bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient tumor synergistic chemoimmunotherapy by self-augmented ROS-responsive immunomodulatory polymeric nanodrug
Authors: Song Jinxiao , Cheng Mingyang , Xie Yi , Li Kangkang , Zang Xinlong 
Published: March 2023

AbstractImmunotherapy has emerged as a promising therapeutic strategy for cancer therapy. However, the therapeutic efficacy has been distracted due to poor immunogenicity and immunosuppressive tumor microenvironment. In this study, a self-augmented reactive oxygen species (ROS) responsive nanocarrier with immunogenic inducer paclitaxel (PTX) and indoleamine 2,3-dixoygenase 1 (IDO1) blocker 1-methyl-d, L-tryptophan (1-MT) co-entrapment was developed for tumor rejection. The carrier was composed of poly (ethylene glycol) (PEG) as hydrophilic segments, enzyme cleavable 1-MT ester and ROS-sensitive peroxalate conjugation as hydrophobic blocks. The copolymer could self-assemble into prodrug-based nanoparticles with PTX, realizing a positive feedback loop of ROS-accelerated PTX release and PTX induced ROS generation. Our nanoparticles presented efficient immunogenic cell death (ICD) which provoked antitumor immune responses with high effector T cells infiltration. Meanwhile immunosuppressive tumor microenvironment was simultaneously modulated with reduced regulatory T cells (Tregs) and M2-tumor associated macrophages (M2-TAMs) infiltration mediated by IDO inhibition. The combination of PTX and 1-MT achieved significant primary tumor regression and reduction of lung metastasis in 4T1 tumor bearing mice. Therefore, the above results demonstrated co-delivery of immunogenic inducer and IDO inhibitor using the ROS amplifying nanoplatform with potent potential for tumor chemoimmunotherapy.
Colorectal liver metastases patients prognostic assessment: prospects and limits of radiomics and radiogenomics
Authors: Granata Vincenza , Fusco Roberta , Setola Sergio Venanzio , Galdiero Roberta , Maggialetti Nicola , Patrone Renato , Ottaiano Alessandro , Nasti Guglielmo , Silvestro Lucrezia , Cassata Antonio , Grassi Francesca , Avallone Antonio , Izzo Francesco , Petrillo Antonella 
Published: March 2023

AbstractIn this narrative review, we reported un up-to-date on the role of radiomics to assess prognostic features, which can impact on the liver metastases patient treatment choice. In the liver metastases patients, the possibility to assess mutational status (RAS or MSI), the tumor growth pattern and the histological subtype (NOS or mucinous) allows a better treatment selection to avoid unnecessary therapies. However, today, the detection of these features require an invasive approach. Recently, radiomics analysis application has improved rapidly, with a consequent growing interest in the oncological field. Radiomics analysis allows the textural characteristics assessment, which are correlated to biological data. This approach is captivating since it should allow to extract biological data from the radiological images, without invasive approach, so that to reduce costs and time, avoiding any risk for the patients. Several studies showed the ability of Radiomics to identify mutational status, tumor growth pattern and histological type in colorectal liver metastases. Although, radiomics analysis in a non-invasive and repeatable way, however features as the poor standardization and generalization of clinical studies results limit the translation of this analysis into clinical practice. Clear limits are data-quality control, reproducibility, repeatability, generalizability of results, and issues related to model overfitting.
Sex differences in myocardial injury after non-cardiac surgery and postoperative mortality
Authors: Kwon Ji-Hye , Park Jungchan , Lee Seung-Hwa , Hyun Cheol Won , Kim Jihoon , Yang Kwangmo , Min Jeong Jin , Lee Jong Hwan , Lee Sangmin Maria , Choi Jin-ho , Lee Sang-Chol , Gwon Hyeon-Cheol , Her Sukyoung , Kim Kyunga , Ahn Joonghyun 
Published: March 2023

Abstract

Background
Myocardial injury after non-cardiac surgery (MINS) has recently been accepted as a predictor of mortality. However, sex differences in the incidence of MINS and survival thereafter are not fully understood. This study aimed to compare the incidence of MINS and mortality among male and female patients.

Methods
This single-center study was conducted using the database of a large tertiary referral hospital. Consecutive patients with cardiac troponin (cTn) detected within 30 days after non-cardiac surgery performed between January 2010 and June 2019 were grouped according to sex. The incidence of MINS and mortality of patients with MINS were compared between men and women.

