bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide-based PET tracer targeting LAG-3 for evaluating the efficacy of immunotherapy in melanoma
Authors: Yuan Peizhe , Long Yu , Wei Nannan , Wang Yan , Zhu Ziyang , Han Jinquan , Jiang Dawei , Lan Xiaoli , Gai Yongkang 
Published: July 2024

BackgroundLymphocyte activation gene 3 (LAG-3) is expressed on activated immune cells and has emerged as a promising target for immune checkpoints blockade. However, conflicting findings have been reported regarding the association between LAG-3 expression in tumors and patient prognosis, indicating the need for further investigation into the significance of LAG-3 expression levels in tumor therapies. In this study,68Ga-NOTA-XH05, a novel peptide-based positron emission tomography (PET) tracer targeting LAG-3, was constructed to non-invasively detect LAG-3 expression in melanoma after CpG oligonucleotide (CpG) treatment and explore the relationship between LAG-3 expression and therapeutic effect.MethodsThe tracer68Ga-NOTA-XH05 was identified by high-performance liquid chromatography after being prepared and purified. Cell uptake and blocking essays were performed to verify the specificity of the tracer in vitro. The expression of LAG-3 in B16-F10 subcutaneous tumors was monitored by flow cytometry, and its correlation with the tracer uptake was analyzed to evaluate the tracer specificity. PET imaging and biodistribution studies were conducted after CpG treatment of unilateral or bilateral B16-F10 subcutaneous tumor models to assess the ability of68Ga-NOTA-XH05 in monitoring immunotherapy efficacy and the abscopal effect of CpG.ResultsFollowing purification,68Ga-NOTA-XH05 exhibited high radiochemical purity and specificity. Flow cytometry analysis revealed a positive correlation between LAG-3 expression in tumors and the uptake of68Ga-NOTA-XH05. In B16-F10 bearing mice treated with CpG, PET imaging using68Ga-NOTA-XH05 demonstrated a higher tumor to blood ratio (TBR) compared with the control group. Furthermore, TBR values obtained from CpG-treated mice allowed for differentiation between responders and non-responders. In a bilateral subcutaneous tumor model where only right-sided tumors were treated with intratumoral injection of CpG, TBR values of left-sided tumors were significantly higher than those in the control group, indicating that68Ga-NOTA-XH05 could effectively monitor the systemic effect of local CpG injection.ConclusionOur findings highlight the detection capability of68Ga-NOTA-XH05 in assessing LAG-3 expression levels within tumors and evaluating response to immunotherapy, thereby suggesting promising clinical translational prospects.
The benefit of favorable venous outflow profiles is mediated through the reduced risk of intracranial hemorrhage in acute ischemic stroke patients undergoing endovascular treatment
Authors: Jiang Shuyu , Gong Chen , Huang Liping , Wang You , Wang Zhiyuan , Chen Yankun , Yuan Jinxian , Wang Li , Gong Siyin , Tan Dandan , Zhang Peng , Huang Yunyi , Wen Yuetao , Hu Yang , Li Zhipeng , Li Wenze , Liu Jin , Guo Jing , Chen Shengli , Chen Yangmei , Xu Tao 
Published: July 2024

