bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular landscape and classification of vascular anomalies
Authors: Seront Emmanuel , Queisser Angela , Boon Laurence M. , Vikkula Miikka 
Published: December 2024

Abstract
Vascular malformations, which result from anomalies in angiogenesis, include capillary, lymphatic, venous, arteriovenous, and mixed malformations and affect specific vessel types. Historically, treatments such as sclerotherapy and surgery have shown limited efficacy in complicated cases. Most vascular malformations occur sporadically, but some can be inherited. They result from mutations similar to oncogenic alterations, activating pathways such as PI3K-AKT-mTOR or Ras-MAPK-ERK. Recognizing these parallels, we highlight the potential of targeted molecular inhibitors, repurposing anticancer drugs for the treatment of vascular malformations. This case-based review explores recent developments in precision medicine for slow-flow and fast-flow vascular malformation.
Hypoxia-inducible factor activators: a novel class of oral drugs for the treatment of anemia of chronic kidney disease
Authors: Haase Volker H. , Tanaka Tetsuhiro , Koury Mark J. 
Published: December 2024

Abstract
Anemia is a hallmark of chronic kidney disease (CKD), worsens with disease progression, and profoundly affects a patient's well-being. Major pathogenic factors are inadequate kidney erythropoietin (EPO) production and absolute and functional iron deficiency. The 2 mainstays of current anemia treatment are a) replacement therapy with recombinant EPO or 1 of its glycosylated derivatives, administered subcutaneously or intravenously, and b) intravenous (IV) iron injections. Over the past 5 years, hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitors (HIF-PHIs) have been approved in many countries for the management of anemia in both nondialysis and dialysis-dependent patients with CKD. Due to cardiovascular safety concerns, only 2 HIF-PHIs, daprodustat and vadadustat, have been approved for marketing in the United States, and only for patients on maintenance dialysis. HIF-PHIs are oral agents that are effective at improving and maintaining hemoglobin levels by activating HIF signaling in anemic patients with CKD. They stimulate the production of endogenous EPO, increase total iron-binding capacity through their direct effects on transferrin gene transcription, lower plasma hepcidin indirectly, and have beneficial effects on red blood cell parameters. Here, we discuss the mechanisms of action and pharmacologic properties of different HIF-PHIs. We discuss unwanted on-target and off-target effects, review cardiovascular and other safety concerns, and provide a benefit/risk-based perspective on how this new class of oral drugs might impact current anemia management in CKD. A clinical case is presented that highlights the clinical complexities and therapeutic challenges in managing anemia in CKD.
Troubleshooting heparin resistance
Authors: Maier Cheryl L. , Connors Jean M. , Levy Jerrold H. 
Published: December 2024

Abstract
The term heparin resistance is likely best defined as the failure of an appropriate dose of unfractionated heparin (UFH) to achieve a predetermined level of anticoagulation. Unfortunately, and despite many prior reports, there is no established consensus as to what either the appropriate dose or the predetermined level should be. Traditionally, assays used to monitor anticoagulation with UFH have been clot based, including the activated partial thromboplastin time, used for patients on the ward or intensive care unit, and the activated clotting time, used for patients undergoing vascular interventions and cardiopulmonary bypass. Unfortunately, these tests may be highly influenced by other factors occurring in many patients, especially those with inflammation or acute infection, as noted during the COVID-19 pandemic. Many hospitals have thus moved to anti-Xa testing for heparin monitoring. Another important factor in defining heparin resistance includes dosing, whether weight-based or total daily dosing is used, as initial reports of heparin resistance described daily doses independent of body weight. Multiple causes of apparent heparin resistance include hypercoagulability, antithrombin deficiency, andexanet alfa used for direct oral anticoagulant reversal, thrombocytosis, and antiphospholipid antibody syndromes. Treatment options for managing patients with heparin resistance include weight-based dosing and administration of additional UFH, antithrombin supplementation, or the use of an alternative anticoagulant such as the direct thrombin inhibitors bivalirudin or argatroban.
Sequencing bispecific antibodies and CAR T cells for FL
Authors: Russler-Germain David A. , Bartlett Nancy L. 
Published: December 2024

