bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya 
Published: March 2024

Abstract

Purpose:
Emerging evidence underscores the critical role of extrinsic factors within the microenvironment in protecting leukemia cells from therapeutic interventions, driving disease progression, and promoting drug resistance in acute myeloid leukemia (AML). This finding emphasizes the need for the identification of targeted therapies that inhibit intrinsic and extrinsic signaling to overcome drug resistance in AML.

Experimental Design:
We performed a comprehensive analysis utilizing a cohort of ∼300 AML patient samples. This analysis encompassed the evaluation of secreted cytokines/growth factors, gene expression, and ex vivo drug sensitivity to small molecules. Our investigation pinpointed a notable association between elevated levels of CCL2 and diminished sensitivity to the MEK inhibitors (MEKi). We validated this association through loss-of-function and pharmacologic inhibition studies. Further, we deployed global phosphoproteomics and CRISPR/Cas9 screening to identify the mechanism of CCR2-mediated MEKi resistance in AML.

Results:
Our multifaceted analysis unveiled that CCL2 activates multiple prosurvival pathways, including MAPK and cell-cycle regulation in MEKi-resistant cells. Employing combination strategies to simultaneously target these pathways heightened growth inhibition in AML cells. Both genetic and pharmacologic inhibition of CCR2 sensitized AML cells to trametinib, suppressing proliferation while enhancing apoptosis. These findings underscore a new role for CCL2 in MEKi resistance, offering combination therapies as an avenue to circumvent this resistance.

Conclusions:
Our study demonstrates a compelling rationale for translating CCL2/CCR2 axis inhibitors in combination with MEK pathway-targeting therapies, as a potent strategy for combating drug resistance in AML. This approach has the potential to enhance the efficacy of treatments to improve AML patient outcomes.
Deprogramming Implicit Bias: The Case for Public Interest
Technology
Authors: Walker Darren 
Published: March 2024

Abstract
New technologies have fundamentally transformed the systems that govern modern life, from criminal justice to health care, housing, and beyond. Algorithmic advancements promise greater efficiency and purported objectivity, but they risk perpetuating dangerous biases. In response, the field of public interest technology has emerged to offer an interdisciplinary, human-centered, and equity-focused approach to technological innovation. This essay argues for the widespread adoption of public interest technology principles, including thinking critically about how and when technological solutions are deployed, adopting rigorous training to educate technologists on ethical and social context, and prioritizing the knowledge and experiences of communities facing the disproportionate harms or uneven benefits of technology. Tools being designed and deployed today will shape our collective future, and collaboration between philanthropy, government, storytellers, activists, and private-sector technologists is essential in ensuring that these new systems are as just as they are innovative.
Hegemony Approach and Political Struggles over a New Political Order: The Case of Turkey
Authors: Kutay Acar 
Published: March 2024

Abstract
This paper proposes an analytical framework that employs a hegemony approach to political transformations, which bring about significant changes in the fundamental norms and values of a political community, as well as in the organizing principles of the social and economic system. The hegemony approach, drawing inspiration from the works of Ernesto Laclau and Chantal Mouffe, provides political theorists and social scientists with conceptual tools for analyzing struggles over political power. The paper argues that attempts at hegemonic formations, when extended to political transformations, involve articulations around social antagonisms, the construction of the people, establishment of political frontiers, and mobilization of the demands of excluded and oppressed groups. The Justice and Development Party, led by Recep Tayyip Erdogan in Turkey, serves as a unique case study to illustrate this approach.
Prevalence and Associated Factors of Atherosclerotic Plaque and Stenosis in Renal Arteries: A Community-Based Study
Authors: Wang Dongxue , Pan Yuesong , Cai Xueli , Jing Jing , Yan Hongyi , Wang Suying , Meng Xia , Mei Lerong , Zhang Yanli , Li Shan , Wei Tiemin , Zhou Yilun , Wang Yongjun 
Published: March 2024

