bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling
Authors: Luo Ming , Shen Na , Shang Li , Fang Zeng , Xin Ying , Ma Yuxi , Du Min , Yuan Yuan , Hu Chenchen , Tang Yun , Huang Jing , Wei Wei , Lee Myung Ryul , Hergenrother Paul J. , Wicha Max S. 
Published: September 2024

Abstract
Triple-negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSC), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets that include NAD(P)H quinone oxidoreductase 1 (NQO1). In this study, we identified the antioxidant enzymes NQO1 and superoxide dismutase 1 (SOD1) as therapeutic vulnerabilities of ALDH+ epithelial-like CSCs and CD24−/loCD44+/hi mesenchymal-like CSCs in TNBC. Effective targeting of these CSC states was achieved by using isobutyl-deoxynyboquinone (IB-DNQ), a potent and specific NQO1-bioactivatable futile redox cycling molecule, which generated large amounts of reactive oxygen species including superoxide and hydrogen peroxide. Furthermore, the CSC killing effect was specifically enhanced by genetic or pharmacologic inhibition of SOD1, a copper-containing superoxide dismutase highly expressed in TNBC. Mechanistically, a significant portion of NQO1 resides in the mitochondrial intermembrane space, catalyzing futile redox cycling from IB-DNQ to generate high levels of mitochondrial superoxide, and SOD1 inhibition markedly potentiated this effect, resulting in mitochondrial oxidative injury, cytochrome c release, and activation of the caspase-3–mediated apoptotic pathway. Treatment with IB-DNQ alone or together with SOD1 inhibition effectively suppressed tumor growth, metastasis, and tumor-initiating potential in xenograft models of TNBC expressing different levels of NQO1. This futile oxidant-generating strategy, which targets CSCs across the epithelial–mesenchymal continuum, could be a promising therapeutic approach for treating patients with TNBC.
Significance: Combining NQO1-bioactivatable futile oxidant generators with SOD1 inhibition eliminates breast cancer stem cells, providing a therapeutic strategy that may have wide applicability, as NQO1 and SOD1 are overexpressed in several cancers.
Neighborhood Disadvantage and Prostate Tumor Aggressiveness among African American and European American Men
Authors: Boyle Joseph , Yau Jessica , Slade Jimmie L. , Butts Derrick A. , Wimbush Jessica , Park Jong Y. , Hussain Arif , Onukwugha Eberechukwu , Knott Cheryl L. , Wheeler David C. , Barry Kathryn Hughes 
Published: September 2024

Abstract

Background:
Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race.

Methods:
We evaluated associations between aggressive prostate cancer and four ND metrics—Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004–2021).

Results:
We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00–1.30; RI, OR = 1.27, CI, 1.07–1.51; redlining, OR = 1.77; CI, 1.23–2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13–1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men.

Conclusions:
We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race.

Impact:
Findings inform specific ND components that are associated with aggressive prostate cancer and suggest the ND effect is stronger for AA men, which has implications for interventions to reduce disparities.
A First-in-Human Phase I Study of BXQ-350, a First-in-Class Sphingolipid Metabolism Regulator, in Patients with Advanced/Recurrent Solid Tumors or High-Grade Gliomas
Authors: Rixe Olivier , Villano John L. , Wesolowski Robert , Noonan Anne M. , Puduvalli Vinay K. , Wise-Draper Trisha M. , Curry Richard , Yilmaz Emrullah , Cruze Charlie , Ogretmen Besim , Tapolsky Gilles , Takigiku Ray 
Published: September 2024

Abstract

Purpose:
BXQ-350, a nanovesicle formulation of saposin C, is an allosteric sphingolipid metabolism regulator that increases proapoptotic ceramide and decreases oncogenic sphingosine-1-phosphate levels. We conducted a first-in-human phase I study of BXQ-350.

Patients and Methods:
Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7–2.4 mg/kg) in a 3+3 dose escalation and expansion design. The primary endpoints during dose escalation were dose-limiting toxicities and maximum tolerated dose; the primary objective in expansion parts was assessment of antitumor activity (RECIST v1.1/Response Assessment in Neuro-Oncology criteria).

