (SNR) of NLOS sensing from the perspective of communication signals and sensing models, addressing coexistence sensing issues, designing adaptable tasks for dynamic user groups, leveraging techniques like adversarial learning and transfer learning for cross-domain problems, and employing modular deep learning architectures. By providing a comprehensive overview of WiFi-based human identification, this survey not only offers insights into current research but also charts a roadmap for future investigations. It is anticipated that this survey will stimulate innovative research endeavors and foster the expansion of wireless sensing technology across diverse application domains.
Thoracic and Cardiovascular Imaging Manifestations of Lupus
Authors: Gomez Christian J. , Naeem Muhammad , Bechel Meagan A. , Battle Wilson , Amin Sagar , Hamid Aws , Berkowitz Eugene , Veeraraghavan Srihari , Filev Peter
Published: December 2024

Systemic lupus erythematosus has nonspecific and complex features that make rendering a diagnosis challenging and require radiologists to have familiarity with the imaging manifestations and a high level of suspicion based on the risk factors and medical history of the patient.
Breast US: Guide for Beginners
Authors: Lauar Marcela Caetano Vilela , Merigue Gabriela , Ferreira Dias Lavínia , Françolin Federicci Érica Elisangela , Costa Aline Lemgruber Prado , Yonekura Iviny , Lee Michelle V. , Racy Ana Claudia Silveira
Published: December 2024

Use of appropriate operator technique, knowledge of the most common breast pathologic conditions detected at US, and strategies to avoid potential imaging pitfalls enhance the diagnostic accuracy of US in evaluation of suspicious breast lesions.
A Computationally Efficient, Zero-Dimensional Stack Model for Simulating Redox Flow Battery Performance
Authors: Neyhouse Bertrand J. , Price Nicholas A. , Brushett Fikile R.
Published: December 2024

Scaling redox flow battery (RFB) innovations from single cells to stacks is an important step for concept validation, but this procedure is challenging, as new processes emerge that impact performance and durability. Models that facilitate performance predictions from material properties and single-cell measurements can inform stack engineering and streamline iterative design-build-test cycles. Here, we deploy a semi-analytical zero-dimensional modeling framework to rapidly simulate stack cycling performance, focusing on failure modes relevant to RFB scale-up (i.e., shunt currents, pressure losses, crossover). We first investigate the computational efficiency of the model, yielding simulation times under 0.04 s per cycle—significantly faster than prior stack models described in the literature. Next, we explore the role of shunt currents in RFB cycling, discussing the theoretical underpinnings of these parasitic losses and providing generalized stack performance predictions under variable operating conditions. We then apply the model to evaluate engineering considerations for emerging aqueous-organic RFBs—specifically, we show that higher current densities reduce the impact of shunt currents; larger port cross-sections enhance round-trip efficiency, provided requisite port lengths are achieved; and lower membrane resistances facilitate higher current densities, mitigating the impact of shunt currents while amplifying capacity fade via crossover.
Design Aspects, Development, and Sensitivity Analysis of GaN HEMT-Based Biosensing Platform for Label-Free Detection of Interleukin-6
Authors: Thakur Rajiv , KC Sarathlal , Kachhawa Pharyanshu , Kishore Kaushal , Taliyan Rajeev , Chaturvedi Nidhi
Published: December 2024

Severe TBI survivors face long-term brain damage requiring accurate diagnosis and early treatment as the therapeutic time window typically ranges from minutes to hours before the secondary injury. In this work, we report design aspects and development of an ultrasensitive GaN HEMT-based biosensing platform for IL-6 detection along with novel design correlation equations for sensitivity analysis. Design analysis reveals that the lower value of

L

sd

is desirable for enhanced sensitivity as the biosensor with

L

sd

of 10 μm offers a peak sensitivity of 129.20 μA pg−1 ml−1 as compared to 25 and 50 μm with a sensitivity of 70.76 and 35.60 μA pg−1 ml−1 respectively. Furthermore, the peak sensitivity reaches as high as 158.01 μA pg−1 ml−1 when the

W

g

was increased from 100 to 250 μm for biosensors with

L

sd

of 10 μm using conventional gate design. An increase in sensitivity from 70.76 to 88.40 μA pg−1 ml−1 was observed when a meander gate biosensor was used. An analysis of the EDC-NHS coupling process reveals an enhancement in sensitivity from 78.60 to 129.20 μA pg−1 ml−1 for the EDC-NHS coupled biosensor. The peak response of the biosensor for IL-6 detection was observed at 5 min after the drop cast of antigens over the sensing areas.
Controlled Domain in 3C-SiC Epitaxial Growth on Off-oriented 4H-SiC Substrates for Improvement of Photocathode Performance
Authors: Rho Kongshik , Fujita Jun , Kato Masashi
Published: December 2024

