bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Bandwidth Utilization Optimization with Quantum-Inspired Approach
Authors: Tsai Tsung-Hsuan , Chen YiChing , Nien Chin-Fu
Published: June 2023

As the popularity of mobile devices and services continues to increase, the demand for more efficient and effective algorithms to manage network utility is increased. Here, we aim to optimize Network Bandwidth Utilization (NBU) by managing user equipments (UEs) and base stations (BSs) association in 5G ORAN architecture. We consider the network total throughput as an objective function and try to find the suitable Cell Individual Offset (CIO) to trigger UE handover with the A3 event such that the network throughput is optimal. We formulate this problem into a Quadratic Unconstrained Binary Optimization (QUBO) problem such that we can explore the power of Quantum Annealing (QA), which is a promising approach to finding the optimal solution for the NP-Hard problem. We also analyze the penalty coefficients setting problem which impacts the outcome of QA significantly. We test our QUBO formulation on a dataset of 7 BSs and 150 UEs with Fujitsu’s third generation Digital Annealer (DA3). Using our QUBO formulation with DA3 solver with fine-tuning, we can improve the throughput with 60% hit rate on this dataset.
Current Fertility Knowledge of Senior High School Students, Infertile Patients, and Medical Staff at an Infertility Clinic in Japan
Authors: Akamatsu Satomi , Matsubayashi Hidehiko , Fujii Yuta , Takiuchi Tsuyoshi , Ishikawa Tomomoto
Published: June 2023

Background: In a survey on fertility knowledge published in 2013 (Cardiff Fertility Knowledge Scale [CFKS]), Japan ranked 78th among 79 countries. This finding encouraged the Japanese government to revise the curriculum for sex education in 2015. The present study was conducted to assess the current fertility knowledge of senior high school students, infertile patients, and medical staff at an infertility clinic in Japan.

Methods: A cross-sectional study of 899 senior high school students (average age 16.8 years), 461 infertile female patients (36.9 years), and 127 medical staff at our infertility clinic (33.1 years) was performed between July 2020 and January 2021. The questionnaire included 13 items from CFKS and our 12 original items on fertility and infertility treatments.

Results: The positive response rates of senior high school students, infertile female patients, and medical staff were 69.4, 86.9, and 86.5% for CFKS, respectively, and were similar for all 25 items. The positive response rate was higher in all three groups than in the surveys conducted in 2013 (36.0%) and 2015 (44.4%) in Japan.

Conclusions: Although sex education may have improved these scores, other resources (media and social media) may also be responsible for this increase.
Sexual Dysfunction in Infertile Patients with Polycystic Ovarian Syndrome
Authors: Salma Umma , Sultana Nilufar , Rahman Florida , Farhin Kazi Khadeza , Ishrat Shakeela
Published: June 2023

Introduction: Polycystic ovarian syndrome is one of the most common causes of infertility in women of reproductive age. It is a combination of chronic anovulation, obesity, and hyperandrogenism that may affect sexual function in women of reproductive age.

Objectives: The study aimed to assess the sexual dysfunction, its frequency, and predisposing factors in infertile polycystic ovary syndrome (PCOS) patients.

Methods: This descriptive cross-sectional study was conducted among 240 infertile women with a definite diagnosis of PCOS. The study duration was 1 year, from August 2019 to August 2020. Data was collected chronologically by interview, physical examination, and laboratory investigations using a structured questionnaire. The presence of hirsutism was assessed using the modified Ferriman–Gallwey (mFG) scoring system. Sexual function was assessed in the domains of desire, arousal, lubrication, orgasm, satisfaction, and pain using the female sexual function index (FSFI). Patients were also assessed for mental health by the depression, anxiety, and stress scale-21 (DASS-21).

Results: Sexual dysfunction was present in 65.4% of patients with the domains of orgasm and arousal were particularly affected (92.9% and 90.0%, respectively). In this study, age and BMI had a significant negative correlation ([Formula: see text] = − 0.55 and [Formula: see text] = − 0.42, respectively) with sexual function. Increasing age and BMI resulted in a significant reduction in sexual function ( [Formula: see text] 0.001 each), including all domains. Patients with symptoms of depression and anxiety were significantly more likely to suffer from sexual dysfunction than those without these symptoms ([Formula: see text] = 0.041 and [Formula: see text] = 0.001, respectively). Hirsutism, serum testosterone (total) level, and stress were found to have no significant effect on sexual function.

Conclusions: Infertile patients with PCOS markedly suffer from sexual dysfunction. Improvement of sexual dysfunction not only improves sexuality and quality of life, but also may improve fertility outcomes in infertile PCOS patients.
Free-Fall Motion and Time in General Relativity
Authors: Riggs Peter J.
Published: June 2023

Recent attempts at explaining free-fall motion (i.e. motion only under the influence of gravity) in the context of the General Theory of Relativity have invoked a concept of time passing/progressing. Although students who have studied the Special Theory of Relativity will likely know that this concept does not feature in Special Relativity, they may incorrectly accept the concept of time passing/progressing as an aspect of General Relativity if they have encountered these accounts of free-fall motion. It is pointed out that time passing/progressing is not part of General Relativity theory and is briefly shown that free-fall motion in General Relativity is quantitatively described without such a concept.
The Rheic riddle: ocean closed, but no orogen
Authors: Franke Wolfgang
Published: June 2023