Results:
Eighty-six patients were enrolled. Dose-limiting toxicities were not observed during dose escalation (n = 18), and a maximum tolerated dose was not identified. An additional 68 patients received the 2.4 mg/kg dose. Nine patients (10%) discontinued due to adverse events. The most common treatment-related adverse events were nausea (24%) and fatigue (23%). Eight patients had a progression-free survival of ≥6 months. Two of these achieved a partial response, and six had stable disease, among whom three had a reduction in ≥1 target lesion. Of those with progression-free survival of ≥6 months, seven remained on study for &gt;12 months, five for &gt;24 months, and after 7 years, two remained on study without disease progression.

Conclusions:
BXQ-350 was well-tolerated as monotherapy at doses up to 2.4 mg/kg. It provided some lasting clinical benefit in patients with recurrent solid malignancies across several tumor types, consistent with a decreased systemic sphingosine-1-phosphate/ceramide metabolic rheostat. BXQ-350 warrants further clinical investigation alone and combined with standard of care for advanced solid tumors.
c-Myc, AKT, Hsc70, and the T-Box Transcription Factor TBX3 Form an Important Oncogenic Signaling Axis in Breast Cancer
Authors: Ncube Stephanie M. , Nagarajan ArulJothi , Lang Dirk , Sinkala Musalula , Burmeister Carly A. , Serala Karabo , Blackburn Jonathan , Prince Sharon 
Published: September 2024

Abstract
Breast cancer is the second leading cause of death in women globally, and it remains a health burden due to poor therapy response, cancer cell drug resistance, and the debilitating side effects associated with most therapies. One approach to addressing the need to improve breast cancer therapies has been to elucidate the mechanism(s) underpinning this disease to identify key drivers that can be targeted in molecular therapies. The T-box transcription factor, TBX3, is upregulated in breast cancer, in which it contributes to important oncogenic processes, and it has been validated as a potential therapeutic target. Here, we investigated the molecular mechanisms that upregulate TBX3 in breast cancer, and we show that it involves transcriptional activation by c-Myc, post-translational modification by AKT1 and AKT3, and interaction with the molecular chaperone Hsc70. Together, the results from this study provide evidence that c-Myc, AKT, Hsc70, and TBX3 form part of an important oncogenic pathway in breast cancer and thus reveal versatile ways of interfering with the oncogenic activity of TBX3 for the treatment of this neoplasm.
Implications: Targeting the c-Myc/AKT/TBX3/Hsc70 signaling axis may be an effective treatment strategy for TBX3-driven breast cancer.
After Nostalgia: Revisiting Palestine’s Poetics of al-Andalus
Authors: England Samuel 
Published: September 2024

Abstract
During the past thirty years, scholars of Arab cultural politics have struggled to articulate modern Palestinians’ unique ways of viewing the medieval past. Al-Andalus in particular fascinates authors and visual artists of Palestine. Our current theoretical framework within Arabic literature is poorly adapted to the sweeping historiography that these authors and artists create. This article revises the academic consensus that nostalgia is the organizing principle for Palestinian expressions of Andalusi identity. It provides a new way to understand the relationship between modern Palestinian poetics and the idea of a past Arab Iberia. Shifting from the affective theory of nostalgia that culminated in the early 1990s, I argue that Palestine’s version of al-Andalus in the twenty-first century works primarily as an artistic technique of reading Maghrebi texts rather than as an idyllic geographic place.
Tenebrio molitor flour as a partial fish replacer and its effect on the quality of hake sausages
Authors: Rodrı́guez R. , Alvarez-Sabatel S. , Ibargüen M. , Tueros I. , Talens C. 
Published: September 2024