Results
Of the 33,311 patients, 18,546 (55.7%) were men and 14,765 (44.3%) were women. In a multivariable analysis, women showed a significantly lower incidence of MINS than did men (17.9% vs. 14.2%; odds ratio, 0.76; 95% confidence interval [CI], 0.71–0.81; P < 0.001). In patients with MINS, the propensity-score-matched analysis showed that 30-day mortality did not differ according to sex, but mortality in females was significantly lower than that in males during the overall follow-up (33.0% vs. 25.7%; hazard ratio, 0.75; 95% CI, 0.66–0.84; P < 0.001).

Conclusion
The incidence of MINS was lower in women than in men. In patients with MINS, female sex may be associated with a survival benefit. Further studies are needed to confirm these findings.
Cadmium-induced Sertoli Cell Injury Through p38-MAPK and Related Signaling Proteins—A Study by RNA Sequencing
Authors: Wang Lingling , Li Xinyao , Bu Tiao , Wu Xiaolong , Li Linxi , Gao Sheng , Yun Damin , Zhang Yan , Chen Hao , Sun Fei , Cheng C Yan 
Published: March 2023

AbstractEnvironmental toxicants, such as cadmium, found in foods, water, and consumer products are known to induce male reproductive dysfunction. However, the underlying molecular mechanism(s) by which cadmium-induced Sertoli cell injury as manifested by a disruption of the blood-testis barrier (BTB) remains unknown. Interestingly, one of the primary targets of cadmium toxicity in the testis is the cytoskeletons of the Sertoli cells, which, in turn, impedes cell junctions in the seminiferous epithelium. In order to expand these earlier observations and to provide a roadmap for future studies, we embarked a study using RNA sequencing to identify the pertinent genes involved in cadmium-induced Sertoli cell injury. Using bioinformatics analyses, multiple gene sets that regulated actin and microtubule (MT) cytoskeletons were identified along with components of the mitogen-activated protein kinase (MAPK) signaling protein and several signaling pathways. More important, we have also discovered that while the gene expression of p38-MAPK (also JNK or c-Jun) was considerably up- or downregulated during cadmium-induced Sertoli cell injury, the activated (phosphorylated) form was upregulated. Importantly, doramapimod (also known as BIRB 796), a specific p38-MARK inhibitor, that was shown to selectively block cadmium-induced p-p38 MAPK activation via phosphorylation in Sertoli cells, was indeed capable of blocking cadmium-induced Sertoli cell injury including disruption of the Sertoli cell-permeability barrier function, disruptive distribution of BTB-associated proteins, and disruptive organization of the actin and MT cytoskeletons. These data provide a helpful source of information for investigators to probe the role of signaling proteins and/or their signaling cascades, besides MAPKs, that likely utilized by cadmium to induce reproductive dysfunction.
Neurotrans
Authors: Smilges J. Logan 
Published: March 2023

AbstractThis essay makes the case for neurotrans, which names the nexus of neurodivergence and trans as an epistemic source, a place from which neurotrans people think neurotrans thoughts to pursue a neurotrans world. Bringing the interwoven histories of mental disability and trans experience to bear on HIV/AIDS, the author argues that HIV has long served as a racialized weapon of the state to subjugate neurodivergent and gender variant people, especially those of color. The AIDS crisis, following the rise of antipsychotics in psychiatry, offered the medical industrial complex and the criminal punishment system a new opportunity to surveil and control disabled and trans populations. In addition to racializing gender variance and neurodivergence as threats to white supremacy, the state could now use HIV to justify incarcerating neurotrans people, although carceral spaces, such as hospitals, mental institutions, and prisons, are largely responsible for facilitating HIV transmission. Drawing on the life and activism of Black mad and trans activist Marsha P. Johnson, this essay illuminates the entanglement of mental disability and gender nonconformance and the necessity to center mental disability in trans studies, prioritize neurodivergent people in HIV prevention efforts, and advocate for the participation and leadership of neurotrans people in AIDS activism.
102 AI-Based Molecular Classification of Diffuse Gliomas using Rapid, Label-Free Optical Imaging
Authors: Hollon Todd Charles , Golfinos John G. , Orringer Daniel A. , Berger Mitchel , Hervey-Jumper Shawn L. , Muraszko Karin M. , Freudiger Christian , Heth Jason , Sagher Oren , Jiang Cheng , Chowdury Asadur , Moin Mustafa Nasir , Kondepudi Akhil , Aabedi Alexander Arash , Adapa Arjun R. , Al-Holou Wajd , Wadiura Lisa , Widhalm Georg , Neuschmelting Volker , Reinecke David , Camelo-Piragua Sandra 
Published: March 2023

INTRODUCTION:
Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. Access to timely molecular diagnostic testing for brain tumor patients is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment.