Although the Rheic Ocean was the widest to be closed during the assembly of Pangaea, its suture zone is dominated by a younger (Rhenohercynian) Wilson Cycle. The present paper briefly summarizes the Rhenohercynian and reviews the relicts of the Rheic. The absence of a Rheic orogen is mainly due to bipolar subduction of the Rheic Ocean, which created two magmatic arcs and largely destroyed the passive margin prisms, thus depriving the collision zone of building material. Also, displacement of Variscan zones in England, France and Germany along a curvature of the dextral Bristol/Bray/Bohemia shear zone has effected their anticlockwise rotation. Younger, ENE-trending reverse faults have truncated the NE-trending structural boundaries and excised pre-Devonian, Rheic-related rocks west of the River Rhine, while the northern Rheic Arc and Cambrian–Silurian deposits of the Rheic Ocean have been preserved further east. Opening of the Rhenohercynian successor ocean to the Rheic put a brake on plate convergence and hindered formation of a large collisional belt. Scarce relicts of the southern Rheic Arc and rocks with Silurian deformation exist in the (largely eroded) upper plate of the Rhenohercynian collisional belt, mostly in the form of clasts and detrital zircons in Upper Devonian/lower Carboniferous flysch and in tectonic mélange at the base of the allochthon.
Zero-shot Scene Graph Generation via Triplet Calibration and Reduction
Authors: Li Jiankai , Wang Yunhong , Li Weixin
Published: June 2023

Scene Graph Generation (SGG) plays a pivotal role in downstream vision-language tasks. Existing SGG methods typically suffer from poor compositional generalizations on unseen triplets. They are generally trained on incompletely annotated scene graphs that contain dominant triplets and tend to bias toward these seen triplets during inference. To address this issue, we propose a Triplet Calibration and Reduction (T-CAR) framework in this article. In our framework, a triplet calibration loss is first presented to regularize the representations of diverse triplets and to simultaneously excavate the unseen triplets in incompletely annotated training scene graphs. Moreover, the unseen space of scene graphs is usually several times larger than the seen space, since it contains a huge number of unrealistic compositions. Thus, we propose an unseen space reduction loss to shift the attention of excavation to reasonable unseen compositions to facilitate the model training. Finally, we propose a contextual encoder to improve the compositional generalizations of unseen triplets by explicitly modeling the relative spatial relations between subjects and objects. Extensive experiments show that our approach achieves consistent improvements for zero-shot SGG over state-of-the-art methods. The code is available at
https://github.com/jkli1998/T-CAR
.
Accurate Summary-based Cardinality Estimation Through the Lens of Cardinality Estimation Graphs
Authors: Chen Jeremy , Huang Yuqing , Wang Mushi , Salihoglu Semih , Salem Kenneth
Published: June 2023

We study two classes of summary-based cardinality estimators that use statistics about input relations and small-size joins: (i) optimistic estimators, which were defined in the context of graph database management systems, that make uniformity and conditional independence assumptions; and (ii) the recent pessimistic estimators that use information theoretic linear programs (LPs). We show that optimistic estimators can be modeled as picking bottom-to-top paths in a cardinality estimation graph (CEG), which contains subqueries as nodes and edges whose weights are average degree statistics. We show that existing optimistic estimators have either undefined or fixed choices for picking CEG paths as their estimates and ignore alternative choices. Instead, we outline a space of optimistic estimators to make an estimate on CEGs, which subsumes existing estimators. We show, using an extensive empirical analysis, that effective paths depend on the structure of the queries. We next show that optimistic estimators and seemingly disparate LP-based pessimistic estimators are in fact connected. Specifically, we show that CEGs can also model some recent pessimistic estimators. This connection allows us to provide insights into the pessimistic estimators, such as showing that they have combinatorial solutions.
Worsening of lung perfusion to tissue density distributions during early acute lung injury
Authors: Motta-Ribeiro Gabriel C. , Winkler Tilo , Costa Eduardo L. V. , de Prost Nicolas , Tucci Mauro R. , Vidal Melo Marcos F.
Published: June 2023

Perfusion redistribution does not follow lung density redistribution in the first 16–24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.
Bilateral Ovarian Serous Borderline Tumor with Non-Invasive Endometrial Implants
Authors: Malham Melissa Bou , Mehawej Jordy , Filippaios Andreas , Kushnir Christina , Mhawech-Fauceglia Paulette
Published: June 2023

Herein, we are presenting a case of a 33-year-old woman who presented to the emergency department complaining of persistent lower abdominal pain of one-day duration. Physical examination revealed abdominal tenderness with right lower quadrant rebound tenderness. Computed tomography abdomen/pelvis showed a 6 cm possible necrotic mass of the left ovary with moderate amount of complex ascites. A laparoscopic left oophorectomy with bilateral salpingectomy, right ovarian biopsy, and appendectomy were performed without complications. The cut surface of the left ovary showed a

