bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies
Authors: Carneiro Ana , Hahn Amanda , Ellmark Peter , Enell Smith Karin , Schultz Lena , Ambarkhane Sumeet , Yachnin Jeffrey , Ullenhag Gustav J. 
Published: January 2025

BackgroundATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cell death.MethodsIn this first-in-human, multicenter, phase I study, ATOR-1017 was administered intravenously every 21 days as a monotherapy to patients with advanced, unresectable solid tumors having received multiple standard-of-care treatments. The study used single patient cohorts for rapid dose escalation up to 40 mg; thereafter a modified 3+3 design up to 900 mg. Escalating doses were given until disease progression, unacceptable toxicity, or withdrawal of consent. The primary objective of the study included determination of the maximum tolerated dose (MTD) via assessment of adverse events and dose-limiting toxicities (DLTs). Secondary objectives included determination of the pharmacokinetics, immunogenicity and clinical efficacy assessed with CT scans using immune Response Evaluation Criteria in Solid Tumors. Exploratory objectives included pharmacodynamic (PD) assessment of immune system biomarkers.ResultsOf the 27 patients screened, 25 received treatment with ATOR-1017. The median time on study was 13.1 weeks (range 4.3–92.3). The MTD of ATOR-1017 was not reached. Treatment-related adverse events (TRAEs) were reported in 13 (52%) of 25 patients; most common (≥10%) were fatigue (n=4 (16.0%) patients) and neutropenia (n=3 (12.0%) patients). Five patients experienced a severe (≥ grade 3) TRAE; neutropenia (n=2), febrile neutropenia (n=1), chest pain (n=1), increased liver enzymes (n=1), and leukopenia and thrombocytopenia (n=1). No patients discontinued due to TRAEs and no DLTs were observed. Pharmacokinetic data demonstrated approximate dose-proportional kinetics. Dose-dependent increases in PD biomarkers, including soluble 4-1BB, are indicative of target-mediated biological activity. Best response was stable disease in 13 out of 25 patients (52%), maintained for 6 months or longer in six patients (24%).ConclusionsTreatment with ATOR-1017 was safe and well tolerated at all dose levels and demonstrated biological activity. Furthermore, almost one-third of patients experienced long-lasting stable disease in this heavily pretreated population. The encouraging safety and preliminary efficacy data warrant further clinical development of ATOR-1017, possibly in combination with other anticancer agents.
Working years lost in people with epilepsy: a population-based cohort study
Authors: Dreier Julie Werenberg , Trabjerg Betina B , Lolk Kasper , Plana-Ripoll Oleguer , Christensen Jakob 
Published: January 2025

BackgroundWe quantify the loss of working years for people with epilepsy compared with the general population and consider variation by aetiology, psychiatric comorbidity, sex and age.MethodsThis population-based cohort study included all individuals aged 18–65 years living in Denmark from 1995 to 2018. Using nationwide registers since 1977, we identified people with epilepsy and obtained information on the main source of income or employment for each year during follow-up from 1995 to 2020. The main outcome was number of working years lost in people with epilepsy compared with the general population of same sex and age, capturing both working life lost due to permanent (death, disability pension, early retirement) and temporary (unemployment, sick leave) factors.ResultsThe study comprised 5 466 140 individuals, including 74 980 (1.4%) with epilepsy. In people with epilepsy, the number of working years was on average reduced by 6.6 (95% CI: 6.5 to 6.7) years compared with the general population, largely due to disability pension (4.8 years, 95% CI: 4.7 to 4.9) and premature death (1.6 years, 95% CI: 1.6 to 1.7). Loss of working life was more pronounced in those with a presumed underlying aetiology (9.0 years (95% CI: 8.9 to 9.2) vs 5.4 years (95% CI: 5.2 to 5.5) in those with unknown aetiology), those with psychiatric comorbidity (14.5 years (95% CI: 14.2 to 14.7) vs 5.6 years (95% CI: 5.5 to 5.7) in those without), men (7.2 years (95% CI: 7.1 to 7.3) vs 5.9 (95% CI: 5.8 to 6.0) years in women) and people with early onset of epilepsy (eg, 11.5 years (95% CI: 11.3 to 11.7) among those with onset <20 years).ConclusionsEpilepsy was associated with significant loss of working life resulting from both disability and premature death.
Roadmap for the transition to robotic radial cystectomy for patients with bladder cancer in a tertiary urology unit: planning for change
Authors: Keenan Robert Anthony 
Published: January 2025

