bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifibrotic treatment adherence, efficacy and outcomes for patients with idiopathic pulmonary fibrosis in Spain: a real-world evidence study
Authors: Romero Ortiz Ana Dolores , Jiménez-Rodríguez Beatriz María , López- Ramírez Cecilia , López- Bauzá Ángela , Pérez- Morales María , Delgado-Torralbo José Antonio , Villalba Moral Cristina , Alcazar-Navarrete Bernardino 
Published: April 2024

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood.MethodsAn observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected.Results232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity.Conclusionsin this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.
Myeloid-derived suppressor cells attenuate the antitumor efficacy of radiopharmaceutical therapy using90Y-NM600 in combination with androgen deprivation therapy in murine prostate tumors
Authors: Muralidhar Anusha , Hernandez Reinier , Morris Zachary S , Comas Rojas Hansel , Bio Idrissou Malick , Weichert Jamey P , McNeel Douglas G 
Published: April 2024

RationaleAndrogen deprivation therapy (ADT) is pivotal in treating recurrent prostate cancer and is often combined with external beam radiation therapy (EBRT) for localized disease. However, for metastatic castration-resistant prostate cancer, EBRT is typically only used in the palliative setting, because of the inability to radiate all sites of disease. Systemic radiation treatments that preferentially irradiate cancer cells, known as radiopharmaceutical therapy or targeted radionuclide therapy (TRT), have demonstrable benefits for treating metastatic prostate cancer. Here, we explored the use of a novel TRT,90Y-NM600, specifically in combination with ADT, in murine prostate tumor models.Methods6-week-old male FVB mice were implanted subcutaneously with Myc-CaP tumor cells and given a single intravenous injection of90Y-NM600, in combination with ADT (degarelix). The combination and sequence of administration were evaluated for effect on tumor growth and infiltrating immune populations were analyzed by flow cytometry. Sera were assessed to determine treatment effects on cytokine profiles.ResultsADT delivered prior to TRT (ADT→TRT) resulted in significantly greater antitumor response and overall survival than if delivered after TRT (TRT→ADT). Studies conducted in immunodeficient NRG mice failed to show a difference in treatment sequence, suggesting an immunological mechanism. Myeloid-derived suppressor cells (MDSCs) significantly accumulated in tumors following TRT→ADT treatment and retained immune suppressive function. However, CD4+ and CD8+ T cells with an activated and memory phenotype were more prevalent in the ADT→TRT group. Depletion of Gr1+MDSCs led to greater antitumor response following either treatment sequence. Chemotaxis assays suggested that tumor cells secreted chemokines that recruited MDSCs, notably CXCL1 and CXCL2. The use of a selective CXCR2 antagonist, reparixin, further improved antitumor responses and overall survival when used in tumor-bearing mice treated with TRT→ADT.ConclusionThe combination of ADT and TRT improved antitumor responses in murine models of prostate cancer, however, this was dependent on the order of administration. This was found to be associated with one treatment sequence leading to an increase in infiltrating MDSCs. Combining treatment with a CXCR2 antagonist improved the antitumor effect of this combination, suggesting a possible approach for treating advanced human prostate cancer.
Identification of DAGLA as an autoantibody target in cerebellar ataxia
Authors: Miske Ramona , Scharf Madeleine , Borowski Kathrin , Specht Ina , Corty Merle , Loritz Monika-Johanna , Rombach Frederik , Laureys Guy , Rochow Nadine , Radzimski Christiane , Schnitter Linda , Ratuszny Dominica , Skripuletz Thomas , Wattjes Mike P , Hahn Stefanie , Denno Yvonne , Guerti Khadija , Oyaert Matthijs , Benkhadra Farid , Bien Corinna Ines , Nitsch Sophie , Wandinger Klaus-Peter , van Pesch Vincent , Probst Christian , Teegen Bianca , Komorowski Lars , Sühs Kurt-Wolfram 
Published: April 2024

