bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentiation of apoptosis in drug-resistant mantle cell lymphoma cells by MCL-1 inhibitor involves downregulation of inhibitor of apoptosis proteins
Authors: Li Yijing , Lee Heng-Huan , Jiang Vivian Changying , Che Yuxuan , McIntosh Joseph , Jordan Alexa , Vargas Jovanny , Zhang Tianci , Yan Fangfang , Simmons Margaret Elizabeth , Wang Wei , Nie Lei , Yao Yixin , Jain Preetesh , Wang Michael , Liu Yang 
Published: November 2023

AbstractBruton’s tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption capacity in MCL cell lines irrespective of their BTKi or venetoclax sensitivity. This combination also dramatically inhibited tumor growth and prolonged mouse survival in two aggressive MCL patient-derived xenograft models. Mechanistically, the augmented cell lethality was accompanied by the synergistic suppression of IAPs. Supporting this notion, the IAP antagonist BV6 induced dramatic apoptosis in resistant MCL cells and sensitized the resistant MCL cells to venetoclax. Our study uncovered another unique route for MCL-1 inhibitor to trigger apoptosis, implying that the pro-apoptotic combination of IAP antagonists and apoptosis inducers could be further exploited for MCL patients with multiple therapeutic resistance.
Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time
Authors: Kenny Grace , O’Reilly Sophie , Wrigley Kelly Neil , Negi Riya , Gaillard Colette , Alalwan Dana , Saini Gurvin , Alrawahneh Tamara , Francois Nathan , Angeliadis Matthew , Garcia Leon Alejandro Abner , Tinago Willard , Feeney Eoin R. , Cotter Aoife G. , de Barra Eoghan , Yousif Obada , Horgan Mary , Doran Peter , Stemler Jannik , Koehler Philipp , Cox Rebecca Jane , O’Shea Donal , Olesen Ole F. , Landay Alan , Hogan Andrew E. , Lelievre Jean-Daniel , Gautier Virginie , Cornely Oliver A. , Mallon Patrick W. G. ,   The All Ireland Infectious Diseases Cohort Study, Leon Alejandro Garcia , Feeney Eoin , de Barra Eoghan ,   VACCELERATE Consortium EU-COVAT-1-AGED Part A Study Group, Mallon Patrick 
Published: November 2023

AbstractSARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67–89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77–94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies.
Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field
Authors: Dey Ranadhir , Alshaweesh Jalal , Singh Kamaleshwar P. , Lypaczewski Patrick , Karmakar Subir , Klenow Laura , Paulini Kayla , Kaviraj Swarnendu , Kamhawi Shaden , Valenzuela Jesus G. , Singh Sanjay , Hamano Shinjiro , Satoskar Abhay R. , Gannavaram Sreenivas , Nakhasi Hira L. , Matlashewski Greg 
Published: November 2023

AbstractThe leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical disease. Due to a lack of antigen used for the intradermal injection, the leishmanin skin test is no longer available. As leishmaniasis control programs are advancing and new vaccines are entering clinical trials, it is essential to re-introduce the leishmanin skin test. Here we establish a Leishmania donovani strain and describe the production, under Good Laboratory Practice conditions, of leishmanin soluble antigen used to induce the leishmanin skin test in animal models of infection and vaccination. Using a mouse model of cutaneous leishmaniasis and a hamster model of visceral leishmaniasis, soluble antigen induces a leishmanin skin test response following infection and vaccination with live attenuated Leishmania major (LmCen-/-). Both the CD4+ and CD8+ T-cells are necessary for the leishmanin skin test response. This study demonstrates the feasibility of large-scale production of leishmanin antigen addressing a major bottleneck for performing the leishmanin skin test in future surveillance and vaccine clinical trials.
Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer
Authors: Saatci Ozge , Cetin Metin , Uner Meral , Tokat Unal Metin , Chatzistamou Ioulia , Ersan Pelin Gulizar , Montaudon Elodie , Akyol Aytekin , Aksoy Sercan , Uner Aysegul , Marangoni Elisabetta , Sajish Mathew , Sahin Ozgur 
Published: November 2023

