bluuebunny/crossref_metadata_2025_split huggingface dataset:
CoMeT: An Integrated Interval Thermal Simulation Toolchain for 2D, 2.5D, and 3D Processor-Memory Systems
Authors: Siddhu Lokesh , Kedia Rajesh , Pandey Shailja , Rapp Martin , Pathania Anuj , Henkel Jörg , Panda Preeti Ranjan 
Published: June 2022

Processing cores and the accompanying main memory working in tandem enable modern processors. Dissipating heat produced from computation remains a significant problem for processors. Therefore, the thermal management of processors continues to be an active subject of research. Most thermal management research is performed using simulations, given the challenges in measuring temperatures in real processors. Fast yet accurate interval thermal simulation toolchains remain the research tool of choice to study thermal management in processors at the system level. However, the existing toolchains focus on the thermal management of cores in the processors, since they exhibit much higher power densities than memory.The memory bandwidth limitations associated with 2D processors lead to high-density 2.5D and 3D packaging technology: 2.5D packaging technology places cores and memory on the same package; 3D packaging technology takes it further by stacking layers of memory on the top of cores themselves. These new packagings significantly increase the power density of the processors, making them prone to overheating. Therefore, mitigating thermal issues in high-density processors (packaged with stacked memory) becomes even more pressing. However, given the lack of thermal modeling for memories in existing interval thermal simulation toolchains, they are unsuitable for studying thermal management for high-density processors.To address this issue, we present the first integrated Core and Memory interval Thermal (CoMeT) simulation toolchain.CoMeTcomprehensively supports thermal simulation of high- and low-density processors corresponding to four different core-memory (integration) configurations—off-chip DDR memory, off-chip 3D memory, 2.5D, and 3D.CoMeTsupports several novel features that facilitate overlying system research.CoMeTadds only an additional ~5% simulation-time overhead compared to an equivalent state-of-the-art core-only toolchain. The source code ofCoMeThas been made open for public use under theMITlicense.
Exact Solutions of Three-Dimensional Max-Type System of Difference Equations
Authors: Khaliq Abdul , Sadiq Stephen , Khan Abdul Qadeer , Ibrahim Tarek F. 
Published: June 2022

In this paper, we deal with the form and the periodicity of the solutions of the max-type system of difference equations

u

n
+
1

=
max

A

n

/

v

n

−
1

,

u

n

−
1

,

v

n
+
1

=
max

B

n

/

w

n
−
1

,

w

n
+
1

=
max

C

n

/

u

n
−
1

,

w

n
−
1

where the initial conditions

u

−
1

,

u

0

∈

0
,
∞

,

v

−
1

,

v

0

∈

0
,
∞

,

w

−
1

,

w

0

∈

0
,
∞

and

A

n

n
∈

N

0

,

B

n

n
∈

N

0

,

C

n

n
∈

N

0

are positive two-periodic sequences.
GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1-Mediated Hypermethylation of NR4A3 Promoter
Authors: Lv Zhou , Sun Deping , Li Xin , Wu Gang 
Published: June 2022

Background. Glycogen synthase kinase 3β (GSK3B) is reported to be a protective factor for the degradation of chondrocytes by extracellular mechanisms. Nuclear receptor subfamily 4 group A member 3 (NR4A3) is a proinflammatory factor in osteoarthritis. Their regulation mechanism in posttraumatic osteoarthritis (PTOA) is not fully understood. Methods. GSK3B expression in the cartilage tissue of PTOA patients was analyzed by western blotting. IL-1β-induced chondrocytes were transfected with pcDNA-GSK3B, and then, the cell viability, apoptosis, expression of the chondrocyte extracellular matrix degradation-related genes MMP13, aggrecan, and type II collagen, and secretion of inflammatory factors TNF-α and IL-6 were detected. Co-IP was used to analyze the interaction between GSK3B and DNMT1. Ch-IP and methylation-specific PCR assays were used for methylation. Also, cells were transfected with pcDNA-GSK3B or together with pcDNA-NR4A3, as well as transfected with si-NR4A3, and then, cell functions were tested. Then, the mice subjected to destabilization of medial meniscus (DMM) surgery were intra-articular injected with 100 μL of the following adeno-related virus vectors (empty vector, Ad-GSK3B, scrambled shRNA, and sh-NR4A3), respectively, and the virus titer was

