bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of white matter hyperintensities on subjective cognitive decline phenotype in a diverse cohort of cognitively normal older adults
Authors: Rothstein Aaron , Zhang Yian , Briggs Anthony Q. , Bernard Mark A. , Shao Yongzhao , Favilla Christopher , Sloane Kelly , Witsch Jens , Masurkar Arjun V. 
Published: June 2023

AbstractObjectivesSubjective cognitive decline (SCD) is a preclinical stage of AD. White matter hyperintensities (WMH), an MRI marker of cerebral small vessel disease, associate with AD biomarkers and progression. The impact of WMH on SCD phenotype is unclear.Methods/DesignA retrospective, cross‐sectional analysis was conducted on a diverse cohort with SCD evaluated at the NYU Alzheimer's Disease Research Center between January 2017 and November 2021 (n = 234). The cohort was dichotomized into none‐to‐mild (n = 202) and moderate‐to‐severe (n = 32) WMH. Differences in SCD and neurocognitive assessments were evaluated via Wilcoxon or Fisher exact tests, with p‐values adjusted for demographics using multivariable logistic regression.ResultsModerate‐to‐severe WMH participants reported more difficulty with decision making on the Cognitive Change Index (1.5 SD 0.7 vs. 1.2 SD 0.5, p = 0.0187) and worse short‐term memory (2.2 SD 0.4 vs. 1.9 SD 0.3, p = 0.0049) and higher SCD burden (9.5 SD 1.6 vs. 8.7 SD 1.7, p = 0.0411) on the Brief Cognitive Rating Scale. Moderate‐to‐severe WMH participants scored lower on the Mini‐Mental State Examination (28.0 SD 1.6 vs. 28.5 SD 1.9, p = 0.0491), and on delayed paragraph (7.2 SD 2.0 vs. 8.8 SD 2.9, p = 0.0222) and designs recall (4.5 SD 2.3 vs. 6.1 SD 2.5, p = 0.0373) of the Guild Memory Test.ConclusionsIn SCD, WMH impact overall symptom severity, specifically in executive and memory domains, as well as objective performance on global and domain‐specific tests in verbal memory and visual working/associative memory.
The germinal center in the pathogenesis of B cell lymphomas
Authors: Pasqualucci Laura 
Published: June 2023

AbstractThe adaptive immune system has evolved to allow effective responses against a virtually unlimited number of invading pathogens. This process requires the transient formation of germinal centers (GC), a dynamic environment that ensures the generation and selection of B cells capable to produce antibodies with high antigen affinity, or to maintain the memory of that antigen for life. However, this comes at a cost, as the unique events accompanying the GC reaction pose a significant risk to the genome of B cells, which must endure elevated levels of replication stress, while proliferating at high rates and undergoing DNA breaks introduced by somatic hypermutation and class switch recombination. Indeed, the genetic/epigenetic disruption of programs implicated in normal GC biology has emerged as a hallmark of most B cell lymphomas. This improved understanding provides a conceptual framework for the identification of cellular pathways that could be exploited for precision medicine approaches.
First line therapy of CLL
Authors: Hallek Michael 
Published: June 2023

AbstractChronic lymphocytic leukemia (CLL) is one of the most frequent types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist today and need to be selected. A combination of the BCL2 inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib, acalabrutinib or zanubrutinib, while chemoimmunotherapy (CIT) is disappearing as a therapeutic option.
Management of primary and secondary CNS lymphoma
Authors: Khwaja Jahanzaib , Cwynarski Kate 
Published: June 2023

AbstractCentral nervous system (CNS) lymphoma has traditionally had very poor outcomes however advances in management have seen dramatic improvements and long‐term survival of patients. In primary CNS lymphoma there are now randomised trial data to inform practice, however secondary CNS lymphoma has a lack of randomised trial data and CNS prophylaxis remains a contentious area. We describe treatment strategies in these aggressive disorders. Dynamic assessment of patient fitness and frailty is key throughout treatment alongside delivery of CNS‐bioavailable therapy and enrolment in clinical trials. Intensive high‐dose methotrexate‐containing induction followed by autologous stem cell transplantation is preferred for patients who are fit. Less intensive chemoimmunotherapy, whole brain radiotherapy and novel therapies may be reserved for patients unfit or chemoresistant. It is essential to better define patients at increased risk of CNS relapse, as well as effective prophylactic strategies to prevent it. Future prospective studies incorporating novel agents are key.
Efficacy and safety of lenvatinib plus pembrolizumab vs sunitinib in the East Asian subset of patients with advanced renal cell carcinoma from the CLEAR trial
Authors: Rha Sun Young , Choueiri Toni K. , Matveev Vsevolod B. , Alyasova Anna , Hong Sung‐Hoo , Gordoa Teresa Alonso , Gurney Howard , Bjarnason Georg A. , Buchler Tomas , Pedrazzoli Paolo , Takagi Toshio , Park Se Hoon , Lee Jae Lyun , Perini Rodolfo F. , He Cixin S. , McKenzie Jodi A. , Eto Masatoshi 
Published: June 2023

