bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic accuracy of serum biomarkers to identify giant cell arteritis in patients with polymyalgia rheumatica
Authors: Ramon André , Greigert Hélène , Goueslard Karine , Cladière Claudie , Ciudad Marion , Ornetti Paul , Audia Sylvain , Maillefert Jean Francis , Bonnotte Bernard , Samson Maxime 
Published: August 2024

IntroductionPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used to identify GCA in cases of apparently isolated PMR.Materials and methods45 patients with isolated PMR and 29 patients with PMR/GCA overlap were included. Blood samples were collected before starting glucocorticoids for all patients. Serum biomarkers reflecting systemic inflammation (interleukin-6 (IL-6), CXCL9), vascular remodelling (MMP-2, MMP-3, MMP-9) and endothelial function (sCD141, sCD146, ICAM-1, VCAM-1, vWFA2) were measured by Luminex assays.ResultsPatients with GCA had higher serum levels of sCD141 (p=0.002) and CXCL9 (p=0.002) than isolated PMR. By contrast, serum levels of MMP-3 (p=0.01) and IL-6 (p=0.004) were lower in GCA than isolated PMR. The area under the curve (AUC) was calculated for sCD141, CXCL9, IL-6 and MMP-3. Separately, none of them were >0.7, but combinations revealed higher diagnostic accuracy. The CXCL9/IL-6 ratio was significantly increased in patients with GCA (p=0.0001; cut-off >32.8, AUC 0.76), while the MMP-3/sCD141 ratio was significantly lower in patients with GCA (p<0.0001; cut-off <5.3, AUC 0.79). In patients with subclinical GCA, which is the most difficult to diagnose, sCD141 and MMP-3/sCD141 ratio demonstrated high diagnostic accuracy with AUC of 0.81 and 0.77, respectively.ConclusionCombined serum biomarkers such as CXCL9/IL-6 and MMP-3/sCD141 could help identify GCA in patients with isolated PMR. It could allow to select patients with PMR in whom complementary examinations are needed.
Symptom burden among men treated for castration-resistant prostate cancer: a longitudinal study
Authors: Rönningås Ulrika , Fransson Per , Holm Maja , Beckman Lars , Wennman-Larsen Agneta 
Published: August 2024

ObjectivesDespite rapid expansion of treatments for metastatic castration-resistant prostate cancer (mCRPC) and the importance of symptom management for enhancing quality of life, few studies have focused on men’s experiences of symptom burden over time when receiving one or more lines of treatment in a real-world situation in this phase. The aim was to investigate changes in the multidimensional symptom burden during the first year of life-prolonging treatment of mCRPC.MethodsLongitudinal data from the first year of life-prolonging treatment for 134 men with mCRPC were used. Symptoms were measured with the multidimensional Memorial Symptom Assessment Scale. Data are presented with descriptive statistics, and changes in symptom burden (physical, psychological and number of symptoms) were analysed using linear mixed modelling.ResultsOn average, the men had approximately 10 (0–31) symptoms at inclusion and 12 (0–33) at the last time point. Lack of energy and sweats were the two most reported symptoms at every time point. Sexual problems had the highest scores in all dimensions (frequency, severity, distress). Regarding pain, the distress score was higher than the scores for frequency and severity at t1–t4. Physical symptom burden and the number of symptoms changed significantly over time, towards a higher symptom burden. Psychological symptom burden did not change significantly over time.ConclusionThe different dimensions of physical symptoms in men treated for mCRPC need to be more acknowledged. Early integration of a palliative care approach could possibly help in enhancing symptom management and quality of life for these men.
Exploring the dark energy equation of state with JWST
Authors: Wang Pei , Su Bing-Yu , Zu Lei , Yang Yupeng , Feng Lei 
Published: August 2024

AbstractObservations from the James Webb Space Telescope (JWST) have unveiled several galaxies with stellar masses $$M_*\gtrsim 10^{10} M_\odot$$

M

∗

≳

10
10

M
⊙

at redshifts $$7.4\lesssim z\lesssim 9.1$$

7.4
≲
z
≲
9.1

. These remarkable findings indicate an unexpectedly high stellar mass density, which contradicts the prediction of the $$\Lambda \rm{CDM}$$