AbstractResistance to endocrine therapy and CDK4/6 inhibitors, the standard of care (SOC) in estrogen receptor-positive (ER+) breast cancer, greatly reduces patient survival. Therefore, elucidating the mechanisms of sensitivity and resistance to SOC therapy and identifying actionable targets are urgently needed. Here, we show that SOC therapy causes DNA damage and toxic PARP1 trapping upon generation of a functional BRCAness (i.e., BRCA1/2 deficiency) phenotype, leading to increased histone parylation and reduced H3K9 acetylation, resulting in transcriptional blockage and cell death. Mechanistically, SOC therapy downregulates phosphodiesterase 4D (PDE4D), a novel ER target gene in a feedforward loop with ER, resulting in increased cAMP, PKA-dependent phosphorylation of mitochondrial COXIV-I, ROS generation and DNA damage. However, during SOC resistance, an ER-to-EGFR switch induces PDE4D overexpression via c-Jun. Notably, combining SOC with inhibitors of PDE4D, EGFR or PARP1 overcomes SOC resistance irrespective of the BRCA1/2 status, providing actionable targets for restoring SOC efficacy.
Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus
Authors: Fu Wenhao , Chi Huanyu , Dai Xin , Zhu Hongni , Mesias Vince St. Dollente , Liu Wei , Huang Jinqing 
Published: November 2023

AbstractIt is challenging to characterize single or a few biomolecules in physiological milieus without excluding the influences of surrounding environment. Here we utilize optical plasmonic trapping to construct a dynamic nanocavity, which reduces the diffraction-limited detection volume and provides reproducible electromagnetic field enhancements to achieve high-throughput single-molecule surface-enhanced Raman spectroscopy (SERS) characterizations in aqueous environments. Specifically, we study human Islet Amyloid Polypeptide (amylin, hIAPP) under different physiological pH conditions by combining spectroscopic experiments and molecular dynamics (MD) simulations. Based on a statistically significant amount of time-dependent SERS spectra, two types of low-populated transient species of hIAPP containing either turn or β-sheet structure among its predominant helix-coil monomers are characterized during the early-stage incubation at neutral condition, which play a crucial role in driving irreversible amyloid fibril developments even after a subsequent adjustment of pH to continue the prolonged incubation at acidic condition. Our results might provide profound mechanistic insight into the pH-regulated amyloidogenesis and introduce an alternative approach for investigating complex biological processes at the single-molecule level.
Effect of recombinant human erythropoietin combined with iron sucrose on postoperative hemoglobin in patients undergoing artificial joint replacement
Authors: Yu Wenjiang , Liu Chengyan , Bi Zhiguo 
Published: November 2023

AbstractWith the aging of the population, an increasing number of elderly patients are opting for artificial joint replacement, leading to the exploration of various rapid rehabilitation programs in the perioperative period. In this study, we aimed to investigate the effectiveness of combining recombinant human erythropoietin and iron sucrose in altering the range and trend of postoperative hemoglobin in patients undergoing arthroplasty. Specifically, we will examine whether this combination can effectively alter the rise and fall of postoperative haemoglobin, identify the inflection point of haemoglobin change or recovery after arthroplasty, and assess the effect of treatment on serum iron in postoperative blood. We conducted a retrospective study of 138 patients who underwent unilateral total joint arthroplasty by the same surgeon in the same hospital before July 2022. The results of this study may provide valuable insights for the development of effective rehabilitation programs for patients undergoing arthroplasty.
Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women
Authors: Adebamowo Clement A. ,   The ACCME Research Group as part of the H3Africa Consortium, Adebamowo Sally N. , Offiong Richard , Olaniyan Olayinka , Obende Kayode , Adebayo Amos , Ologun Sanni , Alabi Bunmi , Achara Peter , Erhunmwonsere Juliet Iyosaba , Owoade Yinka , Gbolahan Tolu , Adebamowo Sally N. 
Published: November 2023

AbstractThere has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74–0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24–0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35–0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27–0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01–1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.
Addressing the issue of surface mechanisms and competitive effects in Cr(VI) reductive-adsorption on tin-hydroxyapatite in the presence of co-ions
Authors: Avola Tiziana , Campisi Sebastiano , Polito Laura , Arici Silvia , Ferruti Ludovica , Gervasini Antonella 
Published: November 2023

