bluuebunny/crossref_metadata_2025_split huggingface dataset:
Area deprivation and premature cardiovascular mortality: a nationwide population-based study in South Korea
Authors: Kim Eunji , Lee Hokyou , Lloyd-Jones Donald , Ko Young Gyu , Kim Byoung Gwon , Kim Hyeon Chang 
Published: April 2024

BackgroundRegional disparities in cardiovascular disease (CVD) burden exist. The effect of area deprivation, one of the possible explanations, still needs to be fully understood. This population-based study investigated the association between Area Deprivation Index (ADI) and CVD-related premature death.MethodsADI was derived from 10 socioeconomic indicators in 250 South Korean municipalities using the 2020 Population and Housing Census data. Mortality rates for CVD and its subtypes, namely ischaemic heart diseases, other heart diseases and cerebrovascular diseases, in adults under 65 years were directly standardised by sex and age, referencing the total population structure. Municipalities were categorised by urbanicity, and adjustments for the number of hospitals and geographical area size were made using log-linear regression models.ResultsThe most deprived municipalities showed 41.6% excess mortality for CVD, 30.3% for ischaemic heart diseases, 60.7% for other heart diseases and 36.9% for cerebrovascular diseases compared with the least deprived municipalities. Even after adjusting for the number of hospitals per unit area, the association between ADI and premature CVD death was more significant in metropolitan areas than in other provinces. For each incremental increase in the continuous ADI, the adjusted mortality rate ratios were observed as 1.031 (95% CI, 1.020 to 1.043) in metropolitan areas and 1.009 (95% CI, 1.000 to 1.019) in other provinces. Additional multilevel analyses showed consistent findings of a higher risk in deprived areas.ConclusionThis study highlights a higher risk of premature cardiovascular death in socioeconomically disadvantaged areas. CVD prevention strategies should reflect regional characteristics and focus on reducing the burden in deprived metropolitan areas.
Possible dark energy stars in Rastall gravity
Authors: Ashraf Asifa , Shahzad M. R. , Ma Wen-Xiu 
Published: April 2024

Observational evidence revealed that in the composition of the Universe, the dark energy is in heap proportion which is mainly responsible for the accelerated expansion of the Universe. The astrophysicists hypothesized that every astrophysical object is likely interact with the dark energy Sakti and Sulaksono [Phys. Rev. D 103 (2021) 084042]. Therefore, researchers are intended to study the astrophysical objects with dark energy interaction. In this paper, we proposed a dark energy stars (composed of with dark matter and ordinary matter) model in the Rastall theory of gravity. The Rastall field equations are obtained in the Tolman–Kuchowicz-type metric. To solve the field equations, the arbitrary constants involved in the field equations (due to Tolman–Kuchowicz ansatz) are obtained by matching the interior geometry with the exterior Schwarzschild geometry. The obtained solution is tested physically by computing some analytical results and plotting graphs of different physical parameters like pressure, density for ordinary matter, density for dark matter, mass function, compactness and surface redshift. Stability of the model is also analyzed by different tests like velocity of sound, adiabatic index and TOV equations. The influence of the Rastall parameter on the model has been studied by plotting graphs and computing numerical values of model’s physical parameters for different values of the Rastall parameter. We infer that our propounded model fulfills all the necessary requirements for a physically plausible model.
Floodplain organic-carbon dynamics modulated by meandering-channel migration: Vermilion River, Ontario, Canada
Authors: Barrera Melissa , Ielpi Alessandro 
Published: April 2024

Abstract

Floodplains are important organic carbon (OC) storage sites, and the evolution of watercourses modulates the transport, burial and reworking of organics with cascading effects on watershed CO
2
budgets. Meandering rivers have broadly predictable patterns of channel-planform evolution, providing an opportunity to assess floodplain OC budgets of relation to characteristic migration paces and floodplain ages. However, due to geomorphic complexities of individual meandering rivers, assessments of relationships between channel and OC dynamics have thus far remained limited. We illustrate evolving OC budgets in relation to channel migration in the Vermilion River (Ontario) located in the boreal forest of eastern North America. We combine photogrammetric analyses and dynamic time warping of channel centrelines with analysis of top-soil bulk density and OC. We found that variations of OC stock per unit surface area and soil development are modulated by meander migration through the development of typical boreal-forest vegetation successions. Our results support the hypothesis that meander migration controls soil development, forest age and floodplain OC budgets. We anticipate our study to inform wider applications to rivers in different bioclimates – an approach that may in turn help carbon assessment in the context of changing climate or land use.
Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E. 
Published: April 2024