The epidemiology of renal artery atherosclerosis in community populations is poorly documented. This study aimed to determine the prevalence of renal artery plaque (RAP) and atherosclerotic renal artery stenosis (ARAS), and the association of plaque and stenosis with vascular risk factors and kidney disease markers among community-dwelling adults. We conducted a cross-sectional analysis of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study. RAP and ARAS were evaluated by thoracoabdominal computed tomography angiography. A total of 3045 adults aged 50–75 years were included. The prevalence of RAP and ARAS was 28.7% and 4.8%, respectively. The prevalence of RAP and ARAS was 41.3% and 7.7% in individuals aged ≥60 years, 42.9% and 8.7% in hypertensives, and 45.4% and 8.5% in individuals with chronic kidney disease. Older age, hypertension, higher total cholesterol level, and lower high-density lipoprotein cholesterol level were independently associated with RAP and ARAS. A higher urinary albumin-creatinine ratio was independently associated with RAP, whereas a reduced estimated glomerular filtration rate was independently associated with ARAS. In conclusion, there was a non-negligible prevalence of RAP and ARAS among the older, community population in China.
Polysomnographic Characteristics of Sleep Architecture in Children With Obstructive Sleep Apnea
Authors: Don Debra M. , Osterbauer Beth , Gowthaman Divya , Fisher Laurel , Gillett Emily S. 
Published: March 2024

Background: The conventional measure of sleep fragmentation is via polysomnographic evaluation of sleep architecture. Adults with OSA have disruption in their sleep cycles and spend less time in deep sleep stages. However, there is no available evidence to suggest that this is also true for children and published results have been inconclusive. Objective: To determine polysomnographic characteristics of sleep architecture in children with OSA and investigate effects relative to OSA severity. Methods: Overnight polysomnograms (PSG) of children referred for suspected OSA were reviewed. Subjects were classified by apnea hypopnea index (AHI). PSG parameters of sleep architecture were recorded and analyzed according to OSA severity. Results: Two hundred and eleven children were studied (median age of 7.0 years, range 4-10 years) Stage N1 sleep was longer while stage N2 sleep and REM sleep was reduced in the OSA group when compared to those without OSA (6.10 vs 2.9, P < .001; 42.0 vs 49.7, P < .001; 14.0 vs 15.9, P = .05). The arousal index was also higher in the OSA group (12.9 vs 8.2, P < .001). There was a reduction in sleep efficiency and total sleep time and an increase in wake after sleep onset noted in the OSA group (83.90 vs 89.40, P = .003; 368.50 vs 387.25, P = .001; 40.1 ± 35.59 vs 28.66 ± 24.14, P = .007; 29.00 vs 20.50; P = .011). No significant difference was found in N3 sleep stage (33.60 vs 30.60, P = .14). Conclusion: We found evidence that children with OSA have a disturbance in their sleep architecture. The changes indicate greater sleep fragmentation and more time spent in lighter stages of sleep. Future research is needed and should focus on more effective methods to measure alterations in sleep architecture.
Effect of a Ten-week Sensorimotor Exercise Program on the Side-to-Side LAM Asymmetry of Adolescent Football Players: A Randomized Control Trial
Authors: Sikora Damian , Linek Paweł 
Published: March 2024

In this study we, evaluated the effects of a 10-week sensorimotor exercise program on the thickness and side-to-side asymmetry of the lateral abdominal muscles in adolescent soccer players. From among 120 initially recruited participants, we included 90 athletes (aged 10–17 years old) in our final analysis. Healthy athletes who met our inclusion criteria were randomly divided into comparative experimental and control groups. Sensorimotor exercises were conducted twice weekly for 10-weeks in the experimental group, and the control group received no intervention. We took ultrasound measurements when participants were in supine and standing rest positions. In the supine position, the experimental group (a) reduced the asymmetry of the internal oblique (IO) muscle by 0.4 mm (MD: 0.7; 95% CI 0.6–1.1); (b) increased the thickness of the external oblique (EO) muscle on the right by 0.7 mm (MD: 0.2; 95% CI 0.1–0.6) and on the left by 0.9 mm (MD: 0.2, 95% CI 0.2–0.7); and (c) increased the muscle on the IO right by 0.8 mm (MD: 0.3; 95% CI 0.2–0.9) and on the, left by 1.2 mm (MD: 0.4 95% CI 0.3–1.1). In a standing position the experimental group increased the thickness of the EO on the right by 1.5 mm (MD: 0.6; 95% CI 0.03–1.2) and on the left by 2.1 mm (MD: 0.6; 95% CI 0.1–1.3) and increased the IO on the right by 1.2 mm (MD: 0.7; 95% CI 0.2–1.7) and on the left by 1.1 mm (MD: 0.9; 95%CI 0.1–2.0). Thus, this 10-week program of additional sensorimotor exercises reduced the (side-to-side) asymmetry of the internal oblique muscle and increased the thickness of the EO and IO muscles in young football players.
A metric for quantitative evaluation of glioma margin changes in magnetic resonance imaging
Authors: Hu Binwu , Zhang Zhiqiang , Chen Suting , Xu Qiang , Li Jianrui 
Published: March 2024

