bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer
Authors: Liu Junquan , Chiang Huai-Chin , Xiong Wei , Laurent Victor , Griffiths Samuel C , Dülfer Jasmin , Deng Hui , Sun Xiujie , Yin Y Whitney , Li Wenliang , Audoly Laurent P , An Zhiqiang , Schürpf Thomas , Li Rong , Zhang Ningyan 
Published: June 2023

BackgroundImmune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.MethodsTo develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding epitope of PRTH-101 from the crystal structure of the complex between DDR1 extracellular domain (ECD) and the PRTH-101 Fab fragment with 3.15 Å resolution. We revealed the underlying mechanisms of action of PRTH-101 using both cell culture assays andin vivostudy in a mouse tumor model.ResultsPRTH-101 has subnanomolar affinity to DDR1 and potent antitumor efficacy similar to the parental rabbit mAb after humanization. Structural information illustrated that PRTH-101 interacts with the discoidin (DS)-like domain, but not the collagen-binding DS domain of DDR1. Mechanistically, we showed that PRTH-101 inhibited DDR1 phosphorylation, decreased collagen-mediated cell attachment, and significantly blocked DDR1 shedding from the cell surface. Treatment of tumor-bearing mice with PRTH-101in vivodisrupted collagen fiber alignment (a physical barrier) in the tumor extracellular matrix (ECM) and enhanced CD8+T cell infiltration in tumors.ConclusionsThis study not only paves a pathway for the development of PRTH-101 as a cancer therapeutic, but also sheds light on a new therapeutic strategy to modulate collagen alignment in the tumor ECM for enhancing antitumor immunity.
Predictors and clinical implications of residual mitral regurgitation following left ventricular assist device therapy
Authors: Sharma Harish , Liu Boyang , Yuan Mengshi , Shakeel Iqra , Morley-Smith Andrew , Hatch Alice , Bradley Joseph , Chue Colin , Myerson Saul G , Steeds Richard Paul , Lim Sern 
Published: June 2023

BackgroundCorrection of mitral regurgitation (MR) at the time of left ventricular assist device (LVAD) implantation remains controversial. There is conflicting evidence regarding the clinical impact of residual MR, and studies have not examined whether MR aetiology or right heart function impacts the likelihood of residual MR.MethodsThis is a retrospective single-centre study of 155 consecutive patients with LVAD implantation from January 2011 to March 2020. Exclusion criteria were no MR pre-LVAD (n=8), inaccessible echocardiography (n=9), duplicate records (n=10) and concomitant mitral valve repair (n=1). Statistical analysis was performed using STATA V.16 and SPSS V.24.ResultsCarpentier IIIb MR aetiology was associated with more severe MR pre-LVAD (severe 18/27 (67%) vs non-severe 32/91 (35%), p=0.004) and a higher likelihood of residual MR (8/11 (72%) vs 30/74 (41%), p=0.045). Of 95 patients with significant MR pre-LVAD, 15 (16%) had persistent significant MR, which was associated with higher mortality (p=0.006), post-LVAD right ventricle (RV) dilatation (10/15 (67%) vs 28/80 (35%), p=0.022) and RV dysfunction (14/15 (93%) vs 35/80 (44%), p<0.001). Aside from ischaemic aetiology, other pre-LVAD parameters that were associated with significant residual MR included left ventricular end-systolic diameter (LVESD) (6.9 cm (5.7–7.2) vs 5.9 cm (5.5–6.5), p=0.043), left atrial volume index (LAVi) (78 mL/m2(56–88) vs 57 mL/m2(47–77), p=0.021), posterior leaflet displacement (2.5 cm (2.3–2.9) vs 2.3 cm (1.9–2.7), p=0.042) and basal right ventricular end-diastolic diameter (RVEDD) (5.1±0.8 cm vs 4.5±0.8 cm, p=0.010).ConclusionLVAD therapy improves MR and tricuspid regurgitation severity in the majority, but 14% have persistent significant residual MR, associated with right ventricular dysfunction and higher long-term mortality. This may be predicted pre-LVAD by greater LVESD, RVEDD and LAVi and by ischaemic aetiology.
Joint involvement in RA starts predominantly in the hands: functional, clinical and imaging studies in clinically suspect arthralgia and during progression to RA
Authors: Khidir Sarah J H , van Dijk Bastiaan T , Krijbolder Doortje I , Verstappen Marloes , van Mulligen Elise , van der Helm-van Mil Annette H M 
Published: June 2023