Cubic SiC (3C-SiC) is a promising semiconductor photocathode material for photoelectrochemical (PEC) water splitting. However, defect control in 3C-SiC is critical for achieving high efficiency. In this study, we fabricated single-domain 3C-SiC on off-orientation 4H-SiC substrates by controlling the domain structure of 3C-SiC epilayers. The morphology of the controlled domains was examined using white-light confocal microscopy. Electron backscatter diffraction confirmed the formation of a single-domain 3C-SiC on the off-orientation substrate (off-HPSI). To investigate the effect of the single domain on the PEC properties, we employed microwave photo-conductivity decay (μ-PCD). It was revealed that the excess carrier decay curves in the off-HPSI had an average lifetime of 1/e, approximately 134 ns, which was longer than that of the on-HPSI. The PEC properties of 3C-SiC grown on an off-orientation substrate were investigated using a three-electrode system. Single-domain 3C-SiC on an off-orientation substrate exhibited higher performance than 3C-SiC on an on-orientation substrate. The photon-to-current conversion efficiency was calculated based on the size of the photocurrent and applied bias, and 3C-SiC with controlled domains demonstrated improved photocathode performance. Considering the influence of a single domain on the PEC properties, single-domain 3C-SiC has emerged as a promising semiconductor photocathode for PEC water splitting.
Surfactant Protein-A and its immunomodulatory roles in infant respiratory syncytial virus infection: a potential for therapeutic intervention?
Authors: Mapindra Muhammad Pradhika , Castillo-Hernandez Tania , Clark Howard , Madsen Jens
Published: December 2024

The vast majority of early-life hospital admissions globally highlight respiratory syncytial virus (RSV), the leading cause of neonatal lower respiratory tract infections, as the major culprit behind the poor neonatal outcomes following respiratory infections. Unlike those of older children and adults, the immune system of neonates looks rather unique, therefore mostly counting on the innate immune system and antibodies of maternal origins. The collaborations between cells and immune compartments during infancy inclines bias toward a T-helper 2 (Th2) immune profile and thereby away from a T-helper 1 (Th1) immune response. What makes it more problematic is that RSV infection also tends to elicit a stronger Th2-biased immune response and drive an aberrant allergy-like inflammation. It is thus evident how RSV infections potentially pave the way for wheezing recurrences and childhood asthma later in life. Surfactant, the essential lung substance for normal breathing processes in mammals, has immunomodulatory properties including lung collectins such as Surfactant Protein-A (SP-A), which is the most abundant protein component of surfactant, and also Surfactant Protein-D (SP-D). Deficiency of SP-A and SP-D has been found to be associated with impaired pathogen clearance and exacerbated immune responses during infections. We therefore conducted a review of the literature to describe pathomechanisms of RSV infections during blunted neonatal immunity potentially facilitating allergy-like inflammatory events within the developing lungs and highlight the potential protective role of the humoral collectin SP-A to mitigate these in the “early in life” pulmonary immune system.
Insulin activates parasympathetic hepatic-related neurons of the paraventricular nucleus of the hypothalamus through mTOR signaling
Authors: Martins dos Santos Karoline , Saunders Sandy E. , Antunes Vagner R. , Boychuk Carie R.
Published: December 2024

Increased peripheral insulin concentrations are known to decrease hepatic glucose production through both direct actions on hepatocytes and central autonomic networks. Despite this understanding, how (and in which brain regions) insulin exerts its action is still obscure. Here, we demonstrate that insulin activates parasympathetic hepatic-related PVN neurons (PVNhepatic) and that this effect relies on mammalian target of rapamycin (mTOR) signaling, suggesting that insulin modulates hepatic function through autonomic pathways involving insulin receptor intracellular signaling cascades.
Recovery from spreading depolarization is slowed by aging and accelerated by antioxidant treatment in locusts
Authors: Robertson R. Meldrum , Wang Yuyang
Published: December 2024

Anoxia and similar energetic crises trigger a shutdown of central neural processing in a process of spreading depolarization (SD) that is generally pathological in mammals and protective in insects. We show that older animals are slower to recover from SD in an insect model. Moreover, preventing oxidative stress with an antioxidant speeds recovery. These findings demonstrate the role of oxidative stress in contributing to the vulnerability of the aging insect central nervous system (CNS) in energetic emergencies.
The Changing Incidence of Malaria in Indonesia: A 9‐Year Analysis of Surveillance Data
Authors: Aisyah Dewi Nur , Sitompul Desrina , Diva Haniena , Tirmizi Siti Nadia , Hakim Lukman , Surya Asik , Puspadewi Riskha Tiara , Prameswari Helen Dewi , Adisasmito Wiku , Manikam Logan
Published: December 2024

Objectives: This study aims to track the spatiotemporal incidence rate and endemicity of malaria in 34 provinces of Indonesia from 2014 to 2022 using surveillance data, commenting on trends observed and deriving implications for public health practice for combating malaria in Indonesia.

Methods: This paper is a longitudinal study using routinely collected public health surveillance data. We calculated the incidence rate as both total cases and the number of cases per 1000 person‐years at the provincial level. The endemicity was mapped as the annual parasite index (API) per 1000 at‐risk populations. Trends in malaria incidence rate and endemicity were examined descriptively in Excel Version 16.83.

Results: Nationally, malaria incidence increased by 191,503 from 2014 to 2022. The API at the national level rose by 62.63% from 0.99 cases per 1000 at‐risk populations in 2014 to 1.61 in 2022. Despite the national increase, the endemicity of Sumatra Island and Kalimantan showed strong progress (API less than 1 per 1000 at‐risk population). The incidence and endemicity of malaria remain high in the Eastern Islands, particularly in the provinces of Papua and West Papua. The Eastern Islands accounted for 95.73% (424,569 cases of total cases 443,530) of national cases in 2022.