METHODS:
By combining stimulated Raman histology (SRH), a rapid, label-free, non-consumptive, optical imaging method, and deep learning-based image classification, we are able to predict the molecular genetic features used by the World Health Organization (WHO) to define the adult-type diffuse glioma taxonomy, including IDH-1/2, 1p19q-codeletion, and ATRX loss. We developed a multimodal deep neural network training strategy that uses both SRH images and large-scale, public diffuse glioma genomic data (i.e. TCGA, CGGA, etc.) in order to achieve optimal molecular classification performance.

RESULTS:
One institution was used for model training (University of Michigan) and four institutions (NYU, UCSF, Medical University of Vienna, and University Hospital Cologne) were included for patient enrollment in the prospective testing cohort. Using our system, called DeepGlioma, we achieved an average molecular genetic classification accuracy of 93.2% and identified the correct diffuse glioma molecular subgroup with 91.5% accuracy within 2 minutes in the operating room. DeepGlioma outperformed conventional IDH1-R132H immunohistochemistry (94.2% versus 91.4% accuracy) as a first-line molecular diagnostic screening method for diffuse gliomas and can detect canonical and non-canonical IDH mutations.

CONCLUSIONS:
Our results demonstrate how artificial intelligence and optical histology can be used to provide a rapid and scalable alternative to wet lab methods for the molecular diagnosis of brain tumor patients during surgery.
104 A Safety and Efficacy Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping
Authors: Vajkoczy Peter , Thomé Claudius , Kerschbaumer Johannes , Meyer Bernhard , Wostrack Maria , Adage Tiziana , Breitenbach Jörg , Bavinzski Gerhard , Hirschmann Dorian , Bendszus Martin , Rohde Veit , Mielke Dorothee , Wessels Lars 
Published: March 2023

INTRODUCTION:
Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. Secondary mechanisms of injury can aggravate the high negative impact. Cerebral vasospasm (CV) is one of the most relevant causes of this secondary injury. To improve the current treatment options, NicaPlant® was developed.

METHODS:
The trial was performed as an international randomized, controlled, single-blinded multicenter study. 40 Patients with WFNS grade 3 and 4 SAH undergoing surgical repair of their ruptured aneurysm were randomized to receive ten pellets of NicaPlant® (40 mg) plus standard of care or standard of care alone. The implants were administered immediately following clip ligation of the ruptured aneurysm in proximity to all the exposed cerebral blood vessels. The primary endpoint was the incidence of moderate to severe CV (day 8 ± 1). A blinded independent outcome accessor analyzed all imaging data.

RESULTS:
In the implant group, 20% (4/20) of patients reached the primary endpoint, compared to 58% (11/19) of patients in the control group (p = 0.024). Including mild CV, 75% of all patients in the control group developed CV compared to 30% in the implant group (p = 0.0129). 32% (6/19) of the patients in the control group developed new cerebral infarction, compared to 10% (2/20) in the implant group (p = 0.1273). Endovascular rescue therapy was performed in 10% of the patients in the implant group compared to 58% in the control group (p = 0.002). 4 subjects (20%) in the control group experienced Treatment-emergent adverse events (TEAE), compared with none in the active group.

CONCLUSIONS:
In this prospective randomized multicenter Phase 2b trial, we could demonstrate the safety and efficacy of NicaPlant® implants in preventing CV in patients with SAH.
106 Reimbursement Trends in Neuroendovascular Interventions 2013-2022
Authors: Steiger Kyle , Singh Rohin , Koester Stefan Wolfgang , Nguyen Brandon , Brown Nolan James , Shahrestani Shane , Catapano Joshua , Srinivasan Visish M. , Gendreau Julian Lassiter , Patel Naresh P. , Erben Young 
Published: March 2023

INTRODUCTION:
Neuroendovascular surgeries are increasingly important, particularly with the advent of thrombectomy as the gold standard in the management of large vessel stroke.