AbstractIn the CLEAR trial, lenvatinib plus pembrolizumab met study endpoints of superiority vs sunitinib in the first‐line treatment of patients with advanced renal cell carcinoma. We report the efficacy and safety results of the East Asian subset (ie, patients in Japan and the Republic of Korea) from the CLEAR trial. Of 1069 patients randomly assigned to receive either lenvatinib plus pembrolizumab, lenvatinib plus everolimus or sunitinib, 213 (20.0%) were from East Asia. Baseline characteristics of patients in the East Asian subset were generally comparable with those of the global trial population. In the East Asian subset, progression‐free survival was considerably longer with lenvatinib plus pembrolizumab vs sunitinib (median 22.1 vs 11.1 months; HR 0.38; 95% CI: 0.23‐0.62). The HR for overall survival comparing lenvatinib plus pembrolizumab vs sunitinib was 0.71; 95% CI: 0.30‐1.71. The objective response rate was higher with lenvatinib plus pembrolizumab vs sunitinib (65.3% vs 49.2%; odds ratio 2.14; 95% CI: 1.07‐4.28). Dose reductions due to treatment‐emergent adverse events (TEAEs) commonly associated with tyrosine kinase inhibitors occurred more frequently than in the global population. Hand‐foot syndrome was the most frequent any‐grade TEAE with lenvatinib plus pembrolizumab (66.7%) and sunitinib (57.8%), a higher incidence compared to the global population (28.7% and 37.4%, respectively). The most common grade 3 to 5 TEAEs were hypertension with lenvatinib plus pembrolizumab (20%) and decreased platelet count with sunitinib (21.9%). Efficacy and safety for patients in the East Asian subset were generally similar to those of the global population, except as noted.
Normoglycemia partially recovers the disrupted osteoblast differentiation of mesenchymal stem cells induced by type 1 but not type 2 diabetes mellitus
Authors: Weffort Denise , Adolpho Leticia F. , Souza Alann T. P. , Freitas Gileade P. , Lopes Helena B. , Oliveira Fabiola S. , Bighetti‐Trevisan Rayana L. , Pitol‐Palin Leticia , Matsushita Doris H. , Okamoto Roberta , Beloti Marcio M. , Rosa Adalberto L. 
Published: June 2023

AbstractType 1 (T1DM) and type 2 (T2DM) diabetes mellitus are characterized by changes in glucose metabolism and cause bone damage via a variety of mechanisms, including effects on osteoblasts. We aimed to evaluate the osteoblast differentiation of mesenchymal stem cells (MSCs) from rats with T1DM or T2DM and the effects of removing the hyperglycemic stimulus on the osteogenic potential of these cells. MSCs from healthy rats were cultured in normoglycemic medium, whereas MSCs from rats with T1DM or T2DM were cultured in hyperglycemic or normoglycemic medium. T1DM and T2DM reduced osteoblast differentiation of MSCs grown in hyperglycemic media, with T1DM having a more pronounced effect, as evidenced by alkaline phosphatase activity, RUNX2 protein expression, and extracellular matrix mineralization, and modulated the gene expression of several components of the bone morphogenetic protein signaling pathway. The restoration of the normoglycemic environment partially recovers the osteogenic potential of MSCs from rats with T1DM but not with T2DM. Our findings highlight the need for specific therapies to treat T1DM‐ or T2DM‐induced bone loss, as both disrupt osteoblast differentiation at distinct levels and likely through different mechanisms.
TD‐DFT study of BIPS spiropyran: Effects of functionals and high‐polarity solvent on CspiroO bond dissociation and recovery
Authors: Dobrovolskiy Ivan N. , Kostjukov Victor V. 
Published: June 2023