Λ
CDM

model. Our study utilizes the Chevallier–Polarski–Linder (CPL) parameterization, one of the dynamic dark energy models, to probe the role of dark energy on shaping galaxy formation. By considering varying star formation efficiencies within this framework, our analysis demonstrates that in a universe with a higher proportion of dark energy, more massive galaxies are formed at high redshifts, given a fixed perturbation amplitude observed today. These intriguing results highlight the promising prospect of revealing the nature of dark energy by analyzing the high-redshift massive galaxies.
Exploring for hydrogen, helium and lithium: is it as easy as 1, 2, 3?
Authors: Gluyas Jon G. , Humphreys Madeleine , Karolytė Rūta , Cheng Anran , Sherwood Lollar Barbara , Ballentine Chris 
Published: August 2024

Hydrogen, helium and lithium, elements one two and three of the periodic table, are in demand to enable and enhance low-carbon energy technologies. Anthropogenic hydrogen is manufactured from water via methane reforming or from electrolysis. Both are costly and have environmental impacts. Helium is commonly found in low concentrations in association with petroleum gases. Lithium is mined by brine pumping or from igneous rocks, with consequential serious environmental impacts.
Were it possible to economically find hydrogen in its molecular state, then surely such hydrogen would dominate the market. Similarly, helium generated without associated greenhouse gases would also be a market stimulant for a helium industry. What if hydrogen and helium could be co-produced from a single composite discovery? And what if the water leg to such hydrogen and helium deposits were rich in lithium? It, too, would be produced with costs for all elements shared.
Helium is a natural product of crystalline rocks including granite and its generation can liberate hydrogen from interstitial water. These same rocks can be rich sources of lithium and may also deliver geothermal resources. The energy transition may therefore shift what we consider to be important for energy geoscience. The basement may become as important as the basin.
KHSRP Stabilizes m6A-Modified Transcripts to Activate FAK Signaling and Promote Pancreatic Ductal Adenocarcinoma Progression
Authors: Xu Zilan , Zhou Yifan , Liu Shaoqiu , Zhao Hongzhe , Chen Ziming , Li Rui , Li Mei , Huang Xudong , Deng Shuang , Zeng Lingxing , Zhao Sihan , Zhang Shaoping , He Xiaowei , Liu Ji , Xue Chunling , Bai Ruihong , Zhuang Lisha , Zhou Quanbo , Chen Rufu , Lin Dongxin , Zheng Jian , Zhang Jialiang 
Published: August 2024

Abstract
N 6-Methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV, and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.
Significance: KHSRP is a m6A-binding protein that stabilizes expression of FAK pathway mRNAs and that can be targeted to suppress FAK signaling and curb pancreatic ductal adenocarcinoma progression.
HER2 Antibody–Drug Conjugates Are Active against Desmoplastic Small Round Cell Tumor
Authors: Zhang Tom , Febres-Aldana Christopher A. , Liu Zebing , Dix Jenna-Marie , Cheng Ryan , Dematteo Raymond G. , Lui Allan J.W. , Khodos Inna , Gili Leo , Mattar Marissa S. , Lisanti Jeanine , Kwong Charlene , Linkov Irina , Tipping Murray J. , de Stanchina Elisa , Odintsov Igor , Ladanyi Marc , Somwar Romel 
Published: August 2024

Abstract

Purpose:
Desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive soft tissue sarcoma that arises in the abdominopelvic cavity of young males. Since the discovery of EWSR1::WT1 fusion as the driver of DSRCT, no actionable genomic alterations have been identified, limiting disease management to a combination of surgery, chemotherapy, and radiation, with very poor outcomes. Herein, we evaluated ERBB2/HER2 expression in DSRCT as a therapeutic target.

Experimental Design:
ERBB2/HER2 expression was assessed in clinical samples and patient-derived xenografts (PDX) using RNA sequencing, RT-qPCR, and a newly developed HER2 IHC assay (clone 29D8). Responses to HER2 antibody–drug conjugates (ADC)—trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine—were evaluated in DSRCT PDX, cell line, and organoid models. Drug internalization was demonstrated by live microscopy. Apoptosis was evaluated by Western blotting and caspase activity assays.

