bluuebunny/crossref_metadata_2025 huggingface dataset:
Long term exposure to ambient air pollution and hospital admission burden in Scotland: 16 year prospective population cohort study
Authors: Abed Al Ahad Mary , Demšar Urška , Sullivan Frank , Kulu Hill
Published: December 2024

Objectives

Air pollution is considered a major threat for global health and is associated with various health outcomes. Previous research on long term exposure to ambient air pollution and health placed more emphasis on mortality rather than hospital admission outcomes and was characterised by heterogeneities in the size of effect estimates between studies, with less focus on mental/behavioural or infectious diseases outcomes. In this study, we investigated the association between long term exposure to ambient air pollution and all cause and cause specific hospital admissions.

Design

This was a prospective cohort study.

Setting

Individual level data from the Scottish Longitudinal Study (SLS) were linked to yearly concentrations of four pollutants (nitrogen dioxide (NO2), sulphur dioxide (SO2), particulate matter diameter ≤10 µm (PM10) and particulate matter diameter ≤2.5 µm (PM2.5)) at 1 km2spatial resolution using the individual’s residential postcode for each year between 2002 and 2017.

Participants

The study included 202 237 adult individuals aged ≥17 years.

Outcome measures

The associations between air pollution and all cause, cardiovascular, respiratory, infectious, mental/behavioural disorders and other cause hospital admissions were examined using multi-level, mixed effects, negative binomial regression.

Results

Higher exposure to NO2, PM10and PM2.5was associated with a higher incidence of all cause, cardiovascular, respiratory and infectious hospital admissions before adjusting for the area of residence, and in fully adjusted models when considering cumulative exposure across time. In fully adjusted models, the incidence rate for respiratory hospital admissions increased by 4.2% (95% CI 2.1% to 6.3%) and 1.2% (95% CI 0.8% to 1.7%) per 1 µg/m3increase in PM2.5and NO2pollutants, respectively. SO2was mainly associated with respiratory hospital admissions (incidence rate ratio (IRR)=1.016; 95% CI 1.004 to 1.027) and NO2was related to a higher incidence of hospital admissions for mental/behavioural disorders (IRR=1.021; 95% CI 1.011 to 1.031). Average cumulative exposure to air pollution showed stronger positive associations with higher rates of hospital admissions.

Conclusions

The results of this study support an association between long term (16 years) exposure to ambient air pollution and increased all cause and cause specific hospital admissions for both physical and mental/behavioural illnesses. The results suggest that interventions on air pollution through stricter environmental regulations could help ease the hospital care burden in Scotland in the long term.
Pathological findings at invasive assessment in MINOCA: a systematic review and meta-analysis
Authors: Fedele Damiano , Cavallo Daniele , Bodega Francesca , Suma Nicole , Canton Lisa , Ciarlantini Mariachiara , Ryabenko Khrystyna , Amicone Sara , Marinelli Virginia , Asta Claudio , Pastore Giuseppe , Casuso Alvarez Marcello , Belà Rebecca , Sansonetti Angelo , Angeli Francesco , Armillotta Matteo , Foà Alberto , Bergamaschi Luca , Paolisso Pasquale , Belmonte Marta , Rucci Paola , Barbato Emanuele , Pizzi Carmine
Published: December 2024

Background

Pathological mechanisms of myocardial infarction with non-obstructive coronary arteries (MINOCA) are heterogeneous, with an unknown impact on prognosis, and often remain unrecognised in clinical practice. This study aimed to evaluate the prevalence and prognostic impact of pathological findings by invasive coronary angiography (ICA), optical coherence tomography (OCT), and coronary function testing in MINOCA.

Methods

Studies published until August 2023 were searched on PubMed and SCOPUS and included if reporting the prevalence of patients with non-obstructive coronary arteries (NObs-CA; 1–49% coronary stenosis) versus normal coronary arteries (NCA; 0% coronary stenosis) by ICA, pathological findings by OCT, and/or coronary vasomotor tests in MINOCA. Newcastle-Ottawa Scale was used for quality assessment. The pooled prevalence of pathological findings was estimated with random-effects models. Pooled risk ratios (RRs) with 95% CIs of all-cause death, MI and the composite of both in patients with NObs-CA versus NCA were calculated at short-term (<1 month), 1-year and long-term follow-up (> 1 year).

Results

Forty-five studies including 17 539 patients were analysed. The pooled prevalence of NObs-CA at ICA was 53% (95% CI 0.47 to 0.60). OCT showed acute pathological findings in 62% (95% CI 0.44 to 0.78) of patients and coronary vasomotor tests were positive in 49% (95% CI 0.31 to 0.67). NObs-CA compared with NCA was associated with an increased 1-year risk of all-cause death or MI (RR=1.49 (95% CI 1.17 to 1.90)) and MI alone (RR=1.80 (95% CI 1.26 to 2.59)), whereas the risk of all-cause death was comparable. Similar results were seen at long-term, but not at short-term follow-up.

Conclusions

Stratification of MINOCA into NObs-CA versus NCA has prognostic value. OCT and vasospasm testing, often informative about the pathological mechanism of MINOCA, should be part of an invasive diagnostic algorithm.

PROSPERO registration number

CRD42023468183
LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of PD-L1 protein in non-small cell lung cancer
Authors: Lv Liting , Miao Qing , Zhan Sutong , Chen Peilin , Liu Wei , Lv Jiawen , Yan Wenjie , Wang Dong , Liu Hongbing , Yin Jie , Feng Jian , Song Yong , Ye Mingxiang , Lv Tangfeng
Published: December 2024

Background

Loss-of-function mutations ofliver kinase B(LKB1, also termed asSTK11(serine/threonine kinase 11)) are frequently detected in patients with non-small cell lung cancer (NSCLC). TheLKB1mutant NSCLC was refractory to almost all the antitumor treatments, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy. Unfortunately, mechanisms underlying resistance to immunotherapy are not fully understood. In this study, we deciphered how LKB1 regulated sensitivity to anti-PD-1/PD-L1 immunotherapy.