METHODS:
The Physician Fee Schedule Look-Up Tool was queried from 2013 to 2019 for all primary Current Procedural Terminology (CPT) codes identified by the American Medical Association as pertaining to endovascular procedures of the nervous system (61623, 61624, 61630, 61635, 61626, 61645, and 61650). The facility prices were averaged for each procedure and subsequently adjusted for inflation using the United States Bureau of Labor Statistics’ Consumer Price Index Inflation Calculator as adjusted to January of 2022. Statistical analyses, including data aggregation, exploratory analysis, and propensity adjustment, were performed using R, version 4.0.1 (The R Foundation, Vienna, Austria). The two-sided Mann-Kendall trend test, a non-parametric statistical test that assesses for monotonic trends in either an upward or downward trend, was utilized to assess for trends over time. Within each year analyzed, a Chi-squared test for trend in proportions was used. A significance level of 0.05 was used.

RESULTS:
Decreases in reimbursement were noted for all neuroendovascular procedures. This trend was statistically significant for temporary balloon occlusion, CPT61623 (2013:$677.04; 2022:586.96; p: 0.01), central nervous system transcatheter permanent occlusion or embolization, CPT61624 (2013:$1349.61; 2022:$1175.02; p: 0.02), non-central nervous system transcatheter permanent occlusion or embolization, CPT61626 (2013:$1040.86; 2019:$912.29; p: 0.002), stent placement, CPT61635 (2013:$1697.18; 2022:$1490.68; p: 0.05), and when viewed as aggregate procedures (2013:$1265.01; 2022:$1000.45; p < 0.01).

CONCLUSIONS:
Inflation-adjusted reimbursement is decreasing for certain neuroendovascular procedures over time and for all neuroendovascular procedures when viewed as an aggregate group. This suggests a need for reevaluation of the market value and advocacy for neuroendovascular providers and procedures in the era of value/quality-based care.
107 Nerve Transfers in Spinal Cord Injury: Analysis of Factors Influencing Motor Recovery
Authors: Javeed Saad , Dibble Christopher , Greenberg Jacob K. , Zhang Justin , Khalifeh Jawad M. , Ray Zack 
Published: March 2023

INTRODUCTION:
Nerve transfers have the potential to reanimate lost upper limb function following cervical spinal cord injury (SCI). However, the factors influencing motor recovery following nerve transfers in cervical SCI remains unknown.

METHODS:
A prospective cohort of cervical SCI patients 18 years of age with American Spinal Injury Association [ASIA] grade A-C underwent nerve transfers and followed-up until 48-months. Preoperative variables included age, time-delay post-SCI, neurological level-of-injury, ASIA grades, international classification of surgery of hand in tetraplegia (ICSHT) indicating preserved upper limb function, and recipient-nerve-electrodiagnosis. Univariate analyses were performed followed by multivariable proportional-odds logistic-regression of significant predictors. The primary outcome was motor recovery in medical research council (MRC) grades categorized as: poor-recovery (MRC grades 0-2); good-recovery (grade 3); and excellent-recovery (grades 4-5). The ICSHT was categorized into very-high-level (ICSHT-0; absent-function); high-level (ICSHT 1-2; intact biceps/brachioradialis); and low-level-injury (ICSHT 3-4; intact wrist-extension/pronation).

RESULTS:
21 cervical SCI patients underwent 57 nerve transfers (33 upper limbs) at median of 21 (range: 6-142) months post-SCI. At final follow-up, median-gain in triceps MRC was: 3 ([IQR] 2.5-4, p = 0.011), finger-extensors: 4 (2-4, p < 0.001), and finger-flexors: 2 (1-3, p < 0.001). On univariate analysis, age, time-delay post-SCI, and ICSHT were significantly associated with motor recovery. On multivariable analysis, the low-level-injury (ICSHT 3-4) was significantly associated with superior motor outcomes as compared to higher-level injuries (Odds ratio [OR] 12.2, 95% CI, 2.34-91.4; p = 0.005). Each month delay increased 5% odds of superior motor function (OR 1.05, 95% CI, 1.01-1.11; p = 0.03).