Abstract
The effect of replacing hake with Tenebrio molitor on the physicochemical, nutritional and sensory characteristics of fish sausages was investigated in this study. Two types of samples were prepared, a control hake sausage (HFC, 49.3% hake) and a modified version in which hake was partially replaced by Tenebrio molitor insect flour (HFT, 44.37% hake + 4.93% insect flour). The colour, nutritional profile (including fatty acid profile), instrumental texture (TPA, texture profile analysis) and sensory analyses (QDA, quantitative descriptive analysis) were performed. The results showed that the sample including insect flour was darker, more yellowish and more reddish than the control sample. The replacement of 10% of the hake resulted in a reduction of fat and saturated fatty acids (SFAs) content and an increase in protein and monounsaturated fatty acids (MUFAs) content. The instrumental texture did not show significant differences between samples. The results of the sensory analysis indicated that there were significant differences () between all the parameters, with the exception of non-typical odour and pastiness. The results obtained indicate that Tenebrio molitor flour for partial fish (hake) substitution could be used as a sustainable strategy to promote the consumption of processed fish products, such as sausages, by improving their nutritional profile.
Chapter 3
Authors: Rudy Kathryn M. 
Published: September 2024

Chapter 3 explores the pedagogical use of manuscripts in the Late Middle Ages, particularly how medieval individuals learned to interact with books and adopt reading behaviors. It begins by examining a miniature in a private prayer book from the1440s showing Christ as a teacher and brandishing a book. The image emphasizes how books served as educational tools linking teachers and students in a shared learning experience. This chapter shifts the discussion from production to reception, considering how medieval learners mimicked behaviors through performative demonstrations with books.
The chapter surveys educational practices, from children learning to read to adults engaging in complex religious instruction, and how these practices are reflected in manuscripts' wear patterns. It details the use of “picture Bibles” as educational tools, highlighting the effectiveness of colorful images and simpler texts for children. A key focus is how manuscripts designed for children, featuring alphabets and vivid imagery, prompted codified gestures.
The chapter considers case studies of specific manuscripts, such as a Book of Hours made for the Use of Paris, showcasing how a child's physical engagement with the book could complement her religious and literary education. This chapter also reflects on manuscripts featuring moralizing texts such as the "Ci nous dist" and the "Tafel vanden kersten ghelove," which served as catechisms for both young learners and adults.
The chapter concludes by acknowledging the influential role of educators in setting norms for book handling, which shaped the behaviors of the nobility and wealthy families. Through these interactive learning experiences, people who had access to the tools of literacy were inculcated with a deep respect for the book as a conduit for knowledge, spirituality, and moral guidance.
PixPol: An In-Water Multispectral Polarized Upwelling Radiance Distribution Camera System
Authors: Blocker E. Riley , Voss Kenneth J. 
Published: September 2024

Abstract
PixPol is an in-water multispectral polarized upwelling radiance distribution fisheye camera system. Its imaging sensors utilize a pixel-level polarizer structure allowing for polarimetric retrieval from one image capture, offering an advantage compared to other in-water polarimetric fisheye camera systems that require information from multiple images. When submerged, PixPol images a scene from which the first three Stokes parameters are derived at an angular resolution of 1° within a field of view that encompasses all azimuthal angles up to an elevation of 43° from nadir. For all viewing angles, Stokes parameter I and the linear polarization parameters, Q/I and U/I, are retrieved with an interpixel uncertainty of ±5%, ±0.02%, and ±0.02%, respectively. From these parameters, an uncertainty of ±0.01 is attained for the degree of linear polarization and ±0.9° for the angle of linear polarization. A description of the camera system, its radiometric and polarization calibration, and the associated uncertainties are described. Example images of the distribution of downwelling polarized light in the sky just above the ocean’s surface and upwelling polarized light just below the surface are provided.
Compression-only versus standard cardiopulmonary resuscitation in out-of-hospital cardiac arrest: A meta-analysis of randomized controlled trials
Authors: Ahmed Mushood , Fatima Laveeza , Ahsan Areeba , Jain Hritvik , Zahra Rubab , Asif Muhammad Hamza , Jain Jyoti , Basit Jawad , Ahmed Raheel 
Published: September 2024