Background Gliomas differ from meningiomas in their margins, most of which are not separated from the surrounding tissue by a distinct interface. Purpose To characterize the margins of gliomas quantitatively based on the margin sharpness coefficient (MSC) is significant for clinical judgment and invasive analysis of gliomas. Material and Methods The data for this study used magnetic resonance image (MRI) data from 67 local patients and 15 open patients to quantify the intensity of changes in the glioma margins of the brain using MSC. The accuracy of MSC was assessed by consistency analysis and Bland–Altman test analysis, as well as invasive correlations using receiver operating characteristic (ROC) and Spearman correlation coefficients for subjects. Results In grading the tumors, the mean MSC values were significantly lower for high-grade gliomas (HGG) than for low-grade gliomas (LGG). The concordance correlation between the measured gradient and the actual gradient was high (HGG: 0.981; LGG: 0.993), and the Bland–Altman mean difference at the 95% confidence interval (HGG: −0.576; LGG: 0.254) and the limits of concordance (HGG: 5.580; LGG: 5.436) indicated no statistical difference. The correlation between MSC and invasion based on the margins of gliomas showed an AUC of 0.903 and 0.911 for HGG and LGG, respectively. The mean Spearman correlation coefficient of the MSC versus the actual distance of invasion was −0.631 in gliomas. Conclusion The relatively low MSC on the blurred margins and irregular shape of gliomas may help in benign-malignant differentiation and invasion prediction of gliomas and has potential application for clinical judgment.
Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study
Authors: Kelly-Hedrick Margot , Liu Sunny Yang , Komisarow Jordan , Hatfield Jordan , Ohnuma Tetsu , Treggiari Miriam M. , Colton Katharine , Arulraja Evangeline , Vavilala Monica S. , Laskowitz Daniel T. , Mathew Joseph P. , Hernandez Adrian , James Michael L. , Raghunathan Karthik , Krishnamoorthy Vijay 
Published: March 2024

Background There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking. Objective The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI. Methods We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB+). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication. Results A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB+ group compared to the BB− group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB+ group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality. Conclusion In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population.
A Pilot Study of Pembrolizumab Combined With Stereotactic Ablative Radiotherapy for Patients With Advanced or Metastatic Sarcoma
Authors: Harris Jeremy P. , Park Jino , Ku Eric , Seyedin Steven , Stitzlein Russell , Goldin Amanda , Chen Wen-Pin , McLaren Christine , Chen Allen M. , Chow Warren 
Published: March 2024

Objectives Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. Methods This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. Results In this study we outline testing the feasibility of adding SBRT to pembrolizumab. Conclusion The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.
Laser flare photometry in eyes receiving brolucizumab intravitreal injections for age related macular degeneration
Authors: Chadoulos Nikolaos , Dastiridou Anna , Mitsios Andreas , Tsinopoulos Ioannis , Kalogeropoulos Christos , Androudi Sofia 
Published: March 2024

Purpose To measure aqueous flare levels in treatment naïve eyes suffering from wet age- related macular degeneration (wAMD) treated with intravitreal brolucizumab. Methods Patients with treatment naïve wAMD in one eye were prospectively enrolled. Flare levels were measured with laser flare photometry at baseline, 1 day and 1 month after each of the 3 monthly injections during the loading phase. Results Twenty-two eyes from 22 patients aged 76.7 ± 6.0 years were enrolled. Flare values were 10.6 ± 3.7 photons/msec at baseline and 12.6 ± 5.8 photons/msec at the last follow up visit, 1 month after the third injection ( p = 0.289, repeated measures ANOVA). The mean change in flare after the first injection was 4.2 ± 3.6. photons/msec, 6.6 ± 8.9 photons/msec after the 2nd and 8.6 ± 20.8 photons/msec after the 3rd injection ( p = 0.640, repeated measures ANOVA). No patient had clinical signs of intraocular inflammation. Conclusions Eyes receiving brolucizumab injections for wAMD showed similar flare at baseline, during and 1 month after completion of three-monthly intravitreal injections. There was no evidence of subclinical inflammation during the loading phase of brolucizumab based on laser flare photometry measurements.
The impact of barrier arrangements on the transmission of respiratory infectious diseases in nursing homes in Hong Kong
Authors: Tao Yiqi , Zhong Folong , Miao Yijia , Tang Haida , Li Lingling 
Published: March 2024

