bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vinblastine resets tumor-associated macrophages toward M1 phenotype and promotes antitumor immune response
Authors: Wang Yi-Na , Wang Yuan-Yuan , Wang Jin , Bai Wen-Juan , Miao Nai-Jun , Wang Jing 
Published: August 2023

BackgroundMassive tumor-associated macrophage (TAM) infiltration is observed in many tumors, which usually display the immune-suppressive M2-like phenotype but can also be converted to an M1-like antitumor phenotype due to their high degree of plasticity. The macrophage polarization state is associated with changes in cell shape, macrophage morphology is associated with activation status. M1 macrophages appeared large and rounded, while M2 macrophages were stretched and elongated cells. Manipulating cell morphology has been shown to affect the polarization state of macrophages. The shape of the cell is largely dependent on cytoskeletal proteins, especially, microtubules. As a microtubule-targetting drug, vinblastine (VBL) has been used in chemotherapy. However, no study to date has explored the effect of VBL on TAM shape changes and its role in tumor immune response.MethodWe used fluorescent staining of the cytoskeleton and quantitative analysis to reveal the morphological differences between M0, M1, M2, TAM and VBL-treated TAM. Flow cytometry was used to confirm the polarization states of these macrophages using a cell surface marker-based classification. In vivo antibody depletion experiments in tumor mouse models were performed to test whether macrophages and CD8+T cell populations were required for the antitumor effect of VBL. VBL and anti-PD-1 combination therapy was then investigated in comparison with monotherapy. RNA-seq of TAM of treated and untreated with VBL was performed to explore the changes in pathway activities. siRNA mediated knockdown experiments were performed to verify the target pathway that was affected by VBL treatment.ResultsHere, we showed that VBL, an antineoplastic agent that destabilizes microtubule, drove macrophage polarization into the M1-like phenotype both in vitro and in tumor models. The antitumor effect of VBL was attenuated in the absence of macrophages or CD8+T cells. Mechanistically, VBL induces the activation of NF-κB and Cyba-dependent reactive oxygen species generation, thus polarizing TAMs to the M1 phenotype. In parallel, VBL promotes the nuclear translocation of transcription factor EB, inducing lysosome biogenesis and a dramatic increase in phagocytic activity in macrophages.ConclusionsThis study explored whether manipulating cellular morphology affects macrophage polarization and consequently induces an antitumor response. Our data reveal a previously unrecognized antitumor mechanism of VBL and suggest a drug repurposing strategy combining VBL with immune checkpoint inhibitors to improve malignant tumor immunotherapy.
Impact on collateral flow of devices used for endovascular treatment of stroke: an in-vitro flow model
Authors: Requena Manuel , Li Jiahui , Tiberi Riccardo , Canals Pere , Olive Gadea Marta , de Dios Lascuevas Marta , Jabłońska Magda , Cendrero Judith , Garcia-Tornel Alvaro , Tomasello Alejandro , Ribo Marc 
Published: August 2023

BackgroundCollateral blood supply of distal vessels has been linked to clinical outcome, infarct volume and recanalization rates in patients with large vessel occlusion. Our study aimed to explore the effects of catheterization during mechanical thrombectomy in collaterals.MethodsWe quantified the flow diversion effect secondary to arterial occlusions in an in vitro model which was connected in a flow-loop setup with a saline reservoir and a pump supplying pulsatile flow. Clot analogs were embolized to the middle cerebral artery (MCA) M1 or M2 segments. We used the same model with a clamped anterior communicating artery (AComA) to simulate its absence. An ultrasound flow sensor was placed at the vessel of interest. Flow rates and pressures were evaluated according to the following catheter locations: baseline (1) before and (2) after the occlusion; (3) 8F guiding catheter at the internal carotid artery (ICA) bulb; (4) at the cavernous segment; (5) at the cavernous segment a 0.071” distal access catheter at proximal M1; (6) 8F balloon guide catheter inflated.ResultsCollateral blood flow measured at distal anterior cerebral artery (ACA) (M1-MCA occlusion) and M2-MCA (M2-MCA occlusion) was progressively reduced as catheters were advanced through the ICA and MCA. In the lacking AComA model, the flow was further diminished as compared with the model with a patent AComA.ConclusionOur in vitro study showed a progressive reduction of collateral blood flow due to the advance of catheters during mechanical thrombectomy.
Ancestral diversity in lipoprotein(a) studies helps address evidence gaps
Authors: Lee Moa P , Dimos Sofia F , Raffield Laura M , Wang Zhe , Ballou Anna F , Downie Carolina G , Arehart Christopher H , Correa Adolfo , de Vries Paul S , Du Zhaohui , Gignoux Christopher R , Gordon-Larsen Penny , Guo Xiuqing , Haessler Jeffrey , Howard Annie Green , Hu Yao , Kassahun Helina , Kent Shia T , Lopez J Antonio G , Monda Keri L , North Kari E , Peters Ulrike , Preuss Michael H , Rich Stephen S , Rhodes Shannon L , Yao Jie , Yarosh Rina , Tsai Michael Y , Rotter Jerome I , Kooperberg Charles L , Loos Ruth J F , Ballantyne Christie , Avery Christy L , Graff Mariaelisa 
Published: August 2023