Results:
ERBB2/HER2 was detectable in DSRCT samples from patients and PDXs, with higher sensitivity RNA assays and improved IHC detectability using clone 29D8. Treatment of ERBB2/HER2-expressing DSRCT PDX, cell line, and organoid models with T-DXd or trastuzumab emtansine resulted in tumor regression. This therapeutic response was long-lasting in T-DXd–treated xenografts and was mediated by rapid HER2 ADC complex internalization and cytotoxicity, triggering p53-mediated apoptosis and growth arrest. Xenograft regression was associated with bystander payload effects triggering global tumor niche responses proportional to HER2 status.

Conclusions:
ERBB2/HER2 is a therapeutic target in DSRCT. HER2 ADCs may represent novel options for managing this exceptionally aggressive sarcoma, possibly fulfilling an urgent and historically unmet need for more effective clinical therapy.
Binge Alcohol Consumption Elevates Sympathetic Transduction to Blood Pressure: A Randomized Controlled Trial
Authors: Bigalke Jeremy A. , Greenlund Ian M. , Solis-Montenegro Tatiana X. , Durocher John J. , Joyner Michael J. , Carter Jason R. 
Published: August 2024

BACKGROUND:
Alcohol consumption is associated with cardiovascular disease, and the sympathetic nervous system is a suspected mediator. The present study investigated sympathetic transduction of muscle sympathetic nerve activity to blood pressure at rest and in response to cold pressor test following evening binge alcohol or fluid control, with the hypothesis that sympathetic transduction would be elevated the morning after binge alcohol consumption.

METHODS:

Using a randomized, fluid-controlled (FC) crossover design, 26 healthy adults (12 male, 14 female, 25±6 years, 27±4 kg/m
2
) received an evening binge alcohol dose and a FC. All participants underwent next-morning autonomic-cardiovascular testing consisting of muscle sympathetic nerve activity, beat-to-beat blood pressure, and heart rate during a 10-minute rest period and a 2-minute cold pressor test. Sympathetic transduction was assessed at rest and during the cold pressor test in both experimental conditions.

RESULTS:

Evening alcohol increased heart rate (FC: 60±9 versus alcohol: 64±9 bpm;
P
=0.010) but did not alter resting mean arterial pressure (FC: 80±6 versus alcohol: 80±7 mm Hg;
P
=0.857) or muscle sympathetic nerve activity (FC: 18±9 versus alcohol: 20±8 bursts/min;
P
=0.283). Sympathetic transduction to mean arterial pressure (time×condition;
P
=0.003), diastolic blood pressure (time×condition;
P
=0.010), and total vascular conductance (time×condition;
P
=0.004) was augmented after alcohol at rest. Sympathetic transduction during the cold pressor test was also elevated after evening binge alcohol consumption (
P
=0.002).

CONCLUSIONS:
These findings suggest that evening binge alcohol consumption leads to augmented morning-after sympathetic transduction of muscle sympathetic nerve activity to blood pressure, highlighting a new mechanism whereby chronic or excessive alcohol consumption contributes to cardiovascular disease progression via altered end-organ responsiveness to sympathetic neural outflow.

REGISTRATION:

URL:
https://clinicaltrials.gov/study/NCT03567434
; Unique identifier: NCT03567434.
Impact of Procedural Success Definitions on Long‐Term Outcomes in Patients With Rheumatic Mitral Stenosis Treated With Percutaneous Balloon Mitral Valvuloplasty: A Multicenter, Retrospective Cohort Study
Authors: Manoret Premanan , Thonghong Tasalak , Meemook Krissada , Kosallavat Seththawut , Aroonsiriwattana Suchart , Songsangjinda Thammarak , Suwanugsorn Saranyou , Nilmoje Thanapon , Cheewatanakornkul Sirichai , Wisaratapong Treechada , Limumpornpetch Sunti , Lohawijarn Watchara , Thungthienthong Metus , Chamnarnphol Noppadol , Chandavimol Mann , Suwannasom Pannipa , Jintapakorn Woravut , Chichareon Ply 
Published: August 2024

Background
It is uncertain which percutaneous balloon mitral valvuloplasty (PBMV) success definitions should be used because there are no studies comparing the effects of these definitions on subsequent outcomes. We evaluated the association between 3 success definitions and long‐term clinical outcomes in patients with rheumatic mitral stenosis who underwent PBMV.