Abstract
Treatment for relapsed/refractory (R/R) follicular lymphoma (FL) has evolved over recent years with the introduction of multiple novel immunotherapies: anti-CD3  ×  CD20 bispecific antibody (BsAb) T-cell engagers and anti-CD19 chimeric antigen receptor T cells (CAR T). Both drug classes are highly active, and their adverse event profiles overlap considerably, with cytokine release syndrome, cytopenias, and infections being most common. However, key differences include accessibility and logistical considerations as well as distinct neurologic toxicities, which make recommending a BsAb or CAR T a nuanced decision for each patient with R/R FL. Notably, patients could receive both classes of therapies in sequence; however, data guiding this decision are sparse. Considering the 3 most advanced agents in each class, we generally favor BsAbs before CAR T as the standard-of-care third-line treatment for the typical patient with R/R FL without concern for aggressive histologic transformation (HT). This is based on a 3-year follow-up of the mosunetuzumab phase 2 trial in R/R FL highlighting durable complete responses after a time-limited therapy with an acceptable safety profile for patients of all ages and reasonable performance status. We generally prioritize CAR T before BsAbs for patients with proven or suspected HT given the curative-potential of this approach based on trial data from R/R diffuse large B-cell lymphoma; it is unknown whether BsAbs offer the same long-term benefit in transformed FL. Overall, with the ability to personalize the sequencing of BsAbs and CAR T, the recently expanding portfolio of highly effective immunotherapies for R/R FL is poised to offer considerable benefit to this patient population.
The role of stem cell transplant (auto and allo) in PTCL and CTCL
Authors: Dreger Peter , Schmitz Norbert 
Published: December 2024

Abstract
In contrast to B-cell lymphoma, the advent of modern targeting drugs and immunotherapeutics has not led to major breakthroughs in the treatment of peripheral T-cell lymphoma (PTCL) to date. Therefore, both autologous and allogeneic hematopoietic cell transplantation (HCT) continue to play a central role in the management of PTCL. Focusing on the most common entities (PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, and ALK-negative anaplastic large cell lymphoma), we summarize evidence, indications, and points to consider for transplant strategies in PTCL by treatment line. Although cutaneous T-cell lymphomas (CTCLs) are biologically and clinically distinct from the aforementioned PTCL, both disease groups appear to be susceptible to the graft-versus-lymphoma effects conferred by allogeneic HCT (alloHCT), setting the stage for alloHCT as a potentially curative treatment in otherwise incurable CTCL, such as mycosis fungoides/Sezary syndrome. Nevertheless, specific aspects regarding indication and prerequisites for alloHCT in CTCL need to be considered. Given the inherent toxicity of alloHCT and the significant risk of relapse after transplant, only intelligent strategies embedding alloHCT in current PTCL/CTCL treatment algorithms in terms of patient selection, timing, pretransplant preparation, and posttransplant maintenance provide optimal results. New targeted and cellular therapies, either complementary or competitive to HCT, are eagerly awaited in order to improve PTCL/CTCL outcomes.
Potential and emerging therapeutics for HHT
Authors: Eswaran Harish , Kasthuri Raj S. 
Published: December 2024

Abstract
A 64-year-old woman with hereditary hemorrhagic telangiectasia (HHT) characterized by a pathological variant in ACVRL1 presents to the clinic for follow-up. Manifestations of HHT include frequent epistaxis and gastrointestinal bleeding, leading to iron-deficiency anemia. Bevacizumab is initiated, with resolution of the anemia. While maintained on a regimen of bevacizumab every 6 weeks, she continues to report frequent epistaxis and has ongoing iron-deficiency requiring periodic iron infusions. She also finds the bevacizumab infusions inconvenient. She is interested in discussing other options for managing her disease.
Sickle cell disease in India: the journey and hope for the future
Authors: Gupta Kalpna , Krishnamurti Lakshmanan , Jain Dipty 
Published: December 2024

