bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-Human Clinical Trial of a Small-Molecule EBNA1 Inhibitor, VK-2019, in Patients with Epstein-Barr–Positive Nasopharyngeal Cancer, with Pharmacokinetic and Pharmacodynamic Studies
Authors: Colevas A. Dimitrios , Talebi Zahra , Winters Elizabeth , Even Caroline , Lee Victor Ho-Fun , Gillison Maura L. , Khan Saad A. , Lu Rong , Pinsky Benjamin A. , Soldan Samantha S. , Vladmirova Olga , Lieberman Paul M. , Messick Troy E. 
Published: January 2025

Abstract

Purpose:
A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1).

Patients and Methods:
Pharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment.

Results:
VK-2019 was well tolerated. One patient achieved a partial response. Pharmacokinetic results demonstrated good systemic exposure, with high intersubject variability. Decreases in EBV DNA plasma levels were observed in some patients. VK-2019 reduced EBV genome copy number and viral gene expression in patient tumor samples and induced changes in immune cell markers.

Conclusions:
VK-2019 at dosages up to 1,800 mg daily demonstrated an acceptable safety profile, achieved micromolar plasma concentrations, and showed on-target biological activity in tumors from patients with advanced EBV-positive nasopharyngeal carcinoma.
O warsztacie leksykograficznym Johannesa Reuchlina
Authors: Lenartowicz-Zagrodna Anna 
Published: January 2025

On the Lexicographic Workshop of Johannes Reuchlin
The work of Johannes Reuchlin Vocabularius breviloquus is an important milestone in the history of lexicography. Frequently reissued, it stimulated readers to contemplate the relationships between the Latin and national languages. This is evidenced by copies with Czech or German glosses; one of the copies of the dictionary belonged to Bartholomeus de Bydgostia, who added Polish glosses to some entries – this is how the work containing the most Polish words of that time was created. So far, Reuchlin’s Vocabularius has not attracted significant attention from Polish linguists, although examining this source could yield new insights into Bartholomeus himself, the significance of his achievements, his working methods, as well as the quality of the Polish language and its equivalence. The aim of this study is to provide an initial exploration of the Vocabularius, namely, to present general information about this work, situate it within the tradition of lexicography, and showcase the dictionary itself, its content and the nature of its lexical layer (on selected examples).

O warsztacie leksykograficznym Johannesa Reuchlina
Dzieło Johannesa Reuchlina Vocabularius breviloquus stanowi ważne ogniwo w dziejach leksykografii. Wielokrotnie wznawiane, pobudzało czytelników do rozważań nad relacjami między łaciną a językami narodowymi. Świadczą o tym egzemplarze z glosami czeskimi czy niemieckimi; jeden z egzemplarzy dzieła był własnością Bartłomieja z Bydgoszczy, który dodał do niektórych haseł polskie glosy – tak powstało najobszerniejsze świadectwo zasobów leksykalnych ówczesnej polszczyzny. Vocabularius Reuchlina nie cieszył się dotychczas szczególnym zainteresowaniem polskich językoznawców, choć zbadanie tego źródła może przynieść nowe wnioski na temat samego Bartłomieja, rangi jego dokonań, sposobu pracy czy też jakości polszczyzny i ekwiwalencji. Celem niniejszego opracowania jest wstępne rozpoznanie Vocabulariusa, mianowicie: przedstawienie ogólnych informacji o tym dziele, umiejscowienie go na tle tradycji leksykograficznej, zaprezentowanie samego słownika, jego zawartości i charakteru warstwy leksykalnej (na wybranych przykładach).
Investigating the physico-mechanical and thermal properties of flexible polyurethane foams made with standard and special polyols produced by the variable pressure foaming technique
Authors: Singh Vratika , Gopalasamudram Mahesh N , Maitra Jaya 
Published: January 2025

