bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation Clustering Problem Under Mediation
Authors: Ales Zacharie , Engelbeen Céline , Figueiredo Rosa 
Published: December 2023

In the context of community detection, correlation clustering (CC) provides a measure of balance for social networks as well as a tool to explore their structures. However, CC does not encompass features such as the mediation between the clusters, which could be all the more relevant with the recent rise of ideological polarization. In this work, we study correlation clustering under mediation (CCM), a new variant of CC in which a set of mediators is determined. This new signed graph clustering problem is proved to be NP-hard and formulated as an integer programming formulation. An extensive investigation of the mediation set structure leads to the development of two efficient exact enumeration algorithms for CCM. The first one exhaustively enumerates the maximal sets of mediators in order to provide several relevant solutions. The second algorithm implements a pruning mechanism, which drastically reduces the size of the exploration tree in order to return a single optimal solution. Computational experiments are presented on two sets of instances: signed networks representing voting activity in the European Parliament and random signed graphs. History: Accepted by Van Hentenryck, Area Editor for Pascal. Funding: This work was supported by Fondation Mathématique Jacques Hadamard [Grant P-2019-0031]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0129 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0129 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
Reduction in peripheral arterial stiffness after reactive hyperemia is dependent on increases in blood flow
Authors: Jackson Ronald E. , Lima Natalia S. , Sherman Sara R. , Clifford Philip S. 
Published: December 2023

AbstractThe acute reduction in peripheral arterial stiffness during reactive hyperemia is assumed to be flow‐mediated; however, the mechanism remains unproven. We hypothesized that restricting the blood flow increase during reactive hyperemia would abolish the reduction in peripheral arterial stiffness. Fourteen healthy young adults (5 females, 25 ± 5 years, mean ± SD) underwent reactive hyperemia with a rapid‐release cuff on the upper arm inflated to 220 mmHg for 5 min: once with unrestricted blood flow and once with restricted blood flow by manually applying pressure to the brachial artery. Brachial–radial pulse wave velocity (PWV) was measured with tonometers over brachial and radial arteries before cuff inflation and at 5, 15, and 30 min after release. Brachial blood flow was monitored with Doppler ultrasound. Baseline brachial–radial PWV was similar between conditions (10.3 ± 1.8 vs. 10.7 ± 1.7 m/s). With unrestricted flow, PWV decreased 5 min post‐reactive hyperemia (8.6 ± 1.1 m/s; p < 0.05) and returned near baseline at 15 and 30 min post (p < 0.05). With restricted flow, PWV did not change (p > 0.05) post‐reactive hyperemia. Reactive hyperemia acutely reduced peripheral arterial stiffness, but not when brachial artery blood flow increase was restricted. This suggests that the reduction in peripheral arterial stiffness during reactive hyperemia depends on increased blood flow.
The Push for the Free Transfer of IP Rights in Medical Biotechnology
Authors: Benzvi Elijah 
Published: December 2023

Abstract
Biotechnology is a broad range of technologies that employ living organisms or parts of them to make diverse products. Biotechnology, within the American bioeconomy, is a growing topic of concern with recent investments to help address infectious diseases, food security, and energy security. From vaccine development to comprehensive DNA mapping, the medical biotechnological industry is rapidly expanding at the forefront of technological advancement. The evolution of biotechnology as it is known today began in the 1980s with the commercialization of biotech products. The future of biotechnology is bright with scientific breakthroughs, government incentive offerings, cost-effective research and development, and therapeutic advancements to cure medical conditions that currently have inadequate or no inaccessible therapies.
Confidence in causal inference under structure uncertainty in linear causal models with equal variances
Authors: Strieder David , Drton Mathias 
Published: December 2023

AbstractInferring the effect of interventions within complex systems is a fundamental problem of statistics. A widely studied approach uses structural causal models that postulate noisy functional relations among a set of interacting variables. The underlying causal structure is then naturally represented by a directed graph whose edges indicate direct causal dependencies. In a recent line of work, additional assumptions on the causal models have been shown to render this causal graph identifiable from observational data alone. One example is the assumption of linear causal relations with equal error variances that we will take up in this work. When the graph structure is known, classical methods may be used for calculating estimates and confidence intervals for causal-effects. However, in many applications, expert knowledge that provides an a priori valid causal structure is not available. Lacking alternatives, a commonly used two-step approach first learns a graph and then treats the graph as known in inference. This, however, yields confidence intervals that are overly optimistic and fail to account for the data-driven model choice. We argue that to draw reliable conclusions, it is necessary to incorporate the remaining uncertainty about the underlying causal structure in confidence statements about causal-effects. To address this issue, we present a framework based on test inversion that allows us to give confidence regions for total causal-effects that capture both sources of uncertainty: causal structure and numerical size of non-zero effects.
Synaptic changes in pallidostriatal circuits observed in parkinsonian model triggers abnormal beta synchrony with accurate spatio-temporal properties across the basal ganglia
Authors: Lindi Shiva Azizpour , Mallet Nicolas P. , Leblois Arthur 
Published: December 2023