Conclusions: Progress has been made in province‐level malaria elimination, especially outside Papua and West Papua. To prevent the persistence of endemic malaria pockets in Papua and West Papua, there is a need for greater coordination of and further dedication of financial resources toward efforts to eliminate malaria in these provinces. These efforts should be supported by an improvement in surveillance capacity, the inclusion of information on the parasite species responsible for malaria cases in routine surveillance initiatives, and the use of culturally tailored interventions to maximize health‐seeking behaviors and intervention uptake.
Evaluating the Evolution of Investment Risks in Belt and Road Energy Projects: A Case Study of Belarus’ M5 Thermal Power Station
Authors: Xiao Yao , Wan Anxia , Li Yue , Elahi Ehsan , Peng Benhong
Published: December 2024

Significant energy initiatives within the context of the “Belt and Road” are characterized by substantial financial transactions, intricate technological complexities, and prolonged construction timelines. Furthermore, the array of risk factors involved is diverse and continuously in flux. To identify pivotal risk indicators in investment projects, we employ the ISM‐MICMAC (interpretive structural modeling‐matriced impacts corise‐multiplication appliance classement) method. We integrate the Leaky Noisy‐OR gate model and dynamic Bayesian network (DBN) to formulate a dynamic model depicting the evolution of investment risk. This model enables us to trace the path of risk evolution at various temporal nodes through forward and backward reasoning. In a practical application of our methodology, we conduct an empirical analysis focusing on the M5 thermal power station in Belarus. The study findings reveal the establishment of a multidimensional and all‐encompassing index system. We identify primary factors contributing to project risk, notably including political instability and policy alterations. Additionally, we unveil the intricate interplay among risk factors within major energy projects and highlight specific risks at pivotal junctures in their development. Through the creation of a dynamic risk evolution model and the subsequent analysis of risk evolution paths, our work offers a foundational framework for conducting risk assessments and understanding the evolution of investments in energy projects within the Belt and Road initiative (BRI). The study’s findings have important policy implications for improving the management of risks associated with BRI major energy projects, including enhancing government macroeconomic policies, strengthening industry associations, and optimizing enterprise risk management.
The Mechanism of Doctor–Patient Trust in the Hierarchical Diagnosis and Treatment System (HDTS) From the Perspective of Tripartite Evolutionary Game
Authors: Li Lele , Tian Mengyi
Published: December 2024

Objective: Doctor–patient trust, especially patients’ trust in doctors, represents patients’ compliance with doctors’ behavior and may affect patients’ choice of medical treatment behavior. This paper aims to delve into the profound impact of doctor–patient trust on the hierarchical diagnosis and treatment system. Additionally, it formulates corresponding policy suggestions for reforming this system from a practical perspective, offering a useful reference for the development of both the theory and practice of China’s healthcare protections.

Methods: In this paper, the rank‐dependent expected utility theory was used to construct a tripartite evolutionary game model of hierarchical diagnosis and treatment system for observing the interactions and behaviors between superior hospitals, primary hospitals, and patients under different levels of doctor–patient trust. Meanwhile, descriptive statistics and binary logistic regression methods were used in empirical research for revealing the specific mechanism.

Results: When the doctor–patient trust is at a high level, it is easier for each participant in the hierarchical diagnosis and treatment system to choose cooperative strategies, thus enabling the system to operate smoothly. Specifically, the medical level of healthcare institutions exerts a significantly positive impact on the level of doctor–patient trust and concurrently, an enhanced level of doctor–patient trust promotes patients’ adherence to the hierarchical diagnosis and treatment system when making healthcare choices.

Conclusions: Doctor–patient trust is a significant bridge connecting medical institutions and patients. It is an important factor to realize the orderly operation of hierarchical diagnosis and treatment system. To attain the objective of strengthening doctor–patient trust and fostering the smooth functioning of the hierarchical diagnosis and treatment system, it is essential to capitalize on policy mechanism to motivate healthcare service providers to enhance their medical capabilities and gradually guide patients to make healthcare choices in an orderly manner according to the system design.
Differential Expression of fimH, ihf, upaB, and upaH Genes in Biofilms‐ and Suspension‐Grown Bacteria From Samples of Different Uropathogenic Strains of Escherichia coli
Authors: Rodríguez-Miranda Esmeralda , Reyes-Escogido María de Lourdes , Olmedo-Ramírez Viridiana , Jiménez-Garza Octavio , López-Briones Sergio , Hernández-Luna Marco Antonio
Published: December 2024

