bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runx3-overexpression cooperates with ex vivo AKT inhibition to generate receptor-engineered T cells with better persistence, tumor-residency, and antitumor ability
Authors: Tang Jianghui , Sheng Jianpeng , Zhang Qi , Ji Yongtao , Wang Xun , Zhang Junlei , Wu Jiangchao , Song Jinyuan , Bai Xueli , Liang Tingbo 
Published: February 2023

BackgroundSolid tumors pose unique roadblocks to treatment with chimeric antigen receptor (CAR) T cells, including limited T-cell persistence, inefficient tumor infiltration, and an immunosuppressive tumor microenvironment. To date, attempts to overcome these roadblocks have been unsatisfactory. Herein, we reported a strategy of combiningRunx3(encoding RUNX family transcription factor 3)-overexpression with ex vivo protein kinase B (AKT) inhibition to generate CAR-T cells with both central memory and tissue-resident memory characteristics to overcome these roadblocks.MethodsWe generated second-generation murine CAR-T cells expressing a CAR against human carbonic anhydrase 9 together withRunx3-overexpression and expanded them in the presence of AKTi-1/2, a selective and reversible inhibitor of AKT1/AKT2. We explored the influence of AKT inhibition (AKTi),Runx3-overexpression, and their combination on CAR-T cell phenotypes using flow cytometry, transcriptome profiling, and mass cytometry. The persistence, tumor-infiltration, and antitumor efficacy of CAR-T cells were evaluated in subcutaneous pancreatic ductal adenocarcinoma (PDAC) tumor models.ResultsAKTi generated a CD62L+central memory-like CAR-T cell population with enhanced persistence, but promotable cytotoxic potential.Runx3-overexpression cooperated with AKTi to generate CAR-T cells with both central memory and tissue-resident memory characteristics.Runx3-overexpression enhanced the potential of CD4+CAR T cells and cooperated with AKTi to inhibit the terminal differentiation of CD8+CAR T cells induced by tonic signaling. While AKTi promoted CAR-T cell central memory phenotype with prominently enhanced expansion ability,Runx3-overexpression promoted the CAR-T cell tissue-resident memory phenotype and further enhanced persistence, effector function, and tumor-residency. These novel AKTi-generatedRunx3-overexpressing CAR-T cells exhibited robust antitumor activity and responded well to programmed cell death 1 blockade in subcutaneous PDAC tumor models.ConclusionsRunx3-overexpression cooperated with ex vivo AKTi to generate CAR-T cells with both tissue-resident and central memory characteristics, which equipped CAR-T cells with better persistence, cytotoxic potential, and tumor-residency ability to overcome roadblocks in the treatment of solid tumors.
Five loop anomalous dimension of non-singlet quark currents in the RI$${}^\prime $$ scheme
Authors: Gracey J. A. 
Published: February 2023

AbstractWe construct the five loop anomalous dimensions of the basic fields in Quantum Chromodynamics in a linear covariant gauge in the modified Regularization Invariant ($$\textrm{RI}^\prime $$RI′) scheme. Using these core results we also compute the four loop Green’s function where the quark mass operator and vector current are separately inserted in a quark 2-point function. These are necessary for measurements of the same quantities on the lattice. The Green’s functions are provided in both the modified Minimal Subtraction ($$\overline{\textrm{MS}}$$MS¯) and$$\textrm{RI}^\prime $$RI′schemes. All the results are available for a general Lie group.
Topological black holes in higher derivative gravity
Authors: Pravdová Alena , Pravda Vojtěch , Ortaggio Marcello 
Published: February 2023

AbstractWe study static black holes in quadratic gravity with planar and hyperbolic symmetry and non-extremal horizons. We obtain a solution in terms of an infinite power-series expansion around the horizon, which is characterized by two independent integration constants – the black hole radius and the strength of the Bach tensor at the horizon. While in Einstein’s gravity, such black holes require a negative cosmological constant $$\Lambda $$
Λ
, in quadratic gravity they can exist for any sign of $$\Lambda $$
Λ
and also for $$\Lambda =0$$