Methods

We investigated the mutational landscape ofLKB1mutant NSCLC in next generation sequencing (NGS) data sets. Expression of LKB1, PD-L1 and S-phase kinase-associated protein 2 (Skp2) in NSCLC samples were assessed by immunohistochemistry (IHC). The tumor microenvironment (TME) profiling ofLKB1wild type (WT) and mutant NSCLC was performed using fluorescent multiplex IHC. Mass spectrometry and enrichment analysis were used to identify LKB1 interacting proteins. Mechanistic pathways were explored by immunoblotting, ubiquitination assay, cycloheximide chase assay and immunoprecipitation assay.

Results

By using NGS data sets and histological approaches, we demonstrated that LKB1 status was positively associated with PD-L1 protein expression and conferred a T cell-enriched “hot” TME in NSCLC. Patients with good responses to anti-PD-1/PD-L1 immunotherapy possessed a high level of LKB1 and PD-L1. Skp2 emerged as the molecular hub connecting LKB1 and PD-L1, by which Skp2 catalyzed K63-linked polyubiquitination on K136 and K280 residues to stabilize PD-L1 protein. Inhibition of Skp2 expression by short hairpin RNA or its E3 ligase activity by compound #25 abrogated intact expression of PD-L1 in vitro and generated a T cell-excluded “cold” TME in vivo. Thus, the LKB1-Skp2-PD-L1 regulatory loop was crucial for retaining PD-L1 protein expression and manipulation of this pathway would be a feasible approach for TME remodeling.

Conclusion

LKB1 and Skp2 are required for intact PD-L1 protein expression and TME remodeling in NSCLC. Inhibition of Skp2 resulted in a conversion from “hot” TME to “cold” TME and abrogated therapeutic outcomes of immunotherapy. Screening LKB1 and Skp2 status would be helpful to select recipients who may benefit from anti-PD-1/PD-L1 immunotherapy.
Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment
Authors: Hansen Nils , Peña-Martínez Pablo , Skoog Petter , Reinbach Katrin , Hansen Finja C , Faria Susanne Larsson , Grönberg Caitríona , Abdilleh Kawther , Magnusson Susanne , von Wachenfeldt Karin , Millrud Camilla Rydberg , Liberg David , Järås Marcus
Published: December 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) represents a major clinical challenge due to its tumor microenvironment, which exhibits immune-suppressive properties that facilitate cancer progression, metastasis, and therapy resistance. Interleukin 1 (IL-1) signaling has been implicated as a driver in this process. Mechanistically, both IL-1α and IL-1β bind to the IL-1 receptor type 1, forming a complex with IL-1-receptor accessory protein (IL1RAP), which triggers downstream signaling pathways. The IL1RAP blocking antibody nadunolimab is currently in clinical development, but the precise consequences of inhibiting IL-1 signaling in PDAC remains elusive.

Methods

To evaluate the biological relevance of blocking IL1RAP using nadunolimab in a PDAC animal model, human PDAC cells and cancer-associated fibroblasts (CAFs) were co-transplanted into mice. To study the underlying mechanisms of IL1RAP blockade ex vivo, co-cultured PDAC cells and CAFs were treated with nadunolimab prior to RNA sequencing. Migration assays were performed to assess how nadunolimab affects interactions between CAFs and myeloid immune cells. Finally, to establish a clinical correlation between IL1RAP expression and nadunolimab treatment effects, we analyzed tumor biopsies from a clinical phase I/II study in which nadunolimab was administered to patients.

Results

In the xenograft mouse model, nadunolimab exhibited antitumor effects only when human CAFs were co-transplanted with PDAC cells. IL-1 stimulation induced CAFs to secrete chemokines that recruited neutrophils and monocytes. The secretion of this chemokine and the migration of myeloid cells were inhibited by nadunolimab. Media conditioned by IL-1-stimulated CAFs sustained a neutrophil population with a tissue invasion phenotype, an effect that was reversed by nadunolimab. In a cohort of metastatic late-stage PDAC patients receiving nadunolimab as monotherapy, high IL1RAP expression in tumors was associated with extended progression-free survival.

Conclusions

Our study demonstrates that targeting IL1RAP on CAFs inhibits IL-1-induced chemokine secretion and recruitment of neutrophils and monocytes, thereby counteracting the immunosuppressive microenvironment in PDAC. These findings highlight the therapeutic potential of targeting IL1RAP in PDAC.
Personalized neoantigen hydrogel vaccine combined with PD-1 and CTLA-4 double blockade elicits antitumor response in liver metastases by activating intratumoral CD8+CD69+T cells
Authors: Tang Shichuan , Tang Ruijing , Chen Geng , Zhang Da , Lin Kongying , Yang Huan , Fu Jun , Guo Yutong , Lin Fangzhou , Dong Xiuqing , Huang Tingfeng , Kong Jie , Yin Xiaowei , Ge Aimin , Lin Qizhu , Wu Ming , Liu Xiaolong , Zeng Yongyi , Cai Zhixiong
Published: December 2024

Background

Liver metastasis is highly aggressive and immune tolerant, and lacks effective treatment strategies. This study aimed to develop a neoantigen hydrogel vaccine (NPT-gels) with high clinical feasibility and further investigate its efficacy and antitumor molecular mechanisms in combination with immune checkpoint inhibitors (ICIs) for the treatment of liver metastases.