Uropathogenic Escherichia coli (UPEC) strains are the main bacteria that cause urinary tract infections (UTIs). UPEC are a significant public health hazard due to their high proliferation, antibiotic resistance, and infection recurrence. The ability to form biofilms is a mechanism of antibiotic resistance, which requires the expression of different genes such as fimH, ihf, upaB, and upaH. Despite the relevance of biofilm formation in bacterial pathogenicity, differences in the expression level of these genes among bacterial growth conditions have been little studied. Here, we have characterized the expression of fimH, ihf, upaB, and upaH genes in biofilms and suspension‐grown bacteria of different E. coli strains. These included the UPEC CFT073, the multidrug‐resistant strain CDC‐AR‐0346, and clinical isolates obtained from UTI patients. The expression of fimH, ihf, upaB, and upaH was markedly heterogeneous in clinical isolates, both in terms of transcript levels and response to suspension or biofilm conditions. That expression pattern was distinct from the one in UPEC CFT073, where upaB and upaH were upregulated and ihf and fimH were slightly downregulated in biofilm. In conclusion, the data presented here show that the pattern of biofilm‐associated genes in the clinical isolates from UTI patients is not fully related to the reference strain of UPEC CFT073. However, analysis of a larger number of samples is required.
Multivariable Analysis of Correlation Between Anatomical Features of Mandibular Third Molars and Pericoronitis
Authors: Nguyen Bao-Ngoc Thi , Nguyen-Le Chi-Tam , Nguyen Bich-Ly Thi , Le Son Hoang
Published: December 2024

Objective: The correlation between anatomy features of impacted mandibular third molars (M3Ms) and prevalence of pericoronitis was only interpreted using univariate analysis. This study investigated this correlation using multivariable analysis to determine the relationship between pericoronitis prevalence and the M3Ms’ anatomical features.

Methods: This cross‐sectional study recruited 245 patients with 338 impacted M3Ms. One researcher collected participants’ demographic characteristics such as sexes, age, side, and pericoronitis condition. The radiographic characteristics of M3Ms, including eruption direction and impacted levels according to Pell–Gregory classification, were assessed based on their orthopantomograms. Initially, univariate analyses were used to determine potential demographic and radiographic factors that correlated to pericoronitis. These factors were, then, analyzes using Firth’s logistic regression.

Results: No significant difference was found between non‐ and pericoronitis groups about sexes, age, side (p  > 0.05). The univariate analyses showed that proportion of vertical impacted levels and eruption direction of M3Ms were significantly different between non‐ and pericoronitis groups. Firth’s logistic regression analysis indicated that M3Ms with impacted level A were more likely to suffer from pericoronitis than ones at level B (odds ratio (OR) = 3.34), wheraes M3Ms impacted level II had higher risk of pericorinitis than ones at level I (OR = 1.63). Vertical M3Ms were more likely to develop pericoronitis than horizontal (OR = 5.78) ones.

Conclusion: M3M angulation and impacted level are significant factors relating to pericoronitis prevalence. M3Ms with vertical eruption, vertically level A, and horizontally level B are more likely to have pericoronitis.
CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Authors: Paget James T. , Ward Joseph A. , McKean Andrew R. , Mansfield David C. , McLaughlin Martin , Kyula-Currie Joan N. , Smith Henry G. , Roulstone Victoria , Li Chunhei , Zhou You , Hardiman Thomas , Grigoriadis Anita , O’Brien Coon Devin , Irshad Sheeba , Melcher Alan A. , Harrington Kevin J. , Khan Aadil
Published: December 2024

Radiation-induced fibrosis (RIF) is a progressive pathology deleteriously impacting cancer survivorship. CXCL12 is an immune–stromal signal implicated in fibrosis and innate response. We hypothesized that modulation of CXCL12 would phenotypically mitigate RIF. CXCL12 expression was characterized in a rodent model of RIF and its expression modulated by the intravascular delivery of lentiviral vectors encoding small hairpin RNA to silence (LVShCXCL12) or overexpress (LVOeCXCL12) CXCL12. Multimodal fibrotic outcomes were quantified, and flow cytometry and Y-chromosome lineage-tracking studies performed to examine cellular recruitment and activation after radiotherapy. Whole-tissue RNA sequencing was used to examine matrisomal response. MATBIII tumors were engrafted within tissues with differing levels of CXCL12 expression, and tumoral response to RT was evaluated. CXCL12 was upregulated in irradiated fibroblasts demonstrating DNA damage after radiotherapy, which led to the recruitment of CD68+ macrophages. Silencing CXCL12 with LVShCXCL12 demonstrated reduced RIF phenotype as a result of decreased macrophage recruitment. Transcriptomic profiling identified osteopontin (OPN; SPP1) as being highly differentially expressed in LVShCXCL12-treated tissues. Tumors growing in tissues devoid of CXCL12 expression responded better after RT because of reductions in peritumoral fibrosis as a result of decreased CXCL12 and OPN expression at the tumor/normal tissue interface. This was also associated with greater CD8+ T-cell infiltration in tumors with less fibrosis. Antibody-mediated OPN blockade slowed tumor growth by increased intratumoral CD8+ T-cell activation. The CXCL12/OPN axis is an important node of immune/matrisomal cross-talk in the development of fibrosis. Therapeutic manipulation of this axis may offer greater antitumor efficacy while also reducing adverse effects.
The FcγRIIIA (CD16) L48-H/R Polymorphism Enhances NK Cell–Mediated Antibody-Dependent Cellular Cytotoxicity by Promoting Serial Killing
Authors: Maskalenko Nicholas A. , Zahroun Sam , Tsygankova Oxana , Anikeeva Nadia , Sykulev Yuri , Campbell Kerry S.
Published: December 2024