BackgroundRadical cystectomy has the potential to be a curative strategy for patients with aggressive bladder cancer. Emerging evidence over the last 20 years has shown that minimally invasive surgical approaches using robotics in performing this highly complex and morbid operation can achieve the same oncological outcomes while reducing complications for the patient.ObjectiveThis paper aims to present a managerial and leadership roadmap for change to robotic cystectomy for patients with advanced bladder cancer to achieve improved patient outcomes while embracing technological developments in the delivery of cancer care.MethodsUsing the Irish Health Service Executive guide for change, we propose and detail a three-stage plan (define, design and deliver) to guide the organisation from the concept of the transition to performing the first operative case.ResultsA walkthrough from identifying a vision for change for robotic cystectomy to designing a step-by-step process is discussed. By providing a template for success, this approach can be applied to any health jurisdiction worldwide and can be adapted as needed.ConclusionAlthough challenging, major change within the healthcare setting through a structured approach provides a valuable opportunity for a department to grow, develop and become a champion of patient care.
The Effect of Oral Magnesium Supplement on Postoperative Pain Following Mandibular Third Molar Surgery: A Split‐Mouth Randomized Placebo‐Controlled Trial
Authors: Nimkulrat Sutthipat , Phinyo Phichayut , Powcharoen Warit 
Published: January 2025

Objective: This study aimed to evaluate the analgesic efficacy of oral magnesium supplements, administered as an analgesic adjuvant to ibuprofen, on acute postoperative pain within 72 h following mandibular third molar (MTM) surgery.Materials and Methods: This triple‐blind, placebo‐controlled, split‐mouth randomized study was conducted among 25 patients (50 MTMs), who intended to remove both MTMs. All patients underwent two surgeries separated by an interval of at least 4 weeks. For each surgery period, patients were randomly assigned with either receiving NSAIDs plus oral magnesium supplement (25 MTMs) or NSAIDs plus placebo (25 MTMs) for three days after surgery. The postoperative pain intensity at rest and movement were primarily evaluated at 24 h, postoperatively. Participants were also asked to record pain intensity at 6, 48, and 72 h, postoperatively, rescue analgesic consumption, time to first rescue analgesic, and magnesium‐related adverse events.Results: The combination of ibuprofen plus oral magnesium supplement significantly decreased pain intensity at rest 24 h, postoperatively, compared to placebo (estimated mean difference −15.08; 95%CI −29.01 to −1.14). However, the pain intensity at rest and movement were similar between groups at other time points. There was no significant difference among groups in terms of rescue analgesic consumption and time to first rescue analgesic. No magnesium‐related adverse event was observed.Conclusion: The addition of oral magnesium supplement as an analgesic adjuvant to NSAIDs significantly decreased pain intensity at rest 24 h following MTM surgery. Nevertheless, this result might not provide clinically relevant benefits for pain control following MTM surgery.Trial Registration: ClinicalTrials.gov identifier: TCTR20221003004
ХРОМАТОГРАФІЧНЕ ДОСЛІДЖЕННЯ КОМПОНЕНТНОГО СКЛАДУ І ВМІСТУ ФЕНОЛЬНИХ СПОЛУК ПЕРЕСТРІЧУ ГАЙОВОГО (MELAMPYRUM NEMOROSUM L.)
Authors: Reznik V. V. , Grytsyk A. R. 
Published: January 2025