Λ
=
0

. Different branches of Schwarzschild–Bach–(A)dS or purely Bachian black holes are identified which admit distinct Einstein limits. Depending on the curvature of the transverse space and the value of $$\Lambda $$
Λ
, these Einstein limits result in (A)dS–Schwarzschild spacetimes with a transverse space of arbitrary curvature (such as black holes and naked singularities) or in Kundt metrics of the (anti-)Nariai type (i.e., dS$$_2\times $$

2

×

S$$^2$$

2

, AdS$$_2\times $$

2

×

H$$^2$$

2

, and flat spacetime). In the special case of toroidal black holes with $$\Lambda =0$$

Λ
=
0

, we also discuss how the Bach parameter needs to be fine-tuned to ensure that the metric does not blow up near infinity and instead matches asymptotically a Ricci-flat solution.
Efficacy of Recombinant Human Endostatin plus Neoadjuvant Chemotherapy for Osteosarcoma and Its Influence on Serum VEGF and MMP-9 Levels
Authors: Sui Wei , Lin Guanghui 
Published: February 2023

Objective. To investigate the efficacy of recombinant human endostatin (rh-Endo) plus neoadjuvant chemotherapy (NACT) for osteosarcoma (OSA) and its influence on serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). Methods. The case data of 141 OSA patients presented to the North District, Xiangyang Central Hospital Affiliated to Hubei University of Arts and Sciences from January 2018 to June 2019, were analyzed retrospectively. Patients receiving NACT (methotrexate + ifosfamide + adriamycin) were assigned into the control group (CNG; n = 65), while those treated with rh-Endo plus NACT were included in the combination group (CMG; n = 76). The following aspects were compared: clinical efficacy, serum tumor markers, serum VEGF and MMP-9 contents, inflammatory factors, incidence of adverse reactions, limb function scores at 6 months of follow-up, and prognostic quality of life (QOL). Results. A statistically higher overall response rate (ORR) was determined in CMG versus CNG (84.2% vs. 64.6%,

P

< 0.05). The pretreatment serum bone alkaline phosphatase (BALP), insulin-like growth factor (IGF)-1, serum amyloid A (SAA), VEGF, MMP-9, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 levels differed insignificantly between the two cohorts (

P

> 0.05); while except IL-10 that showed increased expression in both cohorts and was comparatively higher in CMG, the other 8 parameters reduced in both cohorts after 2 weeks of drug withdrawal, and the reduction of each parameter was more significant in CMG (

P

< 0.05). The total adverse reaction rate was 30.2% in CMG, which was higher than that of 36.9% in CNG, albeit without a statistical difference (

P

> 0.05). An evidently higher 2-year survival rate was determined in CMG (

P

< 0.05). Conclusions. rh-Endo plus NACT is more effective than NACT alone in the treatment of osteosarcoma, which can validly restore the balance of vascular endothelial cells, reduce inflammation, and is worth promoting in clinic.
Mediation Effect of Obesity on the Association of Age at Menarche With Blood Pressure Among Women in Southwest China
Authors: Chen Jiayi , Yan Mingxia , Suolang Deji , Han Mingming , Baima Yangji , Mi Fei , Chen Liling , Guan Han , Cai Hui , Zhao Xing , Liu Qiaolan 
Published: February 2023

Background
Previous studies have been inconsistent about the association between age at menarche and high blood pressure. Little is known about such association across a wide range of menarcheal ages in less developed ethnic minority regions in China. We aimed to explore the association between age at menarche and high blood pressure (BP; ≥140/90 mm Hg) and to examine the mediating effect of obesity and the moderating effect of menopausal status on this association.

Methods and Results

A total of 45 868 women from the baseline data of the CMEC (China Multi‐Ethnic Cohort) were included in this study. Binary logistic regression was used to analyze the relationship between age at menarche and high BP, and the mediation model was used to evaluate the mediating effects of body mass index and waist circumference on the association of age at menarche with high BP. The mean age at enrollment and age at menarche of participants in our study were 49.3 (SD=10.7) and 14.7 (SD=2.1) years, respectively. Late menarche was associated with a lower risk of high BP (odds ratio, 0.831 [95% CI, 0.728–0.950]). The risk of high BP decreased by 3.1% with each year's delay in the onset of menarche (
P
for trend <0.001). Body mass index and waist circumference could partially mediate the association of age at menarche and high BP with the indirect effect of body mass index (odds ratio, 0.998 [95% CI, 0.997–0.998]) and waist circumference (odds ratio, 0.999 [95% CI, 0.998–0.999]). In addition, the mediation effects were modified by the status of menopause.