This study demonstrates the technical viability of producing low-density flexible polyurethane foam (14 kg/m³) at low vacuum pressure (600 mbar) using both conventional polyether polyol (Polyol-1) and a special polyether polyol (Polyol-2) with variable pressure foaming (VPF) technology. The foam made with Polyol-2 exhibited superior mechanical properties, including increased elongation, resilience, and softness, compared to Polyol-1. SEM analysis revealed that Polyol-2 foam had a more open, irregular cell structure, contributing to improved elasticity. TGA analysis confirmed that the foam produced from Polyol-2 exhibited greater thermal stability at low vacuum pressure. FTIR characterization confirmed the distinct chemical structure of Polyol-1 and Polyol-2 foam. Low-density foams in the polymer sector are often produced using conventional processes that rely on auxiliary blowing agents such methylene chloride, acetone, pentane, carbon dioxide, trichloroethane, and chlorofluorocarbon. Unfortunately, a lot of these chemicals are restricted because of environmental issues, such as health hazards and ozone layer depletion. In the present research the foams were produced without auxiliary blowing agents (ABA), addressing environmental concerns. This research highlights the potential of Polyol-2 foam for comfort layer applications, offering enhanced mechanical properties, durability, and sustainability over conventional foam production methods.
Biparametric magnetic resonance imaging as a diagnostic tool for differentiating RCC and renal pseudotumor in CKD patients
Authors: Raj Himanshu , Lal Hira , Rustagi Sanchit , Yadav Arpan , Singh Uday Pratap , Baid Anil , Sureka Sanjoy Kumar 
Published: January 2025

Introduction: Pseudotumors are benign lesions which may mimic like a malignant tumor on conventional imaging. They are formed in kidneys which are scarred and deformed by chronic pyelonephritis, glomerulonephritis, trauma or infarction. There is a diagnostic dilemma in most of the cases as to differentiate RCC and pseudotumors. Our study shows bp-MRI (T2w, DW MRI) can distinguish pseudotumors from RCCs and offers a non-contrast non-invasive alternative in CKD patients. Materials and Methods: Prospective evaluation of 80 CKD patients (CKD IV/V), having suspicious renal mass <4 cm on Ultrasound, were subjected to bp-MRI. Two groups were defined on the basis of restriction pattern on DWI. ADC values were calculated. Group I (suspected RCC or malignant tumor) underwent surgical management according to the institutional protocol. Group II (suspected pseudotumor) were subjected to biopsy. ROC curves were drawn to find out area under curve for differentiation of groups and cut-off ADC values calculated so as to achieve highest average sensitivity and specificity. A p-value of <0.05 was considered as statistically significant. Results: Sixty patients (Group I) had restricted pattern on DWI imaging whilst 20 had no restriction (Group II), hence ruling out malignancy. It showed a sensitivity of 81.82%, specificity 96.55% in the correct diagnosis. Mean ADC-value for CKD pseudotumors (Group II) was significantly higher than RCCs and surrounding diseased parenchyma (2.20 vs 1.52 (×10−3 mm2/s; p < 0.0001) and 1.99 (×10−3 mm2/s; p = 0.0001) respectively). ROC analysis for differentiating CKD pseudotumors and RCC yielded high sensitivity (85%) and specificity (99%) for cut-off ADC-value of 1.71 (×10−3 mm2/s). Conclusion: bp-MRI is a highly reliable imaging modality for the evaluation of renal lesions. Its ability to accurately differentiate pseudotumors from renal cell carcinomas, even in the absence of contrast administration can be a boon in the diagnostic armamentarium.
Economic Policy Uncertainty and Corporate Dividend: Does the Presence of Government Shareholders Play a Role?
Authors: Tran Ly Thi Hai , Bao Ho Hoang Gia 
Published: January 2025