ObjectivesIt is unknown whether rheumatoid arthritis (RA) starts in hands or feet. To investigate this, we performed functional, clinical and imaging studies during progression from clinically suspect arthralgia (CSA) to RA. Additionally, we studied whether functional disabilities of hands/feet at CSA onset contribute to predicting RA development.Methods600 patients with CSA were followed for clinical inflammatory arthritis (IA) during median follow-up of 25 months, during which 99 developed IA. Functional disabilities were measured at baseline/4/12/24 months with the Health Assessment Questionnaire Disability Index (HAQ); HAQ items assessing hand disabilities and foot disabilities were selected. The course of disabilities towards IA development (here considered as t=0) was depicted by increasing incidences and analysed using linear mixed models. To evaluate robustness of findings, tender hand/foot joints and subclinical joint inflammation (measured with CE-1.5TMRI) of hand/foot were additionally studied. Associations between disabilities at CSA presentation (here t=0) and future IA development were studied using Cox regression in the total CSA population.ResultsDuring IA development, hand disabilities occurred earlier and more frequently than foot disabilities. Despite both hand disabilities and foot disabilities rose significantly towards IA development, hand disabilities were more severe during this course (mean difference over time: 0.41 units, 95% CI 0.28 to 0.55, p<0.001, on a range 0–3). Similar to functional disabilities, tender joints and subclinical joint inflammation occurred earlier in the hands than feet. In the total CSA population, a single HAQ question on difficulties with dressing (hand functioning) was independently predictive for IA development: HR=2.2, 95% CI 1.4 to 3.5, p=0.001.ConclusionEvaluation of functional disabilities, supported by clinical and imaging findings, revealed that joint involvement starts predominantly in the hands during RA development. Additionally, a single question on dressing difficulties adds value to risk stratification in patients with CSA.
Compression ensembles quantify aesthetic complexity and the evolution of visual art
Authors: Karjus Andres , Canet Solà Mar , Ohm Tillmann , Ahnert Sebastian E. , Schich Maximilian 
Published: June 2023

AbstractTo the human eye, different images appear more or less complex, but capturing this intuition in a single aesthetic measure is considered hard. Here, we propose a computationally simple, transparent method for modeling aesthetic complexity as a multidimensional algorithmic phenomenon, which enables the systematic analysis of large image datasets. The approach captures visual family resemblance via a multitude of image transformations and subsequent compressions, yielding explainable embeddings. It aligns well with human judgments of visual complexity, and performs well in authorship and style recognition tasks. Showcasing the functionality, we apply the method to 125,000 artworks, recovering trends and revealing new insights regarding historical art, artistic careers over centuries, and emerging aesthetics in a contemporary NFT art market. Our approach, here applied to images but applicable more broadly, provides a new perspective to quantitative aesthetics, connoisseurship, multidimensional meaning spaces, and the study of cultural complexity.
RETaliation—Tackling Rare Resistance Alterations to Osimertinib
Authors: Krebs Matthew G. , Popat Sanjay 
Published: June 2023

SummaryRET fusions occur as a rare mechanism of acquired resistance to osimertinib in patients with EGFR mutation–positive non–small cell lung cancer. Inhibiting RET alongside osimertinib shows promising clinical activity, but innovative approaches are needed to seek regulatory approvals in these rare treatment resistance settings.See related article by Rotow et al., p. 2979
An Alternative Mechanism of Subcellular Iron Uptake Deficiency in Cardiomyocytes
Authors: Dai Yuanyuan , Ignatyeva Nadezda , Xu Hang , Wali Ruheen , Toischer Karl , Brandenburg Sören , Lenz Christof , Pronto Julius , Fakuade Funsho E. , Sossalla Samuel , Zeisberg Elisabeth M. , Janshoff Andreas , Kutschka Ingo , Voigt Niels , Urlaub Henning , Rasmussen Torsten Bloch , Mogensen Jens , Lehnart Stephan E. , Hasenfuss Gerd , Ebert Antje 
Published: June 2023

Background:
Systemic defects in intestinal iron absorption, circulation, and retention cause iron deficiency in 50% of patients with heart failure. Defective subcellular iron uptake mechanisms that are independent of systemic absorption are incompletely understood. The main intracellular route for iron uptake in cardiomyocytes is clathrin-mediated endocytosis.