Conclusions
Women with late menarche have a lower risk of high BP, and obesity could be one of the important mediators. Obesity prevention is an efficient strategy to reduce the association between age at menarche and high BP, especially in premenopausal women.
RESCUE‐ICAS: Rationale and Study Design
Authors: Almallouhi Eyad , de Havenon Adam , Asi Khaled , Limaye Kaustubh , Maier Ilko , Starke Robert , Psychogios Marios , Inoa Violiza , Grossberg Jonathan A. , Mascitelli Justin , Samaniego Edgar A , Fragata Isabel , Kass‐Hout Tareq , Capasso Francesco , Dmytriw Adam A. , Jehani Hosam Al , Modovan Krisztina , Yaghi Shadi , Ezzeldin Mohamad , Grandhi Ramesh , Wolfe Stacey , Fargen Kyle , Jabbour Pascal , Naamani Kareem El , Spiotta Alejandro M. , Zaidat Osama O. , Kasab Sami Al 
Published: February 2023

Background
Mechanical thrombectomy (MT) failure occurs in ≈10% to 20% of MTs. Among the common causes of failed MT is residual underlying intracranial stenosis (ICAS), typically attributable to atherosclerotic disease. ICAS large‐vessel occlusion (ICAS‐LVO) remains poorly understood, and management of ICAS‐LVO is unclear. The RESCUE‐ICAS (Registry of Emergent Large Vessel Occlusion Due to Intracranial Stenosis) aims at providing better understanding of the prevalence of ICAS‐LVO, and the overall safety and efficacy of various rescue therapies.

Methods
RESCUE‐ICAS is a multicenter, international, prospective registry that is currently enrolling patients with ICAS‐LVO who underwent MT. All sites are required to report monthly MT cases that meet inclusion criteria. The decision of whether to use rescue therapy is up to the interventionist.

Results
We will collect patients’ demographic, clinical, and radiographic data at baseline. Also, we will capture variables related to the MT procedure and rescue therapy (if performed), and postprocedural clinical and imaging variables. Outcomes include the rate of successful recanalization, defined by modified Thrombolysis in Cerebral Infarction score of ≥2b, the rate of symptomatic intracranial hemorrhage, the 90‐day modified Rankin scale score, and mortality.

Conclusions
No strong evidence is currently available to support an optimal treatment strategy for patients with ICAS‐LVO undergoing MT. RESCUE‐ICAS is a prospective cohort study that will provide important data to help design randomized controlled trials.
Endovascular Stroke Therapy for Posterior Circulation Acute Ischemic Stroke Has Diminishing Benefit with Additional Passes
Authors: Jeevarajan Jerome A. , Kim Hyun‐Woo , Tariq Muhammad Bilal , Marioni Sergio Salazar , Niktabe Arash , Abdelkhaleq Rania , McCullough Louise , Sheth Sunil A. 
Published: February 2023

Background
The relationship between pass number during endovascular stroke therapy (EST) and outcomes in anterior circulation large vessel occlusion (LVO) acute ischemic stroke (AIS) has been well studied. However, the association between EST attempts and outcomes for patients with posterior circulation LVO remains unclear.

Methods
From our prospectively maintained multicenter registry, we identified consecutive patients with LVO AIS who underwent EST. The number of thrombectomy passes and per‐pass reperfusion grades (thrombolysis in cerebral infarction) were recorded prospectively at the time of procedure. The primary outcome was the association of number of EST passes and functional independence (modified Rankin scale 0–2) at 90 days. Secondary outcomes included likelihood of attaining substantial reperfusion (thrombolysis in cerebral infarction 2b‐3).

Results

Among 894 patients with LVO AIS who underwent EST, median age was 68 [interquartile range 58–78], 49% were female, and median National Institutes of Health Stroke Scale was 16 [interquartile range 11–21]. Of this cohort, 86 (9.6%) had posterior circulation LVO, including 65 (7%) with basilar artery occlusion and 9 (1%) with vertebral artery occlusion. The diminishing benefit on successful reperfusion of additional passes was similar for anterior and posterior circulation AIS. Among patients with posterior circulation stroke, successful reperfusion with fewer passes was associated with greater likelihood of good functional outcome at 90 days (40.0% versus 4.8% modified Rankin scale 0–2 with 1–2 versus 3+ passes;
P
= 0.003). The likelihood of good outcome in patients with posterior circulation LVO treated with EST and successful reperfusion in 1–2 passes was comparable to patients with anterior circulation LVO (40.0% versus 40.2%, posterior versus anterior;
P
= 0.553).

