bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early axial spondyloarthritis according to the ASAS consensus definition: characterisation of patients and effectiveness of a first TNF inhibitor in a large observational registry
Authors: Ciurea Adrian , Götschi Andrea , Bräm René , Bürki Kristina , Exer Pascale , Andor Michael , Nissen Michael J , Möller Burkhard , Hügle Thomas , Rubbert-Roth Andrea , Kyburz Diego , Distler Oliver , Scherer Almut , Micheroli Raphael 
Published: December 2023

ObjectiveTo characterise the population fulfilling the Assessment of SpondyloArthritis international Society (ASAS) consensus definition of early axial spondyloarthritis (axSpA) and to determine the effectiveness of a first tumour necrosis factor inhibitor (TNFi) in early versus established axSpA in a large observational registry.MethodsA total of 3064 patients with axSpA in the Swiss Clinical Quality Management registry with data on duration of axial symptoms were included (≤2 years=early axSpA, N=658; >2 years=established axSpA, N=2406). Drug retention was analysed in patients starting a first TNFi in early axSpA (N=250) versus established axSpA (N=874) with multiple-adjusted Cox proportional hazards models. Adjusted logistic regression analyses were used to determine the achievement of the ASAS criteria for 40% improvement (ASAS40) at 1 year.ResultsSex distribution, disease activity, impairments of function and health-related quality of life were comparable between patients with early and established axSpA. Patients with established disease were older, had more prevalent axial radiographical damage and had a higher impairment of mobility. A comparable TNFi retention was found in early versus established disease after adjustment for age, sex, human leucocyte antigen-B27 status, education, body mass index, smoking, elevated C reactive protein and sacroiliac inflammation on MRI (HR 1.05, 95% CI 0.78 to 1.42). The adjusted ASAS40 response was similar in the two groups (OR 1.09, 95% CI 0.67 to 1.78). Results were confirmed in the population fulfilling the ASAS classification criteria.ConclusionConsidering the recent ASAS definition of early axSpA, TNFi effectiveness seems comparable in early versus established disease.
Association between hyperuricaemia and hand osteoarthritis: data from the Xiangya Osteoarthritis Study
Authors: Zhu Yanqiu , Li Jiatian , Zhang Yuqing , Zhang Weiya , Doherty Michael , Yang Zidan , Cui Yang , Zeng Chao , Lei Guanghua , Yang Tuo , Wei Jie 
Published: December 2023

ObjectiveThe pathogenesis of hand osteoarthritis (OA) remains unknown. Hyperuricaemia, which is related to inflammation, may play a role in hand OA, but evidence is lacking. In a large population-based study, we examined the association between hyperuricaemia and hand OA.MethodsParticipants were from the Xiangya OA Study, a community-based observational study. Hyperuricaemia was defined as serum urate >416 µmol/L in men and >357 µmol/L in women. Radiographic hand OA (RHOA) was defined as presence of the modified Kellgren-Lawrence grade ≥2 in any hand joint. Symptomatic hand OA (SHOA) was defined as presence of both self-reported symptoms and RHOA in the same hand. The associations of hyperuricaemia with RHOA or SHOA were examined using generalised estimating equations.ResultsAmong 3628 participants, the prevalence of RHOA was higher in participants with hyperuricaemia than those with normouricaemia (26.9% vs 20.9%), with an adjusted OR (aOR) of 1.34 (95% CI 1.11 to 1.61). The associations were consistent in men (aOR 1.33, 95% CI 1.01 to 1.74) and women (aOR 1.35, 95% CI 1.05 to 1.74). Hyperuricaemia was mainly associated with bilateral RHOA (aOR 1.54, 95% CI 1.18 to 2.01) but not unilateral RHOA (aOR 1.13, 95% CI 0.89 to 1.45). Prevalence of SHOA was higher, although statistically insignificant, in participants with hyperuricaemia (aOR 1.39, 95% CI 0.94 to 2.07).ConclusionIn this population-based study, hyperuricaemia was associated with a higher prevalence of hand OA. Future prospective studies are required to investigate the temporal relationship.Trial registration numberNCT04033757.
Black holes and non-perturbative gravitational waves in f(R) gravity
Authors: Liu Chunmei , Zhang Hongsheng 
Published: December 2023

