bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Zafirlukast Analogues for Improved Antithrombotic Activity Through Thiol Isomerase Inhibition
Authors: Keovilay Justine A. , Howard Kaitlind C. , Taylor Kirk A. , Khan Sabeeya , Wurl Sienna E. , Szahaj Melanie K. , Sage Tanya , Chandrika Nishad Thamban , Hou Caixia , Tsodikov Oleg V. , Gibbins Jonathan M. , Garneau-Tsodikova Sylvie , Kennedy Daniel R. 
Published: February 2025

BACKGROUND:
Thiol isomerases play essential and nonredundant roles in platelet activation, aggregation, and thrombus formation. Thiol isomerase inhibitors have the potential to overcome the 2 major drawbacks of current antithrombotic therapies, as they target both arterial and venous thrombosis without enhancing bleeding risks. Recently, a Food and Drug Administration–approved drug, zafirlukast (ZAF), was shown to be a promising pan-thiol isomerase inhibitor. The objective of this study is to develop analogues of ZAF with optimized thiol isomerase inhibition and antithrombotic activity.

METHODS:
Thirty-five ZAF analogues were tested in an insulin turbidometric assay for thiol isomerase inhibition. Analogues were tested for platelet activation, aggregation, P-selectin expression, and laser-induced thrombosis in mice and compared with the parent compound.

RESULTS:
Of the 35 analogues, 12 retained activity, with 1, compound 21, that demonstrated a greater potency than that of ZAF, 5 had a similar potency to that of ZAF, and 6 had a weaker potency. Analogues demonstrated inhibition of platelet aggregation and P-selectin expression as compared with ZAF, consistent with their potencies. ZAF and compound 21 were shown to be reversible inhibitors of thiol isomerases, and not cytotoxic to cultured, lung, liver, and kidney cells. Finally, in an in vivo assessment of thrombus formation, compound 21 was able to significantly inhibit thrombus formation without affecting bleeding times.

CONCLUSIONS:
A ZAF analogue, compound 21, with properties superior to those of ZAF was synthesized, demonstrating improved inhibition of platelet activation, aggregation, and thrombus formation as compared with the parent ZAF. This approach could yield a promising clinical candidate for treatment and prophylaxis of arterial and venous thrombosis.
Characteristics of Patients With the Arrhythmogenic Mitral Valve Prolapse Syndrome and Sudden Cardiac Arrest and Sustained Ventricular Arrhythmias
Authors: Chakrabarti Apurba , Giudicessi John R. , Ezzeddine Fatima M. , Delling Francesca N. , Dixit Shalini , Lee Yoo Jin , Muser Daniele , Magnani Silvia , Van Wijngaarden Aniek , Ajmone Marsan Nina , Miller Marc A. , Gandhi Jonathan , Trivieri Maria G. , Font Jonaz , Martins Raphael , McCaffrey James A. , Santangeli Pasquale , Marchlinski Francis E. , Chapagain Himal , Mathew Don , Kancharla Krishna , Syed Faisal F. , Abid Ahad , Cerbin Lukasz , Tzou Wendy S. , Garg Lohit , Della Rocca Domenico G. , Natale Andrea , Mohanty Sanghamitra , Sheldon Seth H. , Kuo Ling , Haugaa Kristina H. , Aabel Eivind W. , Enriquez Andres , Maeda Shingo , Deshmukh Amrish , Ghannam Michael , Bogun Frank M. , Ackerman Michael J. , Liang Jackson J. 
Published: February 2025

BACKGROUND:
Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation.

METHODS:
In this descriptive registry, we characterized patients with arrhythmogenic mitral valve prolapse syndrome who survived SCA, sustained VT, or ventricular fibrillation. Deidentified data were abstracted locally and combined centrally.

RESULTS:
We included 148 patients who had SCA or VT/ventricular fibrillation. Patients had a mean age of 43.7±15.4 years; 68% were women, 73% had bileaflet prolapse, 65% had mitral annular disjunction, 67% had nonsustained VT, and 59% had inferolateral T-wave inversions. Syncope (n=54, 48%) and anterolateral T-wave inversion (n=26, 22%) were relatively common. Catheter ablation was performed in 50 (35%) patients for premature ventricular complexes and in 18 (17.7%) patients for VT. Sites of origin for arrhythmias were commonly in the papillary muscles, fascicles, mitral annulus, and inferior/inferolateral left ventricle.