9.7
 
cm
×
8
 
cm
×
4
 
cm

ovarian mass, and the cut surface revealed multiple gray-tan friable papillary excrescence. Microscopic evaluation showed findings consistent with left and right ovarian serous borderline tumor (SBT). Subsequently, a tumor staging was conducted with total laparoscopic hysterectomy, pelvic and periaortic lymph node dissection, and omentectomy. The endometrium sections showed several small foci of SBT within the endometrial stroma, consistent with non-invasive implants of the endometrium. The omentum and lymph nodes were all negative for malignancy. SBTs associated with endometrial implants are very rare with only one case reported in the literature. Their existence can cause diagnostic challenges, and they should be acknowledged for early diagnosis and to plan for patient’s treatment and outcome.
Evaluation and Prediction Model of Intelligent Manufacturing Capability Based on Applied Mathematical Modelling
Authors: Lv Xiaojun
Published: June 2023

With the exponential enhancement of manufacturing effectivity and the structural transformation of the software of manufacturing elements induced by using the new spherical of scientific and technological revolution, the sample of comparative gain of manufacturing elements in the worldwide manufacturing enterprise has passed through profound changes, progressively forming a transformation from the industrial chain to the price chain, therefore promoting the transformation of manufacturing mode and aid utilization mode. Based on the applicable theories of wise manufacturing, this paper proposes an clever manufacturing functionality assessment and prediction mannequin primarily based on utilized mathematical modelling, which integrates the contrast facts of agencies into a database, establishes the corresponding time sequence relationship of the comparison data, and establishes a relationship with the corresponding organization attributes, fashions the assessment data, and combines them into a total prediction mannequin through built‐in learning. By functionality of migration learning, the prediction model applicable to large statistics is migrated to small information to recognize the distinction of the equal type alternatively special entities. Input the comparison facts of the organization to be evaluated into the prediction mannequin to reap the shrewd manufacturing functionality maturity fee of the enterprise. It realizes the automated comparison of shrewd manufacturing capability, saves human cost, and improves the accuracy of evaluation. It solves the troubles that manufacturing companies have no longer deep hold close and understanding of smart manufacturing, inaccurate identification of their very personal smart manufacturing enhancement stage, and unscientific self‐evaluation and diagnosis.
Dietary PHB Supplementation Strengthens the Gill Immune Barrier and Disease Resistance of Carassius auratus gibelio against CyHV-2 Early Infection
Authors: Qiao Guo , Zhang Yichan , Zhang Jiwu , Chen Wei , Wei Chang , Chen Peng , Yang Wenping , Zhu Zhu , Zhang Mingming , Zhao Zhigang , Wan Xihe
Published: June 2023

Gibel carp (Carassius auratus gibelio) is an important economic fish species in China, but its development is seriously restricted by the crucian carp hematopoietic organ necrosis caused by Cyprinid herpesvirus 2 (CyHV-2). Gill is the key portal for CyHV-2 primary invasion, and the gill immune barrier is the first defense line against infection. Our previous studies showed that dietary poly-β-hydroxybutyrate (PHB) supplementation can enhance the disease resistance of gibel carps against CyHV-2 infection, and antioxidants play an important role against this infection. However, the effect of PHB supplementation on the gill immune barrier and primary proliferation of CyHV-2 in the gill is unclear. Herein, results showed that (1) PHB supplementation significantly increased the activities of SOD, GST, and other antioxidant-related enzymes in the gill and gill mucus; (2) PHB significantly upregulated the transcription of genes involved in the JAK/STAT signaling pathway, Th1 and Th2 cell differentiation, tryptophan metabolism, and MAPK signaling pathway; (3) PHB effectively reduced the cumulative mortality of fish post-CyHV-2 infection; (4) PHB significantly inhibited primary CyHV-2 proliferation in the gill; (5) at the early stage (6 hpi) of CyHV-2 infection, the transcription of IFN-γ, IFN-γR, TNF-α, JUN, TCR-β, IL-4R, STAT1, and AhR in the gill was significantly upregulated by 14.15-folds, 6.55-folds, 9.32-folds, 6.77-folds, 9.84-folds, 5.55-folds, 9.11-folds and 13.06-folds, respectively; and (6) during the late stages (96 hpi and 168 hpi) of infection, some genes in the kidney and intestine were continuously upregulated. In conclusion, PHB can improve the antioxidant capacity of the gill, enhance the immune response, and inhibit the viral proliferation in the gill at the early infection stage. It is of great significance for us to develop novel prevention strategies to control CyHV-2 infection, considering immuno-modulation of the primary invasion organ, the gill, and host antioxidation.
Oscillation and Asymptotic Behavior of Three-Dimensional Third-Order Delay Systems
Authors: Naeif Ahmed Abdulhasan , Mohamad Hussain Ali
Published: June 2023

In this paper, oscillation and asymptotic behavior of three-dimensional third-order delay systems are discussed. Some sufficient conditions are obtained to ensure that every solution of the system is either oscillatory or nonoscillatory and converges to zero or diverges astgoes to infinity. A special technique is adopted to include all possible cases for all nonoscillatory solutions (NOSs). The obtained results included illustrative examples.
Characterizing Evolutionary Dynamics Reveals Strategies to Exhaust the Spectrum of Subclonal Resistance in EGFR-Mutant Lung Cancer
Authors: Müller Nina , Lorenz Carina , Ostendorp Jenny , Heisel Felix S. , Friese Ulrich P. , Cartolano Maria , Plenker Dennis , Tumbrink Hannah , Heimsoeth Alena , Baedeker Philipp , Weiss Jonathan , Ortiz-Cuaran Sandra , Büttner Reinhard , Peifer Martin , Thomas Roman K. , Sos Martin L. , Berg Johannes , Brägelmann Johannes
Published: June 2023