Methods

The effects of liver metastasis on survival and intratumor T-cell subpopulation infiltration in patients with advanced tumors were investigated using the Surveillance, Epidemiology, and End Results Program (SEER) database and immunofluorescence staining, respectively. NPT-gels were prepared using hyaluronic acid, screened neoantigen peptides, and dual clinical adjuvants [Poly(I:C) and thymosin α-1]. Then, the efficacy and corresponding antitumor molecular mechanisms of NPT-gels combined with programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 double blockade (PCDB) for the treatment of liver metastases were investigated using various preclinical liver metastasis models.

Results

Liver metastases are associated with poorer 5-year overall survival, characterized by low infiltration of cytotoxic CD8+T cells and high infiltration of regulatory T cells (Tregs). NPT-gels overcame the challenges faced by conventional neoantigen peptide vaccines by sustaining a durable, high-intensity immune response with a single injection and significantly improving the infiltration of neoantigen-specific T-cell subpopulations in different mice subcutaneous tumor models. Importantly, NPT-gels further combined with PCDB could enhance neoantigen-specific T-cell infiltration and effectively unlock the immunosuppressive microenvironment of liver metastases, showing superior antitumor efficacy and inducing long-term immune memory in various preclinical liver metastasis models without obvious toxicity. Mechanistically, the combined strategy can inhibit Tregs, induce the production and infiltration of neoantigen-specific CD8+CD69+T cells to enhance the immune response, and potentially elicit antigen-presenting effects in Naïve B_Ighd+cells and M1-type macrophages.

Conclusions

This study demonstrated that NPT-gels combined with PCDB could exert a durable and powerful antitumor immunity by enhancing the recruitment and activation of CD8+CD69+T cells, which supports the rationale and clinical translation of this combination strategy and provides important evidence for further improving the immunotherapy efficacy of liver metastases in the future.
Adenoviral-vectored neoantigen vaccine augments hyperexpanded CD8+T cell control of tumor challenge in mice
Authors: Dagotto Gabriel , Colarusso Alessandro , Patio Robert C , Li David , Anioke Tochi , Giffin Victoria , Guan Ruoran , Anand Trisha , Mbiwan Esther , Aid Malika , Barouch Dan
Published: December 2024

Background

Neoantigens are promising immunogens for cancer vaccines and are often delivered as adjuvanted peptide vaccines. Adenoviral (Ad) vectors have been shown to induce strong CD8+T cell responses as vaccines against SARS-CoV-2, Ebola, and Zika, but their utility as neoantigen delivery vectors remains largely unexplored. In this study, we examine how an Ad-vectored neoantigen vaccine would impact tumor immunity compared with a peptide neoantigen vaccine.

Methods

We generated Ad serotype 26 (Ad26) vaccine candidates encoding B16-F10-ovalbumin (OVA) and MC38-specific neoantigens. Ad26 vaccines were compared with adjuvanted peptide delivery as prophylactic vaccines in B16-F10-OVA and MC38 challenge models. Immune responses induced by the best Ad26 vaccine (Ad26.VP22.7Epi) were compared with peptide vaccination systemically and within the tumor. Following vaccination with Ad26.VP22.7Epi, peptide, or sham, tumor-infiltrating CD45+cells were analyzed using single-cell RNA sequencing (scRNA-seq) and T cell receptor sequencing (TCR-seq) to identify vaccine-induced differences in the tumor microenvironment.

Results

Single-shot Ad26 vaccines induced greater neoantigen-specific interferon-γ CD8+T cell immune responses than two-shot adjuvanted peptide vaccines in mice, and Ad26.VP22.7Epi also provided superior protective efficacy compared with the peptide vaccine following tumor challenge. Ad26.VP22.7Epi induced a robust immunodominant CD8+T cell response against the Adpgk neoantigen, while the peptide vaccine-induced lower responses against both Adpgk and Reps1 neoantigens. scRNA-seq analysis of CD45+tumor-infiltrating cells demonstrated that both Ad26.VP22.7Epi and peptide vaccine-induced similar numbers of infiltrating CD8+T cells. However, Ad26.VP22.7Epi induced CD8+T cells showed more upregulation of T cell maturation, activation, and Th1 pathways compared with peptide vaccine induced CD8+T cells, suggesting improved functional T cell quality. TCR-seq of these tumor-infiltrating lymphocytes also demonstrated that Ad26.VP22.7Epi generated larger T cell hyperexpanded clones compared with the peptide vaccine.

Conclusions

These results suggest that the Ad26.VP22.7Epi vaccine led to improved tumor control compared with the peptide vaccine due to increased T cell hyperexpansion and functional activation. Our data suggest that future cancer vaccine development strategies should focus on inducing functional hyperexpanded CD8+T cell responses and not only maximizing tumor infiltrating CD8+T cell numbers.
What can we learn from machine learning studies on flow diverter aneurysm embolization? A systematic review
Authors: Bayraktar Esref Alperen , Cortese Jonathan , Jabal Mohamed Sobhi , Ghozy Sherief , Orscelik Atakan , Bilgin Cem , Kadirvel Ramanathan , Brinjikji Waleed , Kallmes David F
Published: December 2024

Background

As the use of flow diverters has expanded in recent years, predicting successful outcomes has become more challenging for certain aneurysms.

Objective

To provide neurointerventionalists with an understanding of the available machine learning algorithms for predicting the success of flow diverters in occluding aneurysms.