IntroductionThe independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.MethodsHere, we examined how ancestrally diverse studies could clarify Lp(a)’s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations.ResultsFourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R2=15% in East Asians) to high (R2=50% in Europeans) accuracy. For all populations, PRS showed promise as a ‘rule out’ for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%–99.9%) across PRS thresholds (80th–99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10−6), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects.ConclusionsOur results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.
Receipt and use of prohibited free samples of tobacco products among US adults who use cigarettes, cigars and smokeless tobacco, 2020
Authors: Inyang Naa A , Loomis Brett R , Nagler Caryn F , Coats Ellen M , Saba Christine , Saunders McKinley , Liu Sherry T 
Published: August 2023

ObjectivesIn the USA, tobacco product free samples (FS) are prohibited, except for smokeless tobacco samples distributed under certain conditions in qualified adult-only facilities. We examined prevalence and frequency of FS receipt among adults who use tobacco, channels of FS distribution and the potential effect of FS use on subsequent product purchase.MethodsFrom 15 April through 12 July 2020, a total of 1989 adult participants in the National Panel of Tobacco Consumer Studies completed a mixed-mode survey on receipt and use of FS of cigarettes, cigars, smokeless tobacco, e-cigarettes and hookah tobacco. We estimated weighted proportions, population totals and 95% CIs. We used χ2tests to assess differences between FS recipients and non-recipients.ResultsAn estimated 11.0% of US adults who use tobacco received an FS in 2020. Similar proportions received FS of cigarettes (3.8%), cigars (3.3%), smokeless tobacco (3.2%) and e-cigarettes (2.7%). Approximately 60.0% of FS recipients used it, and 68.1% of those who used FS said they were likely to purchase the product. More than half (54.2%) received FS on two or more occasions in the past 12 months, most commonly at retail outlets and tobacco specialty stores.ConclusionsWhile prevalence of adults who use tobacco receiving FS is relatively low, findings indicate that FS distribution continues to occur for cigarettes, cigars, smokeless tobacco and e-cigarettes, though in-person FS of smokeless tobacco may be legally distributed under certain conditions in qualified adult-only facilities. Findings suggest that FS are often used by recipients, which can affect future purchase decisions.
Inflation using a triplet of antisymmetric tensor fields
Authors: Ajith Abhijith , Panda Sukanta 
Published: August 2023

AbstractWe study an inflation model driven by a triplet of antisymmetric tensor fields, with minimal and nonminimal couplings to gravity. First, we show that the presence of a triplet of antisymmetric tensor fields can provide inherent background isotropy in the stress–energy tensor contrary to the past studies using an antisymmetric tensor field. Inflation is supported in the presence of non-minimal couplings with gravity. We perform the slow roll analysis and also analyse perturbations to the antisymmetric tensor field as well as the tensor modes of perturbed metric. The speed of gravitational waves manifested from the tensor perturbations is tuned to c. We also study the evolution of the gravitational waves, calculate their power spectrum and tensor spectral index.
Charmoniumlike tetraquarks in a chiral quark model
Authors: Yang Gang , Ping Jialun , Segovia Jorge 
Published: August 2023

AbstractThe lowest-lying charmonium-like tetraquarks$$c{\bar{c}}q{\bar{q}}$$cc¯qq¯$$(q=u,\,d)$$(q=u,d)and$$c{\bar{c}}s{\bar{s}}$$cc¯ss¯, with spin-parity$$J^P=0^+$$JP=0+,$$1^+$$1+and$$2^+$$2+, and isospin$$I=0$$I=0and 1, are systematically investigated within the theoretical framework of complex-scaling range for a chiral quark model that has already been successfully applied in former studies of various tetra- and penta-quark systems. A four-bodyS-wave configuration which includes meson–meson, diquark–antidiquark and K-type arrangements of quarks, along with all possible color wave functions, is comprehensively considered. Several narrow resonances are obtained in each tetraquark channel when a fully coupled-channel computation is performed. We tentatively assign theoretical states to experimentally reported charmonium-like signals such asX(3872),$$Z_c(3900)$$Zc(3900),X(3960),X(4350),X(4685) andX(4700). They can be well identified as hadronic molecules; however, other exotic components which involve, for instance, hidden-color channels or diquark–antidiquark structures play a considerable role. Meanwhile, two resonances are obtained at 4.04 GeV and 4.14 GeV which may be compatible with experimental data in the energy interval 4.0–4.2 GeV. Furthermore, theX(3940) andX(4630) may be identified as color compact tetraquark resonances. Finally, we also find few resonance states in the energy interval from 4.5 to 5.0 GeV, which would be awaiting for discovery in future experiments.
Smart-DNN+: A Memory-efficient Neural Networks Compression Framework for the Model Inference
Authors: Wu Donglei , Yang Weihao , Zou Xiangyu , Xia Wen , Li Shiyi , Hu Zhenbo , Zhang Weizhe , Fang Binxing 
Published: August 2023