Background Bystander-initiated cardiopulmonary resuscitation (CPR) can improve survival rates in individuals with out-of-hospital cardiac arrest (OHCA). Two CPR approaches are commonly utilized, standard (S-CPR) with mouth-to-mouth breathing and compression-only (CO-CPR). We conducted a systematic review and meta-analysis to compare clinical outcomes associated with S-CPR versus CO-CPR in OHCA. Methods A systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. Eligible studies included randomized controlled trials (RCTs) focused on adult OHCA patients receiving CO-CPR or S-CPR. Forest plots were generated for pooled data analysis using Review Manager version 5.4. Random-effect analyses were used, and statistical significance was set at p < .05. Results Four randomized controlled trials were included in the final analysis, encompassing a total sample size of 4987 patients (2482 in the CO-CPR group and 2505 in the S-CPR group). CO-CPR was associated with significantly improved 1-day survival compared with S-CPR (OR = 1.15; 95% CI: 1.02–1.31; p = .03) and survival to hospital discharge (OR = 1.25; 95% CI: 1.01-1.55; p = .04). No heterogeneity was observed among the studies for either outcome. Conclusion CO-CPR emerges as a promising strategy for improving outcomes in OHCA compared to S-CPR. However, further large-scale RCTs are required to generate more robust evidence.
A Nomogram for Predicting Postoperative Pulmonary Complications in Critical Patients Transferred to ICU After Abdominal Surgery
Authors: Wang Bin , Liang Han Sheng , Shen Jia Wei , An You Zhong , Feng Yi 
Published: September 2024

Objective The purpose of this study was to investigate the risk factors associated with postoperative pulmonary complications(PPCs) in critically ill patients transferred to intensive care unit(ICU) after abdominal surgery and develop a predictive model for this disease. Methods Data for 3716 patients who were admitted to ICU after abdominal surgery in Peking University People's Hospital between January 2015 and December 2020 were retrospectively collected and analyzed to identify the risk factors and develop a nomogram prediction model. Data for patients admitted to ICU following abdominal surgery at Peking University People's Hospital from March 2021 to December 2022 were prospectively collected as a validation set to validate and assess the model. Results 10 independent risk factors for PPCs in critically ill patients transferred to ICU after abdominal surgery were identified. A nomogram prediction model was constructed for PPCs in this group patients, the area under ROC curve was 0.771[95%CI: 0.756,0.786] and 0.759[95%CI: 0.726,0.792] in the training set and validation set, respectively. Conclusions In this study, independent risk factors for PPCs in critically ill patients transferred to ICU after abdominal surgery were identified. A nomogram prediction model for PPCs in critically ill surgical population was constructed using these factors, demonstrating a good predictive value.
Implementation of routine HIV testing policy in medical admissions in the sultanate of Oman: An experience from the Middle East
Authors: Al-Habsi Zeyana , Elgalib Ali , Shah Samir , Al-Fouri Maha , Al-Rawahi Bader , Al-Maani Amal 
Published: September 2024

Objectives To tackle the issue of late HIV diagnosis in the country, the Ministry of Health (MOH) in Oman introduced a national policy of routine opt-out HIV in medical admission units in September 2022. We hereby report the implementation and outcomes of this policy. Method All patients aged 16–65 years admitted to a medical ward in secondary and local hospitals were offered an HIV test regardless of their symptoms by medical doctors, with training and support from HIV teams. A retrospective review for the period from September 2022 to September 2023 was conducted to determine the HIV testing rate and outcomes of those testing HIV seropositive. Result Over 12 months, there were 23,399 admissions; 6889 had HIV tests. Thirty-two patients (0.46 %) were diagnosed with HIV; all of them were new diagnoses. Two cases were diagnosed during seroconversion. 12 cases had AIDS-defining illnesses. Four contacts were tested HIV positive. Twenty-five out of 28 alive patients are on ART. Conclusion This is the first national policy of a routine opt-out HIV in medical admission units in the MENA region. Our experience showed that, even in low HIV prevalence and high HIV stigma settings, this policy is feasible, acceptable, and effective.
Efficacy of Direct Versus Peripheral Adjuvant Dexamethasone on Duration and Rebound Pain in Regional Anesthesia for Outpatient Distal Radius Fracture Fixation: A Prospective Randomized Controlled Blinded Study
Authors: Kasper Alexis A. , Plusch Kyle , Voskerijian Armen , Barnabei David , Rivlin Michael , Beredjiklian Pedro K. , Wang Mark L. 
Published: September 2024