AbstractWe performed a theoretical analysis of the BIPS photochemical cycle using an extensive set of forty hybrid functionals and taking into account a highly polar solvent (methanol). The functionals with a small fraction of the exact Hartree‐Fock exchange (%HF) showed the predominant S0 → S2 transition with the strengthening of the CspiroO bond. At the same time, functionals with medium and high %HF (including those with long‐range correction) gave a dominant S0 → S1 transition with weakening or breaking of the CspiroO bond, which corresponds to the experimental results. The influence of a highly polar solvent on the photochemical electrocyclic transformations of BIPS turned out to be significant. The number of functionals causing dissociation of the CspiroO bond decreased from 10 to 7 compared to the gas phase. The magnitude of the oscillator strength has increased by approximately one and a half times. Structural distortions of the BIPS molecule during excitation (both with and without CspiroO bond cleavage) significantly decreased in methanol compared to the gas phase. The two strong hydrogen bonds of methanol molecules with the oxygen and nitrogen atoms of spiropyran also have a significant effect on its excitation. They lead to a change in the predominant transition from S0 → S2 to S0 → S1 for five functionals. The number of functionals giving dissociation of the CspiroO bond decreased from seven to four (M08HX, M052X, CAM‐B3LYP, and M11). After the opening of the excited BIPS molecule, both of its strong H‐bonds with methanol are preserved. Of this set of four functionals, only M052X and CAM‐B3LYP exhibited the dominant HOMO‐1 → LUMO configuration observed in high‐level computations by other authors. Therefore, both of these functionals are recommended for modeling the photochemical cycle of this spiropyran. The photochemical cycle of BIPS was theoretically analyzed. The redistribution of the electron density in this cycle was quantitatively described using the differences in NPA of the atomic charges. The most important result of this analysis was the electrostatic mechanism of the approach of Cspiro and oxygen atoms at the fourth stage, which causes further reduction of the CspiroO bond.
Bystander intervention to prevent firearm injury: A qualitative study of 4‐H shooting sports participants
Authors: Trinka Teresa , Oesterle Daniel W. , Silverman Amira C. , Vriniotis Mary G. , Orchowski Lindsay M. , Beidas Rinad S. , Betz Marian E. , Hudson Craven , Kesner Todd , Ranney Megan L. 
Published: June 2023

AbstractThis qualitative study examines how youth and adult members of 4‐H Shooting Sports clubs perceive firearm injury risk and risk reduction, and the applicability of a bystander intervention (BI) risk reduction framework in this community. Semistructured interviews were conducted with 11 youth and 13 adult members of 4‐H Shooting Sports clubs across nine US states from March to December of 2021 until thematic saturation was reached. Deductive and inductive thematic qualitative analyses were performed. Six overarching themes emerged: (1) The tendency to view firearm injury as predominantly unintentional in nature; (2) Acknowledgment of a wide array of risks for firearm injury; (3) Perceived barriers to bystander action to prevent firearm injury including knowledge, confidence, and consequences of action; (4) Facilitators of bystander action including a sense of civic responsibility; (5) Direct and indirect strategies to address potential risks for firearm injury; and (6) Belief that BI skills training would be useful for 4‐H Shooting Sports. Findings lay the groundwork for applying BI skills training as an approach to firearm injury prevention in 4‐H Shooting Sports, similar to how BI has been applied to other types of injury (i.e., sexual assault). 4‐H Shooting Sports club members' sense of civic responsibility is a key facilitator. Prevention efforts should attend to the broad array of ways in which firearm injury occurs, including suicide, mass shootings, homicide, and intimate partner violence, as well as unintentional injury.
Land registry in Syria after a decade of conflict: A tale of three cities
Authors: Alsamar Ammar , Korabi Ahmad , Jalabi Sultan , Khan Imtiaz , te Lintelo Dolf 
Published: June 2023

AbstractThis study offers an original analysis into the nature of the governance of the land registry system in three Syrian cities controlled by armed non‐state actors during the civil war. It adopts aqualitative methodology to compare Douma, al Raqqa and Idlib. The management of the land registry has witnessed both localised transformations and significant resilience. As state institutions collapsed and new non‐state governing actors emerged, the old land registry system has fallen apart, and pre‐existing gaps between official records and realestate ownership have deepened, with significant implications for the possibility of sustainable peace in the country.
Giant cell‐rich osteosarcoma: A match pair analysis of 11 new cases and literature review of 56 patients
Authors: Karczewski Daniel , Gonzalez Marcos R. , Bedi Angad , Ready John E. , Anderson Megan E. , Lozano‐Calderon Santiago A. 
Published: June 2023