Methods:

We investigated subcellular iron uptake mechanisms in patient-derived and CRISPR/Cas–edited induced pluripotent stem cell–derived cardiomyocytes as well as patient-derived heart tissue. We used an integrated platform of DIA-MA (mass spectrometry data-independent acquisition)–based proteomics and signaling pathway interrogation. We employed a genetic induced pluripotent stem cell model of 2 inherited mutations (
TnT
[
troponin T
]-R141W and
TPM1
[
tropomyosin 1
]-L185F) that lead to dilated cardiomyopathy (DCM), a frequent cause of heart failure, to study the underlying molecular dysfunctions of DCM mutations.

Results:

We identified a druggable molecular pathomechanism of impaired subcellular iron deficiency that is independent of systemic iron metabolism. Clathrin-mediated endocytosis defects as well as impaired endosome distribution and cargo transfer were identified as a basis for subcellular iron deficiency in DCM-induced pluripotent stem cell–derived cardiomyocytes. The clathrin-mediated endocytosis defects were also confirmed in the hearts of patients with DCM with end-stage heart failure. Correction of the
TPM1-L185F
mutation in DCM patient–derived induced pluripotent stem cells, treatment with a peptide, Rho activator II, or iron supplementation rescued the molecular disease pathway and recovered contractility. Phenocopying the effects of the
TPM1-L185F
mutation into WT induced pluripotent stem cell–derived cardiomyocytes could be ameliorated by iron supplementation.

Conclusions:
Our findings suggest that impaired endocytosis and cargo transport resulting in subcellular iron deficiency could be a relevant pathomechanism for patients with DCM carrying inherited mutations. Insight into this molecular mechanism may contribute to the development of treatment strategies and risk management in heart failure.
Personality and Risk of Incident Stroke in 6 Prospective Studies
Authors: Stephan Yannick , Sutin Angelina R. , Luchetti Martina , Aschwanden Damaris , Terracciano Antonio 
Published: June 2023

BACKGROUND:
A large literature has examined a broad range of factors associated with increased risk of stroke. Few studies, however, have examined the association between personality and stroke. The present study adopted a systematic approach using a multi-cohort design to examine the associations between 5-Factor Model personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and incident stroke using data from 6 large longitudinal samples of adults.

METHODS:
Participants (age range: 16–104 years old, N=58 105) were from the MIDUS (Midlife in the United States) Study, the HRS (Health and Retirement Study), The US (Understanding Society) study, the WLS (Wisconsin Longitudinal Study), the NHATS (National Health and Aging Trends Study), and the LISS (Longitudinal Internet Studies for the Social Sciences). Personality traits, demographic factors, clinical and behavioral risk factors were assessed at baseline; stroke incidence was tracked over 7 to 20 years follow-up.

RESULTS:

Meta-analyses indicated that higher neuroticism was related to a higher risk of incident stroke (hazard ratio, 1.15 [95% CI, 1.10–1.20];
P
<0.001), whereas higher conscientiousness was protective (HR, 0.89 [95% CI, 0.85–0.93];
P
<0.001). Additional meta-analyses indicated that BMI, diabetes, blood pressure, physical inactivity, and smoking as additional covariates partially accounted for these associations. Extraversion, openness, and agreeableness were unrelated to stroke incidence.

CONCLUSIONS:
Similar to other cardiovascular and neurological conditions, higher neuroticism is a risk factor for stroke incidence, whereas higher conscientiousness is a protective factor.
The Society of Vascular and Interventional Neurology (SVIN) Mechanical Thrombectomy Registry: Outcomes in Patients With Acute Ischemic Stroke and COVID‐19
Authors: Hassan Ameer E. , Tekle Wondwossen G. , Desai Sohum K. , Haussen Diogo C. , Mohammaden Mahmoud , Nogueira Raul G. , Sheth Sunil A., , Salazar‐Marioni Sergio , Czap Alexandra , Linfante Italo , Dabus Guilherme , Starosciak Amy K. , Nguyen Thanh N. , Abdalkader Mohamad , Klein Piers , Siegler James E. , Heslin Mark , Thau Lauren , Oak Solomon , Ortega‐Gutierrez Santiago , Farooqui Mudassir , Vivanco‐Suarez Juan , Majidi Shahram , Fifi Johanna T. , Matsoukas Stavros , Gordon Weston , Linares Guillermo , Rodriguez Wilson , Mehta Brijesh P. , Sugg Rebecca , Jumaa Mohammed , Liebeskind David S. 
Published: June 2023

Background
Clinical and radiographic outcomes after mechanical thrombectomy in the setting of COVID‐19 infection remain poorly characterized. We sought to determine how COVID‐19 status affects mechanical thrombectomy outcomes in the real‐world setting in the United States.