AbstractExact solutions of spherically symmetric black hole and gravitational wave are explored inf(R) gravity in arbitrary dimension. We find two exact solutions for the radiation and absorption of null dust. In the framework of general relativity, the Birkhoff theorem strictly forbids the existence of spherical gravitational waves in vacuum space. We find spherical non-perturbative gravitational waves, which are shear-free, twist-free, but expanding.
Thermodynamics of accelerating AdS$$_4$$ black holes from the covariant phase space
Authors: Kim Hyojoong , Kim Nakwoo , Lee Yein , Poole Aaron 
Published: December 2023

AbstractWe study the charges and first law of thermodynamics for accelerating, non-rotating black holes with dyonic charges in AdS$$_4$$

4

using the covariant phase space formalism. In order to apply the formalism to these solutions (which are asymptotically locally AdS and admit a non-smooth conformal boundary $${\mathscr {I}}$$
I
) we make two key improvements: (1) We relax the requirement to impose Dirichlet boundary conditions and demand merely a well-posed variational problem. (2) We keep careful track of the codimension-2 corner term induced by the holographic counterterms, a necessary requirement due to the presence of “cosmic strings” piercing $${\mathscr {I}}$$
I
. Using these improvements we are able to match the holographic Noether charges to the Wald Hamiltonians of the covariant phase space and derive the first law of black hole thermodynamics with the correct “thermodynamic length” terms arising from the strings. We investigate the relationship between the charges imposed by supersymmetry and show that our first law can be consistently applied to various classes of non-supersymmetric solutions for which the cross-sections of the horizon are spindles.
Extraction Algorithm of HOM–LIE Algebras Based on Solvable and Nilpotent Groups
Authors: Shaqaqha Shadi , Kdaisat Nadeen 
Published: December 2023

Hom–Lie algebras are generalizations of Lie algebras that arise naturally in the study of nonassociative algebraic structures. In this paper, the concepts of solvable and nilpotent Hom–Lie algebras are studied further. In the theory of groups, investigations of the properties of the solvable and nilpotent groups are well‐developed. We establish a theory of the solvable and nilpotent Hom–Lie algebras analogous to that of the solvable and nilpotent groups. We also provide examples to illustrate our results and discuss possible directions for further research.Dedicated to Al Farouk School & Kinder garten-Irbid-Jordan
Adipose Triglyceride Lipase Is a Therapeutic Target in Advanced Prostate Cancer That Promotes Metabolic Plasticity
Authors: Awad Dominik , Cao Pham Hong Anh , Pulliam Thomas L. , Spradlin Meredith , Subramani Elavarasan , Tellman Tristen V. , Ribeiro Caroline F. , Muzzioli Riccardo , Jewell Brittany E. , Pakula Hubert , Ackroyd Jeffrey J. , Murray Mollianne M. , Han Jenny J. , Leng Mei , Jain Antrix , Piyarathna Badrajee , Liu Jingjing , Song Xingzhi , Zhang Jianhua , Klekers Albert R. , Drake Justin M. , Ittmann Michael M. , Coarfa Cristian , Piwnica-Worms David , Farach-Carson Mary C. , Loda Massimo , Eberlin Livia S. , Frigo Daniel E. 
Published: December 2023

Abstract

Lipid metabolism plays a central role in prostate cancer. To date, the major focus has centered on de novo lipogenesis and lipid uptake in prostate cancer, but inhibitors of these processes have not benefited patients. A better understanding of how cancer cells access lipids once they are created or taken up and stored could uncover more effective strategies to perturb lipid metabolism and treat patients. Here, we identified that expression of adipose triglyceride lipase (ATGL), an enzyme that controls lipid droplet homeostasis and a previously suspected tumor suppressor, correlates with worse overall survival in men with advanced, castration-resistant prostate cancer (CRPC). Molecular, genetic, or pharmacologic inhibition of ATGL impaired human and murine prostate cancer growth in vivo and in cell culture or organoids under conditions mimicking the tumor microenvironment. Mass spectrometry imaging demonstrated that ATGL profoundly regulates lipid metabolism in vivo, remodeling membrane composition. ATGL inhibition induced metabolic plasticity, causing a glycolytic shift that could be exploited therapeutically by cotargeting both metabolic pathways. Patient-derived phosphoproteomics identified ATGL serine 404 as a target of CAMKK2–AMPK signaling in CRPC cells. Mutation of serine 404 did not alter the lipolytic activity of ATGL but did decrease CRPC growth, migration, and invasion, indicating that noncanonical ATGL activity also contributes to disease progression. Unbiased immunoprecipitation/mass spectrometry suggested that mutation of serine 404 not only disrupts existing ATGL protein interactions but also leads to new protein–protein interactions. Together, these data nominate ATGL as a therapeutic target for CRPC and provide insights for future drug development and combination therapies.