Many tumor-specific monoclonal antibody therapies stimulate antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells through FcγRIIIa (CD16). The efficacy of these ADCC-based immunotherapies is potentiated in patients with the common CD16 polymorphic variant F158-V that increases the binding affinity between the receptor and the IgG Fc domain. However, other CD16 variants are less well characterized. Here, we report that CD16 L48-H and L48-R variants both significantly enhance in vitro ADCC responses in primary NK cells and NK-92 cells. During ADCC responses, NK cells expressing CD16 48-H killed and disengaged from target cells faster than those expressing CD16 48-L, resulting in improved serial killing of tumor cells. We found that CD16 48-H also formed an immunologic synapse with a more compact interface, as well as more robust intracellular calcium signaling and quicker polarization of cytolytic vesicles. The ADCC response observed occurs due to increased cytolytic signaling and target cell disengagement, which drives NK cell–mediated serial killing of tumor cells. The L48-H/R polymorphism has potential to benefit patient responses to cancer antibody therapies and may also potentiate antitumor ADCC responses if incorporated into adoptive NK cell therapeutic platforms.
Preclinical Development of Tuspetinib for the Treatment of Acute Myeloid Leukemia
Authors: Sonowal Himangshu , Rice William G. , Bejar Raphael , Byun Joo-Yun , Jung Seung Hyun , Sinha Ranjeet , Howell Stephen B.
Published: December 2024

Tuspetinib (TUS) is a well-tolerated, once daily, oral kinase inhibitor in clinical development for treatment of acute myeloid leukemia (AML). Nonclinical studies show that TUS targets key prosurvival kinases with IC50 values in the low nmol/L range, including SYK, wild-type (WT) and mutant forms of FLT3, mutant but not WT forms of KIT, RSK2, and TAK1–TAB1 kinases, and indirectly suppresses expression of MCL1. Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3-mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax (VEN) or 5-azacytidine. In vitro, TUS demonstrated potent killing of AML lines [concentration needed to reduce the growth of treated cells to half that of untreated cells (GI50) = 1.3–5.2 nmol/L] and Ba/F3 cells expressing WT (GI50 = 9.1 nmol/L) or various mutant forms of FLT3 (GI50 = 2.5–56 nmol/L). In AML lines, the multikinase targeting capacity of TUS suppressed phosphorylation of SYK, FLT3, STAT5, MEK, ERK, AKT, mTOR, 4E-BP1, and S6K kinases. Cells selected for stable acquired resistance to TUS exhibited increased BAX and hypersensitivity to VEN (1900 fold), navitoclax, and MCL1 inhibitors. MV-4-11 FLT3-ITD clones expressing NRASG12D revealed that high-level expression of NRASG12D generated modest resistance to TUS and greater resistance to VEN, yet the TUS/VEN combination exhibited synergy in the NRASG12D AML model. Favorable preclinical safety and pharmacology properties, the efficacy of the TUS/VEN combination in a murine model, and the synthetic lethal vulnerability to VEN that accompanies TUS resistance provide the basis for exploration of the TUS/VEN combination in patients with relapsed or refractory AML.

Significance:

This article reports preclinical development of TUS, an oral kinase inhibitor currently in clinical development for treatment of AML. The article covers the studies of TUS activities on cellular targets and the nonclinical studies that supported the advancement of TUS to a phase I/II trial of TUS/VEN in refractory AML and a phase I/II trial of TUS/VEN/5-azacytidine in newly diagnosed patients with AML (NCT03850574).
Clinical and Biometric Factors Associated with Prediction Errors Related to Lens Position in Vitrectomized Patients
Authors: Debourdeau Eloi , Pineau Pierre , Chamard Chloe , Plat Julien , Hoa Didier , Manna Frederico , Akouete Sandrine , Mura Thibault , Villain Max , Molinari Nicolas , Daien Vincent
Published: December 2024

Introduction: The aim of the study was to evaluate clinical and biometric factors leading to a prediction error related to lens position in pars plana vitrectomy. Methods: This study was conducted as a consecutive retrospective case series at the Department of Ophthalmology, Montpellier University Hospital. All medical files and PCI biometrical reports from a single surgeon were reviewed from 2017 to 2019. Patients who had phacoemulsification with the ASPHINA 509 MP® intraocular lens were selected and stratified into 3 groups: phacoemulsification alone (group 1), phacoemulsification and vitrectomy with gas tamponade (group 2), and phacoemulsification and vitrectomy without tamponade (group 3). Clinical factors and biometry factors from initial and final biometry were collected. Refractive error, actual lens position, C constant, axial length delta, and pre-operative and post-operative anterior and posterior segment variation parameters were calculated. Results: A total of 140 eyes were analyzed, 90 in group 1, and 25 in group 2 and 3. The mean prediction error was 0.10 ± 0.55 D (group 1); −0.36 ± 0.74 D (group 2); and −0.12 ± 0.54 D (group 3) with p < 0.05 for group 1 vs. group 2. The mean actual lens position was 5.25 ± 0.29 mm; 5.66 ± 0.60 mm; and 5.50 ± 0.43 mm for the 3 groups, respectively (p < 0.001). Axial length delta was −0.10 ± 0.13 mm in group 1, −0.062 ± 0.20 mm in group 2, and −0.022 ± 0.17 mm in group 3 (p = 0.015). Multilinear regression analysis found a significant and independent influence of vitrectomy and gas tamponade on prediction error. Conclusion: Myopic shift in the case of vitrectomy is multifactorial, effective lens position is modified by vitrectomy and vitreous refractive index is changing. The integration of these data in formulas may improve refractive outcome after cataract and vitrectomy surgery.
Primary Mediastinal Synovial Sarcoma with Pericardial Involvement: A Case Report
Authors: Michaels Kenan C. , Dougherty Sean C. , Kurpiel Brett R. , Douvas Michael G.
Published: December 2024