AbstractOur group recently proposed an innovative sustainable reductant-adsorbent material, tin(II)-hydroxyapatite (Sn/HAP, ca. 10 wt% Sn) for the interfacial Cr(VI) reductive adsorption process. In this study, Cr(VI) removal capacity was evaluated in multi-component solutions containing representative background ions (i.e., CaCl2, Ca(NO3)2, MgSO4, Na2SO4, Fe(NO3)3, AlCl3, Zn(NO3)2, or Mn(NO3)2). Sn/HAP was able to reduce Cr(VI) with complete Cr3+ adsorption on HAP surface, except in the presence of Fe3+ and Al3+ ions. Some metal ions co-existing in solution, such as Fe3+, Al3+, Zn2+, and Mn2+, were also adsorbed on HAP surface. Reuse experiments of the Sn/HAP sample, up to 7 runs, resulted in a total amount of reduced Cr(VI) of ca. 15–18 mg g−1. Fast kinetics of Cr(VI) reductive adsorption at 25 °C in a multi-metal component solution was observed. The pseudo-second order model was in excellent agreement with the experimental kinetic data, leading to a rate constant (k25°C) value of ca. 30 M−1 s−1. The collection of adsorption isotherms of Cr3+ and Fe3+, together with TEM–EDX analysis permitted the unveiling of competitive adsorption phenomena between metal ions. The obtained results demonstrate that Sn/HAP could be an efficient material for the removal of hexavalent chromium in aqueous solutions containing high concentrations of inorganic impurities.
Reliability of resting-state EEG modulation by continuous and intermittent theta burst stimulation of the primary motor cortex: a sham-controlled study
Authors: Rodionov Andrei , Ozdemir Recep A. , Benwell Christopher S. Y. , Fried Peter J. , Boucher Pierre , Momi Davide , Ross Jessica M. , Santarnecchi Emiliano , Pascual-Leone Alvaro , Shafi Mouhsin M. 
Published: November 2023

AbstractTheta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation designed to induce changes of cortical excitability that outlast the period of TBS application. In this study, we explored the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) versus sham TBS stimulation, applied to the left primary motor cortex, on modulation of resting state electroencephalography (rsEEG) power. We first conducted hypothesis-driven region-of-interest (ROI) analyses examining changes in alpha (8–12 Hz) and beta (13–21 Hz) bands over the left and right motor cortex. Additionally, we performed data-driven whole-brain analyses across a wide range of frequencies (1–50 Hz) and all electrodes. Finally, we assessed the reliability of TBS effects across two sessions approximately 1 month apart. None of the protocols produced significant group-level effects in the ROI. Whole-brain analysis revealed that cTBS significantly enhanced relative power between 19 and 43 Hz over multiple sites in both hemispheres. However, these results were not reliable across visits. There were no significant differences between EEG modulation by active and sham TBS protocols. Between-visit reliability of TBS-induced neuromodulatory effects was generally low-to-moderate. We discuss confounding factors and potential approaches for improving the reliability of TBS-induced rsEEG modulation.
Using a Bayesian hierarchical approach to study the association between non-pharmaceutical interventions and the spread of Covid-19 in Germany
Authors: Khazaei Yeganeh , Küchenhoff Helmut , Hoffmann Sabine , Syliqi Diella , Rehms Raphael 
Published: November 2023

AbstractNon-Pharmaceutical Interventions (NPIs) are community mitigation strategies, aimed at reducing the spread of illnesses like the coronavirus pandemic, without relying on pharmaceutical drug treatments. This study aims to evaluate the effectiveness of different NPIs across sixteen states of Germany, for a time period of 21 months of the pandemic. We used a Bayesian hierarchical approach that combines different sub-models and merges information from complementary sources, to estimate the true and unknown number of infections. In this framework, we used data on reported cases, hospitalizations, intensive care unit occupancy, and deaths to estimate the effect of NPIs. The list of NPIs includes: “contact restriction (up to 5 people)”, “strict contact restriction”, “curfew”, “events permitted up to 100 people”, “mask requirement in shopping malls”, “restaurant closure”, “restaurants permitted only with test”, “school closure” and “general behavioral changes”. We found a considerable reduction in the instantaneous reproduction number by “general behavioral changes”, “strict contact restriction”, “restaurants permitted only with test”, “contact restriction (up to 5 people)”, “restaurant closure” and “curfew”. No association with school closures could be found. This study suggests that some public health measures, including general behavioral changes, strict contact restrictions, and restaurants permitted only with tests are associated with containing the Covid-19 pandemic. Future research is needed to better understand the effectiveness of NPIs in the context of Covid-19 vaccination.
Doubly elastic net regularized online portfolio optimization with transaction costs
Authors: Yao Xiaoting , Zhang Na 
Published: November 2023

AbstractOnline portfolio optimization with transaction costs is a big challenge in large-scale intelligent computing community, since its undersample from rapidly-changing market and complexity from varying transaction costs. In this paper, we focus on this problem and solve it by machine learning system. Specifically, we reformulate the optimization problem with the minimization over simplex containing three items, which are negative expected return, the elastic net regularization of transaction costs controlled term and portfolio variable, respectively. We propose to apply linearized augmented Lagrangian method (LALM) and the alternating direction method of multipliers (ADMM) to solve the optimization model in a higher efficiency, meanwhile theoretically guarantee their convergence and deduce closed-form solutions of their subproblems in each iteration. Furthermore, we conduct extensive experiments on five benchmark datasets from real market to demonstrate that the proposed algorithms outperform compared state-of-the-art strategies in most cases in six dimensions.
Machine learning-based prediction model for emergency department visits using prescription information in community-dwelling non-cancer older adults
Authors: Park Soyoung , Lee Changwoo , Lee Seung-Bo , Lee Ju-yeun 
Published: November 2023

AbstractOlder adults are more likely to require emergency department (ED) visits than others, which might be attributed to their medication use. Being able to predict the likelihood of an ED visit using prescription information and readily available data would be useful for primary care. This study aimed to predict the likelihood of ED visits using extensive medication variables generated according to explicit clinical criteria for elderly people and high-risk medication categories by applying machine learning (ML) methods. Patients aged ≥ 65 years were included, and ED visits were predicted with 146 variables, including demographic and comprehensive medication-related factors, using nationwide claims data. Among the eight ML models, the final model was developed using LightGBM, which showed the best performance. The final model incorporated 93 predictors, including six sociodemographic, 28 comorbidity, and 59 medication-related variables. The final model had an area under the receiver operating characteristic curve of 0.689 in the validation cohort. Approximately half of the top 20 strong predictors were medication-related variables. Here, an ED visit risk prediction model for older people was developed and validated using administrative data that can be easily applied in clinical settings to screen patients who are likely to visit an ED.
Doxorubicin-induced modulation of TGF-β signaling cascade in mouse fibroblasts: insights into cardiotoxicity mechanisms
Authors: Patricelli Conner , Lehmann Parker , Oxford Julia Thom , Pu Xinzhu 
Published: November 2023

AbstractDoxorubicin (DOX)-induced cardiotoxicity has been widely observed, yet the specific impact on cardiac fibroblasts is not fully understood. Additionally, the modulation of the transforming growth factor beta (TGF-β) signaling pathway by DOX remains to be fully elucidated. This study investigated DOX’s ability to modulate the expression of genes and proteins involved in the TGF-β signaling cascade in mouse fibroblasts from two sources by assessing the impact of DOX treatment on TGF-β inducible expression of pivotal genes and proteins within fibroblasts. Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX in the presence of TGF-β1 to assess changes in protein levels by western blot and changes in mRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our results revealed a dose-dependent reduction in cellular communication network factor 2 (CCN2) protein levels upon DOX treatment in both NIH3T3 and CFs, suggesting an antifibrotic activity by DOX in these fibroblasts. However, DOX only inhibited the TGF-β1 induced expression of COL1 in NIH3T3 cells but not in CFs. In addition, we observed that DOX treatment reduced the expression of BMP1 in NIH3T3 but not primary cardiac fibroblasts. No significant changes in SMAD2 protein expression and phosphorylation in either cells were observed after DOX treatment. Finally, DOX inhibited the expression of Atf4 gene and increased the expression of Cdkn1a, Id1, Id2, Runx1, Tgfb1, Inhba, Thbs1, Bmp1, and Stat1 genes in NIH3T3 cells but not CFs, indicating the potential for cell-specific responses to DOX and its modulation of the TGF-β signaling pathway.