Мета роботи. Визначити компонентний склад флавоноїдів, фенолкарбонових кислот і катехінів у траві перестрічу гайового (Melampyrum nemorosum L.) вітчизняної заготівлі.
Матеріали і методи. Траву M. nemorosum заготовляли у 2022 р. у фазі цвітіння в околицях с. Микитинці Косівського району Івано-Франківської області. Компонентний склад фенолкарбонових кислот, флавоноїдів і катехінів визначали методом високоефективної рідинної хроматографії (ВЕРХ) на рiдинному хроматографi “Agilent Technologies 1200”, який укомплектований проточним вакуумним дегазатором, чотириканальним насосом градієнта низького тиску, автосамплером, термостатом колонок, діодноматричним детектором, з використанням колонок Zorbax SB-С18 та Zorbax SB-Aq.
Результати й обговорення. Методом ВЕРХ у траві M. nemorosum ідентифіковано та встановлено їх кількісний вміст 9 флавоноїдів (рутин, кверцетин-3-β-глюкозид, нарингін, неогесперидин, кверцетин, нарінгенін, апігенін, рамнетин, кемпферол), серед яких 5 флавонолів, 3 флавонони і 1 флавон. Крім того, було виявлено 3 катехінові сполуки (катехін, епікатехін, та галокатехін), а також 9 фенолкарбонових кислот (гідроксифенілоцтова, хлорогенова, кофейна, сирінгова, бензойна, n-кумарова, транс-ферулова, синапова, транс-корична) .
Висновки. 1. За допомогою ВЕРХ-аналізу визначено компонентний склад флавоноїдів, фенолкарбонових кислот і катехінів трави M. nemorosum, яку заготовлено в Україні. 2. Серед сполук флавоноїдної природи переважали рутин (3388,58 мкг/г), кверцетин (716,44 мкг/г), нарингін (679,21 мкг/г), рамнетин (662,69 мкг/г) та неогесперидин (588,90 мкг/г). Серед фенолкарбонових кислот домінувала бензойна кислота (948,54 мкг/г), а серед катехінів – епікатехін (415,71 мкг/г). 3. Перспективним напрямком подальших досліджень є вивчення компонентного складу фенольних сполук трави M. nemorosum, які заготовлено у різних регіонах України.
СИНТЕЗ ПОХІДНИХ 6-АРИЛ/ГЕТЕРИЛТРИАЗОЛО[3,4-b][1,3,4]ТІАДІАЗОЛІВ ТА ДОСЛІДЖЕННЯ ЇХ ПРОТИМІКРОБНОЇ АКТИВНОСТІ
Authors: Myrko I. I. 
Published: January 2025

Мета роботи. Синтез нових 6-арил/гетерилтриазоло[3,4-b][1,3,4]тіадіазолів та дослідження їх антибактеріальної та протигрибкової активності.
Матеріали і методи. Органічний синтез, елементний аналіз, 1Н ЯМР спектроскопія, фармакологічний скринінг, докінг.
Результати й обговорення. Здійснено синтез похідних 6-феніл/піридил-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазолу. Досліджено їх протимікробну активність. Встановлено, що 3-(4-хлоробензил)-6-феніл-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазол 2 володіє високою антибактеріальною активністю по відношенню до S. aureus ATCC 43300, а 3-(4-хлор/метоксибензил)-6-піридин-3-іл-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазоли 3, 4a, b ефективно інгібують ріст штаму грибків C. Neoformans ATCC 208821. Використовуючи докінгові дослідження сполук, що проявили протигрибкову активність, визначено величину енергії зв’язування, конформаційне розташування лігандів в активному центрі ланостерол 14α-деметилази, а також природу амінокислотних залишків і тип взаємодії, який реалізується.
Висновки. Розроблено метод синтезу похідних 6-феніл/піридил-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазолу. Ідентифіковано сполуки, що володіють високою протимікробною активністю по відношенню до штамів S. aureus ATCC 43300 та C. Neoformans ATCC 208821.
Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility
Authors: Isaacs Aaron , Zeemering Stef , Winters Joris , Batlle Montserrat , Bidar Elham , Boukens Bas , Casadei Barbara , Chua Winnie , Crijns Harry J.G.M. , Fabritz Larissa , Guasch Eduard , Hatem Stephane N. , Hermans Ben , Kääb Stefan , Kawczynski Michal , Maesen Bart , Maessen Jos , Mont Lluis , Sinner Moritz F. , Wakili Reza , Verheule Sander , Kirchhof Paulus , Schotten Ulrich , Stoll Monika 
Published: January 2025

BACKGROUND:
Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease etiology. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrium (LA) and right atrium (RA) may provide insight into diseases such as atrial fibrillation.

METHODS:
Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design. The design took advantage of the availability of 32 paired samples, for which both LA and RA tissue were obtained, as a discovery cohort, and 98 LA and 69 RA unpaired samples utilized as a replication cohort.

RESULTS:

A total of 714 transcripts were identified and replicated as differentially expressed (DE) between LA and RA, as well as 98 exons in 55 genes. Approximately 50% of DE transcripts were colocated with another frequently correlated DE transcript (
P
FDR
≤0.05 for 579 regions). These “transcription disequilibrium” blocks contained examples including side-specific differential exon usage, such as the
PITX2
locus, where
ENPEP
showed evidence of differential exon usage. Analysis of this region in conjunction with
BMP10
identified rs9790621 as associated with
ENPEP
transcription in LA, while rs7687878 was associated with
BMP10
expression in RA. In RA,
BMP10
and
ENPEP
were strongly correlated in noncarriers, which was attenuated in risk-allele carriers, where
BMP10
and
PITX2
expression were strongly correlated.