Respiratory infectious diseases have affected the health of the elderly. This study investigated the optimization of physical barriers as a low-cost design strategy to reduce the risk of infection in nursing homes for the elderly in Hong Kong, which were significantly affected by the outbreak of COVID-19. First, data on two types of rooms, single and multi-occupancy, were collected from a field investigation of typical local nursing homes. Subsequently, Computational Fluid Dynamics (CFD) simulations were employed to analyse the effects of various barrier heights on the propagation, suspension, deposition and elimination of aerosol particles in these room types, thereby evaluating infection risks. The findings reveal that in single-occupancy rooms, a barrier height of 2.1 m is effective in curtailing the spread of the virus over distances. Conversely, in multi-occupancy rooms, while a 1.8-m barrier is necessary, the rate of particle suspension is considerably higher, necessitating additional ventilation measures. Based on these findings, the study provides quantitative criteria for the implementation of physical barriers as a low-cost physical measure in nursing homes and provides recommendations for the effective prevention of respiratory infectious diseases through design modifications.
Comparison of Low-Dose Computed Tomography Versus Conventional-Dose Computed Tomography in the Evaluation of Distal Radius Fractures
Authors: Zeng Steven L. , Grier A. Jordan , Langdell Hannah C. , Blevins Kier M. , Tian William M. , French Robert J. , Mithani Suhail K. , Hammert Warren C. , Klifto Christopher S. 
Published: March 2024

Background: Distal radius fractures (DRFs) are common upper extremity fractures and often require surgical fixation when they are intraarticular. Preoperative computed tomography (CT) has emerged as a surgical planning tool to evaluate intraarticular DRFs. Although CT affords additional details, patients receive higher radiation doses than standard radiographs. We aim to develop a low-dose CT (LDCT) protocol, relative to the institutional standard-dose CT wrist for intraarticular DRFs although providing adequate detail for surgical decision-making. Methods: A single-institution prospective study was conducted on patients with intraarticular DRFs who underwent closed reduction and below-elbow splinting who otherwise would undergo wrist CT. Observations were defined as total measurements taken, with each view undergoing 44 measurements. Patients underwent 2 scans with a standard dose and a 10× dose reduction. Articular step and gap measurements were recorded in the sagittal and coronal images. Results: A total of 11 patients were enrolled (7 women and 4 men). The mean age was 55 years (SD = 20.1). There were a total of 4 reviewers: 1 attending surgeon, 2 resident physicians, and 1 student. When comparing LDCT and conventional-dose CT (CDCT), there were no significant differences in step and gap measurements across all reviewers. Conclusion: This study demonstrated that LDCT provides comparable imaging quality for surgical planning as a CDCT without significant diagnostic decay in the setting of DRFs. This comes with the added benefit of a 10-fold reduction in radiation exposure. These results suggest that LDCT is an opportunity to reduce effective radiation in patients although providing beneficial preoperative imaging.
Thoracic endovascular repair of descending thoracic aorta aneurysm using thoracic stent graft in a challenging complex patient: An innovative access technique during an emergency using a mini-thoracotomy approach
Authors: Altoijry Abdulmajeed 
Published: March 2024

Objectives Repairing thoracic aortic aneurysms with endovascular aortic repair (TEVAR) is a safe and minimally invasive method with low morbidity and short postoperative recovery. We developed a novel method to treat descending thoracic aortic aneurysms using a mini-thoracotomy approach in complex patients with difficult access. Methods A 56-year-old male patient presented with a 3-day history of chest pain. His past surgical history included infrarenal aortic ligation and right axillobifemoral bypass. Thoracic computed tomography angiography (CTA) revealed a saccular aortic aneurysmal dilatation at zone 2 measuring 4.4 × 4 cm. Owing to his surgical history, vascular access through the femoral and iliac arteries or abdominal aorta was impossible. We developed a new technique using a left posterolateral mini-thoracotomy approach to gain vascular access and perform TEVAR, avoiding the need for an open thoracotomy repair. Results and Conclusions Thoracic CTA performed before discharge revealed complete aneurysmal exclusion and no endoleaks. Postoperative follow-up CTA (6 months and annually thereafter) revealed no aneurysm formation or aortic restenosis. The femoral artery, followed by the iliac artery, is the traditional access route for TEVAR. Left posterolateral mini-thoracotomy may be required as an alternative access in complex patients.