Deep Neural Networks (DNNs) have achieved remarkable success in various real-world applications. However, running a Deep Neural Network (DNN) typically requires hundreds of megabytes of memory footprints, making it challenging to deploy on resource-constrained platforms such as mobile devices and IoT. Although mainstream DNNs compression techniques such as pruning, distillation, and quantization can reduce the memory overhead of model parameters during DNN inference, they suffer from three limitations: (i) low model compression ratio for the lightweight DNN structures with little redundancy, (ii) potential degradation in model inference accuracy, and (iii) inadequate memory compression ratio is attributable to ignoring the layering property of DNN inference. To address these issues, we propose a lightweight memory-efficient DNN inference framework called Smart-DNN+, which significantly reduces the memory costs of DNN inference without degrading the model quality. Specifically, ① Smart-DNN+ applies a layerwise
binary-quantizer
with a remapping mechanism to greatly reduce the model size by quantizing the typical floating-point DNN weights of 32-bit to the 1-bit signs layer by layer. To maintain model quality, ② Smart-DNN+ employs a
bucket-encoder
to keep the compressed quantization error by encoding the multiple similar floating-point residuals into the same integer bucket IDs. When running the compressed DNN in the user’s device, ③ Smart-DNN+ utilizes a
partially decompressing strategy
to greatly reduce the required memory overhead by first loading the compressed DNNs in memory and then dynamically decompressing the required materials for model inference layer by layer.

Experimental results on popular DNNs and datasets demonstrate that Smart-DNN+ achieves lower 0.17%–0.92% memory costs at lower runtime overheads compared with the states of the art without degrading the inference accuracy. Moreover, Smart-DNN+ potentially reduces the inference runtime up to 2.04× that of conventional DNN inference workflow.
Structural Racism, Lifestyle Behaviors, and Obesity-related Cancers among Black and Hispanic/Latino Adults in the United States: A Narrative Review
Authors: Pichardo Margaret S. , Ferrucci Leah M. , Molina Yamile , Esserman Denise A. , Irwin Melinda L. 
Published: August 2023

Abstract
One in three adults in the United States has obesity; a chronic disease that is implicated in the etiology of at least 14 cancers. Cancer is the leading cause of death among U.S. Hispanic/Latino adults and the second most common cause of death, after cardiovascular disease, for Black adults. Our country's legacy in overt discrimination (e.g., slavery, segregation) generated inequities across all spheres in which people function as defined by the socioecological model—biological, individual, community, structural—and two of the many areas in which it manifests today are the disproportionate burden of obesity and obesity-related cancers in populations of color. Inequities due to environmental, social, and economic factors may predispose individuals to poor lifestyle behaviors by hindering an individual's opportunity to make healthy lifestyles choices. In this review, we examined the evidence on obesity and the lifestyle guidelines for cancer prevention in relation to cancer risk and outcomes for Black and Hispanic/Latino adults. We also discussed the role of structural and societal inequities on the ability of these two communities to adopt and maintain healthful lifestyle behaviors in accordance with the lifestyle guidelines for cancer prevention and control.
Molecular Characterization of Endometrial Carcinomas in Black and White Patients Reveals Disparate Drivers with Therapeutic Implications
Authors: Weigelt Britta , Marra Antonio , Selenica Pier , Rios-Doria Eric , Momeni-Boroujeni Amir , Berger Michael F. , Arora Kanika , Nemirovsky David , Iasonos Alexia , Chakravarty Debyani , Abu-Rustum Nadeem R. , Da Cruz Paula Arnaud , Dessources Kimberly , Ellenson Lora H. , Liu Ying L. , Aghajanian Carol , Brown Carol L. 
Published: August 2023