Methods

This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the four major medical databases (PubMed, Embase, Scopus, Web of Science) were screened. The study included original research articles that evaluated the predictive abilities of various machine learning algorithms for determining the success of flow diverters in achieving aneurysm occlusion.

Results

Five studies out of 217 were included based on our criteria. The included studies used various variables (patient demographics, aneurysm and parent artery characteristics, flow diverter and hemodynamic-related features, and angiographic parametric imaging) to predict flow diverter treatment outcomes. The machine learning algorithms used, along with their respective accuracy rates, were as follows: logistic regression (61% and 85%), support vector machine (88%), Gaussian support vector machine (90%), linear support vector machine (85%), decision tree (80%), random forest (87%), k-nearest neighbors (83% and 85%), XGBoost (87%), CatBoost (86%), deep neural networks (77.9%), and recurrent neural networks (74%).Two studies trained the machine learning models with both all features and the most significant features. Both studies observed that the accuracy of machine learning models decreased by removing the insignificant features.

Conclusion

The current literature indicates that machine learning algorithms can be trained to predict the success of flow diverters with an accuracy of up to 90%.
Vessel wall MRI evaluation for the safety of endovascular recanalization of non-acute intracranial anterior circulation artery occlusions
Authors: Meng Yao , Yang Yun , Magigi Miyengi Cosmas , Li Weili , Song Yun , Zhao Wei , Zheng Meimei , Sun Lili , Yin Hao , Wang Wei , He Xiao , Zhang Jun , Han Ju
Published: December 2024

Background

Vessel wall MRI (VWMRI) can reveal the morphological features of intracranial artery occlusion (ICAO). This study aimed to investigate the imaging features of ICAO on VWMRI and explore their correlation with perioperative complications of endovascular recanalization for non-acute ICAO.

Methods

The study retrospectively included consecutive patients with recurrent ischemic stroke due to non-acute ICAO in the anterior circulation who underwent preoperative VWMRI evaluation and endovascular recanalization. Perioperative complications included ischemic and hemorrhagic strokes within 30 days after operation. Imaging features of the occluded segments were evaluated on precontrast and post-contrast VWMRI, including occlusion length and site, vessel wall area, signal intensity, angle, and shape of the occluded segment. The associations between the clinical and imaging features and perioperative complications were examined.

Results

One hundred and four patients were included in the analysis, of whom 22.1% (23/104) had perioperative complications. After adjusting for multiple confounding variables, four imaging risk factors were identified that were independently associated with perioperative complications, that is, the angle between the occluded and pre-occluded artery segments (OR 11.60, 95% CI 2.73 to 49.29), occluded artery segment shape (OR 13.07, 95% CI 2.82 to 60.67), vessel wall collapse before occlusion (OR 2.91, 95% CI 0.96 to 8.77), and post-contrast mean signal intensity ratio at the ¼ point of the occluded artery segment <1.24 (OR 6.14, 95% CI 1.67 to 22.51). From no risk factors to four risk factors, the incidence of perioperative complications gradually increased (0, 6.2%, 23.5%, 52.9%, and 100% respectively; p<0.001).

Conclusions

VWMRI may be helpful to select patients with non-acute ICAO who are suitable for endovascular recanalization.
CT perfusion for lesion-symptom mapping in large vessel occlusion ischemic stroke
Authors: Garrard James William , Neuhaus Ain , Carone Davide , Joly Olivier , Zarrintan Armin , Rabinstein Alejandro A , Huynh Thien , Harston George , Brinjikji Waleed , Kallmes David F
Published: December 2024

Background

Identifying eloquent regions associated with poor outcomes based on CT perfusion (CTP) may help inform personalized decisions on selection for endovascular therapy (EVT) in patients with large vessel occlusion (LVO) ischemic stroke. This study aimed to characterize the relationship between CTP-defined hypoperfusion and National Institutes of Health Stroke Scale (NIHSS) subitem deficits.

Methods

Patients with anterior circulation LVO, baseline CTP, itemized NIHSS at presentation and 24 hours were included. CTP was analyzed using e-CTP (Brainomix, UK). Time to maximal contrast (Tmax) prolongation was defined as >6 s, and penumbra as the difference between Tmax and ischemic core (relative cerebral blood flow<30%). Voxel-lesion-symptom mapping was performed using sparse canonical correlation analysis. For each NIHSS subitem, and total NIHSS, the associations were plotted between Tmax voxels with baseline NIHSS, and penumbra voxels with delta NIHSS (24 hours minus baseline).

Results

This study included 171 patients. Total NIHSS was predicted by hypoperfusion in left frontal cortex and subcortical white matter tracts. Voxels associated with neurological recovery were symmetrical and subcortical.

Limb deficits were associated with respective motor cortex regions and descending motor tracts, with negative correlation within the contralateral hemispheres. A similar but smaller cluster of voxels within the penumbra was associated with NIHSS improvement. Language impairment correlated with left frontal cortex and superior temporal gyrus voxels. With the exception of dysarthria, significant associations were observed and more diffusely distributed in all other NIHSS subitems.

Conclusions

These results demonstrate the feasibility of hypoperfusion-to-symptom mapping in LVO. Symptom-based mapping from presenting imaging could refine treatment decisions targeting specific neurological deficits.
Elective outpatient middle meningeal artery embolization for chronic subdural hematoma is safe
Authors: McGrath Margaret , Gallagher Aaron , Raub Spencer , Carroll Kate T , Abecassis Zachary A , Ruiz Rodriguez Juan Francisco , Philbrick Brandon D , Kellner Christopher P , Sioutas Georgios S , Scott Kyle , Srinivasan Visish M , Burkhardt Jan-Karl , Shaikh Hamza A , Khalife Jane , Tonetti Daniel A , Lam Nicholas , Ares William J , Gomez-Paz Santiago , Budohoski Karol , Grandhi Ramesh , Levitt Michael R
Published: December 2024

Background

Middle meningeal artery embolization (MMAE) is a safe and effective treatment for chronic subdural hematoma (cSDH); however, the appropriate level of postoperative care is unknown.