CONCLUSIONS:
In this international descriptive registry of patients with arrhythmogenic mitral valve prolapse syndrome and SCA, patients were young, women, and had bileaflet mitral valve prolapse, mitral annular disjunction, inferolateral T-wave inversions, and nonsustained VT. A history of syncope and anterolateral T-wave inversions was relatively common in patients who survived SCA or sustained VT/ventricular fibrillation.
Situating Religious Beliefs
Authors: Ringmar Erik 
Published: February 2025

Abstract
Recent scholarship in cognitive theory emphasizes the situatedness of cognitive processes, which occur not only in minds but in bodies engaging with their environments. This article relies on these insights to rethink the concept of religious beliefs. It argues that to believe in something is more fundamental than to believe that something is the case. Religious beliefs are primarily expressions of trust rather than propositional statements. To believe in God is to trust in God, reflecting cognitive processes rooted in embodied and enacted experiences.
The European Union’s Influence on the Organisation of National Healthcare Systems. Navigating the Trends after the COVID-19 Pandemic
Authors: Zapotoczna Zuzanna 
Published: February 2025

Abstract
The COVID-19 pandemic has hit national healthcare systems on an unprecedented scale. At the same time, European societies are witnessing an ongoing war, growing migration and climate crisis. In order to respond to the global challenges facing national healthcare systems, the European Union (EU) is stepping up its actions to promote resilience of national healthcare systems. This is to ensure adequate availability of healthcare services in times of health crises through numerous actions. Despite limited powers in health, the EU legal system creates a multidimensional order for protection of various health-related interests which touch upon the organisation of the Member States’ healthcare systems. This paper navigates the ongoing trends with regard to the EU’s health policy and presents the perspective on ‘standardisation’ of the Member States’ healthcare systems.
Re-Appraisal of Legal Systems in Sub-Saharan Africa: Questioning the Legal Pluralism Paradigm
Authors: Macarthy Motese Emmanuel , Uhumuavbi Ikpenmosa 
Published: February 2025

Abstract
The notion that multiple legal systems autonomously coexist in independent states in sub-Saharan Africa due to the interaction of the continent with foreign legal systems is theoretically flawed, misleading and an incorrect application of the concept of legal pluralism. This article examines the nature of legal pluralism in the context of transitioning independent nation-states. It contends that these nation-states, especially in sub-Saharan Africa, do not operate legally pluralistic legal systems, as often presented in scholastic works. Using system and lifecycle theories, this article argues against the prevailing conceptualization of legal pluralism in African legal systems. We argue that the prevailing conceptualization of pluralistic legal systems in sub-Saharan Africa is based on the fallacy of the undistributed middle, leading to flawed conclusions and disastrous governance outcomes. This widespread orthodoxy in legal and sociopolitical scholarship heightens perceived conflicts between imperial universalism and cultural existentialism, which has been the epicenter of legal discussion in Africa’s transitioning nations.
Lo spazio terzo come dimora interiore: l’esperienza dell’esilio e della costruzione identitaria nella poesia di Ġayāṯ al-Madhūn
Authors: Palmegiani Angelika 
Published: February 2025

Abstract
Poetry has occupied a pivotal role within Arab culture since the pre-Islamic era, and its significance has grown exponentially in the wake of the Arab uprisings in 2011. Despite the revolutions not yielding the anticipated socio-political transformations, they have instigated the emergence of novel modes of expression and stylistic approaches that proffer artists a means to navigate social and personal dilemmas. Poets have redirected their focus from the epicentres of the uprisings toward more introspective and secluded domains. This shift in tone and style is inextricably linked to the circumstances of numerous artists who, compelled by necessity, have departed their countries of origin and sought solace in new lands, even before the outbreak of the revolution, due to the oppressive political, economic, and social conditions. Among those resonating with the enduring sense of flux is Ġayāṯ al-Madhūn (1979), a Palestinian-born Syrian poet who moved to Stockholm in 2008 and now lives in Berlin. His verses convey the persistent condition of displacement, the wistful yearning for his homeland, and the solitude borne of migration. Even as his material circumstances have ameliorated, affording him the latitude for creative expression, his newfound residence is tinged with an ineffable discontent, as it remains an imperfect substitute for the home relinquished. This article scrutinises the enigmatic predicament of the poet, who finds within his new milieu a latent but perpetually unfulfilled sense of belonging, while concurrently remaining tethered to the remembrance of the circumstances compelling his refuge-seeking elsewhere.
New Notes on Ǧubrān’s Education in Boston and Its Effect on His Later Career
Authors: Corrao Francesca Maria 
Published: February 2025

