bluuebunny/crossref_metadata_2025_split huggingface dataset:
[Can prostate biopsy be replaced?] Feasibility of mpMRI combined with 18F-PSMA PET/CT in the diagnosis of prostate cancer
Authors: Yang Yunkai , Zhao Changfeng , Wang Zhida , Miu Jia , Zhang Xinyu , Zhang Qi , Qi Xiaolong , Bai Yuchen , Zhang Dahong 
Published: September 2024

Abstract

Objective
To investigate whether multiparameter magnetic resonance imaging (mpMRI) combined with 18F-Prostate-specific membrane antigen (PSMA) PET/CT can replace prostate biopsy in the diagnosis of prostate cancer.
Materials and methods
This is a prospectively Three-arm Clinical Trial which enrolled 150 patients with suspected prostate cancer (PI-RADs ≥ 3 score) from Zhejiang Provincial People's Hospital between September 2020 to January 2023. Patients were screened and divided into three cohorts to undergo the PSMA-PET procedure, transperineally MRI-targeted biopsy (TB-TRUS), and conventional transrectal ultrasound-guided systematic biopsy (SB-TRUS). All patients required radical prostatectomy according to the treatment procedure and perioperative information was collected. Comparison of baseline patient characteristics, detection and omission rates for various screening methods, and perioperative information between the three groups.
Results
A total of 109 patients were included in this study. The median age was 68.4 (64.0-73.5) years old. The median PSA was 13.0 (7.1–15.0) ng/ml, the median prostate volume was 42.0 (24.6–53.8) ml, and the median PSA density (PSAD) was 0.36 (0.19–0.47) ng/ml2. 48 patients had PI-RADS scores of 3, 41 patients had scores of 4, and 20 patients had scores of 5. The median SUVmax of 18F-PSMA PET/CT was 15.41 (12.18–17.58). There were no significant differences in baseline characteristics among the three cohorts. The detection rate of prostate cancer in the Sa cohort was much lower than that in the Pa and Ma cohorts (P<0.001), and the missed diagnosis rate in the Sa cohort was much higher than that in the other two groups (P<0.001). The Intraoperative bleeding, surgery time and Hospitalization days in the Pa cohort were much higher than those in the other two cohorts (P<0.001).
Conclusion
MpMRI combined with 18F-PSMA PET/CT has high accuracy in the diagnosis of prostate cancer. For patients with highly suspected localized prostate cancer, radical prostatectomy without biopsy is safe, and can be attempted on the premise of adequate communication.
Predictive Value of the Systemic Immune-Inflammation Index for Periprocedural Complications in Flow Diverter Treatment for Patients with Intracranial Aneurysms
Authors: Huang Jiwan , Huang Yaxian , Feng Xin , Huang Chi , Huang Mengshi , Wen Zhuohua , Xu Anqi , Ge Runze , Yuan Hao , Shi Hongyu , Ma Gengwu , Li Can , Lin Jiancheng , Yi Ruizhe , Hu Yuqi , Jin Yuheng , Liang Shuyin , Bi Yiming , Su Shixing , Zhang Xin , Li Xifeng , Duan Chuanzhi 
Published: September 2024

Abstract

Flow-diverter devices (FDs) are effective in treating intracranial aneurysms (IAs) but carry substantial periprocedural risks, particularly ischemic complications. This study aimed to determine if elevated Systemic Immune-Inflammation Index (SII) can independently predict these risks and assess the impact of age and dual antiplatelet therapy on this association. We conducted a retrospective analysis of patients treated with FDs between February 2016 and August 2023, using blood samples taken within six days before surgery to calculate SII. Logistic regression and decision tree analyses assessed the link between SII and periprocedural complications, with subgroups exploring influencing factors. Multivariable analysis identified high SII as an independent predictor of periprocedural complications (OR=5.306, 95% CI: 1.367-18.455; P=0.009). The decision tree model confirmed SII > 0.437 as a critical threshold. Subgroup analysis showed a pronounced association of SII with periprocedural complications in patients ≥65 years (OR=36.979, 95% CI: 2.103-650.134; P=0.014) and in those on clopidogrel therapy (OR=16.921, 95% CI: 2.733-104.746; P=0.002). An elevated Systemic Immune-Inflammation Index (SII) >0.437 significantly correlates with increased periprocedural complications (6.5% vs. 1.8%, P=0.017). Although not statistically significant, higher SII is associated with a greater rate of ischemic events (3.9% vs. 0.9%). Elevated preoperative SII independently predicts periprocedural complications, particularly ischemic events, in patients undergoing FDs treatment for intracranial aneurysms. This association is especially significant in older patients and those on clopidogrel therapy.
Trial Registration: ClinicalTrials.gov (NCT06446778). Registered on May 22, 2024.
GDF15 propeptide promotes bone metastasis of castration-resistant prostate cancer by augmenting the bone microenvironment
Authors: Yamamichi Gaku , Kato Taigo , Arakawa Noriaki , Ino Yoko , Ujike Takeshi , Nakano Kosuke , Koh Yoko , Motoyama Yuichi , Outani Hidetatsu , Myoba Shohei , Ishizuya Yu , Yamamoto Yoshiyuki , Hatano Koji , Kawashima Atsunari , Fukuhara Shinichiro , Uemura Hiroji , Okada Seiji , Morii Eiichi , Nonomura Norio , Uemura Motohide 
Published: September 2024