Methods and Results

This multicenter retrospective study included patients with severe rheumatic mitral stenosis who underwent PBMV. Three definitions were used as follows: (A) post‐PBMV mitral valve area (MVA) ≥1.5 cm
2
or ≥50% increase in MVA with MR <3+; (B) post‐PBMV MVA ≥1.5 cm
2
and MR ≤2+; and (C) post‐PBMV MVA ≥1.5 cm
2
or ≥50% increase in MVA, with no more than 1‐grade increment in MR. Multivariable Cox regression analyses were performed to evaluate the associations between PBMV success and the composite of all‐cause mortality, mitral surgery, and repeat PBMV. Successful PBMV, according to definitions A, B, and C was associated with a lower risk of the composite outcomes (definition A—hazard ratio [HR], 0.55 [95% CI, 0.43–0.69], definition B—HR, 0.55 [95% CI, 0.43–0.69], definition C—HR, 0.55 [95% CI, 0.44–0.69]). Patients meeting all 3 success definitions had the lowest risk compared with those who did not meet any definition or met 1 or 2 definitions.

Conclusions

All 3 success definitions had a prognostic impact on outcomes. Patients who achieved post‐PBMV MVA ≥1.5 cm
2
, irrespective of the percentage increase in MVA, and MR ≤grade 2, with no more than a 1‐grade increment in MR, had the most favorable outcomes.
Prediction for Perioperative Stroke Using Intraoperative Parameters
Authors: Oh Mi‐Young , Jung Young Mi , Kim Won‐Pyo , Lee Hyung‐Chul , Kim Tae Kyong , Ko Sang‐Bae , Lim Jaehyun , Lee Seung Mi 
Published: August 2024

Background
Perioperative stroke is a severe complication following surgery. To identify patients at risk for perioperative stroke, several prediction models based on the preoperative factors were suggested. Prediction models often focus on preoperative patient characteristics to assess stroke risk. However, most existing models primarily base their predictions on the patient's baseline characteristics before surgery. We aimed to develop a machine‐learning model incorporating both pre‐ and intraoperative variables to predict perioperative stroke.

Methods and Results

This study included patients who underwent noncardiac surgery at 2 hospitals with the data of 15 752 patients from Seoul National University Hospital used for development and temporal internal validation, and the data of 449 patients from Boramae Medical Center used for external validation. Perioperative stroke was defined as a newly developed ischemic lesion on diffusion‐weighted imaging within 30 days of surgery. We developed a prediction model composed of pre‐ and intraoperative factors (integrated model) and compared it with a model consisting of preoperative features alone (preoperative model). Perioperative stroke developed in 109 (0.69%) patients in the Seoul National University Hospital group and 11 patients (2.45%) in the Boramae Medical Center group. The integrated model demonstrated superior predictive performance with area under the curve values of 0.824 (95% CI, 0.762–0.880) versus 0.584 (95% CI, 0.499–0.667;
P
<0.001) in the internal validation; and 0.716 (95% CI, 0.560–0.859) versus 0.505 (95% CI, 0.343–0.654;
P
=0.018) in the external validation, compared to the preoperative model.

Conclusions
We suggest that incorporating intraoperative factors into perioperative stroke prediction models can improve their accuracy.
Technological Advances Are Associated With Better Clinical Outcomes of Percutaneous Coronary Intervention in Patients With Unprotected Left Main Disease
Authors: Zhang Dong , Yan Ruohua , Wang Hao‐Yu , Zhang Rui , Zhao Zhiyong , Gao Guofeng , Yang Min , Wang Hao , Liu Shuai , Fu Rui , Yin Dong , Zhu Chenggang , Feng Lei , Yang Yuejin , Dou Kefei 
Published: August 2024

Background
Few large‐scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM‐CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM‐CAD and to assess the impact of PCI technological advances on long‐term clinical outcomes.

Methods and Results
A total of 4512 consecutive patients who underwent unprotected LM‐CAD PCI at Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, or target vessel revascularization). The incidence of 3‐year MACEs was 9.0% (406/4512). Four new PCI techniques were identified as the independent protective factors of MACEs, including second‐generation drug‐eluting stents (hazard ratio [HR], 0.61 [95% CI, 0.37–0.99]), postdilatation (HR, 0.75 [95% CI, 0.59–0.94]), final kissing balloon inflation (HR, 0.78 [95% CI, 0.62–0.99]), and using intravascular ultrasound (HR, 0.78 [95% CI, 0.63–0.97]). The relative hazard of 3‐year MACEs was reduced by ≈50% with use of all 4 techniques compared with no technique use (HR, 0.53 [95% CI, 0.32–0.87]).