Methods
The prospectively maintained multicenter mechanical thrombectomy registry from the Society of Vascular and Interventional Neurology was queried for baseline clinical characteristics among patients with and without COVID‐19 who underwent mechanical thrombectomy between March 1 and December 31, 2020 at 12 sites. Primary outcome was the likelihood of good neurological outcomes (90 day modified Rankin scale 0–2) among patients with COVID‐19 treated with endovascular thrombectomy, which was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b, 2c, and 3). Secondary outcomes included National Institutes of Health Stroke Scale at 24 hours.

Results
Among 915 patients who underwent mechanical thrombectomy during the study period, 51 patients were positive for COVID‐19 (5.6%). Univariate analysis revealed that compared with patients who were COVID‐19 negative, patients who were positive for COVID‐19 were more likely to be male, nonsmokers, have lower Alberta Stroke Program Early CT Score, and present with intracranial internal carotid artery occlusions (Table 1). They were also less likely to achieve successful reperfusion. Multivariable analysis, however, failed to identify any independent associations with COVID‐19 positive status.

Conclusion
In our cohort, patients postive for COVID‐19 with acute ischemic stroke who undergo mechanical thrombectomy have similar baseline characteristics, imaging features, procedural, and clinical outcomes compared to patients who are negative for COVID‐19 in multivariate analysis. Further analyses are warranted.
External Validation of Atherosclerotic Neuroimaging Biomarkers in Emergent Large‐Vessel Occlusion
Authors: Siddiqui Fazeel M. , Fletcher Jeffrey J. , Barnes Andrew V. , Henry Alayna N. , Elias Augusto E. , Rajah Gary , PA‐C Alexis Carroll , Dandapat Sudeepta , Ume Kiddy L. , Farooqui Mudassir , Rodriguez‐Calienes Aaron , Pandey Aditya S. , Ortega‐Gutierrez Santiago 
Published: June 2023

Background
Intracranial atherosclerosis related large vessel occlusion (ICAS‐LVO) is the major cause of failed mechanical thrombectomy. ICAS‐LVO causes reocclusion or a fixed focal stenosis, leading to suboptimal revascularization and poor functional outcomes. We aimed to externally validate 4 preidentified imaging biomarkers of ICAS‐LVO: absent hyperdense sign, Hounsfield units (Hu ratio ≤1.1 and Delta Hu <6) and truncal‐type occlusion, observed on admission noncontrast computed tomography and computed tomography angiography in patients presenting with emergent large‐vessel occlusion (ELVO).

Methods
We conducted a retrospective cohort observational study of consecutive patients presenting with acute M1/terminal internal carotid artery occlusions undergoing mechanical thrombectomy. Inability to locate a hyperdense vessel on noncontrast computed tomography at the corresponding ELVO on computed tomography angiography was labeled absent hyperdense sign. Delta Hu and Hu ratio were defined as the difference and ratio of the Hu of the ELVO on noncontrast computed tomography and its mirror contralateral patent vessel, respectively. ELVO was classified as truncal‐type occlusion if the bifurcation distal to the occlusion was spared on computed tomography angiography. ICAS‐LVO was defined as the presence of fixed focal stenosis or reocclusion after mechanical thrombectomy. Statistical analysis was performed using C statistics, receiver operating characteristic curve analysis, and multivariate logistic regression.

Results

Of 161 patients, 30 (18.6%) had suspected ICAS‐LVO. Absent hyperdense sign had a sensitivity of 90% and specificity of 87% (area under the curve [AUC], 0.88), in predicting ICAS‐LVO. Hu ratio ≤1.1 (AUC, 0.89) and Delta Hu <6 (AUC, 0.96) had sensitivity of 100% and 97% and specificity of 79% and 95%, respectively. Truncal‐type occlusion showed a sensitivity of 75% and specificity of 98% (AUC, 0.87). When comparing receiver operating characteristic AUC, Delta Hu <6 was significantly better than absent hyperdense sign (
P
=0.006); Hu ratio ≤1.1 (
P
=0.006); and truncal‐type occlusion (
P
=0.02).