AbstractBackgroundLimited remains known on giant cell‐rich osteosarcoma (GCRO) with current studies being case reports or smaller series. This investigation compared GCRO and conventional osteoblastic osteosarcoma (OOS) with regard to demographics and survival.MethodsAn institutional tumor registry was used to identify 11 patients (six males) treated for GCRO. Mean age was 43 years. Staging showed American Joint Committee on Cancer (AJCC) stages IIA in four and IIB in seven patients. Mean follow‐up was 14 years. Study initiatives were: (1) Comparison of demographics between GCRO and 167 OOS from our institutional registry, (2) Differences in survival between GCRO and 33 OOS case controls (based on sex and AJCC stage), as well as 10 OOS using an age‐based propensity match, and (3) Summary of all GCRO cases reported in the literature.Results(1) Sex (p = 0.53), grading (p = 0.56), AJCC stage (p = 0.42), and chemotherapeutic response rate (p = 0.67) did not differ between groups. Age was significantly increased in GCRO (p = 0.001). (2) Case–control and propensity‐matched groups revealed no difference in disease‐free survival, local recurrence, and distant disease‐free survival at 2 years (p > 0.05). (3) Mean age of 56 patients (50% males) reported in the literature was 26 years. After merging with our 11 cases, the 2‐year disease‐free survival was 66%.ConclusionsGCRO remains a rare disease with high short‐term mortality. Although affecting older patients more than conventional osteosarcoma, GCRO should not be viewed as a predictor of survival compared to OOS.
Surface Eroding Methacrylic Anhydride Copolymers and Model Drug Release
Authors: Santefort Arielle L. , Appolon Alayna C. , Cowart Luke J. , Shipp Devon A. 
Published: June 2023

AbstractMethacrylic anhydride (MAA)‐based copolymers are synthesized to probe how comonomer composition and type affect the erosion profiles. Anhydrides readily undergo hydrolysis, which when combined with high crosslink density and hydrophobicity tend to exhibit an ideal surface erosion mechanism for drug delivery, tissue adhesives, and biocement applications. The cylindrical (10 mm diameter × 5 mm height) polyanhydrides are degraded under pseudo‐physiological conditions and surface erosion is qualitatively observed via photographs. The non‐anhydride comonomer can be utilized to tune erosion profiles while retaining degradability and product solubility. The comonomer can accelerate or slow the degradation process to a greater extent at low MAA concentrations. Drug release is conducted using purpurin to model hydrophobic drugs. Purpurin concentration is quantified using UV–visible spectral analysis. Purpurin extends the degradation profile due to a combination of local pH changes, hydrophobicity, and molecular diffusion. Linear purpurin release is observed as a function of polymer erosion (0.9897 R2) thus confirming a surface erosion‐mediated drug release mechanism.
Curvature loci of 3‐manifolds
Authors: Benedini Riul Pedro , Oset Sinha Raúl , Ruas Maria Aparecida Soares 
Published: June 2023

AbstractWe refine the affine classification of real nets of quadrics in order to obtain generic curvature loci of regular 3‐manifolds in and singular corank one 3‐manifolds in . For this, we characterize the type of the curvature locus by the number and type of solutions of a system of equations given by four ternary cubics (which is a determinantal variety in some cases). We also study how singularities of the curvature locus of a regular 3‐manifold can go to infinity when the manifold is projected orthogonally in a tangent direction.
IL‐17 induces non‐small cell lung cancer metastasis via GCN5‐dependent SOX4 acetylation enhancing MMP9 gene transcription and expression
Authors: Ge Wen , Gong Yajuan , Li Ya , Wu Ningxia , Ruan Yuting , Xu Tongpeng , Shu Yongqian , Qiu Wen , Wang Yingwei , Zhao Chenhui 
Published: June 2023

AbstractInterleukin‐17 (IL‐17), a potent proinflammatory cytokine, can trigger the metastasis of non‐small cell lung cancer (NSCLC). However, the underlying mechanism involved in IL‐17‐induced NSCLC cell metastasis remains unclear. In this study, we found that not only the expression of IL‐17, IL‐17RA, and/or general control nonrepressed protein 5 (GCN5), SRY‐related HMG‐BOX gene 4 (SOX4), and matrix metalloproteinase 9 (MMP9) was increased in the NSCLC tissues and in the IL‐17‐stimulated NSCLC cells, but also IL‐17 treatment could enhance NSCLC cell migration and invasion. Further mechanism exploration revealed that IL‐17‐upregulated GCN5 and SOX4 could bind to the same region (−915 to −712 nt) of downstream MMP9 gene promoter driving its gene transcription. In the process, GCN5 could mediate SOX4 acetylation at lysine 118 (K118, a newly identified site) boosting MMP9 gene expression as well as cell migration and invasion. Moreover, the SOX4 acetylation or MMP9 induction and metastatic nodule number in the lung tissues of the BALB/c nude mice inoculated with the NSCLC cells stably infected by corresponding LV‐shGCN5 or LV‐shSOX4, LV‐shMMP9 plus IL‐17 incubation were markedly reduced. Overall, our findings implicate that NSCLC metastasis is closely associated with IL‐17‐GCN5‐SOX4‐MMP9 axis.
On reservation prices in the all‐pay contest with correlated information
Authors: Tang Beiyu , Fu Hongpeng , Wu Ying Cheng 
Published: June 2023