Abstract
Ǧubrān’s cultural training in Boston fostered the young Arab immigrant’s rapid success. The poet’s universalist vision enabled a fruitful dialogue between East and West in the nation-forming years of the Arab states. The dissemination of such ideas through literary journals ferried the renewal of modern poetry from New York to Cairo and Tunis.
Numerous studies have delved into the main elements and indications that emerged from his writings (on the contribution of Christianity, Nietzsche, and the cultural milieu of the Arab Nahḍa), while his American education has been investigated less. Here we shall examine some aspects that prove useful in reconstructing the contribution of Transcendentalism and its epigones in the Boston intellectual milieu.
DLAT activates EMT to promote HCC metastasis by regulating GLUT1-mediated aerobic glycolysis
Authors: Yin Qian , Yao Yinye , Ni Jiaojiao , Zhang Yiwen , Wu Jia , Zeng Hui , Wu Wei , Zhuo Wei , Ying Jieer , Li Jingjing 
Published: February 2025

Abstract

Background
Metabolic reprogramming is a hallmark of hepatocellular carcinoma (HCC) progression, driving aberrant cellular processes in response to pathological stimuli. While dihydrolipoyl transacetylase (DLAT) has been implicated in the development of various cancers, its specific role and underlying mechanisms in HCC remain unclear. This study aimed to investigate the expression, function, and mechanistic impact of DLAT in HCC.

Methods
A comprehensive analysis was conducted using RNA sequencing data, tissue microarrays, in vitro and in vivo functional assays, and mechanistic studies to evaluate DLAT expression, its functional role in tumor progression, and associated molecular pathways in HCC.

Results
Our study revealed a significant upregulation of DLAT expression in HCC, which was linked to a poor prognosis. Furthermore, we discovered that DLAT facilitated tumor metastasis by driving metabolic reprogramming in HCC cells. Mechanistically, DLAT was found to enhance glucose transporter 1 (GLUT1) expression via H3K18 acetylation, thereby promoting aerobic glycolysis and epithelial-to-mesenchymal transition (EMT), which subsequently augmented metastasis of HCC both in vitro and in vivo. Finally, we confirmed a positive correlation between DLAT and GLUT1 expression in HCC tissues.

Conclusions
These findings establish DLAT as a key regulator in HCC progression and suggest its potential as a promising predictive biomarker and therapeutic target for improving HCC diagnosis and treatment.
Higher nonunion rates with locking plates compared to dynamic compression plates in forearm diaphyseal fractures: a multicenter study
Authors: Tseng Tzu-Hao , Hung Chih-Chien , Yen Hung-Kuan , Chen Ho-Min , Wang Chen-Yu , Tzeng Shi-Chien , Fu Shau-Huai 
Published: February 2025

Abstract

Background
Dynamic compression plate (DCP) osteosynthesis is the gold standard for treating forearm diaphyseal fractures, providing stability and promoting healing. Locking plates (LPs) are increasingly used in modern fracture management but may increase the risk of nonunion if applied with excessive rigidity and without proper fracture site compression. The purpose of this study is to compare the nonunion rate between LPs and DCPs.

Materials and methods
We conducted a retrospective study by reviewing the medical records and radiographs of 515 patients diagnosed with radial and/or ulnar shaft fractures at three trauma centers between 2014 and 2019. Inclusion criteria were patients treated with locking plates (LPs), locking compression plates (LCPs), or dynamic compression plates (DCPs) who had at least 9 months of outpatient follow-up and imaging assessments. Exclusion criteria included treatment with other methods, hospitalization for pathological fractures or implant removal, or incomplete surgical records. Data on patient demographics, injury details, and surgical outcomes were collected to compare nonunion rates, as well as early and late complications, between the LP and DCP groups.