CONCLUSIONS:
These results significantly expand knowledge of the intricate, tissue-specific transcriptional landscape in human atria, including DE transcripts and side-specific isoform expression. Furthermore, they suggest the existence of blocks of transcription disequilibrium influenced by genetics.
Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy
Authors: Ibrahim Ayman M. , Roshdy Mohamed , Latif Najma , Elsawy Amr , Sarathchandra Padmini , Hosny Mohammed , Hekal Soha , Attia Ahmed , Elmozy Wesam , Elaithy Amany , Elguindy Ahmed , Afifi Ahmed , Aguib Yasmine , Yacoub Magdi 
Published: January 2025

BACKGROUND:
Changes in the phenotype and genotype in hypertrophic cardiomyopathy (HCM) are thought to involve the myocardium as well as extracardiac tissues. Here, we describe the structural and functional changes in the ascending aorta of obstructive patients with HCM.

METHODS:
Changes in the aortic wall were studied in a cohort of 101 consecutive patients with HCM undergoing myectomy and 9 normal controls. Biopsies were examined histologically, immunohistochemically, and by electron microscopy. Changes in protein expression were quantified using morphometry and Western blotting. Pulse wave velocity was measured using cardiac magnetic resonance in 85 patients with HCM and compared with 117 age-matched normal controls.

RESULTS:
In HCM, the number of medial lamellar units was significantly decreased, associated with an increase in interlamellar distance and aortic wall thickness, as compared with controls. Electron microscopy showed an altered lamellar structure with disorientation of elastin fibers from the circumferential direction. There was a significant decrease in collagen content, α-smooth muscle actin, smooth muscle myosin, smooth muscle 22 and integrin β1, as well as a significant increase in calponin and caspase-3. Fibulins 1, 2, and 5 showed reduced expression in HCM-aortic biopsies. Functionally, pulse wave velocity was significantly higher in patients with HCM compared with healthy controls, with an association between higher pulse wave velocity and more severe molecular and clinical parameters.

CONCLUSIONS:
The increased wall stiffness observed in the aortas of obstructive patients with HCM is associated with structural alterations in the medial lamellar unit, including changes in smooth muscle cells and the extracellular matrix, indicating potential arterial dysfunction.
Ocean-Land Teleconnections and Chaotic Atmospheric Variability
Authors: Koster Randal D. , Schubert Siegfried D. , DeAngelis Anthony M. , Chang Yehui , Scaife Adam A. 
Published: January 2025

Abstract
A large ensemble of multidecadal atmospheric general circulation model (AGCM) simulations is examined to determine a quantity central to the model’s potential predictability – the fraction of the simulated monthly air temperature (T2M) variability that is tied to the imposed sea surface temperature (SST) boundary conditions as opposed to the background atmospheric noise. Combining this information with ensemble simulation data from other AGCMs in turn allows an inter-model comparison of two separate quantities: model potential T2M predictability and the underlying (in the absence of noise) teleconnections between SSTs and continental T2M. To a large extent, the models tend to agree with each other regarding both – they all show, for example, the expected highest predictability in the Tropics as well as low potential predictability in Central Asia, and, particularly for DJF and MAM, they show very similar ocean-land teleconnections throughout the Americas. However, the models do show some differences in teleconnections, indicating room for model improvement that could, in principle, lead to benefits for long-term prediction. Importantly, by combining the model results with observational temperature data, we provide a new estimation of real-world predictability, a property of Nature that is not directly observable. The latter results suggest, with caveats, that for monthly T2M in the Tropics, AGCMs tend to overestimate the ratio of predictable variance to noise-derived variance.
Semantic abnormalities in schizophrenia and bipolar disorder: A natural language processing approach
Authors: Jo Young Tak , Joo Yeon Ho 
Published: January 2025