AbstractAlthough the incidence of endometrial carcinoma (EC) is similar in Black and White women, racial disparities are stark, with the highest mortality rates observed among Black patients. Here, analysis of 1,882 prospectively sequenced ECs using a clinical FDA-authorized tumor–normal panel revealed a significantly higher prevalence of high-risk histologic and molecular EC subtypes in self-identified Black (n = 259) compared with White (n = 1,623) patients. Clinically actionable alterations, including high tumor mutational burden/microsatellite instability, which confer benefit from immunotherapy, were less frequent in ECs from Black than from White patients. Ultramutated POLE molecular subtype ECs associated with favorable outcomes were rare in Black patients. Results were confirmed by genetic ancestry analysis. CCNE1 gene amplification, which is associated with aggressive clinical behavior, was more prevalent in carcinosarcomas occurring in Black than in White patients. ECs from Black and White patients display important differences in their histologic types, molecular subtypes, driver genetic alterations, and therapeutic targets.Significance:Our comprehensive analysis of prospectively clinically sequenced ECs revealed significant differences in their histologic and molecular composition and in the presence of therapeutic targets in Black versus White patients. These findings emphasize the importance of incorporating diverse populations into molecular studies and clinical trials to address EC disparities.This article is featured in Selected Articles from This Issue, p. 2293
Loss of 12-Lipoxygenase Improves the Post-Transfusion Function of Stored Platelets
Authors: Larsen Hannah J. , Byrne Daire , Özpolat Tahsin , Chauhan Aastha , Bailey S. Lawrence , Rhoads Nicole , Reed Franklin , Stolla Massiel C. , Adili Reheman , Holinstat Michael , Fu Xiaoyun , Stolla Moritz 
Published: August 2023

BACKGROUND:
Platelets for transfusion are stored for 5 to 7 days. Previous studies have shown that HETE levels in the storage bag negatively correlate with platelet performance in vivo, suggesting that the dysregulation of bioactive lipid mediators may contribute to the storage lesion. In the current study, we sought to understand how genetic deletion and pharmacological inhibition of 12-LOX (12-lipoxygenase) affects platelets during storage and after transfusion.

METHODS:

Platelets from 12-LOX
+/+
(wild-type [WT]) and 12-LOX
−/−
mice were stored for 24 and 48 hours and profiled using liquid chromatography-tandem mass spectrometry–multiple reaction monitoring or transfused into thrombocytopenic hIL4R (human interleukin 4 receptor)-transgenic mice. Platelet function was assessed by flow cytometry and in vivo thrombosis and hemostasis models. To test the role of the COX-1 (cyclooxygenase-1) pathway, donor mice were treated with acetylsalicylic acid. Human platelets were treated with the 12-LOX inhibitor, VLX-1005, or vehicle, stored, and transfused to NOD/SCID (nonobese diabetic/severe combined immunodeficiency) mice.

RESULTS:

Polyunsaturated fatty acids increased significantly in stored platelets from 12-LOX
−/−
mice, whereas oxylipin concentrations were significantly higher in WT platelets. After transfusion to thrombocytopenic mice, we observed significantly more baseline αIIbβ3 integrin activation in 12-LOX
−/−
platelets than in WT platelets. Stored platelets from 12-LOX
−/−
mice occluded vessels significantly faster than stored WT platelets. In hemostasis models, significantly more stored 12-LOX
−/−
than WT platelets accumulated at the site of venous injury leading to reduced blood loss. Inhibition of COX-1 abrogated both increased integrin activation and thromboxane generation in stored 12-LOX
−/−
platelets, highlighting the critical role of this pathway for improved post-transfusion function. Consistent with our mouse studies, human platelets stored with VLX-1005, showed increased integrin activation compared with vehicle-treated platelets after transfusion.

CONCLUSIONS:
Deleting 12-LOX improves the post-transfusion function of stored murine platelets by increasing thromboxane generation through COX-1–dependent arachidonic acid metabolism. Future studies should determine the feasibility and safety of 12-LOX–inhibited platelets transfused to humans.
Association of Supine Hypertension Versus Standing Hypotension With Adverse Events Among Middle-Aged Adults
Authors: Earle William B. , Kondo Jordan K. , Kendrick Karla N. , Turkson-Ocran Ruth-Alma , Ngo Long , Cluett Jennifer L. , Mukamal Kenneth J. , Daya Malek Natalie , Selvin Elizabeth , Lutsey Pamela L. , Coresh Josef , Juraschek Stephen P. 
Published: August 2023

BACKGROUND:
Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension.

OBJECTIVES:
To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH.

METHODS:
The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope.

RESULTS:

Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status (
P
-interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68–1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02–1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37–1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00–1.14]).

CONCLUSIONS:
Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension.