bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current status of drug development for patients with multiple myeloma: a review of comparison in China and the rest of world
Authors: Huang Lei , Zhang Jingyu , Punnoose Elizabeth , Xiao Zhenyu , Li Wenjin 
Published: May 2023

Abstract
Multiple myeloma (MM) is a highly heterogeneous malignancy. The treatment of MM has been significantly advanced in recent years. B cell maturation antigen (BCMA)-targeted immunotherapy and chimeric antigen receptor T (CAR-T) cell therapy have been approved for the treatment of relapsed and refractory MM (RRMM), which will be launched in China shortly. The CD38 (cluster of differentiation 38) antibody, daratumumab, improves the clinical outcomes both RRMM and newly diagnosed MM patients. The combination of daratumumab, bortezomib and dexamethasone achieved favorable outcomes as the first-line therapy in China. However, high-risk patients have limited benefits from these advanced therapeutics, and usually relapse early, progressing into aggressive end-stage MM. Therefore, novel therapies are sought to improve the cancer prognosis in these patients. This review furnishes an overview of the recent clinical developments of these novel drugs and compares the drug candidates under development in China to the rest of the world.
157 Keynote: Understanding Exposure, Hazard Identification, and Human Health Effects: How Ultrafine/Nano Particle Toxicology Influenced Occupational Safety and Health
Authors: Erdely Aaron 
Published: May 2023

Abstract
Particles and fibers, whether process-derived, engineered, or environmental, have the possibility to cause adverse health effects when inhaled. Historic occupational particulates, such as coal, silica, and asbestos were clearly associated with human disease and induced a human health burden. This necessitated worldwide formation of national institutes to evaluate and mitigate exposures and mechanisms. The scientific evaluation of historic exposures set the stage for conducting air pollution/particulate matter research demonstrating that adverse health outcomes from particulates created potential risk for the general population, not just an occupational workforce. Research soon showed that adverse effects were not confined to the primary target site (e.g., lung) but also included cardiovascular, neurological, and developmental dysfunction. The evaluation of particulate matter, especially the fine and ultrafine fraction, quickly adapted to the rapid expansion of engineered nanomaterials. However, the study of novel engineered nanomaterials required a transition to preventative measures when interpreting controlled toxicity evaluations. Shifting the paradigm of particulate toxicology from explaining a chronic disease to intervening prior to a health burden brought many challenges to toxicologic research, exposure science, and responsible commercialization. Challenges included physicochemical characterization of nanoscale material, toxicologic research proceeding without exposure science guidance, and epidemiological investigations without post-exposure timepoints sufficient for evaluating potential induction of chronic disease. The navigation of these challenges shaped current approaches for evaluating multiple emerging technologies as well as influenced perspective on historic particles, especially those which resurface as part of complex mixtures.
111 Toxicity Assessment of a Carbon Nanotube Embedded Concrete
Authors: Kodali Vamsi , Lee Eun Gyung , Gill Ryan , Afshari Aliakbar , McKinney Walter , Casuccio Gary , Bunker Kristin , Lersch Traci , Rickabaugh Keith , Erdely Aaron 
Published: May 2023

Abstract
Carbon nanotube (CNT) as a reinforcement enhances durability and performance of concrete composites. Exposure to some forms of CNT is known to cause adverse pathological outcomes. To understand potential toxicity arising from use of CNT-enabled concrete composites as it goes through various occupational life cycle stages, we evaluated 1) the physicochemical characteristics and toxicity of the as-produced CNT and 2) how particulate release during concrete manipulation (e.g., cutting) is altered by CNT incorporation. Physical dimensional profiling indicated a geometric mean length of 0.72 µm and 32 nm in diameter. The toxicity of the as-produced CNT was similar to an agglomerated CNT studied in our previous research, lacking the more severe toxicity associated with longer length and diameter CNT. Four concrete test samples, three different formulations with CNT and one without, were cut in a specialized chamber to simulate an occupational scenario. The mass median aerodynamic diameters from varying CNT incorporated composites did not change and was 5.23 µm in diameter. No free CNT was captured in the aerosols or was visible on the surface of the concrete. The toxicity of the released particulate is currently being investigate using in vitro screening tests designed to investigate mechanisms of potential toxicity. There were minimal changes in the particulate size distribution profiles after cutting, suggesting adding CNT to concrete may have subtle effects on the toxicity of the generated particulate.
6 Characterization of Aerosolized Particles Generated During Cutting of Carbon Nanotubes-Embedded Concrete
Authors: Lee Eun Gyung , Gill Ryan , Afshari Aliakbar , McKinney Walter , Kodali Vamsi , Casuccio Gary , Bunker Kristin , Lersch Traci , Rickabaugh Keith , Erdely Aaron 
Published: May 2023

Abstract
Engineered nanomaterials are revolutionizing many industries, but little is known about potential exposures during the life cycle of nano-enabled composites. This study was conducted to characterize aerosolized particles using direct-reading instruments and integrated air samplers during cutting multi-walled carbon nanotubes (MWCNT)-embedded concrete cylinder blocks. Three types of blocks, 0% (reference), low%, and high% MWCNT, were tested in a specially designed enclosure housing an apparatus for the cutting of a block with an automated computer-controlled process. The highest particle number concentration (163,821 particles/cm3) was measured for the reference cylinder, while others showed similar concentrations (131,689 particles/cm3 and 140,954 particles/cm3 for the low% and high% blocks, respectively). Regardless of the cylinder type, the size-selected particle number concentrations revealed one main mode with a peak at 0.72 µm indicating no shift in the size distribution from addition(s) of MWCNT. Respirable mass concentrations were 342 mg/m3, 405 mg/m3, and 432 mg/m3 for the reference, low%, and high% blocks, respectively. The mass median aerodynamic diameters were similar, 5.23 µm for the reference and 5.05 µm for both low% and high% blocks, indicating a predominant respirable fraction. Respirable particles (quartz, feldspar, paste, etc.) often appeared to be agglomerated materials that included both paste and aggregate minerals. No free MWCNT were observed by electron microscopy from low% and high% samples. These initial studies found no evidence of free MWCNT by cutting concrete test blocks and only minor differences in the particulate aerosol generated, which included a general increase in respirable mass with increasing % CNT.
A demographic approach for predicting population responses to multifactorial stressors
Authors: Zettlemoyer Meredith A 
Published: May 2023

Abstract
Populations face a suite of anthropogenic stressors acting simultaneously, which can combine additively or interact to have complex effects on population persistence. Yet we still know relatively little about the mechanisms underlying population-level responses to multifactorial combinations of stressors because multiple stressor impacts across organisms’ life cycles have not been systematically considered in population models. Specifically, different anthropogenic stressors can have variable effects across an organism’s life cycle, resulting in non-intuitive results for long-term population persistence. For example, synergistic or antagonistic interactions might exacerbate or alleviate the effects of stressors on population dynamics, and different life-history stages or vital rates might contribute unequally to long-term population growth rates. Demographic modelling provides a framework to incorporate individual vital rate responses to multiple stressors into estimates of population growth, which will allow us to make more informed predictions about population-level responses to novel combinations of anthropogenic change. Without integrating stressors’ interactive effects across the entire life cycle on population persistence, we may over- or underestimate threats to biodiversity and risk missing conservation management actions that could reduce species’ vulnerability to stress.
A linear adjustment-based approach to posterior drift in transfer learning
Authors: Maity Subha , Dutta Diptavo , Terhorst Jonathan , Sun Yuekai , Banerjee Moulinath 
Published: May 2023

Summary
We present new models and methods for the posterior drift problem where the regression function in the target domain is modelled as a linear adjustment, on an appropriate scale, of that in the source domain, and study the theoretical properties of our proposed estimators in the binary classification problem. The core idea of our model inherits the simplicity and the usefulness of generalized linear models and accelerated failure time models from the classical statistics literature. Our approach is shown to be flexible and applicable in a variety of statistical settings, and can be adopted for transfer learning problems in various domains including epidemiology, genetics and biomedicine. As concrete applications, we illustrate the power of our approach (i) through mortality prediction for British Asians by borrowing strength from similar data from the larger pool of British Caucasians, using the UK Biobank data, and (ii) in overcoming a spurious correlation present in the source domain of the Waterbirds dataset.
O001 A novel molecular HLA mismatch algorithm to identify transplant patients at low risk of primary alloimmunity
Authors: Copley H , Wiebe C , Kim J , Manook M , Williams E , Mohorianu I , Kabelitz D , Kling C , Leach A , Nickerson P , Kosmoliaptsis V 
Published: May 2023

Abstract

Introduction
There is an unmet need for prognostic biomarkers for alloimmune risk stratification to guide personalised recipient care kidney transplantation.

Methods
We used three molecular Mismatch (molMM) algorithms - Amino-Acid-Mismatch-Score (AAMS), Electrostatic-Mismatch-Score (EMS3D) and NetMHCIIpan in a dataset of patients receiving standardised donor lymphocyte injections to predict de-novo donor-specific-antibody (dnDSA) at the individual HLA level (n=665). Risk thresholds were derived for HLA-DR/DQ mismatch and algorithms combined. External validation was performed in two extensively-phenotyped kidney transplant cohorts (Manitoba, n=856, Denver n=404) and in the NHSBT kidney transplant registry (2000–2020, n=27,028).

Results
External validation (Manitoba cohort, 10-year follow-up) showed all algorithms predicted dnDSA development using experimentally derived HLA-DR/DQ molMM risk thresholds (HLA-DQ AUC: 0.78-0.80; HLA-DR AUC:0.76-0.81). AAMS and EMS3D had improved risk stratification (low-medium-high risk groups for HLA-DR+DQ dnDSA) vs NetMHCIIpan (p=NS). A combined AAMS+EMS3D molMM algorithm further improved discrimination and identified a large patient cohort (15.4% patients) at very-low risk of Class-II dnDSA (1.3% at 10 years). Multivariate analysis confirmed correlation with primary alloimmune events (dnDSA p&lt;0.001, TCMR p&lt;0.001, ABMR p=0.0049) and all-cause graft loss (p=0.0038). Further external validation of the combined molMM algorithm in an ethnically diverse cohort (Denver) confirmed the dnDSA risk association (p&lt;0.0001), and in the UK registry cohort confirmed significant association with all-cause graft loss (p&lt;0.001).

Conclusion
We developed and validated a novel molMM algorithm, incorporating information from HLA amino-acid sequence and tertiary structurebthat may be used as a prognostic biomarker of primary alloimmunity risk and to enrich prospective clinical trials in kidney transplantation.
O105 The impact of experimental hyperchloraemic acidosis on porcine isolated visceral arterial contractility
Authors: Skorepa P , Lobo D N , Wilson V 
Published: May 2023

Abstract

Introduction
Hyperchloraemic acidosis is known to be associated with impaired renal function in post-operative patients. We have experimentally investigated whether elevation in chloride and hydrogen ions have the potential to negatively impact the porcine renal vasculature.

Methods
Porcine renal (RA) and mesenteric (MA) arteries were placed in Krebs-Henseleit solution (K-H), gassed with 95%O2/5%CO2, and prepared for isometric tension recordings. 60mM KCl was used for standardized contractions and preparations were then exposed to the thromboxane-mimetic U46619, followed 6-18mM of either NaCl or Na Gluconate (NaGlu). Preparations were also exposed to increasing concentrations of noradrenaline in normal K-H (pH 7.4) and K-H pH 7.2.

Results
U46619 (10-20nM) produced stable contractions in RA and MA equivalent to 50% of that to 60mM KCl. 18mM NaCl caused a further contraction in RA (19.8±4.2%, n=9, p &lt; 0.01), while 18mM NaGlu (3.8±4.4%, n=9) did not. Neither 6-18mM NaCl nor 6-18mM NaGlu caused responses in MA (&lt; 4%, n=6). Noradrenaline produced concentration-dependent contractions in MA in normal K-H solution (logEC50 5.43±0.11: Max’ 226.8±24.6% 60mM KCl, n=6) that were significantly reduced (p &lt; 0.05) in K-H pH 7.2 (logEC50 5.13±0.02: Max’ 174.4.8±3.3%, 60mM KCl, n=6). In contrast, in the RA noradrenaline contractions (logEC50 5.80±0.08: Max’ 162.8±12.0% 60mM KCl, n=11) were not affected (p &gt; 0.05) by K-H solution pH 7.2 (logEC50 5.71±0.07: Max’ 177.8±15.3% 60mM KCl, n=11).

Conclusion
Elevation of chloride ions (experimental hyperchloraemia) selectively constricts porcine renal blood vessels, while corresponding elevation in hydrogen ions (acidosis) selectively dilates the mesenteric vasculature.
Mapping the neuroanatomical heterogeneity of OCD using a framework integrating normative model and non-negative matrix factorization
Authors: Han Shaoqiang , Xu Yinhuan , Fang Keke , Guo Hui-Rong , Wei Yarui , Liu Liang , Wen Baohong , Liu Hao , Zhang Yong , Cheng Jingliang 
Published: May 2023

Abstract
Obsessive–compulsive disorder (OCD) is a spectrum disorder with high interindividual heterogeneity. We propose a comprehensible framework integrating normative model and non-negative matrix factorization (NMF) to quantitatively estimate the neuroanatomical heterogeneity of OCD from a dimensional perspective. T1-weighted magnetic resonance images of 98 first-episode untreated patients with OCD and matched healthy controls (HCs, n = 130) were acquired. We derived individualized differences in gray matter morphometry using normative model and parsed them into latent disease factors using NMF. Four robust disease factors were identified. Each patient expressed multiple factors and exhibited a unique factor composition. Factor compositions of patients were significantly correlated with severity of symptom, age of onset, illness duration, and exhibited sex differences, capturing sources of clinical heterogeneity. In addition, the group-level morphological differences obtained with two-sample t test could be quantitatively derived from the identified disease factors, reconciling the group-level and subject-level findings in neuroimaging studies. Finally, we uncovered two distinct subtypes with opposite morphological differences compared with HCs from factor compositions. Our findings suggest that morphological differences of individuals with OCD are the unique combination of distinct neuroanatomical patterns. The proposed framework quantitatively estimating neuroanatomical heterogeneity paves the way for precision medicine in OCD.
The rape-pregnancy plots of Roman comedy and their reception in nineteenth-century Greece: the case of The Pot of Basil by Antonios Matesis
Authors: Jotischky Christopher 
Published: May 2023

Abstract
Plots in which a woman is raped and left pregnant are common in Roman comedy, but the cultural meaning of unwanted pregnancy and its relationship to women’s personal freedoms and bodily autonomy varies across reception contexts. Antonios Matesis (1794–1875) translated Terence’s Hecyra into vernacular Greek in the 1820s before going on to compose a comedy of his own, The Pot of Basil, which is influenced by Terence’s play. Nevertheless, Matesis refocuses the emotional dynamics of Terence’s plot in order to focus on Garoufalia, the pregnant woman, whose counterpart in Terence never appears onstage. This narrative trajectory situates the play within a local Zakynthian context, with contemporary literary works such as the Autobiography of Elisavet Moutzan-Martinengou (1801–32) also offering a critical examination of women’s life on the island. The influence of Terence places Matesis squarely in a European tradition of Roman comic reception, but reading his play alongside Moutzan-Martinengou’s work demonstrates how closely Matesis is entwined with debates concerning the status of women in the area which was the historical faultline between Venetian and Ottoman spheres of influence.
Public Meetings, Respectable Requisitions, and Popular Politics in Great Britain and Ireland, c.1769–1850
Authors: Huzzey Richard 
Published: May 2023

Abstract
This article examines the practice of ‘requisitioning’ public meetings in Great Britain and Ireland. These written requests to office-holders emerged in Ireland and then Great Britain, following bitter contests over the authenticity and authority of addresses and meetings claiming to represent a county or town in the decade after 1769. If the Seditious Meetings Acts privileged meetings officially convened by local elites, they also codified the practice of householders signing their own advertisements to requisition meetings under magisterial oversight. This would, especially when revolutionary threats receded and local justices’ sympathies permitted, allow local organisers some legal and constitutional claims to public assembly, even if Peterloo demonstrated the continuing threat of the Riot Act. Alongside bi-partisan opportunism encouraging public meetings, the article emphasises the creative use of constitutional and legal claims by ‘political entrepreneurs’. Comparison with Ireland demonstrates ministers’ greater recourse to new legislation and executive powers, but also the exchange of political practices with Great Britain. The prosecution of intimidating numbers, rather than seditious conduct, after 1842 diminished the role of requisitions, as did the hybridisation of ‘public meetings’. This was not so much the loss of a demotic form of community deliberation, but a proliferation and multiplication of the meetings—and voices—claiming to represent public opinion. The changing uses of a subscriptional practice can illuminate the relationship between government initiatives and local enforcement, and highlight the talents of those forging new meanings of the law, the constitution, and the political nation from restrictive procedures.
Challenges in heart failure care in four European countries: a comparative study
Authors: Steiner Bianca , Neumann Anne , Pelz Yannick , Ski Chantal F , Hill Loreena , Thompson David R , Fitzsimons Donna , Dixon Lana J , Brandts Julia , Verket Marlo , Schütt Katharina , Eurlings Casper G M J , Boyne Josiane J J , Gingele Arno J , De Maesschalck Lieven , Murphy Marguerite , Furtado da Luz Ermelinda , Barrett Matthew , Windle Karen , Hoedemakers Thom , Helms Thomas M , Brunner-La Rocca Hans-Peter , Zippel-Schultz Bettina 
Published: May 2023

Abstract

Background
In Europe, more than 15 million people live with heart failure (HF). It imposes an enormous social, organizational and economic burden. As a reaction to impending impact on healthcare provision, different country-specific structures for HF-care have been established. The aim of this report is to provide an overview and compare the HF-care approaches of Germany, Ireland, the Netherlands and the UK, and to open the possibility of learning from each other’s experience.

Methods
A mixed methods approach was implemented that included a literature analysis, interviews and questionnaires with HF-patients and caregivers, and expert interviews with representatives from healthcare, health service research and medical informatics.

Results
The models of HF-care in all countries analyzed are based on the European Society of Cardiology guidelines for diagnosis and treatment of HF. Even though the HF-models differed in design and implementation in practice, key challenges were similar: (i) unequal distribution of care between urban and rural areas, (ii) long waiting times, (iii) unequal access to and provision of healthcare services, (iv) information and communication gaps and (v) inadequate implementation and financing of digital applications.

Conclusion
Although promising approaches exist to structure and improve HF-care, across the four countries, implementation was reluctant to embrace novel methods. A lack of financial resources and insufficient digitalization making it difficult to adopt new concepts. Integration of HF-nurses seems to be an effective way of improving current models of HF-care. Digital solutions offer further opportunities to overcome communication and coordination gaps and to strengthen self-management skills.
Health-care providers’ perspectives on an HIV patient navigation training to improve uptake of PrEP among Black sexual minority men
Authors: Burns Paul A , Anyimukwu Chizoba , Omondi Angela A , Monger Mauda , Ward Lori , Poteat Tonia 
Published: May 2023

Abstract
This article examines implementational factors associated with an HIV patient navigation training intervention for health care professionals working with Black sexual minority men to improve access to and uptake of HIV prevention services among Black MSM. Utilizing qualitative analysis to better understand healthcare professionals’ perceptions of the training program, we conducted a thematic content analysis based on constructs from Professional Network and Reach Model-Systems Model Approach (PNRSMA) framework. Data analysis revealed four major themes: 1) Knowledge and skill building, 2) Novel and Innovation, 3) Barriers to Implementation, and 4) Recommendations and Future Directions. Implementation factors such as appropriate facilitators, content, mode of delivery, learning strategies, and understanding structural barriers were important to training success. Participants highlighted innovation strategies such as the use of social media and interactive communication (e.g. role-playing and bi-directional communication) enhanced learning and skill-building. The expansion of training to include other affected groups such as women and bisexual individuals and increasing the duration of the training emerged as areas for improvement and effectiveness. Our analysis of an HIV patient navigation training revealed important findings to improve the implementation process to increase uptake of PrEP and other HIV prevention, care and treatment services.