AbstractThis paper investigates the effects of reservation prices in all‐pay auctions based on the Bayesian Nash equilibrium of symmetric distributions with binary and correlated types. Our study finds that reservation prices affect players' behavior in two ways. Given the reservation price, some give up the original strategy of offering a bid lower than such minimum requirement. Therefore, the reservation prices may discourage the effort supply of weaker players. However, stronger innovators do not modify their strategies: They will start giving bids above the reservation price. Hence, setting a quality standard is effective in boosting effort supply. Our study contributes to the function of this particular pattern in the contests, thereby gaining more insight into designing and assessing such competition under different circumstances.
A 34.16–39.6 GHz low phase noise VCO for frequency‐modulated continuous‐wave radar in a 28‐nm CMOS
Authors: Fu Haipeng , Yuan Fenglin , Ma Kaixue 
Published: June 2023

AbstractA dual‐core voltage‐controlled oscillator (VCO) using harmonic resonance is presented in this letter. Without an additional switch capacitor bank, harmonic resonance implemented in VCO is realized by only a single control voltage, satisfying the requirement of frequency‐modulated continuous‐wave radar. Two pairs of varactors are added to the transformer‐based tank, which ensures a constant ratio between the two resonant frequencies of the tank in the entire tuning range. Robustly single‐frequency oscillation is obtained by increasing the coupling coefficient of the transformer and the coupling capacitor's capacitance. Implemented in a 28‐nm complementary metal–oxide–semiconductor, the VCO shows a 14.75% frequency tuning range covering 34.16–39.6 GHz. The measured results show it exhibits −102.13 dBc/Hz phase noise at a 1 MHz offset from the 34.16 GHz. The oscillator core draws 21–28 mA from a 0.9 V supply.
A digital score of peri‐epithelial lymphocytic activity predicts malignant transformation in oral epithelial dysplasia
Authors: Bashir Raja Muhammad Saad , Shephard Adam J , Mahmood Hanya , Azarmehr Neda , Raza Shan E Ahmed , Khurram Syed Ali , Rajpoot Nasir M 
Published: June 2023

AbstractOral squamous cell carcinoma (OSCC) is amongst the most common cancers, with more than 377,000 new cases worldwide each year. OSCC prognosis remains poor, related to cancer presentation at a late stage, indicating the need for early detection to improve patient prognosis. OSCC is often preceded by a premalignant state known as oral epithelial dysplasia (OED), which is diagnosed and graded using subjective histological criteria leading to variability and prognostic unreliability. In this work, we propose a deep learning approach for the development of prognostic models for malignant transformation and their association with clinical outcomes in histology whole slide images (WSIs) of OED tissue sections. We train a weakly supervised method on OED cases (n = 137) with malignant transformation (n = 50) and mean malignant transformation time of 6.51 years (±5.35 SD). Stratified five‐fold cross‐validation achieved an average area under the receiver‐operator characteristic curve (AUROC) of 0.78 for predicting malignant transformation in OED. Hotspot analysis revealed various features of nuclei in the epithelium and peri‐epithelial tissue to be significant prognostic factors for malignant transformation, including the count of peri‐epithelial lymphocytes (PELs) (p < 0.05), epithelial layer nuclei count (NC) (p < 0.05), and basal layer NC (p < 0.05). Progression‐free survival (PFS) using the epithelial layer NC (p < 0.05, C‐index = 0.73), basal layer NC (p < 0.05, C‐index = 0.70), and PELs count (p < 0.05, C‐index = 0.73) all showed association of these features with a high risk of malignant transformation in our univariate analysis. Our work shows the application of deep learning for the prognostication and prediction of PFS of OED for the first time and offers potential to aid patient management. Further evaluation and testing on multi‐centre data is required for validation and translation to clinical practice. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.