Introduction: Synovial sarcoma is a rare, malignant neoplasm accounting for approximately 5–10% of all soft tissue sarcomas. Synovial sarcomas generally occur in the extremities of adolescent or young adult (AYA)-aged patients; however, they have been reported to affect virtually every organ system. The mediastinum is an exceptionally rare location for synovial sarcoma and malignant pericardial effusions occurring secondary to synovial sarcoma can occur. Case Presentation: This case describes a 29-year-old male who presented with 3 weeks of dyspnea and leg swelling. An echocardiogram demonstrated a large pericardial effusion with early tamponade physiology. A subsequent pericardiocentesis returned a lymphocytic predominance with negative flow cytometry and cytology. Cross-sectional imaging with computed tomography (CT) scans of the chest, abdomen, and pelvis was negative for lymphadenopathy or detectable mass. He was discharged where repeat echocardiogram demonstrated recurrence of the effusion, but his symptoms had improved. Ultimately, he was readmitted with refractory dyspnea and edema where cardiac magnetic resonance imaging demonstrated a large mediastinal mass invading the pericardium. The biopsy demonstrated a high-grade spindle cell malignancy positive for a rearrangement of the SS18 gene, a finding diagnostic of synovial sarcoma. He passed away after one round of doxorubicin due to septic and obstructive shock (tamponade). Conclusion: Mediastinal synovial sarcomas are rare, aggressive, and highly morbid neoplasms. In some cases, they may present insidiously due to their sole presenting clinical manifestation being pericardial effusion. Particular care should be taken to rule out malignancy with MRI or PET-guided imaging in the AYA-aged population when idiopathic, recurrent pericardial effusion is found.
The Association between Short Telomere Length and Cardiovascular Disease
Authors: Fragkiadaki Persefoni , Apetroaei Miruna-Maria , Kouvidi Elisavet , Vakonaki Elena , Renieri Elissavet , Fragkiadoulaki Irene , Spanakis Marios , Baliou Stella , Alegakis Athanasios , Tsatsakis Aristidis
Published: December 2024

Introduction: Telomeres, repetitive DNA sequences at chromosome ends, shorten with cell division, countered by telomerase. Short telomeres are linked to cardiovascular disease (CVD), alongside its risk factors like aging, hypertension, diabetes, obesity, inactivity, and smoking. Many studies have claimed the implication of telomere length (TL) in cardiac diseases. This study examined TL’s impact on heart conditions using quantitative fluorescence in situ hybridization (Q-FISH) technology. Methods: Thirteen CVD patients (nine men and four women) aged 30–70 years and aged-matched healthy participants from the BIOTEL population TL database, were included in the study. Each chromosome’s TL from peripheral blood cells was measured using metaphase Q-FISH. An independent sample t test was used to compare participants’ mean or median TL with various medical factors and habits. Results: The mean TL of whole and short telomeres in cardiac disease patients was lower compared to aged-matched healthy controls; however, there was no statistical significance due to the limited patient sample. The mean TL of short telomeres in cardiac disease patients showed a remarkable decline with advanced age. Accordingly, the mean TL of whole and short telomeres in patients with cardiac diseases showed a similar reduced trend. Conclusion: In our study, shorter TL was observed in cardiac disease patients compared to those of healthy controls by using metaphase Q-FISH. However, more cases need to be studied to elucidate the use of TL as a potential biomarker for the diagnosis of patients with CVD.
Challenges in Diagnosing Rare Retroperitoneal Tumors: A Case Report of Extrarenal Giant Angiomyolipoma
Authors: López Delgado Darío Sebastián , Ricaurte-Fajardo Andres , Mueses-Tulcán Carlos Stiven , Benavides Ayala Omar Eduardo , Carlosama-Rosero Yeison Harvey
Published: December 2024

Introduction: Extrarenal angiomyolipomas are extremely rare tumors, with only isolated reports in the literature. Their diagnosis is challenging as these lesions are often misdiagnosed as more common retroperitoneal tumors. This report presents a case of a retroperitoneal extrarenal angiomyolipoma, emphasizing its clinical, imaging, and histopathological features to facilitate accurate diagnosis and avoid errors. Case Presentation: A 58-year-old male with a history of benign prostatic hyperplasia presented with progressive abdominal distension and weight gain. Imaging studies revealed a giant retroperitoneal mass displacing the left kidney and abdominal aorta. A core needle biopsy initially suggested a well-differentiated liposarcoma T4N0M0, leading to neoadjuvant chemotherapy with doxorubicin and ifosfamide. Surgical resection of a 20 × 30 × 25-cm mass was performed. Histopathological and immunohistochemical analysis of the specimen confirmed the diagnosis of retroperitoneal extrarenal angiomyolipoma. Chemotherapy was discontinued, and the patient remains stable under follow-up. Discussion and Conclusion: Retroperitoneal extrarenal angiomyolipomas are rare, presenting significant diagnostic challenges due to their resemblance to other retroperitoneal neoplasms such as liposarcomas. This case highlights the importance of comprehensive imaging, histopathological examination, and immunohistochemical studies for accurate diagnosis. Increased awareness of this entity can help clinicians avoid unnecessary treatments and ensure appropriate management of similar cases.
Aportes para la educación de la Inteligencia Emocional desde la Educación Infantil
Authors: Fernández-Martínez Ana María , Montero-García Inmaculada
Published: December 2024