Conclusions
The number of EST passes has a significant association with functional independence at 90 days for patients with posterior circulation LVO AIS. After 2 passes, there is significantly reduced benefit conferred by additional passes. Overall clinical outcomes in patients with successful reperfusion with 1–2 passes were similar in patients with posterior circulation compared with anterior circulation LVO.
On the Open-Endedness of Detecting Open-Endedness
Authors: Stepney Susan , Hickinbotham Simon 
Published: February 2023

Abstract
We argue that attempting to quantify open-endedness misses the point: The nature of open-endedness is such that an open-ended system will eventually move outside its current model of behavior, and hence outside any measure based on that model. This presents a challenge for analyzing Artificial Life systems, leading us to conclude that the focus should be on understanding the mechanisms underlying open-endedness, not simply on attempting to quantify it. To demonstrate this, we apply several measures to eight long experimental runs of the spatial version of the Stringmol automata chemistry. These experiments were originally designed to examine the hypothesis that spatial structure provides a defense against parasites. The runs successfully show this defense, but also show a range of innovative, and possibly open-ended, behaviors involved in countering a parasitic arms race. Commencing with system-generic measures, we develop and use a variety of measures dedicated to analyzing some of these innovations. We argue that a process of analysis, starting with system-generic measures but going on to system-specific measures, will be needed wherever the phenomenon of open-endedness is involved.
The Moral Economy of High-Tech Modernism
Authors: Farrell Henry , Fourcade Marion 
Published: February 2023

Abstract
While people in and around the tech industry debate whether algorithms are political at all, social scientists take the politics as a given, asking instead how this politics unfolds: how algorithms concretely govern. What we call “high-tech modernism”- the application of machine learning algorithms to organize our social, economic, and political life-has a dual logic. On the one hand, like traditional bureaucracy, it is an engine of classification, even if it categorizes people and things very differently. On the other, like the market, it provides a means of self-adjusting allocation, though its feedback loops work differently from the price system. Perhaps the most important consequence of high-tech modernism for the contemporary moral political economy is how it weaves hierarchy and data-gathering into the warp and woof of everyday life, replacing visible feedback loops with invisible ones, and suggesting that highly mediated outcomes are in fact the unmediated expression of people's own true wishes.
High-Tech Modernism: Limits & Extensions
Authors: Janeway William H. 
Published: February 2023

Abstract
High-tech modernism is a powerful construct for reading the broad range of effects of digitalization on society. This response to Henry Farrell and Marion Fourcade's essay “The Moral Economy of High-Tech Modernism” first notes that high-tech modernism seems initially specified for application to advanced, quasi-liberal political economies. It then identifies three dimensions along which that construct could usefully be extended: 1) to take account of the limits of machine learning techniques of data analysis; 2) to consider the manner in which algorithmic digitalization transforms both the content and the management of work; and 3) to examine political responses to high-tech modernism, reminiscent of Karl Polanyi ‘s “double movement,” increasingly observable across a spectrum that runs from competition policy to the labor market.
Long-Term Follow-up of 64 Patients With Idiopathic Subglottic Stenosis: Treatment Pathways, Outcomes, and Impact of Serial Intralesional Steroid Injections
Authors: Schoeff Stephen , Hoffman Matthew R. , Zhang Yanchen , Yang Qiuyu , Dailey Seth H. 
Published: February 2023