The emergence of resistance to targeted therapies restrains their efficacy. The development of rationally guided drug combinations could overcome this currently insurmountable clinical challenge. However, our limited understanding of the trajectories that drive the outgrowth of resistant clones in cancer cell populations precludes design of drug combinations to forestall resistance. Here, we propose an iterative treatment strategy coupled with genomic profiling and genome-wide CRISPR activation screening to systematically extract and define preexisting resistant subpopulations in an EGFR-driven lung cancer cell line. Integrating these modalities identifies several resistance mechanisms, including activation of YAP/TAZ signaling by WWTR1 amplification, and estimates the associated cellular fitness for mathematical population modeling. These observations led to the development of a combination therapy that eradicated resistant clones in large cancer cell line populations by exhausting the spectrum of genomic resistance mechanisms. However, a small fraction of cancer cells was able to enter a reversible nonproliferative state of drug tolerance. This subpopulation exhibited mesenchymal properties, NRF2 target gene expression, and sensitivity to ferroptotic cell death. Exploiting this induced collateral sensitivity by GPX4 inhibition clears drug-tolerant populations and leads to tumor cell eradication. Overall, this experimental in vitro data and theoretical modeling demonstrate why targeted mono- and dual therapies will likely fail in sufficiently large cancer cell populations to limit long-term efficacy. Our approach is not tied to a particular driver mechanism and can be used to systematically assess and ideally exhaust the resistance landscape for different cancer types to rationally design combination therapies.

Significance:

Unraveling the trajectories of preexisting resistant and drug-tolerant persister cells facilitates the rational design of multidrug combination or sequential therapies, presenting an approach to explore for treating EGFR-mutant lung cancer.
Thyroid Cancers Exhibit Oncogene-Enhanced Macropinocytosis that Is Restrained by IGF1R and Promote Albumin–Drug Conjugate Response
Authors: Hu Huiyu , Ng Thomas S.C. , Kang Mikyung , Scott Ella , Li Ran , Quintana Jeremy M. , Matvey Dylan , Vantaku Venkata R. , Weissleder Ralph , Parangi Sareh , Miller Miles A.
Published: June 2023

Purpose:

Oncogene-driven macropinocytosis fuels nutrient scavenging in some cancer types, yet whether this occurs in thyroid cancers with prominent MAPK–ERK and PI3K pathway mutations remains unclear. We hypothesized that understanding links between thyroid cancer signaling and macropinocytosis might uncover new therapeutic strategies.

Experimental Design:

Macropinocytosis was assessed across cells derived from papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), non-malignant follicular thyroid, and aggressive anaplastic thyroid cancer (ATC), by imaging fluorescent dextran and serum albumin. The impacts of ectopic BRAFV600E and mutant RAS, genetic PTEN silencing, and inhibitors targeting RET, BRAF, and MEK kinases were quantified. BrafV600E p53−/− ATC tumors in immunocompetent mice were used to measure efficacy of an albumin–drug conjugate comprising microtubule-destabilizing monomethyl auristatin E (MMAE) linked to serum albumin via a cathepsin-cleavable peptide (Alb-vc-MMAE).

Results:

FTC and ATC cells showed greater macropinocytosis than non-malignant and PTC cells. ATC tumors accumulated albumin at 8.8% injected dose per gram tissue. Alb-vc-MMAE, but not MMAE alone, reduced tumor size by >90% (P < 0.01). ATC macropinocytosis depended on MAPK/ERK activity and nutrient signaling, and increased by up to 230% with metformin, phenformin, or inhibition of IGF1Ri in monoculture but not in vivo. Macrophages also accumulated albumin and express the cognate IGF1R ligand, IGF1, which reduced ATC responsiveness to IGF1Ri.

Conclusions:

These findings identify regulated oncogene-driven macropinocytosis in thyroid cancers and demonstrate the potential of designing albumin-bound drugs to efficiently treat them.
A CAPTIVATEing Analysis for Higher-Risk CLL
Authors: Rogers Kerry A.
Published: June 2023

In an exploratory analysis of the phase II CAPTIVATE study, previously untreated patients with chronic lymphocytic leukemia with a higher-risk feature of immune globulin heavy chain variable (IGHV) unmutated status, del(17p), and/or TP53 mutation had similar efficacy and safety outcomes compared with patients without a higher-risk feature when treated with fixed-duration ibrutinib and venetoclax.