(descriptivo): La labor de los maestros y maestras no es solo la trasmisión de conocimientos académicos, sino la de guiar a nuestros alumnos y alumnas para que vivan la experiencia del aprendizaje para la vida de manera enriquecedora e innovadora. De esta forma, garantizamos que afronten los retos con mayor comprensión, creatividad y sentido de la responsabilidad. La educación emocional puede ser un importante instrumento para este logro. Sin embargo, durante mucho tiempo no se ha trabajado en las escuelas porque se consideraba que entorpecía el desarrollo cognitivo.Gracias a los resultados de numerosos estudios, en la actualidad sabemos que no solo emoción y cognición son compatibles, sino que además son inseparables y se benefician mutuamente a través de las relaciones circulares existentes entre ellas. Propondremos finalmente algunas actuaciones que, desde la educación infantil, contribuyen a propiciar dicho proceso.
O “Primeiro Programa” de cidades médias do Brasil (1976): definições conceituais, institucionalizações e profissionais
Authors: Nunes Orlando Vinicius Rangel , Faria Rodrigo de
Published: December 2024

Este estudio analiza los Programas para Ciudades Medianas (PCPM) entre 1976 y 1986, centrándose en el "primer Programa" de 1976, elaborado por el Instituto de Investigaciones Económicas Aplicadas – IPEA en colaboración con el Instituto Brasileño de Geografía y Estadística – IBGE y el cambio del concepto de ciudad mediana. Utilizando procedimientos de interpretación histórica basados ​​en el análisis documental, se investigó la formación de las políticas urbanas y sus instituciones. Basado teoricamente en documentos oficiales y estudios académicos, se revela la evolución del concepto de ciudad medina y su influencia en las políticas urbanas, visando la integración de estas ciudades al sistema urbano nacional. La flexibilidad en la definición buscó adaptar las políticas a las diferentes realidades regionales, pero la falta de precisión presentó desafíos en la gestión del Programa. La conclusión pone de relieve la importancia de comprender la definición de este concepto al analizar políticas para ciudades medianas, reconociendo la necesidad de considerar la dinámica en el tiempo.
A tool for detection of the connection between domestic violence and companion animal mistreatment in Botucatu, São Paulo, Brazil
Authors: Tremori Tália Missen , Everson Mariel Adan , Santeramo Juliana , Gomes Laiza Bonela , Reis Sérvio Túlio Jacinto , Ribas Laila Massad , Massad Mara Rita Rodrigues , Rocha Noeme Sousa
Published: December 2024

There is a well-established link intersecting animal cruelty and interpersonal violence that suggests domestic violence can be an indicator of pet mistreatment and other forms of aggression. In Brazil, despite the high rate of domestic violence, there has been little research on the link between domestic violence and animal cruelty. This study aims to propose a tool for detecting animal cruelty in homes where domestic violence against women occurs and for clinical evaluation of animal victims. For the study, 145 Incident Reports (BO) from the Defense of Women Police Station (DDM) of Botucatu, SP, Brazil, were analyzed, and 55 women responded to a voluntary questionnaire about violence against animals. Thirty-one women claimed to own animals at their residence, totaling 54 dogs and 26 cats. Among those women who had animals and answered the questionnaire, it was verified that 14 women (45%) revealed physical violence towards animals by the same aggressor. The clinical examination of animals confirmed that 11 animals had a poor body score index and were in a mistreatment situation. The questionnaire provided valuable information and represented a potential tool that can be used by veterinarians, security, and social professionals to assess cases of domestic violence and comprehension of the welfare of pet animals.
Não Basta Ser Cidadão de Bem: a construção social dos beneficiários no Programa Auxílio Emergencial do governo federal para o enfrentamento da crise causada pela pandemia da COVID-19
Authors: Lima Luciana Leite , Rosa Júlia Gabriele Lima da , Aguiar Rafael Barbosa de
Published: December 2024

On March 11, 2020, the World Health Organization characterized COVID-19 as a pandemic and urged countries to take aggressive measures. In Brazil, the President has denied the social problem and disrespects the isolation measures taken by subnational governments. However, social problems have emerged, and the Brazilian federal government launched the Emergency Aid Program aiming to mitigate the pandemics’ economic impacts on the low-income populations. This paper analyzes how the policy design socially constructs the target population, and how it is translated into implementation instruments that impose burdens on citizens. We adopted an exploratory and descriptive methodological strategy, using categorical and documentary content analysis techniques. We found that the policy constructed the target population as a dependent, which translated into implementation instruments that imposed barriers to access the benefit, putting pressure on beneficiaries in situations of moral humiliation and the danger of COVID-19 contagion.
A produção em processo das capas de jornais brasileiros
Authors: Ferreira Júnior José
Published: December 2024