2
×

10

8

TU
/
mL

. Cartilage integrity was evaluated by safranin O/fast green staining, HE staining, and Osteoarthritis Research Society International (OARSI) score. Results. The expression of GSK3B protein was downregulated in PTOA patients. GSK3B overexpression alleviated IL-1β-induced chondrocyte apoptosis and extracellular matrix degradation, as well as cartilage mineralization in PTOA model mice. NR4A3 overexpression reversed the effect of GSK3B on IL-1β-induced chondrocyte functions. GSK3B could recruit DNMT1 to the NR4A3 promoter region to promote the methylation of NR4A3 and inhibit the expression of NR4A3 protein. Similarly, NR4A3 interference alleviated cartilage degradation under stimulating conditions by inhibiting the activation of the JAK2/STAT3 signaling pathway. Conclusion. GSK3B recruits DNMT1 to the NR4A3 promoter region and inhibits the activation of the NR4A3-mediated JAK2/STAT3 signaling pathway, thereby alleviating PTOA.
Proliferation of the Fallopian Tube Fimbriae and Cortical Inclusion Cysts: Effects of the Menstrual Cycle and the Levonorgestrel Intrauterine Contraceptive System
Authors: Park Kay J. , Broach Vance , Chi Dennis S. , Linkov Irina , Stanczyk Frank Z. , Patel Prusha , Jotwani Anjali , Pearce Celeste Leigh , Pike Malcolm C. , Kauff Noah D. 
Published: June 2022

Abstract

Background:
The objectives of this study were (i) to explore whether differences in cell proliferation may help explain why most high-grade serous ovarian cancers (HGSOC) arise in the fallopian tube fimbriae (FTF) rather than in ovarian cortical inclusion cysts (CIC); (ii) to compare premenopausal and postmenopausal FTF proliferation as a reason why the age incidence of HGSOC increases at a slower rate after menopause; and (iii) to compare FTF proliferation in cycling women and women using the levonorgestrel intrauterine contraceptive system (Lng-IUS) to see whether proliferation on the Lng-IUS was lower.

Methods
We studied 60 women undergoing a salpingo-oophorectomy. We used Ki67, paired-box gene 8 (PAX8, Müllerian marker), and calretinin (mesothelial marker) to study FTF and CIC proliferation.

Results:
FTF Ki67%+ was greater in the follicular than in the luteal phase (4.9% vs. 1.5%; P = 0.003); postmenopausal Ki67%+ was 1.7%. Ki67%+ in PAX8 negative (PAX8−) CICs was extremely low. Proliferation in PAX8+ CICs did not vary by menstrual phase or menopausal status. Follicular Ki67%+ was 2.6-fold higher in FTF than PAX8+ CICs. FTF Ki67%+ from 10 women using the Lng-IUS was not lower than in cycling women.

Conclusions:
Overall FTF Ki67%+ is greater than overall CIC Ki67%+. Overall FTF Ki67%+ in postmenopausal women is lower than in premenopausal women. The Lng-IUS is not associated with lower FTF Ki67%+.

Impact:
Ki67%+ provides an explanation of the preponderance of FTF-derived HGSOCs, and of the slower increase of HGSOCs after menopause. The Lng-IUS may not be associated with a protective effect against HGSOCs.
Depletion of Mannose Receptor–Positive Tumor-associated Macrophages via a Peptide-targeted Star-shaped Polyglutamate Inhibits Breast Cancer Progression in Mice
Authors: Lepland Anni , Malfanti Alessio , Haljasorg Uku , Asciutto Eliana K. , Pickholz Monica , Bringas Mauro , Đorđević Snežana , Salumäe Liis , Peterson Pärt , Teesalu Tambet , Vicent María J. , Scodeller Pablo 
Published: June 2022