Conclusions
PCI technological advances including postdilatation, second‐generation drug‐eluting stent, final kissing balloon inflation, and intravascular ultrasound guidance were associated with improved clinical outcomes in patients who underwent unprotected LM‐CAD PCI.
Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease
Authors: Xu Yunwen , Ballew Shoshana H. , Chang Alexander R. , Inker Lesley A. , Grams Morgan E. , Shin Jung‐Im 
Published: August 2024

Background
Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high‐risk patients remains unclear.

Methods and Results

Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m
2
) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m
2
; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person‐years; subdistribution hazard ratio [sub‐HR], 0.53 [95% CI, 0.39–0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person‐years; sub‐HR, 0.80 [95% CI, 0.59–1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person‐years; HR, 1.03 [95% CI, 0.82–1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person‐years; sub‐HR, 1.65 [95% CI, 1.10–2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub‐HR, 0.53 [95% CI, 0.36–0.78]).

Conclusions
These real‐world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.
Mendelian Randomization and Bayesian Colocalization Analysis Implicate Glycoprotein VI as a Potential Drug Target for Cardioembolic Stroke in South Asian Populations
Authors: Wu Siwei , Meena Devendra , Yarmolinsky James , Gill Dipender , Smith Alexander , Dib Marie‐Joe , Chauhan Ganesh , Rohatgi Anand , Dehghan Abbas , Tzoulaki Ioanna 
Published: August 2024

Background
Circulating plasma proteins are clinically useful biomarkers for stroke risk. We examined the causal links between plasma proteins and stroke risk in individuals of South Asian ancestry.

Methods and Results

We applied proteome‐wide Mendelian randomization and colocalization approaches to understand causality of 2922 plasma proteins on stroke risk in individuals of South Asian ancestry. We obtained genetic instruments (proxies) for plasma proteins from the UK Biobank (N=920). Genome‐wide association studies summary data for strokes (N≤11 312) were sourced from GIGASTROKE consortium. Our primary approach involved the Wald ratio or inverse‐variance‐weighted methods, with statistical significance set at false discovery rate <0.1. Additionally, a Bayesian colocalization approach assessed shared causal variants among proteome, transcriptome, and stroke phenotypes to minimize bias from linkage disequilibrium. We found evidence of a potential causal effect of plasma GP6 (glycoprotein VI) levels on cardioembolic stroke (odds ratio [OR]
Wald ratio
=2.53 [95% CI, 1.59–4.03];
P
=9.2×10
−5
, false discovery rate=0.059). Generalized Mendelian randomization accounting for correlated single nucleotide polymorphisms (SNPs), with the
P
value threshold at
P
<5×10
−8
and clumped at
r
2
=0.3, showed consistent direction of effect of GP6 on cardioembolic stroke (OR
generalized inverse‐variance‐weighted
=2.21 [95% CI, 1.46–3.33];
P
=1.6×10
−4
). Colocalization analysis indicated that plasma GP6 levels colocalize with cardioembolic stroke (posterior probability=91.4%). Multitrait colocalization combining transcriptome, proteome, and cardioembolic stroke showed moderate to strong evidence that these 2 traits colocalize with
GP6
expression in the coronary artery and brain tissues (multitrait posterior probability>50%). The potential causal effect of GP6 on cardioembolic stroke was not significant in European populations (OR
inverse‐variance‐weighted
=1.08 [95% CI, 0.93–1.26];
P
=0.29).

Conclusions
Our joint Mendelian randomization and colocalization analyses suggest that genetically predicted GP6 is potentially causally associated with cardioembolic stroke risk in individuals of South Asian ancestry. As genetic data on individuals of South Asian ancestry increase, future Mendelian randomization studies with larger sample size for plasma GP6 levels should be implemented to further validate our findings. Additionally, clinical studies will be necessary to verify GP6 as a therapeutic target for cardioembolic stroke in South Asians.