Significance:
ATGL promotes prostate cancer metabolic plasticity and progression through both lipase-dependent and lipase-independent activity, informing strategies to target ATGL and lipid metabolism for cancer treatment.
Serial Circulating Tumor DNA Analysis with a Tumor-Naïve Next-Generation Sequencing Panel Detects Minimal Residual Disease and Predicts Outcome in Ovarian Cancer
Authors: Heo Jinho , Kim Yoo-Na , Shin Saeam , Lee Kyunglim , Lee Ji-Hyun , Lee Yong Jae , Choi Zisun , Park Jihyang , Min Seungki , Kim Sang Wun , Choi Jong Rak , Kim Sunghoon , Lee Seung-Tae , Lee Jung-Yun 
Published: December 2023

Abstract

Circulating tumor DNA (ctDNA) may aid in personalizing ovarian cancer therapeutic options. Here, we aimed to assess the clinical utility of serial ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Samples were collected at baseline (initial diagnosis or surgery) and every 3 months after that, resulting in a total of 811 blood samples. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of 9 genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN. Pathogenic somatic mutations were identified in 69.2% (139/201) of patients with ovarian cancer at baseline but not in those with benign or borderline disease. Detection of ctDNA at baseline and/or at 6 months follow-up was predictive of progression-free survival (PFS). PFS was significantly poorer in patients with detectable pathogenic mutations at baseline that persisted at follow-up than in patients that converted from having detectable ctDNA at baseline to being undetectable at follow-up; survival did not differ between patients without pathogenic ctDNA mutations in baseline or follow-up samples and those that converted from ctDNA positive to negative. Disease recurrence was also detected earlier with ctDNA than with conventional radiologic assessment or CA125 monitoring. These findings demonstrate that serial ctDNA testing could effectively monitor patients and detect minimal residual disease, facilitating early detection of disease progression and tailoring of adjuvant therapies for ovarian cancer treatment.

Significance:
In ovarian cancer, serial circulating tumor DNA testing is a highly predictive marker of patient survival, with a significantly improved recurrence detection lead time compared with conventional monitoring tools.
Abstract B095: Sacituzumab govitecan-based drug combinations overcome platinum/PARP inhibitor resistance in ovarian cancer models
Authors: Conlon Neil T , Möhrle Elena , Stockmann Luna , Crown John 
Published: December 2023

Abstract
Background: Ovarian cancer causes more deaths than any other gynaecological cancer per year in the USA. Sacituzumab govitecan (SG) is a TROP2-targeted antibody-drug conjugate, approved for the treatment of triple-negative and hormone receptor-positive breast cancers. TROP2 is commonly overexpressed in ovarian cancer and represents an attractive, potential therapeutic target in ovarian cancer. This study investigated the in vitro activity of SG alone and in combination with targeted therapies/chemotherapies in ovarian cancer cell line models.
Methods: This study utilized the PEO1 and PEO4 cell lines, which were derived from the same patient, with PEO4 acquiring a secondary restorative BRCA2 mutation to confer platinum resistance. Olaparib-resistant PEO1 (PEO1-Ola) cells were generated through continuous exposure to olaparib, to a maximum 13 μM, for four months. The anti-proliferative effects of SG, talazoparib, olaparib, carboplatin, and paclitaxel were tested in PEO1, PEO1-Ola, and PEO4 cell lines. Synergism was assessed using Combenefit software with the Loewe additivity model. Induction of caspase 3/7 activation, a marker of apoptosis, was tested with single agents and combinations using kinetic, fluorescent microscopy with the Incucyte S3 imaging system.
Results: Olaparib and carboplatin resistance did not result in their cross-resistance. PEO1-Ola showed similar sensitivity to carboplatin as PEO1 parental cells, while carboplatin-resistant PEO4 cells displayed clinically achievable sensitivity to olaparib and talazoparib. SG was highly effective in all models tested. SG in combination with carboplatin or talazoparib was synergistic across all cell lines and resulted in induction of apoptosis.
Conclusions: This pre-clinical study showed that TROP2-targeting ADC-based drug combinations warrant further investigation for the treatment of ovarian cancer.
Citation Format: Neil T Conlon, Elena Möhrle, Luna Stockmann, John Crown. Sacituzumab govitecan-based drug combinations overcome platinum/PARP inhibitor resistance in ovarian cancer models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B095.
Abstract LB_C14: EAI-432: A mutant-selective allosteric EGFR inhibitor for L858R-mutant non-small cell lung cancer
Authors: Eck Michael J. , Scott David A. , Janne Pasi , Beyett Tyler S. , Jiang Jie , Gokhale Praful , Gero Thomas W. 
Published: December 2023