Abstract

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance antitumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand IgG Fc (Fcγ) receptor binding for therapeutic benefit. In this study, we showed that combining Fc-enabled (Fce) or Fc-silent (Fcs) anti-TIGIT with antiprogrammed cell death protein 1 in mice resulted in enhanced control of tumors by differential mechanisms: Fce anti-TIGIT promoted the depletion of intratumoral Treg, whereas Fcs anti-TIGIT did not. Despite leaving Treg numbers intact, Fcs anti-TIGIT potentiated the activation of tumor-specific exhausted CD8+ populations in a lymph node–dependent manner. Fce anti-TIGIT induced antibody-dependent cell-mediated cytotoxicity against human Treg in vitro, and significant decreases in Treg were measured in the peripheral blood of patients with phase I solid tumor cancer treated with Fce anti-TIGIT. In contrast, Fcs anti-TIGIT did not deplete human Treg in vitro and was associated with anecdotal objective clinical responses in two patients with phase I solid tumor cancer whose peripheral Treg frequencies remained stable on treatment. Collectively, these data provide evidence for pharmacologic activity and antitumor efficacy of anti-TIGIT antibodies lacking the ability to engage Fcγ receptor.

Significance:
Fcs-silent anti-TIGIT antibodies enhance the activation of tumor-specific pre-exhausted T cells and promote antitumor efficacy without depleting T regulatory cells.
Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy
Authors: Low Jacob C.M. , Cao Jianbo , Hesse Friederike , Wright Alan J. , Tsyben Anastasia , Alshamleh Islam , Mair Richard , Brindle Kevin M. 
Published: April 2024

Abstract

Metabolic subtypes of glioblastoma (GBM) have different prognoses and responses to treatment. Deuterium metabolic imaging with 2H-labeled substrates is a potential approach to stratify patients into metabolic subtypes for targeted treatment. In this study, we used 2H magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging (MRSI) measurements of [6,6′-2H2]glucose metabolism to identify metabolic subtypes and their responses to chemoradiotherapy in patient-derived GBM xenografts in vivo. The metabolism of patient-derived cells was first characterized in vitro by measuring the oxygen consumption rate, a marker of mitochondrial tricarboxylic acid cycle activity, as well as the extracellular acidification rate and 2H-labeled lactate production from [6,6′-2H2]glucose, which are markers of glycolytic activity. Two cell lines representative of a glycolytic subtype and two representative of a mitochondrial subtype were identified. 2H magnetic resonance spectroscopy and MRSI measurements showed similar concentrations of 2H-labeled glucose from [6,6′-2H2]glucose in all four tumor models when implanted orthotopically in mice. The glycolytic subtypes showed higher concentrations of 2H-labeled lactate than the mitochondrial subtypes and normal-appearing brain tissue, whereas the mitochondrial subtypes showed more glutamate/glutamine labeling, a surrogate for tricarboxylic acid cycle activity, than the glycolytic subtypes and normal-appearing brain tissue. The response of the tumors to chemoradiation could be detected within 24 hours of treatment completion, with the mitochondrial subtypes showing a decrease in both 2H-labeled glutamate/glutamine and lactate concentrations and glycolytic tumors showing a decrease in 2H-labeled lactate concentration. This technique has the potential to be used clinically for treatment selection and early detection of treatment response.

Significance:
Deuterium magnetic resonance spectroscopic imaging of glucose metabolism has the potential to differentiate between glycolytic and mitochondrial metabolic subtypes in glioblastoma and to evaluate early treatment responses, which could guide patient treatment.
The circMYBL2-Encoded p185 Protein Suppresses Colorectal Cancer Progression by Inhibiting Serine Biosynthesis
Authors: Zhao Ning , Cao Yinghao , Tao Ruikang , Zhu Xiuxian , Li Runze , Chen Yajun , Tao Kaixiong , Li Lei , Chen Hengyu , Ma Xianxiong 
Published: April 2024

Abstract
Circular RNAs are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circular RNA. In this study, we found that circMYBL2 in colorectal cancer encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth and aggressiveness of colorectal cancer cells in vitro and in vivo. Mechanistically, p185 counteracted ubiquitin C-terminal hydrolase L3 (UCHL3)–mediated deubiquitination of phosphoglycerate dehydrogenase (PHGDH) by competitively binding to the C1 domain of UCHL3, resulting in PHGDH degradation and a subsequent reduction in serine and glycine biosynthesis. These data revealed that the circMYBL2-encoded p185 isoform serves as a tumor suppressor to inhibit the progression of colorectal cancer by reducing serine biosynthesis.
Significance: A p185 protein encoded by circMYBL2 functions as a tumor suppressor that inhibits the progression of colorectal cancer by increasing the degradation of PHGDH to reduce serine biosynthesis.
PARP-ish: Gaps in Molecular Understanding and Clinical Trials Targeting PARP Exacerbate Racial Disparities in Prostate Cancer
Authors: Cunningham Moriah L. , Schiewer Matthew J. 
Published: April 2024