Objective

To evaluate whether elective MMAE for cSDH could be safely performed in an outpatient setting.

Methods

This was a multicenter, retrospective study of patients with cSDH who underwent elective MMAE. Patients were categorized as either inpatient (admitted for ≥1 night of hospitalization after MMAE) or outpatient (discharged on the same day of MMAE). Patient demographics, radiological data, procedural details, and follow-up data were collected. The primary endpoint was periprocedural complications, and secondary outcomes included emergency department (ED) visits or unplanned readmission within 24 hours, 1–7 days, and 8–30 days after MMAE.

Results

Elective MMAE procedures were carried out in 190 patients, of which 45.3% (n=86) were outpatient procedures and 54.7% (n=104) inpatient. There were 7 (3.7%) periprocedural complications (one outpatient, six inpatient; P=0.12). Five patients presented to the ED and were readmitted within 24 hours of MMAE (three outpatient, two inpatient). Six patients presented to the ED 1–7 days after MMAE (three outpatient, three inpatient); three were subsequently admitted (one outpatient and two inpatient). Nine patients presented to the ED 8–30 days after MMAE (two outpatient and seven inpatient); three were subsequently readmitted (all inpatient). No elective outpatient MMAE resulted in a readmission attributable to the procedure within the examined time frame.

Conclusion

Elective MMAE can be safely performed as an outpatient procedure without increased risk of postprocedural adverse events in most eligible patients with cSDH.
Enhancing thrombectomy outcomes with Adaptive Pulsatile Aspiration (APA): the role of complete clot ingestion in reducing thrombectomy time and distal embolization
Authors: Lu Victor M , Thompson John , Elarjani Turki , Jaman Emade , Sherman Josiah , Hanser Manning , Abuawad Mazen , Limaye Kaustubh , Guerrero Waldo R , Vakharia Kunal , Walzman Daniel , Abecassis Isaac Josh , De Leacy Reade Andrew , Crowley R Webster , Starke Robert M
Published: December 2024

Background

Complete clot ingestion (CCI) is defined as full ingestion of the clot into the catheter or pump canister without any external clot remnants at the catheter tip. The aim of this study was to demonstrate that using the CCI metric in vitro, partially ingested (‘corked’) clots pose a higher risk of distal emboli given distal emboli may exist in the setting of Thrombolysis In Cerebral Infarction 3 (TICI 3) revascularization.

Methods

Thrombectomies using an in vitro synthetic clot analog were conducted across six catheters using the novel ALGO Smart Pump with Adaptive Pulsatile Aspiration (APA) (Von Vascular Inc, Sunrise, FL) and compared against the Penumbra static Engine Pump (Alameda, CA).

Results

A total of 360 aspiration thrombectomies were completed with an overall CCI rate of 56.9%. Cases achieving CCI were significantly faster (P<0.001) and those with successful CCI had no instances of distal embolization, whereas cases with incomplete clot ingestion (‘corking’) showed a 5.2% rate of distal embolization (P<0.001). The overall rate of first pass effect was comparable between two systems. ALGO’s APA mode achieved a significantly higher rate of CCI compared with the Penumbra Engine Pump’s continuous aspiration (77.2% vs 36.7%, P<0.001), as well as shorter mean aspiration (43.7 s vs 73.2 s, P<0.001). Additionally, these trends were also reflected across all individually tested catheter types between the pump systems.

Conclusions

Our findings demonstrate that CCI is a feasible and valuable metric for assessing thrombectomy efficacy in vitro, resulting in more favorable CCI outcomes with the ALGO system compared with the Penumbra system.
How well do plasma Alzheimer’s disease biomarkers reflect the CSF amyloid status?
Authors: Hazan Jemma , Abel Emily , Rosa Grilo Miguel , Alawode Deborah , Laranjinha Ines , Heslegrave Amanda J , Liu Kathy Y , Schott Jonathan M , Howard Robert , Zetterberg Henrik , Fox Nick C
Published: December 2024

Background

Can plasma biomarkers as well as cerebrospinal fluid (CSF) perform in the separation of amyloid-beta-positive (Aβ+) vs amyloid-beta-negative (Aβ−) groups across an age range seen in an NHS cognitive disorder clinic?

Methods

As part of the routine diagnostic investigation of 111 clinic patients who had contemporaneous blood and CSF samples taken, patients were categorised into Aβ+ and Aβ− groups based on their CSF in an Aβ42/40 ratio. We then evaluated four single molecule array (Simoa) Quanterix assays, quantifying single plasma analytes and ratios (p-tau217, p-tau217/Aβ42 ratio, p-tau181, p-tau181/Aβ42 ratio and Aβ42/40 ratio) in their ability to distinguish between these groups and the effect of age.

Results

The median (range) age of participants was 66 (55–79) years with 48 females (43.2%). The areas under the curve (AUC), not accounting for age, for the ability to discriminate Aβ+ from Aβ− groups were plasma p-tau217 AUC=0.94, Aβ42/40 AUC=0.78 and p-tau181 AUC=0.77. Combining p-tau217/Aβ42 increased the AUC to 0.97. The difference between the groups was influenced by age with less separation in older individuals: a significant negative interaction term between age and group for plasma p-tau217 concentrations (−0.037, p=0.013) and p-tau217/Aβ42 ratio (−0.007, p=0.008).