Abstract
While osimertinib is highly efficacious in lung cancers with sensitizing mutations in EGFR, there is a major unmet need for agents that overcome resistance to it and other covalent third-generation EGFR TKIs due to the C797S mutation. Furthermore, osimertinib extends overall survival in patients with exon19 deletions but offers little improvement in overall survival in patients with the L858R mutation relative to the first-generation inhibitors. We are developing EAI-432 with the goal of improving outcomes for patients with EGFRL858R+ lung cancer. EAI-432 is a mutant-selective allosteric inhibitor that is effective against L858R and its common resistance variants, L858R/T790M, L858R/C797S, and L858R/T790M/C797S while sparing WT EGFR. The compound induces tumor regressions in a L858R/T790M/C797S mouse xenograft model at low doses (5 mg/kg). In the H1975 (L858R/T790M) xenograft model, EAI-432 induced marked tumor regressions in both subcutaneous and intracranial implants. EAI-432 co-binds with osimertinib, allowing double-drugging of the mutant receptor. The distinct binding site and allosteric mechanism of EAI-432 are expected to confer exquisite kinome-wide selectivity and orthogonal resistance mechanisms as compared with osimertinib and other ATP-competitive TKIs, properties that are highly desirable in a combination agent. The compound has efficacy, mutant-selectivity, and pharmacokinetic properties including brain-penetrance that support its further development as a therapeutic agent for EGFRL858R+ lung cancer alone or in combination with osimertinib.
Citation Format: Michael J. Eck, David A. Scott, Pasi Janne, Tyler S. Beyett, Jie Jiang, Praful Gokhale, Thomas W. Gero. EAI-432: A mutant-selective allosteric EGFR inhibitor for L858R-mutant non-small cell lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C14.
Agreement Between Guideline Thresholds Using an “All‐in‐One” Device to Measure Office, Home, and Ambulatory Blood Pressures
Authors: Kario Kazuomi , Tomitani Naoko , Hoshide Satoshi , Nishizawa Masafumi , Yoshida Tetsuro , Kabutoya Tomoyuki , Fujiwara Takeshi , Mizuno Hiroyuki ,   the HI‐JAMP Study Group
Published: December 2023

Background
Blood pressure (BP) thresholds for diagnosing and managing hypertension vary for office, home, and ambulatory readings, and between guideline documents. This analysis determined corresponding office, home, and ambulatory BP thresholds using baseline data from the HI‐JAMP (Home‐Activity Information and Communication Technology–Based Japan Ambulatory Blood Pressure Monitoring Prospective) study, which used a validated “all‐in‐one” BP monitoring device.

Methods and Results

Data from 2322 treated patients with hypertension who underwent office BP measurement, then 24‐hour ambulatory BP monitoring, then home BP monitoring for 5 days were analyzed. Corresponding BP thresholds for office, home, and ambulatory measurements were determined using Deming regression. Values equivalent to office systolic BP (SBP) of 120 and 140 mm Hg were as follows: 115.9 and 127.7 mm Hg for 24‐hour ambulatory SBP; 120.8 and 134.0 mm Hg for daytime ambulatory SBP; 104.9 and 117.9 mm Hg for nighttime ambulatory SBP; and 122.0 and 134.2 mm Hg for morning‐evening average home SBP. Deming regression showed that morning‐evening average home SBP and daytime ambulatory SBP were almost the same (home SBP=0.99×daytime ambulatory SBP+0.27 mm Hg;
r
=0.627). Morning‐evening average home SBP values of 120 and 135 mm Hg were equivalent to daytime ambulatory SBP values of 119.1 and 133.9 mm Hg, respectively. A home SBP threshold of 130 mm Hg corresponded to 24‐hour and nighttime ambulatory SBP values of 123.5 and 113.6 mm Hg, whereas a home SBP threshold of 135 mm Hg corresponded to 24‐hour and nighttime ambulatory SBP values of 128.0 and 119.2 mm Hg.