Conclusion
Combination of neuroimaging biomarkers using noncontrast computed tomography and computed tomography angiography in ELVO identify ICAS‐LVO with high predictive power. Larger, prospective, multicenter studies are warranted to further evaluate their effectiveness in diagnosing ICAS‐LVO.
George G. Simpson and Stephen J. Gould on Values: Shifting Normative Frameworks in Historical Context
Authors: McConwell Alison K. 
Published: June 2023

Abstract
George G. Simpson (1902–1984) and Stephen J. Gould (1941–2002) were both engaged with the normative – i.e., social, cultural, political, and even ethical – consequences of their evolutionary theorizing. However, there is a normative point of departure between Simpson and Gould’s work in that regard that has received little attention. Yet, their motivations converge into a larger program of resistance and social protection from misconstrued and illegitimate overreaches of the biological sciences leading up to and after the peak of the modern synthesis.
On the Ambivalence of Control in Experimental Investigation of Historically Contingent Processes
Authors: Desjardins Eric , Oswick Derek , Fox Craig W. 
Published: June 2023

Abstract
Historical contingency is commonly associated with unpredictability and outcome variability. As such, it can be seen as an undesirable aspect of experimental investigations. Many might agree that experimental methodologies that include enough control help to by-pass this problem and thereby make for more secure knowledge. Against this received view, we argue that, for at least some historically contingent processes, an over-emphasis on control might mislead by obscuring the very object of investigation or by preventing fruitful discoveries. In discussing cases from evolutionary biology, developmental biology, and geochemistry/astrophysics, we show how investigating through approaches that don’t prioritize environmental control, while allowing for greater variability of outcomes, better respects the object/environment entanglement of these systems. Finally, we defend the idea that, despite the lower level of control, these types of experiments do not have a lower epistemic value than more highly controlled experiments.
Of Records and Ruins: Metaphors about the Deep Past
Authors: Currie Adrian 
Published: June 2023

Abstract
Consideration of evidence and data in historical science is dominated by textual metaphor: we reconstruct the past on the basis of various incomplete records. I suggest that although textual metaphors are often apt, they also lead philosophers and scientists to think about historical evidence in particular ways, and that other perspectives might be fruitful. Towards this, I explore the notion of natural historical evidence being thought of as ‘ruins’. This has several potential benefits. First, the architectural aspect of the metaphor emphasizes the contingency of historical subjects and the coherency of design-based reconstruction. Second, historical data, like ruins, are co-constructed, involving intimate interaction with materials.
Les convertis noirs au Judaïsme en France
Authors: Mokoko Gampiot Aurélien 
Published: June 2023

Résumé
Si les conversions au Judaïsme sont un phénomène encore méconnu en France, les convertis noirs, originaires d’Afrique ou des Antilles, sont parmi les plus invisibles. Embrassant le Judaïsme dans la diversité de ses courants, leurs histoires de vie reflètent une variété de parcours. Il est question de cerner leurs profils individuels religieux et identitaires, les modalités par lesquelles la conversion lie ces Africains et Antillais au monde juif et les processus de recomposition identitaire à l’œuvre. Quels sont leurs choix et motivations ? Comment s’inscrivent-ils dans le paysage juif de France ?
Living Insider Positionality with Co-ethnics in Everyday Life
Authors: Tewolde Amanuel Isak 
Published: June 2023

Abstract
In this article I reflect on how I was perceived by members of my own ethnic community in Pretoria, South Africa, in everyday interactions. In these interactions, I was viewed as an integral part of the community, rather than a detached academic. I employ the theory of community researcher and the theory of the everyday to frame my experiences and my argument. Recent debates on insider/outsider positionalities conceptualize co-ethnic migrant researchers as situational insiders. Drawing on my lived experiences, however, I argue that my insiderness has been consistently embraced by my co-ethnics. To establish strong rapport with members of their co-ethnics, migrant researchers need to maintain close social contact, informality and casualness, in their everyday interactions to enhance their positionality as trusted insiders during future actual research encounters. This study contributes to theoretical understandings of migration studies and researcher positionalities.