Conclusions

There was variable performance of plasma biomarkers to recapitulate the CSF assay. Both p-tau217 and p-tau217/Aβ42 showed excellent promise as surrogates of CSF amyloid status, although with slightly reduced performance in older individuals. There was poorer discriminatory ability for p-tau181 and Aβ42/40. Further research is needed to address potential age-related confounds.
Left atrial appendage occlusion in patients with atrial fibrillation and intracerebral haemorrhage associated with cerebral amyloid angiopathy: a multicentre observational study and pooled analysis of published studies
Authors: Thiankhaw Kitti , Best Jonathan , Srivastava Sonal , Prachee Ishika , Agarwal Smriti , Tan Serena , Calvert Patrick A , Chughtai Asim , Ang Richard , Segal Oliver R , Werring David J
Published: December 2024

Background

Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral haemorrhage (ICH) with a high recurrence risk. Left atrial appendage occlusion (LAAO) is a method for ischaemic stroke prevention in patients with atrial fibrillation (AF), potentially reducing the risk of intracranial bleeding in CAA-associated ICH. We aimed to determine the outcomes of patients with AF with CAA-associated ICH undergoing LAAO.

Methods

We conducted a multicentre study of patients with CAA-associated ICH who underwent LAAO for stroke prevention. We pooled our findings with data from a systematic review of relevant published studies of LAAO for AF in ICH survivors reporting CAA diagnosis.

Results

We included data from two published studies (n=65) with CAA-specific data and our cohort study (n=37), providing a total of 102 participants (mean age 76.2±8.0 years, 74.6% male) with CAA-related symptomatic ICH and AF treated with LAAO. The median follow-up period was 9.4 months (IQR 4.2–20.6). Postprocedural antithrombotic regimens varied between single (73.0%) or dual antiplatelet therapy (16.2%), or direct oral anticoagulant (DOAC) (10.8%), with a median duration of 42 days (IQR 35–74). Postprocedural complications were uncommon, but included transient arrhythmias (2.1%) and non-life-threatening tamponade (2.1%). Pooled incidence rates of ischaemic stroke and ICH during follow-up were 5.16 (95% CI 1.36 to 17.48) and 2.73 (95% CI 0.41 to 13.94) per 100 patient years, respectively.

Conclusions

LAAO followed by short-term antithrombotic therapy might be a safe and effective ischaemic stroke preventive strategy in people with CAA-associated ICH and AF. However, randomised controlled trials are needed to determine how LAAO compares with long-term DOAC in this population.

PROSPERO registration number

CRD42023415354.
Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial
Authors: De Angelis Floriana , Cameron James R , Eshaghi Arman , Parker Richard , Connick Peter , Stutters Jonathan , Plantone Domenico , Doshi Anisha , John Nevin , Williams Thomas , Calvi Alberto , MacManus David , Barkhof Frederik , Chandran Siddharthan , Weir Christopher J , Toosy Ahmed , Chataway Jeremy
Published: December 2024

Background

Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS).

Methods

We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks. We measured peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses. Statistical analysis included correlations, multivariable linear regressions and mixed-effects models.

Results

Of the 212 participants recruited at baseline, 192 attended at 96 weeks follow-up. Baseline pRNFL and GCIPL thickness correlated with Symbol Digit Modalities Test (SDMT) (respectively, r=0.33 (95% CI 0.20 to 0.47); r=0.39 (0.26 to 0.51)) and deep grey matter volume (respectively, r=0.21 (0.07 to 0.35); r=0.28 (0.14 to 0.41)).

pRNFL was associated with Expanded Disability Status Scale (EDSS) score change (normalised beta (B)=−0.12 (−0.23 to −0.01)). Baseline pRNFL and GCIPL were associated with Timed 25-Foot Walk change (T25FW) (respectively, B=−0.14 (−0.25 to −0.03); B=−0.20 (−0.31 to −0.10)) and 96-week percentage brain volume change (respectively, B=0.14 (0.03 to 0.25); B=0.23 (0.12 to 0.34)). There were significant annualised thinning rates: pRNFL (−0.83 µm/year) and GCIPL (−0.37 µm/year).

Conclusions

In our cohort of people with SPMS and long disease duration, OCT measures correlated with SDMT and deep grey matter volume at baseline; EDSS, T25FW and whole brain volume change at follow-up.
Implementing a new model of residential rehabilitation: findings and future recommendations
Authors: Vickerstaff Anne , Hayhurst D , Morrison P , McHugh R
Published: December 2024

Introduction

Musculoskeletal injury is one of the leading causes of medical discharge in the UK Armed Forces. Residential rehabilitation (RR) courses are part of Defence rehabilitation, for service personnel (SP) who do not respond to treatment at primary care. Historically, it was delivered as a 3-week block model. As a quality improvement project, rolling admissions were introduced aiming to improve access to RR and deliver outcomes that met the requirements of primary care referrers.

Method

Clinical outcomes were assessed for SP with either spinal or lower limb pathology using the Musculoskeletal Health Questionnaire (MSK-HQ) on course admission and discharge and the Medical Deployment Standard (MDS) on admission and 6 months post course. Wait times were also recorded. Outcomes were compared with the block admission using retrospective audit data. Referrer feedback was gathered using a questionnaire pre introduction and post introduction of rolling admissions.