Introduction The diagnostic boundaries between schizophrenia and bipolar disorder are controversial due to the ambiguity of psychiatric nosology. From this perspective, it is noteworthy that formal thought disorder has historically been considered pathognomonic of schizophrenia. Given that human thought is partially based on language, we can hypothesize that alterations in language may help differentiate between schizophrenia and bipolar disorder. Method In this exploratory study, we employed natural language processing techniques to identify differences in language abnormalities between patients with schizophrenia and bipolar disorder. The KoBERT and KoGPT language models were used to determine sentence acceptability, assessing how natural and therefore acceptable a given sentence is to the general population. In addition, semantic word networks were constructed for each group, and network measures were compared. Results Patients with schizophrenia or bipolar disorder used less acceptable sentences than controls. Post hoc analysis revealed that the schizophrenia group used less acceptable sentences than the bipolar disorder group. Furthermore, the semantic word networks of the three groups were significantly different in the three network measures. Post hoc analysis revealed a significant difference between the schizophrenia and bipolar disorder networks. The bipolar disorder network generally fell between the schizophrenia and control networks, except in terms of the average clustering coefficient. Conclusions Patients with schizophrenia and bipolar disorder showed significant differences in sentence acceptability as calculated by the language model, as well as in the network metrics estimated by semantic network analysis. Thus, language abnormalities may represent surrogate markers of thought disorders and help differentiate between schizophrenia and bipolar disorder.
Evaluation of in-stent restenosis after carotid artery stenting with superb microvascular imaging: initial findings
Authors: Keskin Berna , Conkbayir Isık , Birgi Erdem , Ergun Onur , Hekimoğlu Azad , Tangobay Erdi , Hekimoğlu Baki 
Published: January 2025

Background Carotid artery stenting (CAS) is an interventional management in preventing ischemic stroke caused by carotid artery stenosis. After the treatment with CAS, in-stent restenosis caused by neointimal hyperplasia may develop. Purpose This study aims to obtain a better determination of neointimal hyperplasia using superb microvascular imaging (SMI), which provides a high-quality visualization of the endoluminal lesions, and to compare these results with B-mode and Doppler ultrasound (US). Material and Methods A total of 106 patients who underwent CAS in our interventional radiology unit between 2018 and 2020 were retrospectively analyzed. In total, 44 patients whose procedure images and post-procedural follow-up Doppler US and SMI data could be accessed were included. Results There were nine patients who had in-stent restenosis. One patient had no velocity increase; however, on SMI the measurements showed in-stent restenosis both in area and diameter. The other eight patients had a stenosis degree in the range of 50%–79% on Doppler US. Five patients had in-stent restenosis, both in Doppler US and SMI, by area and diameter measurements. Two patients underwent digital subtraction angiography (DSA). Conclusion We suggest that using SMI with duplex sonography improves detecting neointimal hyperplasia and in-stent restenosis. With SMI, better visualization of the stent lumen may improve the patient selection for DSA.
Steroid-induced diabetes in lupus nephritis patients: Classic risk factors or a different type of diabetes?
Authors: Dimas-Ramírez Cristian Alejandro , Fortanell-Meza Luis André , San Agustín-Morales Diego , Brenner-Muslera Eduardo , Mejía-Vilet Juan Manuel , Almeda-Valdes Paloma , Vázquez-Cárdenas Paola , Merayo-Chalico Javier , Barrera-Vargas Ana 
Published: January 2025

Background Glucocorticoids are frequently employed in systemic lupus erythematosus (SLE) patients and play a critical role in the induction therapy of lupus nephritis (LN), despite their many side effects, including steroid-induced diabetes (SID). Information regarding SID in SLE patients is quite scant. Purpose The aim of this study was to determine risk factors associated with the development of SID in patients with LN. Research Design A nested case-control study was conducted. Study sample We included patients with biopsy-proven LN, who received induction treatment with steroids. Data Collection and/or Analysis Out of the total of 358 patients, 35 (9.7%) developed SID. Results Patients with SID had more metabolic risk factors, including the metabolic score for insulin resistance (METS-IR); more factors related with lupus activity, with higher SLEDAI and SLICC-DI scores; and lower cumulative pre-induction steroid dose. A higher percentage of patients who developed SID received steroid pulses and a lower percentage received antimalarials. After logistic regression, the variables significantly associated with the development of SID were the SLEDAI index (OR 1.25 [95% CI 1.04–1.50], p 0.01), SLICC-DI (OR 4.93 [95% CI 2.14–11.3], p < 0.001), METS-IR (OR 1.17 [95% CI 1.04–1.32], p 0.009), delta METS-IR at 6 months (OR 1.20 [95% CI 1.03–1.39], p 0.01), and the use of antimalarials (OR 0.14, [95% CI 0.02–0.85], p 0.03). After propensity score matching, METS-IR remained a significant predictor of SID. Patients with METS-IR >36.8 were at higher risk (OR: 2.83, 95% CI: 1.09–7.36, p = 0.034). Conclusions In conclusion, SDI development in patients receiving induction therapy for LN is associated with both classic metabolic risk factors and SLE-specific factors, and antimalarial use could be associated with a protective effect. Rheumatologists should be aware of this potential complication, in order to implement appropriate management strategies.