Abstract
India, the most populous nation in the world, also has a high frequency of the sickle hemoglobin (HbS) allele globally. The Arab Indian HbS haplotype in India is characterized by a relatively high percentage of fetal Hb, with widely varying frequencies of α-thalassemia. Hence, sickle cell disease (SCD) in India was perceived to be mild. Advances in the past decade in screening and SCD management have revealed that the severity of SCD in India is comparable to many other parts of the world. Clinical features in India include vaso-occlusive crisis, acute chest syndrome, avascular necrosis, renal involvement, stroke, etc, at a relatively young age. Once a fatal disease of childhood, the majority of patients born with SCD are expected to survive into adulthood, largely because of improvements in comprehensive care programs including newborn screening, penicillin prophylaxis, transcranial Doppler, and hydroxyurea therapy. Several centers are performing hematopoietic stem cell transplants successfully for SCD. To address the urgent need to control and manage SCD in India's population, the Government of India launched the National Sickle Cell Anaemia Elimination Mission, with significant funding for large-scale measures to screen, treat, counsel, educate, and develop technologies and novel therapies and gene therapies.
Triolein alleviates ischemic stroke brain injury by regulating autophagy and inflammation through the AKT/mTOR signaling pathway
Authors: Wang Chaoqun , Li Yuntao , Zhang Yonggang , Smerin Daniel , Gu Lijuan , Jiang Shuting , Xiong Xiaoxing 
Published: December 2024

Abstract
Background
Triolein, a symmetric triglyceride exhibiting anti-inflammatory and antioxidant properties, has demonstrated potential in mitigating cellular damage. However, its therapeutic efficacy in ischemic stroke (IS) and underlying molecular mechanisms remain elusive. Given the critical roles of inflammation and autophagy in IS pathogenesis, this study aimed to elucidate the effects of triolein in IS and investigate its mechanism of action.

Methods
We evaluated the impact of triolein using both in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) and in vivo middle cerebral artery occlusion (MCAO/R) models. Neurological function and cerebral infarct volume were assessed 72 h post-reperfusion. Autophagy was quantified through monodansyl cadaverine (MDC) labeling of autophagic vesicles and Western blot analysis of autophagy-related proteins. Microglial activation was visualized via immunofluorescence, while inflammatory cytokine expression was quantified using RT-qPCR. The cytoprotective effect of triolein on OGD/R-induced HT22 cells was evaluated using Cell Counting Kit-8 and lactate dehydrogenase release assays. The involvement of the Protein kinase B/Mechanistic target of rapamycin kinase (AKT/mTOR) pathway was assessed through Western blot analysis.

Results
Triolein administration significantly reduced infarct volume, enhanced neurological recovery, and attenuated M1 microglial activation and inflammation in MCAO/R-induced mice. Western blot analysis and MDC labeling revealed that triolein exerted an inhibitory effect on post-IS autophagy. Notably, in the BV2-induced OGD/R model, triolein demonstrated an autophagy-dependent suppression of the inflammatory response. Furthermore, triolein inhibited the activation of the AKT/mTOR signaling pathway, consequently attenuating autophagy and mitigating the post-IS inflammatory response.

Conclusions
This study provides novel evidence that triolein exerts neuroprotective effects by inhibiting post-stroke inflammation through an autophagy-dependent mechanism. Moreover, the modulation of the AKT/mTOR signaling pathway appears to be integral to the neuroprotective efficacy of triolein. These findings elucidate potential therapeutic strategies for IS management and warrant further investigation.

Graphical abstract
Genome-wide identification, gene cloning, subcellular location and expression analysis of the OPR gene family under salt stress in sweetpotato
Authors: Li Wenxing , Li Yongping , Xu Yuan , Kumar Sunjeet , Liu Yi , Zhu Guopeng 
Published: December 2024

Abstract
Background
The 12-oxo-phytodienoic acid reductase (OPR) enzyme is crucial for the synthesis of jasmonates (JAs), and is involved in the plant stress response. However, the OPR gene family in sweetpotato, an important horticultural crop, remains unidentified.