Results

Rolling admissions reduced course wait times from an average of 55 days to 19 days. Of SP who attended a rolling admission course with spinal pathology (n=23), 58% showed an increase in MDS, 65% showed an increase of the minimally important change in MSK-HQ. With lower limb pathology (n=35) 57% increased MDS, 49% increased MSK-HQ. For the block model, of those with spinal pathology (n=30) 43% increased MDS, 67% increased MSK-HQ, with lower limb pathology (n=30) 60% increased MDS, 33% increased MSK-HQ. Referrer feedback improved with rolling admissions with feedback most positive in relation to the model’s responsiveness for admitting SP onto the course.

Conclusion

Rolling admission provided similar clinical outcomes as the previous block model in a shorter time frame with lower wait times and better met the needs of referrers. Future study recommendations include longer term follow-up and looking at alternative ways to measure the success of RR within the care pathway.
Variation in plasmid conjugation among nontyphoidal Salmonella enterica serovars
Authors: Laidlaw Anna , Blondin-Brosseau Madeleine , Shay Julie A. , Dussault Forest , Rao Mary , Petronella Nicholas , Tamber Sandeep
Published: December 2024

Conjugation is a complex phenomenon involving multiple plasmid, bacterial, and environmental factors. Here we describe an IncI1 plasmid encoding multidrug antibiotic resistance to aminoglycosides, sulfonamides, and third-generation cephalosporins. This plasmid is widespread geographically among animal, human, and environmental sectors. We present data on the transmissibility of this plasmid from Salmonella enterica ser. Kentucky into 40 strains of S. enterica (10 strains each from serovars Enteritidis, Heidelberg, Infantis, and Typhimurium). Thirty seven out of 40 strains were able to take up the plasmid. Rates of conjugation were variable between strains ranging from 10−8 to 10−4. Overall, serovars Enteritidis and Typhimurium demonstrated the highest rates of conjugation, followed by Heidelberg, and then Infantis. No relationships were observed between the recipient cell surface and rate of conjugation. Recipient cell numbers correlated positively with conjugation rate and strains with high conjugation rates had marginally but significantly higher growth parameters compared to strains that took up the plasmid at lower frequencies. Environmental conditions known to impact cell growth, such as temperature, nutrient availability, and the presence of antibiotics, had a modulating effect on conjugation. Collectively, these results will further understanding of plasmid transmission dynamics in Salmonella, which is a critical first step towards the development of mitigation strategies.
Quantum differential cryptanalysis based on Bernstein-Vazirani algorithm
Authors: Xu Rong-Xue , Sun Hong-Wei , Zhang Ke-Jia , Du Gang , Li Dan-Dan
Published: December 2024

Recent research has demonstrated the potential of quantum algorithms to exploit vulnerabilities in various popular constructions, such as certain block ciphers like Feistel, Even-Mansour, and multiple MACs, within the superposition query model. In this study, we delve into the security of block ciphers against quantum threats, particularly investigating their susceptibility to cryptanalysis techniques, notably exploring quantum adaptations of differential cryptanalysis. Initially, we introduce a BV-based quantum algorithm for identifying linear structures with a complexity of $O(n)$
O
(
n
)
, where n denotes the number of bits in the function. Subsequently, we illustrate the application of this algorithm in devising quantum differential cryptanalysis techniques, including quantum differential cryptanalysis, quantum small probability differential cryptanalysis, and quantum impossible differential cryptanalysis, demonstrating polynomial acceleration compared to prior approaches. By treating the encryption function as a unified entity, our algorithm circumvents the traditional challenge of extending differential paths in differential cryptanalysis.
Targeting Autophagy with Geniposide Ameliorates Atherosclerosis in ApoE−∕− Mice
Authors: Yang Xiaodan , Shi Jiaxi , He Weifeng , Li Junlong , Li Rui , Pi Jianbin , Luo Yuan , Gu Mingyang , Wang Xiaolong , Wu Wei , Qing Lijin
Published: December 2024

Atherosclerosis (AS) is a major cause of mortality worldwide. Geniposide (GP) has lipolytic and anti-inflammatory effects and is widely administered for the treatment of cardiovascular disease. There is considerable evidence for the importance of autophagy in the cardiovascular system, and GP can promote autophagy and improve AS. However, the underlying mechanism is still unclear; network pharmacology and molecular docking suggest that GP may play anti-atherosclerotic roles by regulating the PI3K/Akt/mTOR pathway, which is a typical autophagy signal transduction approach. We further hypothesized that GP ameliorates AS by regulating autophagy through the PI3K/Akt/mTOR pathway. Oil Red O, Sirius Red, and Masson’s trichrome staining revealed that GP can inhibit atherosclerotic lipid accumulation and stabilize plaques. Macrophages absorb lipids, form foam cells, and destabilize plaques. Immunohistochemical staining revealed that GP reduces the expression of F4/80, a major macrophage marker. We used western blotting (WB) and immunofluorescence (IF) to measure the protein levels of PI3K/Akt/mTOR, sequestosome-1, Beclin1, and long-chain base 3 (LC3). The experimental results revealed that GP can increase the expression of LC3, increase the expression of Beclin1, and decrease P62. Additionally, it inhibits the phosphorylation of PI3K/Akt/mTOR. In conclusion, GP can effectively treat AS by enhancing autophagy through the PI3K/Akt/mTOR pathway.
SQTRNG: Spintronic Quaternary True Random Number Generator
Authors: Amirany Abdolah , Mohebbi Ladan
Published: December 2024

In this paper, a quaternary true random number generator (QTRNG) is designed and simulated. The proposed QTRNG capitalizes on the stochastic behavior of the magnetic tunnel junction (MTJ) device at currents below the critical current, alongside the adjustable threshold voltage of the carbon nanotube field-effect transistor (CNTFET). To maintain uniformity in the ratio of numbers generated by the QTRNG and mitigate the impact of fabrication process variations, a mid-level processing block has been incorporated. Simulation results show that the proposed QTRNG occupies at least 7% less area and can produce 36% more digits per second compared to existing binary and ternary true random number generators.
Scene Adaptive Context Modeling and Balanced Relation Prediction for Scene Graph Generation
Authors: Xu Kai , Wang Lichun , Li Shuang , Gao Tong , Yin Baocai
Published: December 2024