Abstract

Background
Bone metastasis (BM) is a common and fatal condition in patients with castration-resistant prostate cancer (CRPC). However, there are no useful blood biomarkers for CRPC with BM, and the mechanism underlying BM is unclear. In this study, we investigated precise blood biomarkers for evaluating BM that can improve the prognosis of patients with CRPC.
Methods
We comprehensively examined culture supernatants from four prostate cancer (PCa) cell lines using Orbitrap mass spectrometry to identify specific proteins secreted abundantly by PCa cells. The effects of this protein to PCa cells, osteoblasts, osteoclasts were examined, and BM mouse model. In addition, we measured the plasma concentration of this protein in CRPC patients for whom bone scan index (BSI) by bone scintigraphy was performed.
Results
A total of 2,787 proteins were identified by secretome analysis. We focused on GDF15 propeptide (GDPP), which is secreted by osteoblasts, osteoclasts, and PCa cells. GDPP promoted the proliferation, invasion, and migration of PC3 and DU145 CRPC cells, and GDPP aggravated BM in a mouse model. Importantly, GDPP accelerated bone formation and absorption in the bone microenvironment by enhancing the proliferation of osteoblasts and osteoclasts by upregulating individual transcription factors such as RUNX2, OSX, ATF4, NFATc1, and DC-STAMP. In clinical settings, including a total of 386 patients, GDPP was more diagnostic of BM than prostate-specific antigen (PSA) (AUC = 0.92 and 0.78) and the seven other blood biomarkers (alkaline phosphatase, lactate dehydrogenase, bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, procollagen I N-terminal propeptide and mature GDF15) in patients with CRPC. The changes in BSI over time with systemic treatment were correlated with that of GDPP (r = 0.63) but not with that of PSA (r = -0.16).
Conclusions
GDPP promotes a vicious cycle in the BM microenvironment and is a novel blood biomarker of BM in CRPC, which could lead to early treatment interventions in patients with CRPC.
Exploring the Role of Refined White Matter Segmentation in Head Finite Element Models for Studying Repetitive Subconcussive Head Impacts
Authors: Bouvette Véronique , Guay Samuel , Beaumont Louis , Petit Yvan , Vinet Sophie-Andrée , Wagnac Eric 
Published: September 2024