Results
In this study, we employed bioinformatics techniques to identify nine IbOPR genes. Phylogenetic analysis revealed that these genes could be divided into Group I and Group II. Synteny analysis indicated that IbOPR evolution was driven by tandem duplication, whole-genome duplication (WGD), and segmental duplication events. The promoter sequences of IbOPRs were found to be associated with stress and hormonal responses. Additionally, we successfully cloned four IbOPRs from "Haida HD7791" and "Haida HD7798" using homologous cloning technology. These sequences were 1203 bp, 1200 bp, 1134 bp, and 1137 bp in length and encoded 400, 399, 377, and 378 amino acids, respectively. The protein sequence similarity between the salt-tolerant variety "Haida HD7791" and the salt-sensitive variety "Haida HD7798" was determined to be 96.75% for IbOPR2, 99.75% for IbOPR3, 92.06% for IbOPR6, and 98.68% for IbOPR7. Phylogenetic analysis categorized IbOPR2 and IbOPR3 proteins into Group II, while IbOPR6 and IbOPR7 proteins belonged to Group I. Subcellular localization experiments showed IbOPR2 protein present in the peroxisome, while IbOPR3, IbOPR6, and IbOPR7 proteins were found in the cytoplasm and nucleus. Salt stress induction experiments demonstrated that IbOPR2, IbOPR3, and IbOPR7 were significantly upregulated only in 'Haida HD7791' after 6 h. In contrast, IbOPR6 was induced in 'Haida HD7798' at 6 h but inhibited in 'Haida HD7791' at later time points (12, 24, 48, and 72 h), highlighting functional differences in salt stress responses.

Conclusions
Our findings suggest that IbOPR2 may play a crucial role in sweetpotato's response to salt stress by participating in JAs synthesis. These results provide a foundation for future functional analyses of OPR genes in sweetpotato.
Cone-beam computed tomographic evaluation of styloid process: a retrospective study of 498 patients with maxillofacial diseases
Authors: Yang Zhang , Yuzi Jing , Beibei Liang 
Published: December 2024

Abstract
Purpose
The purpose of this study was to assess the structural characteristics of the styloid process (SP) using cone-beam computed tomography (CBCT) examination in patients with maxillofacial diseases. The study aimed to determine the prevalence of elongated styloid process (ESP) and its relationship to gender in the study population. Radiographic records of 498 subjects were evaluated retrospectively. Radiological examinations including measurements of the structure, length, volume, and angulations of styloid process were performed on CBCT images. Males had significantly longer styloid process in both sides than females in the study population and a strong positive linear relationship was found between left and right sides’ process length (r = 0.83; p < 0.001). The mean internal oblique angle of styloid process differed between genders, but there were no statistically significant differences in the mean anterior oblique angle. Out of 498 subjects, 62 (24.13%) females and 101 (41.91%) males had elongated left styloid process (≥ 30 mm), while 75 (29.18%) and 90 (37.34%) had right side respectively.

Methods
Radiographic records of 498 subjects were evaluated retrospectively. Radiological examinations including measurements of the structure, length, volume, and angulations of styloid process were performed on CBCT images.

Results
Males had significantly longer styloid process in both sides than females in the study population and a strong positive linear relationship was found between left and right sides’ process length (r = 0.83;
p < 0.001). The mean internal oblique angle of styloid process differed between genders, but there were no statistically significant differences in the mean anterior oblique angle. Out of 498 subjects, 62 (24.13%) females and 101 (41.91%) males had elongated left styloid process (≥30 mm), while 75 (29.18%) and 90 (37.34%) had right side respectively.

Conclusions
This study presents the CBCT as an alternative method to CT or panoramic radiographs for the measurement and the assessment of the styloid process. Within the study in 498 subjects in China, it was observed that the males, on average, had significantly longer styloid process and narrower internal oblique angle than females either in left or right side. Around 33% of the study population had ESP.
Pseudo-static analytical formulation for seismic thrust on cantilever retaining walls in C-Φ soils considering double failure planes
Authors: Ayman Gharbi , Fadoua El Khannoussi , Bouraida El Yamouni , Abdellatif Khamlichi 
Published: December 2024

AbstractThis study proposes a pseudo-static analytical formulation for calculating the active thrust force on cantilever retaining walls under seismic loads. The formula incorporates the effects of soil cohesion and failure surface shape and is applied to short-heel and long-heel cantilever walls. The results are compared to classic analytical methods and a numerical model. The proposed formula provides a good representation of wall behavior under low to medium seismic loads, with an extended range compared to classical methods. However, using 100% of the peak ground acceleration (PGA) overestimates the active force for medium to strong earthquakes, so reduced PGA values are recommended. The formula accurately predicts the failure surface inclination, with an accuracy of approximately 10°. Soil cohesion has no significant effect on the failure mechanism, but the heel length influences its effect on active force reduction. Overall, the study offers an improved analytical approach for assessing the seismic response of cantilever retaining walls.
HER2-low breast cancer. Diagnostics, treatment and its adverse events
Authors: Bartkowiak Hanna , Grubski Damian , Ziarnik Kacper , Nadolny Filip , Jabłoński Jędrzej , Kania Martyna , Adamowska Agnieszka , Śniatała Alicja 
Published: December 2024

Introduction:
Breast cancer is one of the most commonly diagnosed malignant tumors among women worldwide. HER2 receptor is a protein that plays a role in cell growth, division, and repair. Approximately 50% of HER2 –negative breast cancers express low levels of HER2 receptors. HER2-low breast cancer is a newly characterized subtype of breast cancers that express low levels of HER2 receptor but do not meet the criteria for HER2 positivity and HER2 negative with SCORE - 0 in immunohistochemistry. Recent studies have discovered that HER2-targeted therapies can be effective even at low HER2 expression levels.

Aim of study:
The purpose of this review was to increase awareness of HER2- low breast cancer. The objective was also to underscore the importance of detecting low and very low expression of HER2 receptors. The other goal of this project is to raise awareness of potential new directions in oncological treatments including antibody–drug conjugates.

Materials and methods:
The review was based on the analysis of materials collected in the „Pubmed” and Google Scholar databases. The search was performed using the keywords: „HER2-low breast cancer”, trastuzumab deruxtecan antibody–drug conjugates”, „HER2-low diagnostic algorithm”.

Conclusion:
The results of the DESTINY - Breast04 study shows that trastuzumab-deruxtecan significantly improved both progression-free survival and overall survival among all patients including hormone-positive patients cohort compared to chemotherapy. While trastuzumab-deruxtecan is highly effective, it does come with specific safety considerations that necessitate close monitoring.
An Operations Research–Based Teaching Unit for Grade 12: The ROAR Experience, Part III
Authors: Colajanni Gabriella , Gobbi Alessandro , Picchi Marinella , Raffaele Alice , Taranto Eugenia 
Published: December 2024

In this paper, we finish describing the project and the experimentation of Ricerca Operativa Applicazioni Reali (ROAR; in English, Real Applications of Operations Research), a three-year project for higher secondary schools. ROAR is composed of three teaching units addressed to grades 10, 11, and 12, respectively. To improve students’ interest, motivation, and skills related to science, technology, engineering, and mathematics disciplines, ROAR integrates the teaching of mathematics and computer science through operations research. Its implementation started in 2021 in a grade 10 class at the scientific high school IIS Antonietti in Iseo (Brescia, Italy). We provided the details of the first two units in previous papers. Here, we focus on the third and last unit, carried out from October 2022 to January 2023, with the same students, then in a grade 12 class. Similarly to the first two units, we describe objectives, prerequisites, topics and methods, the organization of the lectures, digital technologies used, and a challenging final project that, this time, involved the manufacturer company Filtrec S.p.A. with a case. After analyzing the feedback from students, teachers, and practitioners engaged in the experimentation, we reflect on the entire experimentation and provide some insights to replicate a similar experience. Funding: G. Colajanni was partially supported by the research project Programma Ricerca di Ateneo UNICT 2020-22 linea 2, Ottimizzazione di Modelli di Network slIce 5G con UAV, the Italian Ministry of University and Research and the European Union for the Programma Operativo Nazionale project on Research and Innovation 2014-2020, D.M. 1062/2021, and the GNAMPA-INdAM Group. A. Raffaele was partially supported by the National Group for Scientific Computation. E. Taranto was partially supported by the National Group for Algebraic and Geometric Structures, and their Applications. Supplemental Material: The online appendices are available at https://doi.org/10.1287/ited.2023.0065 .