Conclusions
Ambulatory and home BP thresholds in this analysis were similar to those proposed by existing guidelines. The similarity between the home BP and daytime ambulatory BP thresholds was a clinically relevant finding.
Outside the Laboratory Assessment of Upper Limb Laterality in Patients With Stroke: A Cross-Sectional Study
Authors: Gulde Philipp , Vojta Heike , Schmidle Stephanie , Rieckmann Peter , Hermsdörfer Joachim 
Published: December 2023

BACKGROUND:
The rehabilitation of upper limb sensorimotor performance after stroke requires the assessment of daily use, the identification of key levels of impairment, and monitoring the course of recovery. It needs to be answered, how laboratory-based assessments and everyday behavior are connected, which dimension of metrics, that is, volume, intensity, or quality, is most sensitive to reduced function, and what sensor, that is, gyroscope or accelerometer, is best suited to gather such data.

METHODS:
Performance in laboratory-based sensorimotor tests, as well as smartwatch-derived kinematic data of everyday life relative upper limb activity, during 1 day of inpatient neurorehabilitation (Germany, 2022) of 50 patients with stroke, was cross-sectionally assessed and resulting laterality indices (performance ratios) between the limbs were analyzed using ANCOVAs and principal component analysis.

RESULTS:
Laboratory-based tests revealed the strongest laterality indices, followed by smartwatch-based (intensity>quality>volume) metrics. Angular velocity-based metrics revealed higher laterality indices than acceleration-based ones. Laterality indices were overall well associated; however, a principal component analysis suggested upper limb impairments to be unidimensional.

CONCLUSIONS:
Our findings suggest that the use of sensors can deliver valid information of stroke-related laterality. It appeared that commonly used metrics that estimate the volume of use (ie, energy expenditure) are not the most sensitive. Especially reached intensities could be well used for monitoring, because they are more dependent on the performance of the sensorimotor system and less on confounders like age. The unidimensionality of the upper limb laterality suggests that an impaired limb with reduced movement quality and the inability to reach higher intensities will be used less in everyday life, especially when it is the nondominant side.
Development and Human Factors Evaluation of a Portable Auditory Localization Training System
Authors: Thompson Brandon S. , Lee Kichol , Casali John G. , Cave Kara M. 
Published: December 2023

Objective To design and develop a Portable Auditory Localization Acclimation Training (PALAT) system capable of producing psychoacoustically accurate localization cues; evaluate the training effect against a proven full-scale, laboratory-grade system under three listening conditions; and determine if the PALAT system is sensitive to differences among electronic level-dependent hearing protection devices (HPDs). Background In-laboratory auditory localization training has demonstrated the ability to improve localization performance with the open (natural) ear, that is, unoccluded, and while wearing HPDs. The military requires a portable system capable of imparting similar training benefits as those demonstrated in laboratory experiments. Method In a full-factorial repeated measures design experiment, 12 audiometrically normal participants completed localization training and testing using an identical, optimized training protocol on two training systems under three listening conditions (open ear, TEP-100, and ComTac™ III). Statistical tests were performed on mean absolute accuracy score and front-back reversal errors. Results No statistical difference existed between the PALAT and laboratory-grade DRILCOM systems on two dependent localization accuracy measurements at all stages of training. In addition, the PALAT system detected the same localization performance differences among the three listening conditions. Conclusion The PALAT system imparted similar training benefits as the DRILCOM system and was sensitive to HPD localization performance differences. Application The user-operable PALAT system and optimized training protocol can be employed by the military, law enforcement, and various industries, to improve auditory localization performance in conditions where auditory situation awareness is critical to safety.