Although many studies have explored the depletion of tumor-associated macrophages (TAM) as a therapeutic strategy for solid tumors, currently available compounds suffer from poor efficacy and dose-limiting side effects. Here, we developed a novel TAM-depleting agent (“OximUNO”) that specifically targets CD206+ TAMs and demonstrated efficacy in a triple-negative breast cancer (TNBC) mouse model. OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX). In the TNBC model, a fluorescently labeled mUNO-decorated St-PGA homed to CD206+ TAMs within primary lesions and metastases. OximUNO exhibited no acute liver or kidney toxicity in vivo. Treatment with OximUNO reduced the progression of primary tumor lesions and pulmonary metastases, significantly diminished the number of CD206+ TAMs and increased the CD8/FOXP3 expression ratio (indicating immunomodulation). Our findings suggest the potential benefit of OximUNO as a TAM-depleting agent for TNBC treatment. Importantly, our studies also represent a novel design of a peptide-targeted St-PGA as a targeted therapeutic nanoconjugate.Significance:A peptide-targeted nanoformulation of DOX exclusively eliminates mannose receptor+ TAMs in breast cancer models, generating response without off-target effects (a drawback of many TAM-depleting agents under clinical study).
Moderate‐ and High‐Intensity Exercise Improves Lipoprotein Profile and Cholesterol Efflux Capacity in Healthy Young Men
Authors: Stanton Kelly M. , Kienzle Vivian , Dinnes Donna Lee M. , Kotchetkov Irina , Jessup Wendy , Kritharides Leonard , Celermajer David S. , Rye Kerry‐Anne 
Published: June 2022

Background
Exercise is associated with a reduced risk of cardiovascular disease. Increased high‐density lipoprotein cholesterol (HDL‐C) levels are thought to contribute to these benefits, but much of the research in this area has been limited by lack of well‐controlled subject selection and exercise interventions. We sought to study the effect of moderate and high‐intensity exercise on HDL function, lipid/lipoprotein profile, and other cardiometabolic parameters in a homogeneous population where exercise, daily routine, sleep patterns, and living conditions were carefully controlled.

Methods and Results

Male Army recruits (n=115, age 22±0.3 years) completed a 12‐week moderate‐intensity exercise program. A subset of 51 subsequently completed a 15‐week high‐intensity exercise program. Fitness increased and body fat decreased after moderate‐ and high‐intensity exercise (
P
<0.001). Moderate‐intensity exercise increased HDL‐C and apolipoprotein A‐I levels (6.6%, 11.6% respectively), and decreased low‐density lipoprotein cholesterol and apolipoprotein B levels (7.2%, 4.9% respectively) (all
P
<0.01). HDL‐C and apolipoprotein A‐I levels further increased by 8.2% (
P
<0.001) and 6.3% (
P
<0.05) after high‐intensity exercise. Moderate‐intensity exercise increased ABCA‐1 (ATP‐binding cassette transporter A1) mediated cholesterol efflux by 13.5% (
P
<0.001), which was sustained after high‐intensity exercise. In a selected subset the ability of HDLs to inhibit ICAM‐1 (intercellular adhesion molecule‐1) expression decreased after the high (
P
<0.001) but not the moderate‐intensity exercise program.

Conclusions
When controlling for exercise patterns, diet, and sleep, moderate‐intensity exercise improved HDL function, lipid/lipoprotein profile, fitness, and body composition. A sequential moderate followed by high‐intensity exercise program showed sustained or incremental benefits in these parameters. Improved HDL function may be part of the mechanism by which exercise reduces cardiovascular disease risk.
Development and Validation of 3‐Year Atrial Fibrillation Prediction Models Using Electronic Health Record With or Without Standardized Electrocardiogram Diagnosis and a Performance Comparison Among Models
Authors: Yum Yunjin , Shin Seung Yong , Yoo Hakje , Kim Yong Hyun , Kim Eung Ju , Lip Gregory Y. H. , Joo Hyung Joon 
Published: June 2022

Background
Improved prediction of atrial fibrillation (AF) may allow for earlier interventions for stroke prevention, as well as mortality and morbidity from other AF‐related complications. We developed a clinically feasible and accurate AF prediction model using electronic health records and computerized ECG interpretation.

Methods and Results
A total of 671 318 patients were screened from 3 tertiary hospitals. After careful exclusion of cases with missing values and a prior AF diagnosis, AF prediction models were developed from the derivation cohort of 25 584 patients without AF at baseline. In the internal/external validation cohort of 117 523 patients, the model using 6 clinical features and 5 ECG diagnoses showed the highest performance for 3‐year new‐onset AF prediction (C‐statistic, 0.796 [95% CI, 0.785–0.806]). A more simplified model using age, sex, and 5 ECG diagnoses (atrioventricular block, fusion beats, marked sinus arrhythmia, supraventricular premature complex, and wide QRS complex) had comparable predictive power (C‐statistic, 0.777 [95% CI, 0.766–0.788]). The simplified model showed a similar or better predictive performance than the previous models.
In the subgroup analysis, the models performed relatively better in patients without risk factors. Specifically, the predictive power was lower in patients with heart failure or decreased renal function.