See related article by Allan et al., p. 2593
FDA Approval Summary: Futibatinib for Unresectable Advanced or Metastatic, Chemotherapy Refractory Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Other Rearrangements
Authors: Gandhy Shruti U. , Casak Sandra J. , Mushti Sirisha L. , Cheng Joyce , Subramaniam Sriram , Zhao Hong , Zhao Miao , Bi Youwei , Liu Guansheng , Fan Jianghong , Adeniyi Oluseyi , Charlab Rosane , Kufrin Dubravka , Thompson Matthew D. , Jarrell Kristin , Auth Doris , Lemery Steven J. , Pazdur Richard , Kluetz Paul G. , Fashoyin-Aje Lola A.
Published: June 2023

On September 30, 2022, the FDA granted accelerated approval to futibatinib for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions or other rearrangements. Approval was based on Study TAS-120–101, a multicenter open-label, single-arm trial. Patients received futibatinib 20-mg orally once daily. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) as determined by an independent review committee (IRC) according to RECIST v1.1. ORR was 42% (95% confidence interval, 32%–52%). Median DoR was 9.7 months. Adverse reactions occurring in ≥30% patients were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, and abdominal pain. The most common laboratory abnormalities (≥50%) were increased phosphate, increased creatinine, decreased hemoglobin, and increased glucose. Ocular toxicity (including dry eye, keratitis, and retinal epithelial detachment) and hyperphosphatemia are important risks of futibatinib, which are listed under Warnings and Precautions. This article summarizes the FDA's thought process and data supporting the approval of futibatinib.
Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction
Authors: Jung In-Young , Bartoszek Robert L. , Rech Andrew J. , Collins Sierra M. , Ooi Soon-Keat , Williams Erik F. , Hopkins Caitlin R. , Narayan Vivek , Haas Naomi B. , Frey Noelle V. , Hexner Elizabeth O. , Siegel Donald L. , Plesa Gabriela , Porter David L. , Cantu Adrian , Everett John K. , Guedan Sonia , Berger Shelley L. , Bushman Frederic D. , Herbst Friederike , Fraietta Joseph A.
Published: June 2023

Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematologic cancers, but resistance is common and efficacy is limited in solid tumors. We found that CAR T cells autonomously propagate epigenetically programmed type I interferon signaling through chronic stimulation, which hampers antitumor function. EGR2 transcriptional regulator knockout not only blocks this type I interferon–mediated inhibitory program but also independently expands early memory CAR T cells with improved efficacy against liquid and solid tumors. The protective effect of EGR2 deletion in CAR T cells against chronic antigen-induced exhaustion can be overridden by interferon-β exposure, suggesting that EGR2 ablation suppresses dysfunction by inhibiting type I interferon signaling. Finally, a refined EGR2 gene signature is a biomarker for type I interferon–associated CAR T cell failure and shorter patient survival. These findings connect prolonged CAR T cell activation with deleterious immunoinflammatory signaling and point to an EGR2–type I interferon axis as a therapeutically amenable biological system.

Significance:

To improve CAR T cell therapy outcomes, modulating molecular determinants of CAR T cell–intrinsic resistance is crucial. Editing the gene encoding the EGR2 transcriptional regulator renders CAR T cells impervious to type I interferon pathway–induced dysfunction and improves memory differentiation, thereby addressing major barriers to progress for this emerging class of cancer immunotherapies.

This article is highlighted in the In This Issue feature, p. 1501
Redox Dysregulation of Vascular Smooth Muscle Sirtuin-1 in Thoracic Aortic Aneurysm in Marfan Syndrome
Authors: Budbazar Enkhjargal , Sulser Ponce De Leon Sandra , Tsukahara Yuko , Liu Hanxiao , Huangfu Yuhao , Wang Yu , Seabra Pedro Maria , Yang Xiaoqiu , Goodman Jena Brooke , Wan Xueping , Chitalia Vipul , Han Jingyan , Seta Francesca
Published: June 2023

BACKGROUND:

Thoracic aortic aneurysms (TAAs) are abnormal aortic dilatations and a major cardiovascular complication of Marfan syndrome. We previously demonstrated a critical role for vascular smooth muscle (VSM) SirT1 (sirtuin-1), a lysine deacetylase, against maladaptive aortic remodeling associated with chronic oxidative stress and aberrant activation of MMPs (matrix metalloproteinases).

METHODS:

In this study, we investigated whether redox dysregulation of SirT1 contributed to the pathogenesis of TAA using fibrillin-1 hypomorphic mice (Fbn1
mgR/mgR
), an established model of Marfan syndrome prone to aortic dissection/rupture.

RESULTS:

Oxidative stress markers 3-nitrotyrosine and 4-hydroxynonenal were significantly elevated in aortas of patients with Marfan syndrome. Moreover, reversible oxidative post-translational modifications (rOPTM) of protein cysteines, particularly S-glutathionylation, were dramatically increased in aortas of Fbn1
mgR/mgR
mice, before induction of severe oxidative stress markers. Fbn1
mgR/mgR
aortas and VSM cells exhibited an increase in rOPTM of SirT1, coinciding with the upregulation of acetylated proteins, an index of decreased SirT1 activity, and increased MMP2/9 activity. Mechanistically, we demonstrated that TGFβ (transforming growth factor beta), which was increased in Fbn1
mgR/mgR
aortas, stimulated rOPTM of SirT1, decreasing its deacetylase activity in VSM cells. VSM cell–specific deletion of SirT1 in Fbn1
mgR/mgR
mice (SMKO-Fbn1
mgR/mgR
) caused a dramatic increase in aortic MMP2 expression and worsened TAA progression, leading to aortic rupture in 50% of SMKO-Fbn1
mgR/mgR
mice, compared with 25% of Fbn1
mgR/mgR
mice. rOPTM of SirT1, rOPTM-mediated inhibition of SirT1 activity, and increased MMP2/9 activity were all exacerbated by the deletion of Glrx (glutaredoxin-1), a specific deglutathionylation enzyme, while being corrected by overexpression of Glrx or of an oxidation-resistant SirT1 mutant in VSM cells.