BackgroundWe aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis.MethodsSerum and cerebrospinal fliud (CSF) samples from four index patients were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IIFA). Immunoprecipitation, mass spectrometry and recombinant protein assays were used to identify the autoantigen. Sera from 101 patients with various neurological symptoms and a similar tissue staining pattern as the index patient samples, and 102 healthy donors were analysed in recombinant cell-based IIFA (RC-IIFA) with the identified protein. Epitope characterisation of all positive samples was performed via ELISA, immunoblot, immunoprecipitation and RC-IIFA using different DAGLA fragments.ResultsAll index patients were relatively young (age: 18–34) and suffered from pronounced gait ataxia, dysarthria and visual impairments. Paraclinical hallmarks in early-stage disease were inflammatory CSF changes and cerebellar cortex hyperintensity in MRI. Severe cerebellar atrophy developed in three of four patients within 6 months. All patient samples showed the same unclassified IgG reactivity with the cerebellar molecular layer. DAGLA was identified as the target antigen and confirmed by competitive inhibition experiments and DAGLA-specific RC-IIFA. In RC-IIFA, serum reactivity against DAGLA was also found in 17/101 disease controls, including patients with different clinical phenotypes than the one of the index patients, and in 1/102 healthy donors. Epitope characterisation revealed that 17/18 anti-DAGLA-positive control sera reacted with a C-terminal intracellular DAGLA 583–1042 fragment, while the CSF samples of the index patients targeted a conformational epitope between amino acid 1 and 157.ConclusionsWe propose that anti-DAGLA autoantibodies detected in CSF, with a characteristic tissue IIFA pattern, represent novel biomarkers for rapidly progressive cerebellitis.
Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease
Authors: Gui Xianhua , Li Wangzhong , Jiang Hanyi , Wang Rujia , Yu Min , Zhao Tingting , Ma Miao , Ding Jingjing , Jin Ziyi , Qiu Yuying , Qiu Xiaohua , Zhang Yingwei , Cao Min , Huang Mei , Cao Mengshu , Dai Jinghong , Cai Hourong , Xin Xiaoyan , Xiao Yonglong 
Published: April 2024

ObjectivesRisk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD.MethodsThis prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis.ResultsOverall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model.ConclusionsWe developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.
Optimising gout treatment: insights from a nurse-led cohort study
Authors: Rasmussen Claus , Larsen Jesper Walther , Christensen Heidi Mächler , Larsen Monica Bak , Thomsen Anna Marie , Leishmann Tinna , Kragh Jette , Nielsen Gunnar Lauge 
Published: April 2024

ObjectivesCurrently, gout management, particularly urate-lowering therapy (ULT), is often suboptimal. Nurses successfully manage various diseases including gout. As gout prevalence is rising, and rheumatologists and general practitioners face shortages, a new approach is imperative. This real-life prospective cohort study evaluated the effectiveness of nurse-led care employing a treat-to-target strategy for gout management over a 2-year period.MethodsAll consecutively confirmed gout patients were included. The nurse-led clinic provided a structured treatment plan with consultations, patient leaflets, telephone contacts and laboratory monitoring. After a year of nurse-led care, patients transitioned to continued care in general practice. Follow-up data were complete through registries. The primary outcome was achieving target p-urate levels (<0.36 mmol/L) at 2 years after diagnosis. Secondary outcomes included treatment continuation and achievement of target p-urate levels in specific subgroups. The results were compared with patients diagnosed in the same clinic but followed up in ‘usual care’.ResultsIn the nurse-led group (n=114), 83% achieved target p-urate levels and ULT was continued by 98%. This trend persisted across various patient subgroups. Only 44% of patients in usual care achieved target p-urate and with insufficient doses of allopurinol . Nurse-led care involved an average of two visits and three telephone contacts over 336 days. The 2-year mortality rate was 15%.ConclusionsNurse-led gout care, employing a targeted approach, was associated with a very high uptake of and adherence to ULT. The encouraging results were not achieved in usual care although a direct comparison might be influenced by selection bias.
Geochemistry and magmatic petrology of meta-ophiolites from the Bajgan Complex (Makran Accretionary Prism, SE Iran): new insights on the nature of the Early Cretaceous Middle East Neotethys
Authors: Saccani Emilio , Barbero Edoardo , Delavari Morteza , Dolati Asghar , Brombin Valentina , Marroni Michele , Pandolfi Luca 
Published: April 2024