Conclusions
Although the 3‐year AF prediction model using both clinical and ECG variables showed the highest performance, the simplified model using age, sex, and 5 ECG diagnoses also had a comparable prediction power with broad applicability for incident AF.
Low‐Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific
Authors: Cupido Arjen J. , Asselbergs Folkert W. , Schmidt A. Floriaan , Hovingh G. Kees 
Published: June 2022

Background
Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex‐specific differential effect of genetically increased low‐density lipoprotein cholesterol (LDL‐C) on cardiovascular disease (CVD) and other lipid‐associated diseases.

Methods and Results

This is a 2‐sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80‐variant LDL‐C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex‐specific LDL‐C effects on lipids, carotid‐intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL‐C effect on CVD events was sex specific: per SD genetically increased LDL‐C, female participants had a higher LDL‐C increase but an attenuated CVD risk increase compared with male participants (LDL‐C: female participants 0.71 mmol/L, 95% CI, 0.70–0.72 and male participants 0.57 mmol/L, 95% CI, 0.56–0.59.
P
for interaction: 5.03×10
−60
; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24–1.40 and male participants: OR, 1.52; 95% CI, 1.46–1.58.
P
for interaction: 9.88×10
−5
). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL‐C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL‐C was also associated with an attenuated carotid‐intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex‐specific weighted genetic scores showed similar results.

Conclusions
We found that genetically increased LDL‐C has a sex‐specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL‐C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL‐C targeted therapies for CVD management than female patients and warranting investigations into the sex‐specific relative contribution of risk factors for CVD.
Characterization of “ICU‐30”: A Binary Composite Outcome for Neonates With Critical Congenital Heart Disease
Authors: Gardner Monique M. , Keim Garrett , Hsia Jill , Mai Anh D. , William Gaynor J. , Glatz Andrew C. , Yehya Nadir 
Published: June 2022

Background
Neonates with heart disease requiring cardiopulmonary bypass surgery are at high risk for mortality and morbidity. As it is rare, short‐term mortality is difficult to use as a primary outcome for clinical studies. We proposed “ICU‐30” as a binary composite “poor” outcome consisting of: (1) mortality within 30 days, (2) intensive care unit (ICU) admission ≥30 days, or (3) ICU readmission before day 30. To measure the utility of this composite, we assessed its prognostic properties for 6‐ and 12‐month mortality.

Methods and Results

This was a retrospective single‐center cohort study of neonates requiring cardiopulmonary bypass between 2013 and 2020. Mortality among patients with and without the ICU‐30 outcome was compared using log‐rank tests and Cox regression. Areas under the receiver operating characteristic curves assessed the ability of the composite to predict 12‐month mortality. In 887 neonates, 232 (26.2%) experienced the ICU‐30 outcome, with more prolonged ICU stays and readmissions (both ≥9%) than 30‐day mortality (4.2%). ICU‐30 was associated with higher rates of 6‐ and 12‐month mortality (log‐rank
P
<0.001) and predicted 12‐month mortality with area under the receiver operating characteristic of 0.81 (95% CI, 0.77–0.85). In 30‐day survivors, both prolonged ICU stay (hazard ratio, 12.3; 95% CI, 6.70–22.7;
P
<0.001) and ICU readmission (hazard ratio, 2.99; 95% CI, 1.17–7.63;
P
=0.02) were associated with 12‐month mortality.

Conclusions
ICU‐30, a composite outcome of mortality, ICU length of stay, or ICU readmission by 30 days was associated with 6‐ and 12‐month mortality in neonates requiring cardiopulmonary bypass. ICU‐30 is captured in routine data collection and appears to be a valid binary patient‐centered outcome.
Hobbes and Mathematical Method
Authors: Jesseph Douglas M. 
Published: June 2022