CONCLUSIONS:

Our novel findings strongly suggest a causal role of S-glutathionylation of SirT1 in the pathogenesis of TAA. Prevention or reversal of SirT1 rOPTM may be a novel therapeutic strategy to prevent TAA and TAA dissection/ruptures in individuals with Marfan syndrome, for which, thus far, no targeted therapy has been developed.
Air Pollution, Built Environment, and Early Cardiovascular Disease
Authors: Zhang Kai , Brook Robert D. , Li Yuanfei , Rajagopalan Sanjay , Kim Juyong Brian
Published: June 2023

As the world’s population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related risk factors. While epidemiological studies have examined the role of a few environmental factors with early cardiovascular disease, the relationship with the broader environment remains poorly defined. In this article, we provide a brief overview of studies that have examined the impact of the environment including the built physical environment, discuss current challenges in the field, and suggest potential directions for future research. Additionally, we highlight the clinical implications of these findings and propose multilevel interventions to promote cardiovascular health among children and young adults.
Imaging Early Life Cardiovascular Phenotype
Authors: Varadarajan Vinithra , Gidding Samuel S. , Wu Colin , Carr J. Jeffrey , Lima Joao A.C.
Published: June 2023

The growing epidemics of obesity, hypertension, and diabetes, in addition to worsening environmental factors such as air pollution, water scarcity, and climate change, have fueled the continuously increasing prevalence of cardiovascular diseases (CVDs). This has caused a markedly increasing burden of CVDs that includes mortality and morbidity worldwide. Identification of subclinical CVD before overt symptoms can lead to earlier deployment of preventative pharmacological and nonpharmacologic strategies. In this regard, noninvasive imaging techniques play a significant role in identifying early CVD phenotypes. An armamentarium of imaging techniques including vascular ultrasound, echocardiography, magnetic resonance imaging, computed tomography, noninvasive computed tomography angiography, positron emission tomography, and nuclear imaging, with intrinsic strengths and limitations can be utilized to delineate incipient CVD for both clinical and research purposes. In this article, we review the various imaging modalities used for the evaluation, characterization, and quantification of early subclinical cardiovascular diseases.
Single-Pill Combination Product Availability of the Antihypertensive Regimens Used for Intensive Systolic Blood Pressure Treatment in the Systolic Blood Pressure Intervention Trial
Authors: King Jordan B. , Derington Catherine G. , Herrick Jennifer S. , Jacobs Joshua A. , Zheutlin Alexander R. , Conroy Molly B. , Cushman William C. , Bress Adam P.
Published: June 2023

BACKGROUND:

Single-pill combination (SPC) antihypertensive products improve blood pressure control and medication adherence among patients with hypertension. It is unknown to what degree commercially available SPC products could be used to target an intensive systolic blood pressure goal of <120 mm Hg.

METHODS:

This cross-sectional analysis included participants randomized to the intensive treatment arm (goal systolic blood pressure <120 mm Hg) of the Systolic Blood Pressure Intervention Trial (SPRINT) using ≥2 antihypertensive medication classes at the 12-month postrandomization visit. Antihypertensive medication data were collected using pill bottle review by research coordinators, and regimens were categorized by the unique combinations of antihypertensive classes. We calculated the proportion of regimens used, which are commercially available as one of the 7 SPC class combinations in the United States as of January 2023.

RESULTS:

Among the 3833 SPRINT intensive arm participants included (median age, 67.0 years; 35.5% female), participants were using 219 unique antihypertensive regimens. The 7 regimens for which there are class-equivalent SPC products were used by 40.3% of participants. Only 3.2% of all medication class regimens used are available as a class-equivalent SPC product (7/219). There are no SPC products available with 4 or more medication classes, which were used by 1060 participants (27.7%).

CONCLUSIONS:

Most SPRINT participants in the intensive arm used an antihypertensive medication regimen, which is not commercially available as a class equivalent SPC product. To achieve the SPRINT results in real-world settings, maximize the potential benefit of SPCs, and reduce pill burden, improvements in the product landscape are needed.