The possibilities for analyzing the graphic-visual evolution of Brazilian newspapers are placed in such a way as to converge towards an interdisciplinary perspective, a way in which the various aspects that influenced the current morphology of the Brazilian press can be contemplated.
O audiovisual imersivo nas obras de arte “The Visitor” e “Figuras na Paisagem”: processos poéticos de criação a partir da evolução do aparato visual
Authors: Sousa Silas Seabra de
Published: December 2024

This article examines the expansion of cinema through immersion and interactivity in exhibition spaces, such as museums and galleries, focusing on the evolution of mediation apparatuses driven by advances in digital technology. The works “The Visitor” by Luc Courchesne and “Figures in the Landscape” by André Parente exemplify hybrid cinema by blending audiovisual elements with other artistic languages, fostering interactive and immersive experiences. Drawing on authors such as Cesar Baio, Natalia Aly, and Philippe Dubois, the research explores how these technological devices reshape the relationship between the viewer and the artwork, transforming the viewer into an active participant in narrative development. The study observes that, with new digital devices, cinema transcends linear storytelling, creating spaces where moving images combine with the environment and public interaction, expanding the boundaries of “exhibition cinema” and offering sensory experiences that uniquely engage the viewer.
“Esta é a malícia da obra”: uma leitura de arquivo em A rainha dos cárceres da Grécia, de Osman Lins
Authors: Couto Pedro Henrique
Published: December 2024

The present essay explores the creative process of Osman Lins (1924–1978), highlighting how his personal correspondence and manuscripts offer a profound insight into the work and the tensions between practical life and literary creation that can be traced in his last novel, A Rainha dos Cárceres da Grécia, from 1976. The study adopts a methodological approach based on close reading and genetic analysis of Lins’ correspondence and manuscripts. The research unfolds through an investigative protocol that involves reading and interpreting textual layers and paratexts, such as notes and citations, aiming to reconstruct the author’s creative path and uncover the influences and dilemmas he faced throughout the writing process of the novel in question. One of the research hypotheses presented in the essay is that A Rainha dos Cárceres da Grécia can be understood as a parody of the theoretical and critical discourses of the time, especially in relation to structuralism, which predominated in the Brazilian academic context of the 1960s and 1970s.
Extracellular Vesicles From Preeclampsia Disrupt the Blood-Brain Barrier by Reducing CLDN5
Authors: Sandoval Hermes , Ibáñez Belén , Contreras Moisés , Troncoso Felipe , Castro Fidel O. , Caamaño Diego , Mendez Lidice , Escudero-Guevara Estefanny , Nualart Francisco , Mistry Hiten D. , Kurlak Lesia O. , Vatish Manu , Acurio Jesenia , Escudero Carlos
Published: December 2024

BACKGROUND:

The physiopathology of life-threatening cerebrovascular complications in preeclampsia is unknown. We investigated whether disruption of the blood-brain barrier, generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as CLDN5 (claudin-5), mediated by VEGF (vascular endothelial growth factor), and activation of KDR (VEGFR2 [VEGF receptor 2]).

METHODS:

We perform a preclinical mechanistic study using sEVs isolated from plasma of pregnant women with normal pregnancy (sEVs-NP; n=9), sEVs isolated from plasma of women with preeclampsia (sEVs-PE; n=9), or sEVs isolated from placentas cultured in normoxia (sEVs-Nor; n=10) or sEVs isolated from placentas cultured in hypoxia (sEVs-Hyp; n=10). The integrity of the blood-brain barrier was evaluated using in vitro (human [hCMEC/D3] and mouse [BEND/3 (brain endothelial cell 3)] brain endothelial cell lines) and in vivo (nonpregnant C57BL/6J mice [4–5 months old; n=13] injected with sEVs-Hyp) models.

RESULTS:

sEVs-PE and sEVs-Hyp reduced total and membrane-associated protein CLDN5 levels (
P
<0.05). These results were negated with sEVs-PE sonication. sEVs-Hyp injected into nonpregnant mice generated neurological deficits and blood-brain barrier disruption, specifically in the posterior area of the brain, associated with brain endothelial cell uptake of sEVs, sEVs-Hyp high extravasation, and reduction in CLDN5 levels in the brain cortex. Furthermore, sEVs-PE and sEVs-sHyp had higher VEGF levels than sEVs-NP and sEVs-Nor. Human brain endothelial cells exposed to sEVs-PE exhibited a reduction in the activation of KDR. Reduction in CLDN5 observed in cells treated with sEVs-Hyp was further enhanced in cells treated with KDR selective inhibitor.

CONCLUSIONS:

sEVs-PE disrupts the blood-brain barrier, an effect replicated with sEVs-Hyp, and involves reduced CLDN5 and elevated VEGF contained within these vesicles. However, our results do not support the participation of KDR activation in the downregulation of CLDN5 observed with sEVs-Hyp. These findings will improve our understanding of the pathophysiology of cerebrovascular alterations in women with preeclampsia.