Objective: To describe treatment pathways and long-term outcomes in 64 patients with idiopathic subglottic stenosis (iSGS), including the impact of serial intralesional steroid injection (SILSI) on degree of stenosis, need for subsequent operation, and patient-reported outcome measures. Methods: Retrospective review of 64 female patients with iSGS undergoing varied management approaches, 57 of whom underwent SILSI as at least part of their care. Treatment pathways included SILSI only, endoscopic intervention followed by SILSI only, endoscopic interventions only, endoscopic intervention followed by SILSI followed by need for repeat endoscopic intervention, open surgery, and tracheotomy. Outcomes assessed included subjectively estimated percent airway stenosis, dyspnea index (DI), modified medical research council (MMRC) dyspnea scale, voice handicap index-10 (VHI-10), number of operative and office-based procedures performed, need for subsequent operative intervention, and inter-operative interval. Results: Treatment pathways included SILSI alone (n = 6), endoscopic intervention(s) followed by SILSI only (n = 31), SILSI followed by additional endoscopic or office-based procedures (n = 16), open surgery (n = 3), and tracheostomy (n = 4). 57 of 64 patients underwent SILSI as at least part of their treatment. Inter-operative interval was increased after starting SILSI. Of patients undergoing SILSI, those with more procedures or shorter inter-operative interval prior to SILSI were more likely to return to the operating room. Estimated stenosis, DI, MMRC, and VHI-10 decreased with SILSI. Stenosis was not correlated with DI, MMRC, or VHI-10, though DI was correlated with both MMRC and VHI-10 score. Conclusion: Of 57 patients undergoing SILSI, 37 did not require further operative intervention. Improvements in inter-operative interval, dyspnea, and voice were observed across patients. Randomized trials to identify which patients may benefit most from SILSI are warranted.
Comparison of the surface morphologies of ceramic reinforced metal matrix composite cams after wear tests under dry and wet conditions
Authors: Cerit Alper A , Nair Fehmi , Zafar Hafız MN , Karamış MB 
Published: February 2023

The integral engine parts, such as camshaft members, are usually not preferably made of ceramic-reinforced MMC because the margin of compromise on the engine performance is small. However, the lightweight and wear-resistant nature of the mentioned materials can benefit fuel consumption without necessarily compromising engine performance. In this study, Al (AA2124) matrix is reinforced with ceramic particles of two different types (SiC, B4C), size distributions (B4C: 1–7, SiC: 2 and 20 μm), and volume fractions (0, 10, 20, 30 vol.%) to manufacture camshaft cams (lobes). While MMC cams are manufactured by powder metallurgy (300 MPa, 615°C, 30 minutes), spherical graphite cast iron (GGG40) cams are prepared by casting, induction hardening, and machining. The wear behavior of MMC cams is compared with the reference unreinforced AA2124 and conventionally used cast iron cams under dry and virtually created engine-like wet conditions. It was attempted to correlate the percentage increase in the roughness and weight loss with the structure of the cams using SEM, EDX, and macroscopy analysis. Results showed that the initiation of a three-body abrasive wear mechanism for 30 vol.% of the larger SiC particles caused lower wear resistance in the cams under dry conditions. As for the wet conditions, although the cams’ wear resistance increased with increasing ceramic particles’ content, it resulted in enhanced wear in the counterface when larger ceramic particles were used as reinforcement. Overall, higher ceramic content and larger particle size encourage three-body abrasive wear between the interacting surfaces and assist in degraded wear resistance under wet conditions.
Quasi-static compressive behaviour of epoxy composites reinforced with crumb rubber
Authors: Shahapurkar Kiran , Kiran MC , Alamir Mohammed A , Tirth Vineet , Alarifi Ibrahim M , Chenrayan Venkatesh 
Published: February 2023

Quasi static compressive response of crumb rubber-epoxy composites was examined by varying the crumb rubber composition (0, 10, 20 and 30 vol.%). All the composites, irrespective of the strain rates, depict elastic regions tailed by a wide plateau area that is credited with the densification of rubber particulates. Higher strains to failure of composites were revealed as compared with neat epoxy signifying higher energy absorption ability of constituents. The modulus of elasticity of composites was noted to be lower than neat epoxy specimens, irrespective of the strain rates. Irrespective of strain rates, the strength of all the composites were inferior to neat epoxy specimens. Energy absorption of EC-30 was higher compared to EC-20 and EC-10 and noted to be increased in the range of 6–14% for 0.1 mm/min strain rate while it increases in the range of 5–9% for 0.01 mm/min strain rate, respectively. Rubber-toughening mechanism was credited with the increase in energy absorption of composites. Higher energy absorption of composites was mainly due to higher strain realisation indicating more deformation ability. Fracture features of specimens were analysed by scanning electron microscope.