Abstract

Head finite element models (hFEMs) are instrumental in understanding injury mechanisms in head impacts. Personalizing hFEMs is crucial for capturing individualized brain responses, with brain volume scaling proving effective. However, the role of refined white matter (WM) segmentation in hFEMs for studying repetitive subconcussive head impacts (rSHIs) in American football remains underexplored. This study evaluated the effect of refined WM segmentation of 34 WM segments on responses variability due to brain volume variations, using peak maximum principal strain (95MPS) and strain rate (95MPSr) as injury predictive metrics. Data from diffusion-weighted imaging (DWI) of 21 Canadian varsity football players were utilized to personalize 21 hFEMs. Simulating four different head impacts, representing 50th and 99th percentile resultant accelerations in frontal and top-right directions, refined WM segmentation better captured variability of strain responses compared to baseline segmentation. Up to 94.76% of 95MPS and 99.05% of 95MPSr responses were significantly different across refined WM segments for players, compared to a maximum of 12.86% of responses with baseline segmentation. This highlights the necessity of refined WM segmentation for capturing player-specific responses. Both impact direction and intensity influenced strain response variations, with lower intensity and frontal impacts showing greater player-specificity. These findings emphasize the importance of refined WM segmentation in hFEMs for comprehensively evaluating strain responses under rSHI. Detailed WM segmentation in hFEMs is crucial for comprehensive injury assessment, enhancing the alignment of hFEMs with imaging studies evaluating changes in WM integrity across segments. The simple and straightforward method presented herein to achieve player-specific strain response is promising for future rSHI studies.
The 1,7-malaria reactive community-based testing and response (1,7-mRCTR) approach in Tanzania: a cost-effectiveness analysis
Authors: Tampi Radhika Pradip , Wang Duoquan , Abdulla Salim , Mahende Muhidin Kassim , Gavana Tegemeo , Msuya Hajirani M , Kuwawenaruwa Augustine , Mihayo Michael , Brown Felix , Msuya Hajirani , Anthony Wilbald , Bruxvoort Katia , Kihwele Fadhila , Chila Godlove , Chang Wei , Castro Marcia , Ning Xiao , Chaki Prosper P , Mlacha Yeromin P , Cohen Jessica , Menzies Nicolas Alan 
Published: September 2024

Abstract

Background: Reactive case detection (RACD) for malaria control has been found effective in low transmission settings, but its impact and cost-effectiveness in moderate-high transmission settings are unknown. We conducted an economic evaluation alongside an empirical trial of a modified RACD strategy (1,7-mRCTR) in three high malaria transmission districts in Tanzania.
Methods: The costs and cost-savings associated with the intervention to passive case detection alone were estimated, and a simulation model was utilized to assess cost-effectiveness in terms of incremental cost-effectiveness ratios (ICERs) for multiple endpoints. Empirical cost data were collected using household surveys. Only intervention-related programmatic costs were included in this analysis. The incremental costs of the intervention were calculated from under a societal perspective. Costs are reported in 2022 US dollars.
The proximal health effects of the intervention were calculated using trial data and malaria registers. OpenMalaria, an open-source microsimulation model, was used to simulate unobserved and distal health effects of the intervention. The model was fit to baseline malaria prevalence and estimated percentage point decline in malaria prevalence from the corresponding impact evaluation.
Cost-effectiveness endpoints include the incremental cost per: (i) person treated, (ii) additional malaria case detected using a combination of passive and reactive case detection, (iii) incident malaria case averted, (iv) malaria death averted, and (v) DALY averted. Propagated uncertainty was assessed via 2nd-order Monte Carlo simulation, including bootstrapping of empirical data distributions. Incremental costs per DALY averted were compared to a willingness-to-pay threshold based on estimated opportunity costs of healthcare spending in Tanzania.
Results: The programmatic cost of the 1,7-mRCTR intervention was $5327 per 1000 population. The combination of reactive and passive case detection in the intervention arm resulted in an additional 445 malaria cases detected per 1000 compared to passive detection alone, yielding an incremental cost per additional case detected of $11.97. For distal health outcomes, the ICER associated with the 1,7-mRCTR intervention is $14,887 per death averted and $163 per DALY averted.
Conclusions: The 1,7-mRCTR intervention appears to be cost-effective under a willingness-to-pay threshold of $417 per DALY averted, showing that modified RACD strategies can provide value for money in high transmission settings.
Engaging Australian adolescents to prevent non-communicable diseases: participation their way
Authors: Partridge Stephanie R. , Mandoh Mariam , Todd Allyson R. , Wardak Sara , Mautner Dominik , Yan Fulin , Phongsavan Philayrath , Redfern Julie , Cheng Hoi Lun , Lee Annabel , Fang Jie , Bower Marlee , Donohoe-Bales Amarina , Mihrshahi Seema , Raeside Rebecca 
Published: September 2024