Results
A total of 368 patients were included in the analysis. Among them, 132 (35.9%) had isolated radial shaft fractures, 116 (31.5%) had isolated ulnar shaft fractures, and 120 (32.6%) had both-bone fractures. Of these, 124 patients received LP implants, 98 were treated with LCPs, and 146 were treated with DCPs. Early complications were comparable among the groups; however, the nonunion rate was significantly higher in the LP group (18.5% versus 11.2% versus 6.2%, p < 0.007). Logistic regression identified LP use [odds ratio (OR): 3.05, 95% confidence interval (CI) 1.24–7.53] as a significant predictor of nonunion. Notably, LPs lacking dynamic compression functionality were associated with markedly higher odds of nonunion in radial shaft fractures (OR: 26.94, 95% CI 3.52–206.15). These findings collectively indicate that LPs increase the nonunion rate in forearm fractures.

Conclusions
Using LPs without compression functionality to treat forearm diaphyseal fractures increases the nonunion rate, particularly in radial shaft fractures. Therefore, we recommend using LCPs or DCPs for forearm diaphyseal fractures to ensure adequate compression at the fracture site during fixation, thereby promoting optimal bone healing rates.

Level of evidence: Level III: retrospective comparative therapeutic study.
Therapeutic potential of a newly isolated bacteriophage against multi-drug resistant Enterococcus faecalis infections: in vitro and in vivo characterization
Authors: Ali Zienab , Abdelkader Karim , Abdel-Fattah Maha M. , Azmy Ahmed Farag , El-Gendy Ahmed O. , Dishisha Tarek 
Published: February 2025

Abstract

Background
In nosocomial settings, vancomycin-resistant Enterococcus faecalis is a major health threat leading to increased morbidities, mortalities, and treatment costs. Nowadays, several approaches are under investigation to enhance the activity of or replace the traditional antibiotics. Bacteriophage therapy was sought as a potential approach for combating E. faecalis infections. The present study focuses on isolating and characterizing bacteriophage against clinical multi-drug resistant (MDR) E. faecalis strain Lb-1492. The phage stability, lytic activity, host-range, latent period, burst size, the ability to detach the pre-formed biofilm and destroy entrapped cells were investigated. The phage genome was purified, sequenced, and subjected to bioinformatics analysis for identifying and characterizing its features, as well as, the suitability for clinical application. Finally, the ability of the phage to rescue mice from deadly, experimentally induced E. faecalis bacteremia was evaluated.

Results
A virulent phage was isolated from sewage water against a clinical MDR E. faecalis isolate. Morphological and genomic studies indicated that the phage belongs to the Efquatrovirus genus, with a long tail, icosahedral head and a linear double-stranded DNA genome of approximately 42.9 kbp. The phage was named vB_Efa_ZAT1 (shortly ZAT1). It demonstrated a shorter latent period and larger burst size than regular-tailed phages, and a characteristic stability over a wide range of pH and temperatures, with the optimum activity at pH 7.4 and 37 °C, respectively. Phage ZAT1 showed a narrow spectrum of activity and a characteristic biofilm disruption ability. The phage managed successfully to control E. faecalis-induced bacteremia in mice models, which was lethal within 48 h in the control group. An intraperitoneal injection of 3 × 108 PFU of the phage solution given 1 h after the bacterial challenge was sufficient to save all the animals, completely reversing the trend of 100% mortality caused by this bacterium.

Conclusions
Phage therapy can be a promising alternative to traditional antibiotics in the post-antibiotic era with a significant antimicrobial and antibiofilm activities against MDR E. faecalis.
Casual effect of ulcerative colitis on chronic heart failure: results from a bidirectional Mendelian randomization study
Authors: Chu Yuzhou , Li Jianhua , Gong Li , Shao Sheng , Chen Hao , He Pengfei , Yan Juntao 
Published: February 2025