This article examines the effect of economic policy uncertainty (EPU) on the dividend policies of Vietnamese listed firms moderated by the role of government shareholders. A wide range of control variables and different regression methods are used to ensure the reliability of the results. We find that firms distribute more cash to shareholders under increased EPU. Notably, the presence of the government shareholder reduces the effect of EPU on dividends. Further analyses indicate that firms with state ownership cut dividends for increasing capital expenditures rather than other purposes such as cash hoarding, debt reduction, inventory expansion, or dealing with declined profits. This article enhances the understanding about the connection between government ownership, EPU, and dividend policy. JEL Codes: C30, C32, C35
Association Between BMI and Neurocognitive Functions Among Middle-aged Obese Adults: Preliminary Findings Using Machine-learning (ML)-based Approach
Authors: Magan Dipti , Yadav Raj Kumar , Aneja Jitender , Pandey Shivam 
Published: January 2025

Background Studies suggest that obesity predisposes individuals to developing cognitive dysfunction and an increased risk of dementia, but the nature of the relationship remains largely unexplored for better prognostic predictors. Purpose This study, the first of its kind in Indian participants with obesity, was intended to explore the use of quantification of different neurocognitive indices with increasing body mass index (BMI) among middle-aged participants with obesity. Additionally, machine-learning models were used to analyse the predictive performance of BMI for different cognitive functions. Methods In the cross-sectional analytical study, a total of 137 ( n = 137) participants were included. Out of the total, 107 healthy obese (BMI = 23.0–30.0 kg m−2; age between 36 and 55 years of both genders) were recruited from the out-patient department of the Department of Endocrinology and General Medicine, and 30 participants were recruited as the control group, between March 2023 to February 2024. The participants underwent neuropsychological assessments, including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and serum levels of brain-derived neurotrophic factor (BDNF). Results Significant ( p < .05) differences were observed for neurocognitive functions for the obese group versus the control group. According to the correlation heatmaps, BMI was significantly ( p < .05) negatively associated with BDNF. Multivariate linear regression analysis revealed a substantial ( p < .05) decline in BDNF with a change in BMI, accenting its significant impact on cognitive ageing. Additionally, consistent decreasing trends were observed across the MoCA and MMSE, confirming the robustness of the findings across diverse analytical methodologies. Furthermore, the linear regression model and super vector machine model contributed additional evidence to the consistency of the trends in cognitive decline linked to BMI variations. Conclusion The preliminary results of the present study support that increased BMI is an important physiological indicator that influences neurocognition and neuroplasticity in individuals with obesity.
Nurturing Wellness: Development and Evaluation of a Novel Herbal Formulation with Immunomodulatory Activity
Authors: Maru Saurabh , Belemkar Sateesh 
Published: January 2025

Background Disease prevention prevailed in the post-COVID world. The global trends are trailing toward prevention and immunity enhancement with alternative therapies and herbal drugs. Purpose The current research was performed to prepare and standardize a herbal formulation reported to have multiple health benefits including immunomodulation. Methods Ethanolic extracts of Asparagus racemosus, Tinospora cordifolia, and Trigonella foenum-graecum were prepared and used in the proportion of 1:1:1. The extracts were analyzed for phytochemicals and further standardized by high-performance thin layer chromatography (HPTLC) with analytical standards for all three drugs, that is, shatavarin IV, trigonelline, and berberine. The A. racemosus, T. cordifolia, and T. foenum-graecum extract blend (ATTEB) was tested for neutrophil adhesion and carbon clearance to check for overall immunomodulatory activity. The effervescent tablets were formulated and evaluated for various pharmacopoeial parameters. Accelerated stability studies of the formulations were done for 6 months duration as per the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) guidelines. Results The phytochemical and HPTLC results confirmed the presence of bioactive constituents in extracts and formulation. The blend of extract ATTEB (neutrophil adhesion: 52.17 ± 0.79, phagocytic index: 0.0292 ± 0.002) enhanced neutrophil adhesion by approximately 35% from the control group (16.91 ± 1.94), with almost five-fold higher phagocytic index compared to the control group (0.0056 ± 0.004) and even higher compared to the standard drug group (0.022 ± 0.001). A ready-to-use formulation of effervescent tablets was prepared and evaluated. The B7 batch showed a suitable formulation based on the various evaluation parameters. The formulation was found to be stable under 6-month accelerated stability studies. Conclusion The research study successfully developed a novel formulation of the blend with immunomodulatory activity.
A Case Report on Hypothalamic Hamartoma—An Odd Cause of Unusual Seizure Presentation and Drug-resistant Epilepsy in Children
Authors: MV Vijitha , MO Nirmala , Vilanilam George C , L Suja Raj 
Published: January 2025