Abstract

Background
Non-communicable diseases (NCDs) are a major global health burden, particularly affecting adolescents due to preventable risk factors. However, adolescents are frequently overlooked in NCD prevention efforts that directly impact them. This study aimed to evaluate adolescents' perspectives, experiences, perceptions, and preferences regarding their participation in NCD prevention activities.
Methods
A mixed-methods study design comprising cross-sectional survey and focus groups, underpinned by community-based participatory research approach. Participants were 13–18 years and residing in Australia. Methodological integration through merging quantitative and qualitative data was employed. A weaving approach through narrative was used to report the findings. Adolescent researchers were actively engaged throughout all phases.
Results
501 survey participants (mean 16.0 years, SD 1.2) and 19 focus group participants (mean 17.0 years, SD 0.9) contributed to this study. Mental health disorders were identified as the most significant health concern. Those with prior volunteer experience showed greater engagement in health-promoting activities. Participants recognised their pivotal role in NCD prevention, highlighting ‘influence’ as crucial for health improvements. They emphasised the importance of visibility, flexibility, and authenticity in engagement methods. Despite a strong willingness to participate in future NCD prevention activities, participants cited barriers such as limited opportunities.
Conclusion
This study highlights the importance of adolescent involvement in NCD prevention and suggests strategies to overcome participation barriers. Recommendations include promoting meaningful engagement, improving accessibility, and fostering collaboration with decision makers. These insights are crucial for guiding future efforts to tackle NCD challenges among adolescents.
Factors influencing unplanned readmission within 30 days in patients with heart failure and their predictive value: a prospective study
Authors: Cui Lingling , Wei Xiaolei , Liang Tao , Yan Rui , Du Minyu , Alimire Tusiyiti , Huang Yuyang , Wang Hua 
Published: September 2024

Abstract

Background Heart failure imposes a significant healthcare burden, with early unplanned readmissions post-discharge linked to poor outcomes. Identifying risk factors and their predictive value is crucial for targeted interventions.
Objective To explore factors influencing 30-day unplanned readmission in heart failure and their predictive value.
Methods A prospective study of heart failure patients hospitalized in Beijing Hospital from October 2023 to March 2024. Patients were assessed for nutritional status using Mini-Nutritional Assessment Scale Short Version (MNA-SF), frailty using Groningen Frailty Index (GFI), and Appendicular Skeletal Muscle Mass Index (ASMI) calculation. Multifactorial COX regression analyse was conducted, and ROC curves plotted for predictive modeling.
Results A total of 121 heart failure patients (60.3% males), aged (69.87±11.9) years were included. Within 30 days-median follow-up duration, 25 (20.7%) patients with readmission. COX regression analysis stratified by gender showed that age, regular smoking, nutritional status, left ventricular ejection fraction(LVEF), brain natriuretic peptide(BNP), GFI, and ASMI were independent influences on readmission within 30 days in patients with heart failure (P<0.050). ROC curve analysis showed that age, BNP, ASMI, smoking status, LVEF, nutritional status, and GFI individually as well as in combination predicted readmission within 30 days in patients with heart failure; the joint model performed optimally, with an AUC value reaching 0.877 (95%CI 0.801~0.952, P<0.001), corresponded to a sensitivity of 0.920 and a specificity of 0.729.
Conclusion A multifactorial approach including age, BNP, ASMI, smoking status, LVEF, nutritional status, and GFI predicts 30-day readmission risk, offering a basis for clinical intervention strategies to improve patient outcomes.
Endothelial -targeted CD39 is protective in a mouse model of global forebrain ischaemia
Authors: Lee Natasha Ting , Savvidou Ioanna , Selan Carly , Wright David K , Brkljaca Robert , Chia Joanne SJ , Calvello Ilaria , Robson Simon C. , Nandurkar Harshal H , Sashindranath Maithili 
Published: September 2024