BackgroundFavorable venous outflow (VO) has been recognized as an independent predictor of excellent clinical outcomes in acute ischemic stroke caused by anterior circulation large vessel occlusion (AIS-LVO) patients who received endovascular treatment (EVT). However, the reasons why VO affects clinical outcomes have not been fully explained. In this study, we aimed to identify the potential mediators of VO affecting prognosis.MethodsWe conducted a multicenter retrospective cohort study of consecutive patients with AIS-LVO who underwent EVT. Baseline computed tomographic angiography (CTA) was applied to assess VO by the Cortical Vein Opacification Score (COVES). The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS) score of 0–2). Classifying subtypes of intracranial hemorrhage (ICH) to explore the relationship between ICH subtypes and VO. Multivariate logistic regression and causal mediation analyses were used to evaluate the relationship among VO, functional independence, and potential mediators.ResultsAmong 860 AIS-LVO patients undergoing EVT, a total of 515 patients were included in the present study after strict screening. In multivariate logistic regression analysis, favorable VO profiles (defined as COVES 3–6) were significantly associated with a lower incidence of ICH (24.2% vs 46.9%, adjusted odds ratio (aOR) 0.48, 95% confidence interval (CI) 0.30 to 0.77, P=0.002) and a higher proportion of functional independence (58.9% vs 15.0%, aOR 4.07, 95% CI 2.41 to 6.88, P<0.001). Mediation analysis showed that favorable VO profiles significantly reduced the incidence of parencuymal hematoma (PH) 2 accounting for 8.0% (95% CI 0.9% to 19.0%) of its beneficial effect on functional independence.ConclusionThis study demonstrated the potential mediating effects of severe ICH for the beneficial effect of favorable VO on clinical prognosis among patients with AIS-LVO who underwent EVT.
Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study
Authors: Salim Hamza Adel , Yedavalli Vivek , Musmar Basel , Adeeb Nimer , E l Naamani Kareem , Henninger Nils , Sundararajan Sri Hari , Kühn Anna Luisa , Khalife Jane , Ghozy Sherief , Scarcia Luca , Tan Benjamin Yong Qiang , Heit Jeremy J , Regenhardt Robert W , Cancelliere Nicole M , Bernstock Joshua D , Rouchaud Aymeric , Fiehler Jens , Essibayi Muhammed Amir , Sheth Sunil A , Puri Ajit S , Barreau Xavier , Colasurdo Marco , Renieri Leonardo , Dyzmann Christian , Marotta Thomas , Spears Julian , Mowla Askan , Jabbour Pascal , Filipe João Pedro , Biswas Arundhati , Harker Pablo , Clarençon Frédéric , Radu Răzvan Alexandru , Siegler James E , Nguyen Thanh N , Varela Ricardo , Ota Takahiro , Gonzalez Nestor , Moehlenbruch Markus A , Altschul David , Gory Benjamin , Costalat Vincent , Stracke Christian Paul , Aziz-Sultan Mohammad Ali , Hecker Constantin , Shaikh Hamza , Liebeskind David S , Baker Amanda , Pedicelli Alessandro , Alexandre Andrea , Faizy Tobias D , Tancredi Illario , Kalsoum Erwah , Lubicz Boris , Patel Aman B , Mendes Pereira Vitor , Guenego Adrien , Dmytriw Adam A 
Published: July 2024

BackgroundThe efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO.MethodsIn this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0–2), excellent outcome (mRS 0–1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts.ResultsAmong 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0–2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15).ConclusionOur findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.
Estimates of unintended pregnancy among US active-duty service women and the impact on Women Peace and Security objectives as measured by potential readiness days lost
Authors: Janvrin Miranda Lynn , Banaag A , Lawry L L , Scott R , Koehlmoos T 
Published: July 2024

IntroductionThe prevalence of unintended pregnancy (UIP) in the United States is high among active-duty service women (ADSW).ObjectiveTo estimate the number of UIPs and the impact these pregnancies have on the ability to meet Women, Peace and Security objectives as measured by maximum potential readiness days lost (mRDL).MethodsUsing data from the Military Health System Data Repository, ADSW aged 18 to 44 years, were identified from fiscal year (FY) 2019 data. Deliveries were identified using Medicare Severity Diagnosis-Related Group codes. The estimated number of UIPs was calculated by multiplying both the number of ADSW and the number of deliveries by age-adjusted rates of UIP. Post partum women do not have to meet height and weight standards or complete a physical fitness test for up to 365 days after a full-term delivery. Lost readiness days were calculated by multiplying the number of UIPs by 365 days. Data were stratified by age, race, rank and branch of service.ResultsA total of 230 596 ADSW were identified in FY2019. Using the number of ADSW, an estimated 12 683 ADSW experienced an unintended pregnancy, resulting in an estimated 4 629 215 mRDL. Using the number of deliveries, an estimated 6785 deliveries were a result of UIPs, resulting in an estimated 2 476 364 mRDL. The highest estimates of UIPs were among ADSW aged 18 to 24 years, of White race, in a Junior Enlisted rank and in the Army.ConclusionEstimates of UIPs among ADSW would result in considerable impact on their military career. Dealng with UIPs proactively, by encouraging comprehensive family planning and instituting additional reproductive health policies for service members by ensuring that service members can make informed decisions about their reproductive health while maintaining operational effectiveness, is important for meeting United States Department of Defense Women, Peace and Security objectives.
Is inflammatory change associated with psychological risk and resilience in high-risk military personnel?
Authors: Bennett Neanne , Lawrence-Wood E , McFarlane A 
Published: July 2024

Introduction
In military populations, the potential for under-reporting of Post-traumatic Stress Disorder (PTSD) symptoms and challenges in recognising early changes can make it difficult to detect an emerging disorder. However, early identification of PTSD symptoms would improve opportunities for intervention, and potentially reduce the likelihood of chronic mental health problems.