CONCLUSIONS:
The preserved motor function in upper limb (ICSHT-grouping) significantly predicts motor outcomes following nerve transfers in cervical SCI. Nerve transfers in chronic SCI (12 months) results in comparable motor outcomes to earlier reinnervation.
109 A Small RNA Signature from Extracellular Vesicles in Patient Plasma Correlates With Recurrence or Progression of High-Grade Gliomas
Authors: Han Jae Ho , Attwood Kathleen , Roy Jeremy , Weeks Adrienne 
Published: March 2023

INTRODUCTION:
Glial cell-derived tumors of the central nervous system make up the largest group of brain tumors. Most are high-grade gliomas (HGG) and are universally fatal despite multimodal therapy. In managing patients with HGG, predicting recurrence, or differentiating between pseudoprogression (radiation necrosis) and true tumor progression would be invaluable in improving overall prognosis. Characterizing small RNA (sRNA) expression profiles from plasma-derived extracellular vesicles (EVs) over the course of a patient’s treatments, may allow for patient-specific treatment modifications and improve outcomes.

METHODS:
Plasma EVs were isolated using Vn96 capture from HGG patients perioperatively and with routine, follow-up surveillance imaging. Small RNA sequencing was conducted and unsupervised hierarchal clustering of sRNA signatures were completed. Expression profiles were grouped longitudinally with the clinical status of patients.

RESULTS:
Cluster analysis of nine HGG patients, has revealed a sRNA signature that is able to distinguish between tumors showing evidence of progression and those remaining stable over time. Those samples obtained from patients where a clinical diagnosis of tumor progression or pseudoprogression were uncertain, were found to cluster into progression vs. stable signatures. Annotation of differentially expressed small RNAs identified from stable vs. clinically progressed patient include small nuclear RNA, ribosomal RNA, and micro RNA among others. MiRNA species we have identified correspond to previously identified miRNA, which have been ascribed functional significance to HGG aggressiveness and progression.

CONCLUSIONS:
These preliminary findings demonstrate the potential utility of sRNA profiling of plasma-derived EVs obtained from patients with high-grade gliomas as non-invasive biomarkers for recurrent/progressive disease or stability/pseudoprogression.
110 Macrophage Cross Talk following Subarachnoid Hemorrhage: Contribution of Peripheral Immune Activation in the Development of Cerebral Vasospasm
Authors: Lucke-Wold Brandon , Hoh Brian Lim 
Published: March 2023

INTRODUCTION:
Microglia respond to the initial insult of aneurysm rupture, but become overwhelmed by ferritin toxicity. These microglia release inflammatory cytokines that cause vasospasm to facilitate peripheral macrophage diapedesis. This process is dependent on the p-STAT3 pathway.

METHODS:
The autologous SAH pre-clinical model was utilized and compared to blood and CSF from human patients. Mouse blood was injected along the skull base to c57/bl6 and CCR2/Cx3CR1 mice. Microglia depletion was done with pexidartinib. Ferritin within microglia, TLR4, and NFKb were measured via immunohistochemistry. Vasospasm was measured via India Ink gelatin assay. The Modified Garcia Scale and right turn test was utilized. Clarity assay was utilized to determine association between macrophages and brain microglia. Cerebral doppler was used to measure spreading cortical depressions. p-STAT3 was measured via western blot. For all experiments, saline sham, subarachnoid hemorrhage, and subarachnoid hemorrhage with p-STAT3 inhibitor were utilized.

RESULTS:
Microglia recruitment occured within parenchyma along the skull base adjacent to subarachnoid blood. Ferritin toxicity was noted by day 5 (r-0.95, p < 0.05) and persisted to day 9 (r-0.98, p < 0.01). A shift in microglia occured following SAH with Cox-2 and INOS predominance (k1 0.76, k2 1.21). Blockade of p-STAT3 resulted in decreased vasospasm (p<0.01), improved modified Garcia scores (p < 0.05), and improved right turn test (p < 0.05) following SAH. Peripheral macrophage diapedesis occured in regions of microglia activation. P-STAT3 blockade improved cerebral blood flow and prevented spreading cortical depressions (p < 0.01). NFKb and TLR4 activation was markedly reduced by p-Stat3 inhibition (p < 0.05). Results correlated closely to human aneurysmal blood and CSF data.

CONCLUSIONS:
Microglia ferritin toxicity contributes to vasospasm to facilitate peripheral macrophage diapedesis. Targeting the p-STAT3 pathway leads to reduced vasospasm and improved behavioral outcomes.