Abstract

Global ischemic brain injury occurs after cardiac arrest or prolonged hypotensive episodes following surgery or trauma. It causes significant neurological deficits even after successful re-establishment of blood flow. It is the primary cause of death in 68% of inpatient and 23% of out-of-hospital cardiac arrest cases, but there are currently no treatments. Endothelial activation and dysfunction impairing small vessel blood flow is the cause of brain damage. Purinergic signaling is an endogenous molecular pathway, where CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia, eATP is released, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Our group developed a bifunctional compound – anti-VCAM-CD39 that targets dysregulated endothelium and promotes adenosine generation at the infarct site, localising antithrombotic and anti-inflammatory effects of CD39. We investigated whether anti-VCAM-CD39 could improve outcome in a murine model of global ischaemia caused by dual carotid artery ligation (DCAL). Test drugs anti-VCAM-CD39 and controls were given 3h after 30min ischaemia. Assessments at 24h included neurological function, infarct volume, perfusion, albumin extravasation to assess blood-brain barrier (BBB) permeability. We showed that there was an overall improvement in neurological deficit in αVCAM-CD39-treated mice after DCAL. MRI revealed that these mice had significantly smaller infarcts and reduced apoptotic activity on the side of permanent occlusion, compared to saline treated mice. There was reduced albumin extravasation in treated mice after DCAL, suggesting anti-VCAM-CD39 conferred neuroprotection in the brain through preservation of blood brain barrier (BBB) permeability. In vitro findings confirmed that αVCAM-CD39-mediated adenosine protected against hypoxia-induced endothelial cell death. anti-VCAM-CD39 is a novel therapeutic that can promote neuroprotection, reduce tissue damage and inflammation in the brain after hypoxic brain injury in mice. These findings suggest that anti-VCAM-CD39 could be a new avenue of cardiac arrest therapy and could potentially be used in other cerebrovascular diseases where endothelial dysfunction is a constant underlying pathology.
Identification of mutation-independent BRCA2 protein deficiency expands diagnostics and selection of pancreatic cancer patients for personalized therapy with PARP1 inhibitors
Authors: Chroscicki Piotr , Samsel Radoslaw , Stepnik Dawid , Roszkowska-Purska Katarzyna , Tybuchowska Anna-Maria , Swatler Julian , Brewinska-Olchowik Marta , Wiech Milena , Jakubowicz Kamil , Franke Jakub , Jazdzewski Krystian , Cichocki Andrzej , Skorski Tomasz , Piwocka Katarzyna 
Published: September 2024

Abstract

Background: Recently, therapies involving poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP1) inhibitors have been approved for metastatic BRCA1/2-mutated pancreatic ductal adenocarcinoma (PDAC). The current scheme of identification of patients with BRCA deficiency relies on genetic screening. Here, we tested the hypothesis that pancreatic tumors have a broader spectrum of BRCAness than can be identified solely by gene mutations. We focused on BRCA2 deficiency, which is predominant in pancreatic ductal adenocarcinoma (PDAC).
Methods: Pancreatic cancer cell lines (wt or BRCA2mutated) were used to set up a protocol to verify antibody specificity and detect BRCA2 protein levels by flow cytometry.Post-surgery pancreatic tumor samples were assessed by spectral cytometry with unsupervised analysis to identify BRCA2-deficient clusters together with the expression of stemness and metastasis markers. Personalized tumor signatures specified BRCAness phenotype and cancer state to increase the accuracy of selection for therapy with PARP1 inhibitors (PARPis). In parallel, BRCA2 mutations were identified by NGS analysis.
Results: We developed a cytometric panel to assess BRCA2 levels associated with sensitivity to PARPis (olaparib and talazoparib). Analysis of BRCA2 protein levels in patients’ samples showed high diversity. Unsupervised cluster analysis identified BRCA2-deficient clusters, together with metastasis and stemness markers, which indicated advanced tumors with dismal prognoses. Cluster composition confirmed the high heterogeneity of pancreatic tumors. In parallel, NGS did not recognize the BRCA2/1 mutations in any of the analyzed tumors. Therefore, based on the current selection, these patients would be excluded from PARPis therapy. Finally, analysis of each tumor personalized signatures of tumor cell subsets potentially sensitive to PARPis were demonstrated.
Conclusions: We found that BRCA2 protein deficiency (BRCAness) is detected with metastasis/stemness markers in pancreatic tumors also in individuals lacking BRCA2 mutations. Our findings show that integrating the flow cytometry-based BRCA2 protein assessment with genetic screening is important to improve the effective selection of PDAC patients for therapy with PARPis. This might also be relevant for other BRCA-deficient tumors.
Mitochondrial viability in neurogenic bladder urothelium after sigmoidocolocystoplasty. Implications for persistent vesicoureteral reflux
Authors: Suda Kazuto , Arii Rumi , Ma Hongzhao , Suzuki Takamasa , Shibuya Soichi , Koga Hiroyuki , Lane Geoffrey J , Yamataka Atsuyuki 
Published: September 2024

Abstract

Purpose We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP).Methods Bladder biopsies obtained 1994–2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson’s trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong = > 50%/weak = < 50%) expression. GDF15+/weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity.Results Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15+ (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + versus GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15+/weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively).Conclusion Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.