Method
This study explored if changes in levels of inflammation, measured by C reactive protein (CRP) and interleukin 6 (IL-6), were associated with the onset of psychological symptoms associated with PTSD. It also examined if changes in inflammation over time contributed to psychological risk and resilience, which was defined by psychological reactivity to deployment-related combat exposures. Participants were special forces personnel who completed psychological self-report questionnaires and had measures of CRP and IL-6 taken pre and post deployment. Regression analysis was used to examine how psychological symptoms predicted change in inflammation, and Analysis of Variance (ANOVA) were used to examine differences between identified subgroups.

Results
Results identify this population as having high levels of combat and trauma exposures, with low-level psychological symptoms. The results also identified a decrease in CRP and an increase in IL-6 over time. A significant difference in inflammation was identified between subgroups (p<0.05). An association between inflammatory markers and subthreshold symptoms related to anger (p<0.01) and sleep (p<0.05) was also identified.

Conclusion
These preliminary findings suggest inflammatory markers may help to identify adaptive responses post deployment. In addition, low-level increases in inflammatory markers may be associated with subthreshold PTSD symptoms. These findings offer potential insights for prevention, early identification and treatment in military and veteran populations.
Sex-specific aspects on prognosis after aortic valve replacement for aortic stenosis: a SWEDEHEART registry study
Authors: Johnston Nina , James Stefan K , Lindhagen Lars , Ståhle Elisabeth , Christersson Christina 
Published: July 2024

ObjectiveTo compare long-term cardiovascular (CV) outcomes between men and women with aortic stenosis (AS) undergoing aortic valve replacement (AVR) by the type of valve implant.MethodsThe study population consisted of 14 123 non-selected patients with AS undergoing first-time AVR and included in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry during 2008–2016. Comparisons were made between men and women and type of valve implant (ie, surgical implantation with a mechanical (mSAVR) (n=1 966) or biological valve (bioSAVR) (n=9 801)) or by a transcatheter approach (TAVR) (n=2 356). Outcomes included all-cause mortality, ischaemic stroke, major bleeding, thromboembolic events, heart failure and myocardial infarction, continuously adjusted for significant comorbidities and medical treatment.ResultsIn the mSAVR cohort, there were no significant sex differences in any CV events. In the bioSAVR cohort, a higher risk of death (HR: 1.14; 95% CI: 1.04 to 1.26, p=0.007) and major bleeding (HR: 1.41; 95% CI: 1.18 to 1.69, p<0.001) was observed in men. In the TAVR cohort, men suffered a higher risk of death (HR: 1.24; 95% CI: 1.07 to 1.45, p=0.005), major bleeding (HR: 1.35; 95% CI: 1.00 to 1.82, p=0.022) and thromboembolism (HR: 1.35, 95% CI: 1.00 to 1.82, p=0.047).ConclusionNo significant long-term difference in CV events was noted between men and women undergoing AVR with a mechanical aortic valve. In both the bioSAVR and TAVR cohort, mortality was higher in men who also had an increased incidence of several other CV events.
No difference in clinical parameters and drug retention in PsA patients receiving b/tsDMARD monotherapy versus combination with methotrexate: data from the RABBIT-SpA registry
Authors: Regierer Anne Constanze , Kiefer David , Schett Georg , Krause Andreas , Weiß Anja , Sewerin Philipp , Strangfeld Anja 
Published: July 2024