Scene graph generation (SGG) aims to perceive objects and their relations in images, which can bridge the gap between upstream detection tasks and downstream high-level visual understanding tasks. For SGG models, over-fitting head predicates can lead to bias in the generated scene graph, which has become a consensus. A series of debiasing methods have been proposed to solve the problem. However, some existing debiasing SGG methods have a tendency to over-fit tail predicates, which is another type of bias. In order to eliminate the one-way over-fitting of head or tail predicates, this article proposes a balanced relation prediction (BRP) module which is model-agnostic and compatible with existing re-balancing methods. Moreover, because the relation prediction is based on object feature representation, this article proposes a scene adaptive context fusion (SACF) module to refine the object feature representation. Specifically, SACF models the context based on a chain structure, where the order of objects in the chain structure is adaptively arranged according to the scene content, achieving visual information fusion that adapts to the scene where the objects are located. Experiments on VG and GQA datasets show that the proposed method achieves competitive results on the comprehensive metric of R@K and mR@K.
A Highly Hardware Efficient ML-KEM Accelerator with Optimised Architectural Layers
Authors: Ni Ziying , Khalid Ayesha , Liu Weiqiang , O'Neill Máire
Published: December 2024

The Module-Lattice-Based Key encapsulation Mechanism (ML-KEM) scheme, which is currently being standardised, is a quantum attack resistant KEM that is based on CRYSTALS-Kyber. CRYSTALS-Kyber is the only Public-key Encryption (PKE)/ KEM scheme selected in the first set of successful candidates as part of the NIST initiated Post-Quantum Cryptography (PQC) process. ML-KEM scheme includes three different security levels, namely security level 1, 3, and 5. In this research, we propose a highly area-time efficient hardware ML-KEM architecture. The architecture comprises three computational layers. The first layer comprises a hash and sampling module; the second layer includes a number theoretic transform (NTT), its inverse (INTT) and a point-wise multiplication (PWM) module; and the third layer comprises addition, compressing and encoding. Intra-layer pipelining and out-of-layer scheduling ensures that either layer 1 or layer 2 operate in the shortest time. In the reduction module, we propose a novel hybrid architecture to obtain the final result within 2 cycles with low area consumption. In the NTT module, the PWM pipelining method is modified and an optimised iterative FIFO access method is adopted to reduce the size of FIFO units by 55% over previous research. Look-up tables are also used to replace the first-stage of the NTT to reduce 8 cycles. Furthermore, the memory unit uses only FIFOs, the size are optimised based on the requirements of the most resource-intensive function in ML-KEM (ML-KEM.CPA.Dec). The results show that the proposed architecture has a 48.2%, 41.2%, and 78.1% reduction in computational time in comparison to previous work for security levels 1, 3, and 5, respectively. In addition, the area of proposed optimised ML-KEM designs is reduced by 73%, 70%, 76% and resulting in an improved area-time (AT) product of 15.8%, 10.7%, and 11.3%, for the Level 1, 3, and 5 security levels respectively, compared with state-of-the-art designs.
Bayesian Machine Learning Meets Formal Methods: An Application to Spatio-Temporal Data
Authors: Vana-Gür Laura , Visconti Ennio , Nenzi Laura , Cadonna Annalisa , Kastner Gregor
Published: December 2024

We propose an interdisciplinary framework that combines Bayesian predictive inference, a well-established tool in machine learning, with formal methods, rooted in the computer science community. Bayesian predictive inference allows for coherently incorporating uncertainty about unknown quantities by making use of methods or models that produce predictive distributions, which in turn inform decision problems. By formalizing these decision problems into properties with the help of spatio-temporal logic, we can formulate and predict how likely such properties are to be satisfied in the future at a certain location. Moreover, we can leverage our methodology to evaluate and compare models directly on their ability to predict the satisfaction of application-driven properties. The approach is illustrated in an urban mobility application, where the crowdedness in the center of Milan is proxied by aggregated mobile phone traffic data. We specify several desirable spatio-temporal properties related to city crowdedness such as a fault-tolerant network or the reachability of hospitals. After verifying these properties on draws from the posterior predictive distributions, we compare several spatio-temporal Bayesian models based on their overall and property-based predictive performance.
Intelligent Generation of Graphical Game Assets: A Conceptual Framework and Systematic Review of the State of the Art
Authors: Fukaya Kaisei , Daylamani-Zad Damon , Agius Harry
Published: December 2024

Procedural content generation (PCG) can be applied to a wide variety of tasks in games, from narratives, levels, and sounds to trees and weapons. A large amount of game content is composed of
graphical assets
, such as clouds, buildings, or vegetation, that do not require gameplay function considerations. There is also a breadth of literature examining the procedural generation of such elements for purposes outside of games. The body of research, focused on specific methods for generating specific assets, provides a narrow view of the available possibilities. Hence, it is difficult to have a clear picture of all approaches and possibilities, with no guide for interested parties to discover possible methods and approaches for their needs and no facility to guide them through each technique or approach to map out the process of using them. Therefore, a systematic literature review has been conducted, yielding 239 accepted papers. This article explores state-of-the-art approaches to
graphical asset
generation, examining research from a wide range of applications, inside and outside of games. Informed by the literature, a conceptual framework has been derived to address the aforementioned gaps.