Background Hypothalamic Hamartoma (HH) is a rare benign mass in the hypothalamus that typically manifests as gelastic seizures (GS) (epileptic events characterized by bouts of laughter inappropriate to the context) resulting in treatment-resistant epilepsy, central precocious puberty (CPP), cognitive decline, or behavioral abnormalities in children. Purpose To find out the menifestations and management of child with HH. Methods We report the case of a two-year-old child diagnosed with HH, which manifested as refractory GS, development of secondary sexual characteristics, and aggressive behavior. Results The child was managed successfully by surgical resection of the mass. The postoperative phase was uneventful, with a good outcome. Timely detection of the condition, parental counseling and education, and early management of the case is important for the best outcome.
Symptomatic Accessory Navicular Treated With Endoscopic Accessory Navicular and Partial Navicular Resection
Authors: Nakajima Kenichiro 
Published: January 2025

Background: This study aims to report the results of the patients with symptomatic accessory navicular (AN) who underwent endoscopic AN and partial navicular resection. Methods: The medical records of patients with type 2 symptomatic AN who underwent the aforementioned surgery at our hospital from November 2019 to May 2022 with a follow-up of >2 years were reviewed. Data on clinical, radiographic, and patient-reported outcomes were obtained. Results: The analysis included 29 patients (20 females; mean age, 19.6 years; mean body mass index, 21.5) with a mean follow-up duration of 39.5 months. Comparing the preoperative and postoperative scores, visual analog scale score improved from 74.6 to 5.4, and the Japanese Society for Surgery of the Foot score improved from 63.0 to 95.9. We had one wound dehiscence and no other recognized complications. Magnetic resonance and ultrasonographic imaging done 1 year postoperatively revealed that the empty space that remained after resection of the AN was filled with tendonlike tissue. Conclusion: Endoscopic AN and partial navicular resection for treating symptomatic AN resulted in good outcomes and only one case with wound complications.
Evaluation of mental disorder related to colposcopy procedure during the COVID period: A cross-sectional study
Authors: Bochicchio Ilaria , Catalano Martina , Deiana Giovanni , Roviello Giandomenico , Marino Pasquale , Calenda Fabrizia , Lettini Alessandro R , Sanseverino Francesca 
Published: January 2025

Background: The Coronavirus Disease (COVID-19) has had a significant impact on healthcare organizations, leading to a reduction in screening. The pandemic period has caused important psychological repercussions in the most fragile patients. Objectives: This study aimed to assess the levels of depression, anxiety, peri-traumatic stress, and physical symptoms in patients undergoing colposcopy during the COVID-19 pandemic and to compare these data with the post-pandemic period. Design: This longitudinal study included 96 individuals undergoing colposcopy, aged between 22 and 64, who were examined between March 2020 and December 2023. Methods: Participants were assessed at four distinct time points, referred to as T0, T1, T2, and T3. T0 encompassed the pandemic period, ranging from March 2020 to August 2020, while T1 occurred 1 year later, T2 and T3 correspond to data collected in 2022 and 2023. Statistical analysis was conducted to assess the impact of the COVID-19 pandemic on various psychological variables. Descriptive statistics, including means, standard deviations, and frequency distributions, were calculated for each psychological variable within each time period. Results: Our findings revealed a significant reduction in peri-traumatic stress and pain levels in the post-pandemic (from 2021 to 2023) period compared to the pandemic period. Conversely, anxiety and depression levels exhibited a statistically significant increase in the post-pandemic period and then gradually decrease in the subsequent follow-up. Conclusion: This study provides valuable insights into the profound impact of the COVID-19 pandemic on psychological distress experienced during the pandemic period itself, as well as its enduring effects on anxiety and depression in the subsequent period.
Association of killer immunoglobulin-like receptor genotypes and haplotypes with acute lymphoblastic leukemia risk
Authors: Al-Tamimi Jameel , Alomar Suliman , Aljuaimlani Ali , Mansour Lamjed 
Published: January 2025