The Bajgan Complex in the North Makran Domain (Makran Accretionary Prism) comprises disrupted meta-ophiolitic sequences originating from oceanic crust protoliths. They include ultramafic and mafic cumulates, isotropic gabbros, plagiogranites and basalts. Ultramafic–mafic cumulates and plagiogranites exhibit compositions akin to rocks formed in mid-ocean ridge settings. Isotropic gabbro and basalt protoliths can be subdivided into three distinct geochemical types. Type-1 rocks are sub-alkaline (Nb/Y < 0.1) with low Th, Nb and Ta contents and La
N
/Yb
N
ratios <1, resembling those of normal mid-ocean ridge basalts (N-MORB). Type-2 rocks display slight enrichment in Th, Ta, Nb (Nb/Y = 0.36–0.45) and La
N
/Yb
N
= 2.12–3.20, resembling the chemistry of enriched (E-) MORB. Type-3 basalts show an alkaline nature (Nb/Y = 0.88–1.82), significant Th, Ta and Nb enrichment, and high La
N
/Yb
N
ratios (7.01–20.08), resembling the chemistry of alkaline basalts (ocean island basalts, OIB). Petrogenetic modelling indicates that N-MORB protoliths originated from a depleted MORB mantle source, whereas E-MORB and OIB protoliths were generated from partial melting of sub-oceanic depleted sources that underwent varying degrees of OIB-type enrichment. The Bajgan meta-ophiolitic protoliths were formed within a Late Jurassic to Cretaceous oceanic basin influenced by mantle plume activity and plume–ridge interaction.

Supplementary material
: Field photographs, micrographs, rocks sampled, analytical methods and results, and supplementary tables are available at
https://doi.org/10.6084/m9.figshare.c.7193937

Thematic collection:
This article is part of the Ophiolites, melanges and blueschists collection available at:
https://www.lyellcollection.org/topic/collections/ophiolites-melanges-and-blueschists
Local Proofs Approaching the Witness Length
Authors: Ron-Zewi Noga , Rothblum Ron 
Published: April 2024

Interactive oracle proofs (IOPs) are a hybrid between interactive proofs and PCPs. In an IOP, the prover is allowed to interact with a verifier (like in an interactive proof) by sending relatively long messages to the verifier, who in turn is only allowed to query a few of the bits that were sent (like in a PCP). Efficient IOPs are currently at the core of leading practical implementations of highly efficient proof-systems.

In this work we construct, for a large class of NP relations, IOPs in which the communication complexity approaches the witness length. More precisely, for any NP relation for which membership can be decided in polynomial-time with bounded polynomial space (i.e., space
n
ξ
for some sufficiently small constant ξ > 0; e.g., SAT, Hamiltonicity, Clique, Vertex-Cover) and for any constant γ > 0, we construct an IOP with communication complexity (1 + γ) ⋅
n
, where
n
is the original witness length. The number of rounds, as well as the number of queries made by the IOP verifier, are constant.

This result improves over prior works on short IOPs/PCPs in two ways. First, the communication complexity in these short IOPs is proportional to the complexity of
verifying
the NP witness, which can be polynomially larger than the witness size. Second, even ignoring the difference between witness length and non-deterministic verification time, prior works incur (at the very least) a large constant multiplicative overhead to the communication complexity.

In particular, as a special case, we also obtain an IOP for CircuitSAT with communication complexity (1 + γ) ⋅
t
, for circuits of size
t
and any constant γ > 0. This improves upon the prior state-of-the-art work of Ben Sasson et al. (ICALP, 2017) who construct an IOP for CircuitSAT with communication length
c ⋅ t
for a large (unspecified) constant
c
≥ 1.

Our proof leverages the local testability and (relaxed) local correctability of high-rate tensor codes, as well as their support of a sumcheck-like procedure. In particular, we bypass the barrier imposed by the low rate of
multiplication codes
(e.g., Reed–Solomon, Reed–Muller, or AG codes)—a key building block of all known short PCP/IOP constructions.
Proteomics, Human Environmental Exposure, and Cardiometabolic Risk
Authors: Perry Andrew S. , Zhang Kai , Murthy Venkatesh L. , Choi Bina , Zhao Shilin , Gajjar Priya , Colangelo Laura A. , Hou Lifang , Rice Mary B. , Carr J. Jeffrey , Carson April P. , Nigra Anne E. , Vasan Ramachandran S. , Gerszten Robert E. , Khan Sadiya S. , Kalhan Ravi , Nayor Matthew , Shah Ravi V. 
Published: April 2024

BACKGROUND:
The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies.

METHODS:
We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models.

RESULTS:

Proteomic signatures of the envirome identified novel/established cardiovascular disease–relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08–1.24];
P
=1.77×10
−5
; JHS: hazard ratio, 1.25 [95% CI, 1.14–1.38];
P
=6.38×10
−6
; hazard ratio expressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors.