REGISTRATION:

URL:
https://www.clinicaltrials.gov/ct2/show/NCT01206062
; Unique identifier: NCT01206062.
The Origins of Mircea Eliade’s Transconscious and the Vicissitudes of the Religious Faculty
Authors: Iagher Matei
Published: June 2023

This article examines the genealogy of the concept of “transconscious,” a key notion in the work of Mircea Eliade. It argues that the “transconscious” is the inheritor of a long psychological tradition in the study of religion, namely that of the religious faculty. The first section looks at the religious faculty in the work of Max Müller and some of his German post-Kantian precursors, namely, Friedrich Jacobi and Jakob Fries. The subsequent sections examine the history of terms such as “super-conscious,” “supra-conscious,” and “trans-conscious” in turn-of-the-century philosophy and theology in the period before 1947. I argue that there are four intellectual strands that go into the making of Eliade’s “transconscious,” namely: (1) psychology of mysticism; (2) occultism; (3) interpretations of yoga; (4) contemporary philosophy and theology. The final section looks at Eliade’s uses of the “transconscious” and at his debate with C. G. Jung regarding religion and the mind.
Governing Health: The Doctor’s Authority, the Patient’s Agency, and the Reading of Regimina sanitatis Literature
Authors: Nicoud Marilyn
Published: June 2023

This article examines the ways in which, in the last centuries of the Middle Ages, the emergence of a literature aimed at preserving health by means of dietary rules or advice establishes a connection between the physician’s authority in matters of health and the capacity of patients and readers to take care of themselves when they are in good health. Born at the same time of social demand and medical necessity (the latter due to the dangers and uncertainties of therapeutic practice), these regimina sanitatis disseminate to a literate public the principles of good hygiene. Some regimina are even adapted to the singularity of a given individual. But the agency of readers, characterized by their capacity for choice and deliberation, also clashes with the claim that a medical authority is necessary for the governance of health.
Astrological Self-Government at the Fifteenth-Century Court of Bourbon
Authors: Vanden Broecke Steven
Published: June 2023

In articulating the uses of their art, late-medieval astrologers often invoked the maxim that “the wise man will rule the stars” (sapiens dominabitur astris). However, it is by no means clear whether this invocation sought to emphasize ‘domination’ over the natural and social world, or the ontological self-government that is at stake in the pursuit of ‘wisdom’. Many historians have interpreted the past pursuit of astrology in terms of an interest in dominance over the natural and social world. Taking inspiration from a recent ‘ascetic turn’ in the history of early modern science and philosophy, however, this article argues that late-medieval astrology was approached and appreciated as an art of self-government (both in body and in soul) and uncovers what this entailed. In so doing, we also demonstrate that the undifferentiated view of astrology as a pre-modern counterpart of modern prospective knowledge practices is anachronistic.
Integrating rough-entropy and rough-TOPSIS methods for evaluating the legatum prosperity pillars of weakest performing countries
Authors: Alshamrani Ahmad M. , Hezam Ibrahim M
Published: June 2023

Although most countries of the world seek to improve their performance to achieve prosperity for their citizens, the performance of some other countries is still disappointing and has witnessed a deterioration in recent years due to civil wars, poverty, and failure to identify shortcomings and work on them. Many global indexes are concerned with ranking and evaluating the performance of countries, the most prominent of which is the Legatum prosperity index. This study presents a novel tool based on the MCDM approach under uncertainty. Twelve pillars were considered as criteria for evaluating the performance of the 19 poorest-performing countries globally, according to the 2021 Legatum prosperity index. The rough-entropy and rough-TOPSIS methods were used to assess the performance of countries and analyze the pillars of prosperity to determine their shortcomings. Further, a comparison with the 2021 Legatum prosperity index and sensitivity analysis is conducted to validate the obtained results. This study analyses and identifies that South Sudan gets the worst ranking while Cameroon is the best. Likewise, the results indicate that the worst performance pillar was the governance pillar, while the best pillar was the health pillar at the level of the studied countries. The proposed approach is essential for researchers working on performance measurement and ranking, as it ensures the robustness and realism of the results. It also gives a glimpse to the leaders of the countries about the actual situation of their countries to work on addressing the failures. In addition, it makes a significant contribution to the current scientific knowledge by providing a novel tool for evaluating performance indexes.
Inside-out strategic coupling for smallholder market integration – Mango production in Malawi as a test case
Authors: Kalvelage Linus , Hardie Craig , Mausch Kai , Conti Costanza , Hall Andy
Published: June 2023

Starting from the observation that value chain research has informed much of agricultural development interventions in recent decades, this paper identifies five key challenges to current agricultural development policies in low- and middle-income countries (LMICs): access to finance, infrastructure, land tenure, local linkages and knowledge transfer. Based on this review, it is argued that recent theoretical advances in the global production network (GPN) approach can help to achieve a more holistic view of agricultural development policies than the more linear value chain research. In particular, three key concepts from the GPN approach are highlighted: mobilisation of regional assets, strategic coupling and territorial embeddedness. These key concepts are used to propose a framework called ‘insight-out strategic coupling for smallholder integration’, which builds on the concept of strategic coupling in GPN research and applies it as a development tool to agricultural production. Using an in-depth case study approach, the usefulness of this framework is tested by examining the experience of Malawi Mangoes, a company established to promote smallholder exports. Malawi Mangoes was initially funded by private equity, but despite a number of challenges along the way, was soon able to attract development funding and integrate smallholders from surrounding villages throughout-grower schemes. Analysis of the case shows both the usefulness of the framework and the lost potential in implementing agricultural development policy. The authors conclude that the framework is useful for linking current debates on agricultural development interventions, but that the findings of critical GPN research need to be taken into account when developing agricultural development interventions in order to respect the ‘do no harm’ principle.
Grounds of Culture: A Metaphorical and Heuristic Approach
Authors: McClure Paul K.
Published: June 2023