Background Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between KIR genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients. Methods A total of 259 Saudi subjects including 145 cases of acute lymphoblastic leukemia (ALL) and 114 healthy controls living in Riyadh were genotyped for 16 KIR genes and the two HLA-C1 and -C2 allotypes using PCR-SSP genotyping method. Results A significant high frequency of the two inhibitory KIR genes; 2DL1 (OR = 2.4; p < 0.0001) and 3DL1(OR = 10.87; p = 0.0068) in ALL compared to healthy group was observed. In contrast, the activating 2DS4 gene was significantly higher in healthy controls (OR = 0.15, p < 0.0001) compared to ALL patients. Haplotype analysis shows that BX haplogroup was strongly associated with the occurrence of ALL (OR = 4.39; p < 0.0001). Further combinatory analysis of KIR genes with their HLA-C1 and -C2 ligands demonstrated strong statistically protective effect of the 2DS1-C2 combination from ALL (OR = 0.06; p = 0.0003). Conclusion This study presents strong evidence supporting the connection between certain KIR genotypes, haplotypes, and KIR-HLA combinations with acute ALL in the Saudi population. The heightened occurrence of inhibitory KIR genes ( 2DL1 and 3DL1) and the BX haplotype in ALL patients indicates a possible involvement of these genetic variability with the dysfunctional of NK cells in the context of ALL disease.
Automatic tool for the reconciliation of serious adverse events for pharmacovigilance: design and implementation of Reconciliaid
Authors: Contu Sara , Schiappa Renaud , Chateau Yann , Chamorey Emmanuel 
Published: January 2025

Background: Reporting serious adverse events (SAEs) is crucial to reduce or avoid toxicities that can lead to major consequences for patient’s health due to treatments tested in clinical trials. Its exhaustiveness is often inadequate, and we observe discrepancies between data published by pharmacovigilance organizations and clinical databases. Objectives: While the process of reconciliation aims at reducing these differences, it remains a very time-consuming and imprecise task. We propose a tool to automate this process. Design: We have developed and tested Reconciliaid, an application that compares the SAEs of the databases of clinical trials collected according to a standard inspired by the Clinical Data Interchange Standards Consortium, and of pharmacovigilance collected according to the international standards ICH-E2B (R3). It generates a reconciliation file that indicates precisely what information does not coincide in the two databases to facilitate the identification of inconsistencies. Methods: Reconciliaid was tested to create 13 reconciliation files, containing 290 SAEs. We inspected these files to determine their ability in identifying the inconsistencies and compared the manual and semi-automated reconciliation time. Four users answered the System Usability Scale (SUS) to measure its usability. Results: The application identified all variables of interest in all reconciliations. Different formats and libraries were automatically harmonized, allowing a perfect identification of inconsistencies for all variables. The matching of the same SAE in the two databases was correct in 97.2% of the reconciliations. Reconciliaid is six times faster than the manual approach for senior data managers (range = 3–24 times). A novice data manager performed three reconciliations 4.8 faster with the help of Reconciliaid than manually (29 min vs 134 min) and with fewer mistakes. Mean SUS score was 92.5. Conclusion: Reconciliaid has a high level of usability, can increase the quality of reconciliation, and reduces considerably the reconciliation time, allowing to increase the frequency of reconciliation processes and to focus resources on patient safety and medical assessment.