Abstract
PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer, and several others are in clinical trials for this disease. Recent clinical trial results have reported differential efficacy based on the specific PARPi utilized as well as patient race. There is a racial disparity in prostate cancer, in which African American males are twice as likely to develop and die from the disease compared with European American males. Despite the disparity, there continues to be a lack of diversity in clinical trial cohorts for prostate cancer. In this review, PARP nuclear functions, inhibition, and clinical relevance are explored through the lens of racial differences. This review will touch on the biological variations that have been explored thus far between African American and European American males with prostate cancer to offer a rationale for investigating PARPi response in the context of race at both basic science and clinical development levels.
Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata
Authors: Kipnis Lindsay M. , Breen Katelyn M. , Koeller Diane R. , Levine Alison Schwartz , Yang Zelei , Jun Hyeji , Tayob Nabihah , Stokes Samantha M. , Hayes Connor P. , Ghazani Arezou A. , Hill Sarah J. , Rana Huma Q. 
Published: April 2024

Abstract

Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata.

Prevention Relevance:
Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed.
Balloon Guide Catheter Versus Non–Balloon Guide Catheter: A MR CLEAN Registry Analysis
Authors: Knapen Robrecht R.M.M. , Goldhoorn Robert‐Jan B. , Hofmeijer Jeannette , Lycklamaà Nijeholt Geert J. , van den Berg René , van den Wijngaard Ido R. , van Oostenbrugge Robert J. , van Zwam Wim H. , van der Leij Christiaan ,   the MR CLEAN Registry Investigators
Published: April 2024

Background
Balloon guide catheters (BGCs) are used to prevent distal emboli during endovascular treatment for acute ischemic stroke. Although literature reports benefit of BGC, these are not universally used, and randomized head‐to‐head comparisons are lacking. This study compared functional, safety, and technical outcomes between patients treated with non‐BGC and with BGC during endovascular treatment in a nationwide prospective multicenter registry.

Methods
Patients from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, 2014 to 2018), who underwent endovascular treatment with a non‐BGC or BGC, were included. Primary outcome was the modified Rankin Scale score at 90 days, and secondary outcomes included procedure time and first‐attempt successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2C). Treatment‐effect modification and subgroups were analyzed according to first‐line thrombectomy technique and different sizes of non‐BGC.

Results
In total 2808 patients were included, and 1671 (60%) were treated with BGC. No differences in the modified Rankin Scale score at 90 days were seen between non‐BGC and BGC groups (adjusted common odds ratio [OR], 0.98 [95% CI, 0.82–1.10]). The non‐BGC was associated with faster procedure times compared with BGC (adjusted β: −2.99 [95% CI, −5.58 to −0.40]). A significant treatment effect was found between BGC use and thrombectomy technique. In subgroup analyses with stent retriever as first‐line technique, 90‐day modified Rankin Scale scores were significantly higher (more disability) in the non‐BGC group compared with the BGC group (adjusted common OR, 0.79 [95% CI, 0.65–0.96]). Direct aspiration combined with non‐BGC resulted in higher first‐attempt rates compared with BGC (adjusted OR, 1.55 [95% CI, 1.06–2.28]).

Conclusions
This large prospective multicenter registry showed no differences in clinical outcome between patients treated with non‐BGC and BGC. Subgroup analyses suggest that BGC outperforms the non‐BGC when stent retriever is used as first‐line technique, whereas non‐BGC outperforms the BGC when aspiration is used.
Structural Analysis of Aspiration Catheters and Procedural Outcomes: An Analysis of the SVIN Registry
Authors: Dolia Jaydevsinh N. , Mohammaden Mahmoud H. , Tarek Mohamed A. , Damiani Mateus , Grossberg Jonathan A. , Pabaney Aqueel , Frankel Michael , Jillella Dinesh V. , Hassan Ameer E. , Tekle Wondwossen G. , Georgiadis Alexandros , Saei Hamzah , Ortega‐Gutierrez Santiago , Vivanco‐Suarez Juan , Galecio‐Castillo Milagros , Rodriguez‐Calienes Aaron , Majidi Shahram , Fifi Johanna , Matsoukas Stavros , Siegler James E. , Penckofer Mary , Rana Ankit , Sheth Sunil A. , Salazar Marioni Sergio A. , Nguyen Thanh N. , Abdalkader Mohamad , Linfante Italo , Dabus Guilherme , Mehta Brijesh P. , Sessa Joy , Jumaa Mouhammad , Sugg Rebecca , Linares Guillermo , Al‐Bayati Alhamza R. , Libeskind David S. , Nogueira Raul G. , Haussen Diogo C. 
Published: April 2024

Background
Rapid expansion of mechanical thrombectomy and swift manufacturing development has translated into significant evolution of large‐bore catheter technology. The objective of this study was to evaluate the association among diverse structural components of large‐bore aspiration catheters on procedural performance.