CONCLUSIONS:
Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.
Artificial Intelligence–Derived Risk Prediction: A Novel Risk Calculator Using Office and Ambulatory Blood Pressure
Authors: Guimarães Pedro , Keller Andreas , Böhm Michael , Lauder Lucas , Fehlmann Tobias , Ruilope Luis M. , Vinyoles Ernest , Gorostidi Manuel , Segura Julián , Ruiz-Hurtado Gema , Staplin Natalie , Williams Bryan , de la Sierra Alejandro , Mahfoud Felix 
Published: April 2024

BACKGROUND:
Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning–derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP).

METHODS:
The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed. Using data from 59 124 patients enrolled in the Spanish ABP Monitoring registry, machine-learning approaches (logistic regression, gradient-boosted decision trees, and deep neural networks) and stepwise forward feature selection were used.

RESULTS:

For the prediction of cardiovascular mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP and ABP outperformed other risk scores. The area under the curve achieved by the novel approach, already when using OBP variables, was significantly higher when compared with the area under the curve of the Framingham risk score, Systemic Coronary Risk Estimation 2, and Atherosclerotic Cardiovascular Disease score. However, the prediction of cardiovascular mortality with ABP instead of OBP data significantly increased the area under the curve (0.870 versus 0.865;
P
=3.61×10
−28
), accuracy, and specificity, respectively. The prediction of ABP phenotypes (ie, white-coat, ambulatory, and masked hypertension) using clinical characteristics was limited.

CONCLUSIONS:
The receiver operating characteristic curves for cardiovascular mortality using ABP and OBP with deep neural network models outperformed all other risk metrics, indicating the potential for improving current risk scores by applying state-of-the-art machine learning approaches. The prediction of cardiovascular mortality using ABP data led to a significant increase in area under the curve and performance metrics.
The Sovereign Debt Crisis in Sri Lanka: Anatomy and Policy Options
Authors: Athukorala Prema-chandra 
Published: April 2024

Abstract
During the COVID-19 pandemic, there was a dramatic increase in national debt levels across the world, with reported cases of downgrading sovereign debt ratings and difficulty of fulfilling debt obligations (“debt distress”), heavily concentrated in low- and middle-income countries. In this context, the unfolding sovereign debt crisis in Sri Lanka has attracted worldwide attention as the canary in the coal mine for what could become a global “development” crisis. This paper examines the Sri Lankan crisis encompassing both the sources of vulnerability to the COVD-19 shock, and stabilization and structural adjustment reforms after the debt default, with emphasis on the systemic “solvency” challenge of dealing with the massive debt overhang evolved over the previous two decades. The prime focus of the Extended Fund Facility (EFF) program that Sri Lanka signed with the IMF in March 2023 is on economic stabilization through fiscal consolidation. This paper makes a strong case for combining economic stabilization with coherent structural adjustment policies to redress the long-standing antitradable bias in the incentive structure that underpinned vulnerability of the economy to external shocks.
A Hopeless Hodge-Podge of Theology?
Authors: McCall Thomas H. 
Published: April 2024

Abstract
Contemporary systematic theology is engaged in the ‘retrieval’ of insights from the Christian tradition. Accordingly, many theologians in the broadly Reformed tradition are seeking to recover, reclaim, and defend what they refer to as ‘classical theism’ as a stark alternative to what is sometimes referred to as ‘theistic personalism’ (and the ‘Social Trinitarianism’ that is said to accompany it). While broadly sympathetic to this enterprise, in this essay I employ the theology of Charles Hodge as a case study to argue that such tidy categorizations can be misleading and unhelpful, and I conclude that his theology raises challenges with respect to both historiography and theology.
Behaviour of Integrated Refugees on Tanzania’s National Security: Experience from Katumba Old Settlement
Authors: Laurent Adventina K. , Ndumbaro Laurean J. 
Published: April 2024

Abstract
Tanzania integrated a historical large number of refugees in 2010 when 162,156 refugees were integrated at once. This article explores whether integrated refugees at Katumba Old Settlement in Tanzania are practising behaviours that threaten national security or not. This work was guided by Tom Kuhlman’s Comprehensive Model of Refugee Integration (1991) as its framework for analysis. Using a survey with a sample of 397 respondents and 31 key informant interviews, the study found that the integrated refugees pose threat to national security. A significant percentage of respondents indicated that integrated refugees: network with relatives and friends to come into Tanzania illegally; host illegal migrants; create social exclusionary networks and are unwilling to accept Tanzania’s core values and behaviours. Efforts to increase awareness among integrated refugees on their rights and responsibilities as new Tanzanian citizens as well as enforcement of laws are suggested as solutions for mitigating these behaviours.