Across courses in the social sciences, instructors confront the challenge of how to teach (theories of) culture, yet no consensus exists as to what helps students best comprehend and digest its full complexity. This article offers a metaphorical and heuristic approach to culture that is accessible, multifaceted, and reflective of a wide range of important sociological theories and concepts. Five metaphors are introduced: culture as a training ground, battleground, playground, campground, and fairgrounds. Practical applications and suggestions for organizing a course around these five metaphorical grounds are discussed and outlined.
Analysis and prediction of the formation of new technical phrases for inventive ideation
Authors: Ren Haiying , Zhang Luyao , Wang Chao
Published: June 2023

Despite the fast pace of technological development, the process of inventive ideation remains fuzzy. Meanwhile, improving innovation efficiency has become critical for research and development (R&D) teams because of the fierce competition. This study claimed that new technical phrases (NTPs) were important carriers of novel inventive ideas, and their formation was key to understanding and improving ideation processes. Therefore, this article proposed a methodology to analyse and predict the formation of NTPs. First, based on the recombinant search theory and link prediction, four variables in the prior co-word network of a phrase that may influence its formation were collected. Thereafter, logistic regression and a classification tree were employed on patent data to explore the effects of these variables on NTPs. Moreover, various machine learning methods were used for developing NTP prediction models, and procedures for applying the prediction models in real-world R&D settings were designed. Finally, a case study was conducted using the proposed methodology for its demonstration and validation in neural network technology. The case study revealed that all the four variables posed significant impact on the formation of NTPs, and the prediction models yielded the highest prediction accuracy of 78.6% on the test set. The proposed methodology would shed light on the ideation process in innovation theory and provide R&D teams with practical tools for generating new technical ideas.
Determinants of Buffer Capital for Banks in India
Authors: Kaur Jasveen , Dogra Manu
Published: June 2023

This study has examined the impact of bank-specific indicators on the buffer capital of banks in India. The impact of key variables return on assets, credit deposit ratio, return on equity and the ratio of non-performing loans to total loans on buffer capital has been examined for banks in India. Using dynamic panel data regression, the results reveal that non-performing loans to total loans, return on assets and return on equity have a positive impact on buffer capital. It is revealed that the banks keep extra capital cushion with an increase in risk elements. Also, the credit deposit ratio is having a negative but significant impact on buffer capital. The results further reveal persistency in buffer capital across all models. The role of the cost of capital in the determination of buffer capital has also been examined. The results can be used by bank policymakers in the formulation of various reformation packages.
CT values of contrast-enhanced CBBCT: A useful diagnostic tool for benign and malignant breast lesions
Authors: Wei Wei , Yi Xian Lin , Yang Jun , Liao Hai , Su DanKe
Published: June 2023

Background

Computed tomography (CT) value studies of cone-beam breast CT (CBBCT) mainly focus on the enhancement value or enhancement rate, and there has been no study on the CT value (Hounsfield units [HU]) of the lesion itself.

Purpose

To investigate the CT values under contrast-enhanced CBBCT (CE-CBBCT) and non-contrast-enhanced CBBCT (NC-CBBCT) in scanning for the differential diagnosis of benign and malignant breast lesions.

Material and Methods

A retrospective analysis was performed on 189 cases of mammary glandular tissues that underwent NC-CBBCT and CE-CBBCT examination. The qualitative CT values of the lesions, standardized Δ(L-A), standardized Δ*(L - G), standardized Δ(L-A) (Post 1st-Pre), and standardized Δ*(L-G) (Post 2nd-Post 1st) between the benign and malignant groups were compared. Prediction performance was evaluated using receiver operating characteristic (ROC) curves.

Results

In total, 58 cases were included in the benign group, 79 cases were included in the malignant group, and 52 cases were included in the normal group. The best diagnostic thresholds of CT values for L (Post 1st-Pre), Δ(L-A) (Post 1st-Pre), and Δ*(L-G) (Post 1st-Pre) were 49.5, 44, and 64.8 HU, respectively. The Δ(L-A) Post-1st rate values of CBBCT had medium diagnostic efficacy (AUC = 0.74, sensitivity = 76.6%, specificity = 69.4%).

Conclusion

CE-CBBCT can improve the diagnostic efficiency of breast lesions compared with NC-CBBCT. The CT values (HU) of lesions do not need to be standardized with fat and can be directly used in clinical differential diagnosis. The first contrast phase (60 s) is recommended to reduce the radiation exposure.
Heat transfer analysis in bio-convection second grade nanofluid with Cattaneo–Christov heat flux model
Authors: Hayat T. , Inayatullah  , Muhammad Khursheed , Alsaedi A.
Published: June 2023

Here we examined heat and mass fluxes in second-grade nanomaterial through the Cattaneo–Christov model along a moving surface. The surface is subject to melting conditions. Nanofluid features are accounted through the Boungiorno model for nanomaterials. Heat transfer is carried through joule heating and, thermal radiation. In addition, the gyrotactic microorganism is addressed. The considered problem is modeled and governing partial differential equations are converted into ordinary differential equations by introducing suitable variables. The analytical technique (homotopy analysis method) is used for the computation of solutions of these ordinary differential equations. For the convergence region, h-cut curves have been sketched and presented graphically. Velocity, concentration, temperature, and microorganism field are evaluated graphically under influential parameters.