Abstract
This article examines Hobbes’s conception of mathematical method, situating his methodological writings in the context of disputed mathematical issues of the seventeenth century. After a brief exposition of the Hobbesian philosophy of mathematics, it investigates Hobbes’s attempts to resolve three important mathematical controversies of the seventeenth century: the debates over the status of analytic geometry, disputes over the nature of ratios, and the problem of the “angle of contact” between a curve and tangent. In the course of these investigations, Hobbes’s account of mathematics and its method is contrasted with the those of Descartes, Isaac Barrow, John Wallis, and Christopher Clavius.
Artificialcanopy bridge use by primates and other arboreal mammals in a fragmented tropical forest of northeast Bangladesh
Authors: Maria Marjan , Al-Razi Hassan , Akbar Ali , Muzaffar Sabir Bin , Nekaris K.A.I. 
Published: June 2022

Abstract
Forest fragmentation has resulted in a breakdown in connectivity for arboreal species. Effects of fragmentation are particularly acute in forest patches in densely populated countries, resulting in high mortality in many species attempting to cross roads to travel between forest patches. We evaluated the use of three, single-line artificial canopy bridges made of polypropylene ropes in a forest patch in northeastern Bangladesh. Camera traps were used to determine the extent of bridge use by different species. A total of 1060 events of bridge use by mammals were observed using our artificial canopy bridges over the 157 camera trap days. Eight mammal species, including five primate species, two squirrel species and one palm civet species were recorded using the bridges at varying levels of frequency. The location of the bridge and season influenced bridge use. We did not observe mortality of mammals from road accidents or electrocution during the study period. We suggest that artificial canopy bridges increased connectivity between forest patches and reduced mortality from road accidents and electrocution. We strongly recommend the use of this and other, simple canopy bridges to prevent mortality of arboreal mammals.
The Problematic Path of Fundamental Rights in the European Union: Continuing the Journey on the Regulation on Clinical Trials
Authors: Di Costanzo Caterina 
Published: June 2022

Abstract
In this paper I have tried to identify and analyse some critical points that Regulation No. 526 of 2014 on clinical trials still presents. I have seen that in the face of a long gestation, the criticisms that have been made of the regulation have been various. If we think of the first criticism identified in the regulation, the so-called law shopping, we must affirm that the subject of experimentation is a very delicate matter since it has a direct and frontal impact on the guarantee of the right to health of European citizens and the use of law shopping does not provide adequate guarantees for the protection of the rights of those participating in a trial. Secondly, the marginalisation of the Ethics Committees whose role is decided at the level of the single national legal system does not ensure that components of independence and representation of the point of view of patients and their associations are guaranteed. This aspect is undoubtedly an important criticism of the regulation as the importance of the role played by the Ethics Committees in the assessment procedures for authorisation applications is not taken into fully consideration. Also, in this case, the economic need for simplification and speed of the evaluation procedure seem to prevail over the need to ensure a thorough and independent scientific and ethical review of authorisation applications. We believe that in the case of Regulation No. 536 of 2014, greater awareness of risks and opportunities will be achieved only by verifying in practice the possible distortions to which this legislation can lead. Only through serious monitoring and reporting of the effects of the regulation on the protection of patients’ rights will it be possible to identify and indicate targeted changes to the rules contained therein and, of course, to adopt the consequent measures to reduce possible damages. In this sense, also on the basis of a possible and foreseeable future phase of gestation of Regulation No. 534 of 2014, we believe that in the European area, in the field of clinical trials but not exclusively, that trend, developed above all in the French context, of the “experimentation of laws” should be further cultivated.
Influences of Béla Bartók’s Piano Compositions on Alberto Ginastera’s Piano Music
Authors: Gularnupong Karn , Buranaprapuk Ampai 
Published: June 2022

Abstract
This study seeks to reveal the musical relationship between Bartók’s and Ginastera’s piano compositions, showing stylistic conceptualizations of twentieth-century Western art music which held many interesting musical aspects, specifically in the classical piano repertoire. This musicological research employs stylistic analysis and theoretical analysis to shed some light on Bartók’s and Ginastera’s piano music vocabulary. Following this methodology, it is revealed that Ginastera’s compositional language was very much influenced by the highly unique characteristics of Bartók’s. Such characteristics include the axial system, Bulgarian peasant rhythmic dance, bi-modality, intervallic cell (Z-cell, 0167), hexachordal sets of octatonic collections, the symmetrical old Hungarian pentatonic scale, polychord, quartal chords, hammering-percussive piano style, secundal chords based on ostinato, and many others. In light of this, one may propose that Ginastera’s compositional strategies in piano music were heavily influenced by Bartók’s rhythmic and harmonic idioms, which contributed to the creation of an innovative musical craft.