Background: Despite increasingly wider use, there remains controversy among anesthesiologists regarding preferred formulations and the role of steroid adjuvants in regional anesthesia. There is also uncertainty in the role of dexamethasone when administered directly versus peripherally. We hypothesize that directly mixing dexamethasone into the regional nerve block rather than peripherally administered intravenous dexamethasone will demonstrate a difference in efficacy concerning duration and rebound pain, decreased postoperative pain scores, or opioid consumption within the short-term postoperative period. Methods: A prospective, randomized controlled blinded study was conducted for patients undergoing open reduction and internal fixation with a volar plate technique for distal radius fractures. Patients were randomized for their preoperative anesthesia. One group had ultrasound-guided supraclavicular block with ropivacaine with a direct mix of dexamethasone 4 mg (Direct group), while the other group had ultrasound-guided supraclavicular block with ropivacaine and peripheral intravenous dexamethasone 4 mg (Indirect group). Data was collected pre, intra, and postoperatively. Results: Fifty patients consented and participated in the study, with 27 participants in the direct group and 23 participants in the indirect group. Compared to intravenous administration, directly administered dexamethasone demonstrated a significant difference in the average time for the block to fade, onset of motor and sensory recovery, and block resolution. Conclusion: Our findings prove that directly mixing dexamethasone compared to peripherally administered intravenous dexamethasone will demonstrate a difference in efficacy with regards to duration and rebound pain, but do not prove that there will be a difference in decreased postoperative pain scores or opioid consumption within the 24-hour postoperative period. Level of Evidence: Prognosis Level I
Managing Major Peripheral Nerves in Forearm-Level Amputations With TMR and RPNI: What’s the Best Recipe?
Authors: Rees Andrew B. , Mastracci Julia C. , Posey Samuel L. , Loeffler Bryan J. , Gaston R. Glenn 
Published: September 2024

Background: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) prevent symptomatic neuroma formation in amputees. Forearm-level amputations present multiple muscular targets, making it challenging to determine the ideal treatment. The purpose of this study was to evaluate the best TMR targets, role of RPNI, and appropriate patient-selection criteria in forearm-level amputations. We hypothesized that deep and distal TMR targets would best prevent symptomatic neuromas, RPNI would prove a success adjunct, and patients with poorly controlled diabetes would not develop symptomatic neuromas regardless of nerve management. Methods: We retrospectively identified forearm-level amputations performed between 2017 and 2022. Patients with TMR by outside providers, follow-up <6 months, or insufficient documentation were excluded. Demographics, surgical nerve management, and postoperative complications were collected. The primary outcome was development of a painful neuroma determined by the Eberlin criteria. Patients undergoing TMR were divided a priori into two groups, superficial and proximal versus deep and distal TMR targets, and were compared. Results: Thirty-nine patients met inclusion criteria, and 16 developed a symptomatic neuroma. No patients with a deep or distal TMR target developed a symptomatic neuroma. One nerve out of 12 treated with RPNI developed a symptomatic neuroma. No patient with poorly controlled diabetes developed a symptomatic neuroma, despite no advanced nerve management. Conclusions: In a case series of forearm amputations, deep and distal TMR targets prevented symptomatic neuroma formation more than superficial and proximal targets. R﻿egenerative peripheral nerve interface is a useful adjunct for neuroma control, especially for the radial sensory nerve. Patients with poorly controlled diabetes may not require advanced nerve management. Level of Evidence: Level IV retrospective case series