BackgroundThe potential benefit of methotrexate (MTX) in combination with biologic (b) and targeted synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) is still a matter of debate.ObjectivesTo compare clinical and patient reported characteristics as well as drug retention rates in PsA patients receiving b/tsDMARD monotherapy or in combination with MTX.MethodsRABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients. In this analysis, PsA patients were stratified into two groups: starting b/tsDMARD as monotherapy or in combination with MTX. Treatment retention was compared by drug survival analysis.Results69% of the patients (n=900) started b/tsDMARD as monotherapy while 31% were treated in combination with MTX (n=405). At baseline, clinical domains like skin, nail and joint affection, dactylitis, enthesitis and axial involvement were similar between the groups. Only the patients’ satisfaction concerning tolerability of the previous treatment was significantly better in the combination group at treatment start. Drug retention rates did not differ between the groups (p=0.4). At 6/12 months, 66%/48% of patients in monotherapy and 67%/48% in the combination group were still on their original treatment.ConclusionsWe did not identify any clinical parameters with notable influence on the choice of b/tsDMARD mono or MTX-combination therapy in PsA. Drug retention rates are similar between mono and combination therapy. It seems that the decision to continue MTX at initiation of b/tsDMARDs is mostly based on the subjective tolerability of MTX treatment.
Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis
Authors: Mena-Vázquez Natalia , Ortiz-Márquez Fernando , Ramírez-García Teresa , Cabezudo-García Pablo , García-Studer Aimara , Mucientes-Ruiz Arkaitz , Lisbona-Montañez Jose Manuel , Borregón-Garrido Paula , Ruiz-Limón Patricia , Redondo-Rodríguez Rocío , Manrique-Arija Sara , Cano-García Laura , Serrano-Castro Pedro J. , Fernández-Nebro Antonio 
Published: July 2024

ObjectiveTo evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.Patients and methodsWe performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA.ResultsThe study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6).ConclusionsPatients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.
Diagnosis challenges in inception cohorts in axial spondyloarthritis: the case of the French national DESIR cohort
Authors: Molto Anna , Serrand Chris , Alonso Sandrine , Berenbaum Francis , Claudepierre Pascal , Combe Bernard , Gossec Laure , Ruyssen-Witrand Adeline , Saraux Alain , Wendling Daniel , Lequerre Thierry , Dougados Maxime 
Published: July 2024

BackgroundInception cohorts aim to describe chronic diseases from diagnosis and over years of follow-up. Axial spondyloarthritis (axSpA) diagnosis might be challenging during the first years of the disease. Thus, identifying the features that will be associated with a confirmed diagnosis over time is key.ObjectivesTo assess the frequency and the predisposing factors for a change of an initial diagnosis in an inception axSpA cohort.MethodsDESIR is an ongoing national multicentre inception axSpA cohort with currently 12.5 years of follow-up. At the entry visit and confirmed at each visit, the diagnosis of axSpA was based on the opinion of the treating rheumatologist. Follow-up was interrupted in case of a change in this initial diagnosis. Multiple imputation was used to estimate the probability of a change in the initial diagnosis of axSpA for each patient lost to follow-up. Factors predisposing to an unchanged diagnosis of axSpA were then assessed using a multivariate logistic regression model on the imputed data sets.ResultsOf the 708 patients included, over 10 years of follow-up, 45 (6.4%) were excluded due to a diagnosis change and 300 (42.4%) patients were lost to follow-up. Based on the imputation of these 300 patients, a change in their initial axSpA diagnosis was estimated in 42 (14.0%). Factors predisposing to an unchanged initial axSpA diagnosis during follow-up were (ORs (95% CIs)): radiographic sacroiliitis: 17.0 (4.1 to 71.0); psoriasis: 5.3 (2.0 to 14.3); CRP≥6 mg/L: 2.7 (1.3 to 5.3); good NSAID response: 2.5 (1.5 to 4.2); HLA B27+: 2.0 (1.3 to 3.3); anterior chest wall pain: 2.0 (1.2 to 3.3) and female sex: 1.9 (1.2 to 3.0).ConclusionThese data suggest that a change in diagnosis in recent onset axSpA exists, but is not frequent, and is less likely to occur in the presence of objective features at baseline.
Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis
Authors: Karpouzas George Athanasios , Ormseth Sarah R , van Riel Piet Leonardus Cornelis Maria , Gonzalez-Gay Miguel A , Corrales Alfonso , Rantapää-Dahlqvist Solbritt , Sfikakis Petros P , Dessein Patrick , Tsang Linda , Hitchon Carol , El-Gabalawy Hani , Pascual-Ramos Virginia , Contreras-Yáñez Irazú , Colunga-Pedraza Iris J , Galarza-Delgado Dionicio Angel , Azpiri-Lopez Jose Ramon , Semb Anne Grete , Misra Durga Prasanna , Hauge Ellen-Margrethe , Kitas George 
Published: July 2024

ObjectivesChronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA.MethodsWe studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease.ResultsOver 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk.ConclusionsRA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.