Methods
Retrospective analysis of a prospectively maintained mechanical thrombectomy consortium (SVIN [Society of Vascular Interventional Neurology] Registry) treated with stand‐alone contact aspiration for the first pass in the middle cerebral artery M1 or intracranial internal carotid artery occlusions from 2012 to 2021. Catheters were stratified on the basis of construction materials, tip technology, catheter sizing, and catheter lining. Factors associated with first‐pass effect (first‐pass eTICI 2c–3 reperfusion) as well as speed of clot engagement were analyzed.

Results
We identified 983 patients with proximal occlusion and aspiration as the first‐pass technique. First‐pass effect was observed in 34% and associated with age (odds ratio [OR], 1.02 [95% CI, 1.01–1.03]), cardioembolic stroke pathogenesis (OR, 1.69 [95% CI, 1.77–2.41]), middle cerebral artery M1 (OR, 2.74 [95% CI, 1.09–1.87]), nongeneral anesthesia (OR, 0.55 [95% CI, 0.39–0.767]), as well as with 0.070‐inch (OR, 2.04 95% CI, 1.01–3.78]), and 0.088‐inch (OR, 3.90 [95% CI, 1.58–9.61]) distal catheter inner diameter in the adjusted analysis. Mean time from arterial access to clot contact was 17 minutes, with faster times observed in younger patients (OR, 0.99 [95% CI, 0.98–0.996]) as well as with the use of aspiration catheters with shorter length of distal outer hydrophilic coating (18–30 cm) on multivariable regression (OR, 0.30 [95% CI, 0.11–0.82]).

Conclusion
Larger aspiration catheter distal inner diameter was associated with higher rates of first‐pass effect. Aspiration catheter construction components were found to influence times from arterial access to clot contact.
Iliac Vein Stenting and Thrombectomy Result in Limb Salvage in Phlegmasia Caerulea Dolens as a Result of Heavy Fibroid Burden
Authors: Zamin Syed A. , Mitchell Marc 
Published: April 2024

Phlegmasia cerulea dolens is a devastating sequelae of propagating deep vein thrombosis causing total venous outflow obstruction of an extremity. It is characterized by significant pain, edema, cyanosis, and critical limb ischemia and may progress toward venous gangrene. Morbidity and mortality rates associated with this phenomenon are high. Treatment options are limited and consist of early and aggressive therapeutic anticoagulation and fluid resuscitation, followed by thrombectomy or thrombolysis if the patient fails to respond clinically in 6-12 hours.
Is Input Subsidy Regime in Indian Agriculture Environmentally Sustainable? An Econometric Investigation
Authors: Zafar Shadman , Tarique Md. 
Published: April 2024

The empirical economics literature is devoid of a study that addresses the environmental effects of the agricultural subsidy regime. This deficiency has put a challenge before the policymakers and they have pursued agricultural subsidy by taking into account its private cost only, whereas social cost is much higher due to the involvement of environmental dynamics into it. The present article works to fill this void by empirically investigating the linkages between agricultural input subsidies and environmental emissions in India. To investigate the dynamic relationship, an autoregressive and distributed lag model is applied to annual time–series data from 1981 to 2019 because this method is best suited for the nature of the underlying data series. Research outcomes infer that while both fertiliser and irrigation subsidies exert positive and significant influences on emissions, irrigation subsidies have a relatively greater emission-enhancing effect. Key findings claim that the existing provision of subsidies is not sustainable because it leads to the excessive use of subsidised key inputs leading to greenhouse gas emission. The fact is that the pollution effects of even a limited amount of input are significant. A reduction in input subsidy which is leading to environmental degradation is a need of the hour. The farmers may be provided direct income support as compensation. Further, making a gradual shift towards subsidising organic farming practices called ‘smart subsidies’ and optimising input use are very crucial to achieve sustainable outcomes from the agricultural sector in the long run. JEL Codes: C22, H25, O13, Q18, Q53