Abstract
This study aimed to detect the causal effect of ulcerative colitis (UC) on heart failure. A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The causal impact of UC on heart failure was determined via MR by performing a genome-wide association study in which 4 UCs descending from European ancestors were set as individual exposures. The inverse-variance weighted (IVW) method was used as the main method, and 4 other methods were set as assistant parameters. Susbequently, the MR results were combined with meta-analysis results. The MR Egger method was employed to investigate pleiotropy. The leave-one-out method was utilized for sensitivity analysis. Furthermore, a reverse-directional study was conducted. There was evidence of the causal effect of UC on heart failure in MR estimates using 4 UC datasets. The IVW method revealed that the odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.01–1.06, P = 0.0441 when the first UC dataset was used; OR = 1.03, 95% CI = 1.01–1.05, P = 0.0445 when the second UC dataset was used; OR = 2046, 95% CI = 1.37-3.05E + 06, P = 0.0409 when the third UC dataset was used; and OR = 8.12E + 04, 95% CI = 29.09-2.27E + 08, P = 0.0052 when the fourth UC dataset was used. A meta-analysis of 4 MR studies revealed that UC had a statistically significant causal effect on heart failure (OR = 1.03, 95% CI = 1.01–1.05; P = 0.0074). Reverse MR analysis revealed that heart failure did not have a causal effect on UC. There was no pleiotropy. This MR study demonstrated that UC had a causal effect on heart failure and that there was no reverse causal effect.
The impact of functional MDM2-polymorphisms on neutrophil counts in breast cancer patients during neoadjuvant chemotherapy
Authors: Hatletvedt Nora D. , Engebrethsen Christina , Geisler Jürgen , Geisler Stephanie , Aas Turid , Lønning Per E. , Gansmo Liv B. , Knappskog Stian 
Published: February 2025

Abstract

Background
Functional polymorphisms in the MDM2 promoters have been linked to cancer risk and several non-malignant conditions. Their potential role in bone marrow function during chemotherapy is largely unknown.

Methods
We investigated the potential associations between genotypes of MDM2 SNP309 (rs2279744), SNP285 (rs117039649) and del1518 (rs3730485) and neutrophil counts in breast cancer patients receiving neoadjuvant sequential epirubicin and docetaxel, with additional G-CSF, in the DDP-trial (NCT00496795). We applied longitudinal ratios, post vs. pre-treatment, of neutrophil counts as our main measure. Differences by genotypes were tested by Jonckheere-Terpstra test for ranked alternatives, while dominant and recessive models were tested by Mann–Whitney U test, and additional sub-analyses were performed for genotype combinations.

Results
The SNP309 reference T-allele was associated with a better sustained neutrophil count (p = 0.035). A similar association was observed for the alternative del-allele of the del1518 (p = 0.049). Additionally, in combined genotype-analyses, patients with the SNP309 TT genotype and at least one copy of the del1518 del-allele had particularly favorable sustained neutrophil counts during chemotherapy treatment (p = 0.005).

Conclusions
Our study provides evidence that MDM2 promoter polymorphisms may be associated with neutrophil counts and bone marrow recovery during chemotherapy treatment in breast cancer patients.

Trial registration
The DDP-trial was registered at ClinicalTrials.gov (NCT00496795; registration date 2007–07-04).
Effectiveness of topical application with dexamethasone during sagittal split osteotomy of the mandible in minimising clinical symptoms of postoperative neurosensory disorders
Authors: Logvynenko Iryna , Dakhno Larysa , Bursova Valeriia 
Published: February 2025

Abstract

Background
The aim of this study was to investigate the effectiveness of topical application with dexamethasone during BSSO due to its anti-inflammatory effect and decreasing of postoperative nerve oedema in minimising clinical symptoms of NSD associated with inferior alveolar nerve (IAN) injury in postoperative period, based on the results of sensory diagnostic tests, such as light touch test and its modifications.

Methods
Through randomisation, 2 groups were selected from 22 patients: the experimental– where topical application with solution of dexamethasone phosphate 0.4% (4 mg/1 ml ampules) during sagittal split osteotomy of the mandible was used, and the control– where the classical technique of BSSO was held.

Results
Authors performed diagnostics of NSD using Light Touch test on 1st day, 1st week, 1st month, 3rd month and 6th month postoperatively. The experimental group showed improvements in sensory recovery compared to the control group, particularly from 1 week to 3 months post-surgery. By 6 months, both groups achieved similar levels of sensitivity restoration.

Conclusions
This confirms the effectiveness of proposed method and opens up further prospects for the updated function of the IAN following the BSSO.

Clinical trial number
Not applicable.