Excessive oscillatory activity across basal ganglia (BG) nuclei in theβfrequencies (12-30 Hz) is a hallmark of Parkinson's disease (PD). While the link between oscillations and symptoms remains debated, exaggeratedβoscillations constitute an important biomarker for therapeutic effectiveness in PD. The neuronal mechanisms ofβ-oscillation generation however remain unknown. Many existing models rely on a central role of the subthalamic nucleus (STN) or cortical inputs to BG. Contrarily, neural recordings and optogenetic manipulations in normal and parkinsonian rats recently highlighted the central role of the external pallidum (GPe) in abnormalβoscillations, while showing that the integrity of STN or motor cortex is not required. Here, we evaluate the mechanisms for the generation of abnormalβoscillations in a BG network model where neuronal and synaptic time constants, connectivity, and firing rate distributions are strongly constrained by experimental data. Guided by a mean-field approach, we show in a spiking neural network that several BG sub-circuits can drive oscillations. Strong recurrent STN-GPe connections or collateral intra-GPe connections drive gamma oscillations (> 40Hz), whereas strong pallidostriatal loops drive low-β(10-15Hz) oscillations. We show that pathophysiological strengthening of striatal and pallidal synapses following dopamine depletion leads to the emergence of synchronized oscillatory activity in the mid-βrange with spike-phase relationships between BG neuronal populations in-line with experiments. Furthermore, inhibition of GPe, contrary to STN, abolishes oscillations. Our modeling study uncovers the neural mechanisms underlying PDβoscillations and may thereby guide the future development of therapeutic strategies.Significance StatementIn Parkinson's disease, neural activity in subcortical nuclei called the basal ganglia displays abnormal oscillatory synchronization that constitutes an important biomarker for therapeutic effectiveness. The neural mechanisms for the generation of these oscillations remain unknown. Here, in a theoretical neuronal network model strongly constrained by anatomical and physiological data, we show that specific circuit modifications in basal ganglia connectivity during Parkinson's disease lead to the emergence of synchronized oscillatory activity in the network with properties that strongly agree with available experimental evidence. This and future theoretical investigations of the neural mechanisms underlying abnormal neuronal activity in Parkinson's disease are necessary to guide the future development of therapeutic strategies to ameliorate symptoms.
Cold atmospheric plasma (CAP) in wound healing: harnessing a dual-edged sword
Authors: Murali Roopak , Evangelina Rachel , Samuel Joanna Pauline , Singh Pooja , Saha Shivangi , Singhal Maneesh , Gandhirajan Rajesh Kumar 
Published: December 2023

Graphical abstract

Abstract
Chronic wounds take longer to heal and, if left untreated, can result in severe repercussions such as sepsis, gangrene, and amputation. The current treatment procedures followed are wound cleaning and debridement, specialized dressings, antibiotics and antiseptics, hyperbaric oxygen therapy, and vacuum-assisted wound closure. Some of the limitations of these treatment options are multidrug resistance and tissue toxicity. Cold plasma is an emerging technology that has opened a new frontier in biomedical applications and is found to have great utility in wound healing. Cold plasma comprises reactive oxygen and nitrogen species (RONS) that can be targeted against bacterial inactivation and improve wound healing. The amount of RONS produced can be controlled by several parameters such as gas composition, flow rate, power, frequency, voltage, distance, and exposure time. The reactive species causes damage to the cell membrane as well as the intracellular components which ultimately lead to bacterial cell death. It can also accelerate wound healing by activating neutrophils, macrophages, endothelial cells, keratinocytes, and fibroblasts. These help in maintaining tissue oxygenation, initiating angiogenesis, collagen synthesis which aids in rapid wound closure. In this review, we summarize the various characteristics of cold plasma that can be optimized to produce an effective antimicrobial effect. The different mechanisms of bacterial inactivation and the stimulation of wound healing processes by the reactive species are discussed. Furthermore, numerous pieces of evidence from in vitro and in vivo experiments and clinical trials that prove that cold plasma is an effective approach are presented.
Evaluation of Ki67, Bax, Bcl-2 and KIT in canine cutaneous mast cell tumours and their relationship with histopathology and prognosis
Authors: Aytemiz Danyer Işıl , Gürel Aydın 
Published: December 2023

AbstractCanine cutaneous mast cell tumours (CCMCTs) are common in dogs and exhibit many unpredictable behaviors. This study aimed to encourage pathology laboratories in developing countries to routinely assess prognosis by applying commonly used histopathological grading systems and immunohistochemistry (IHC) markers. We performed histological grading according to both the Patnaik and Kiupel systems, determined the mitotic count (MC) and carried out IHC for the detection of Ki67, Bax, Bcl-2 and KIT in 54 CCMCT cases. MC was associated with both grading systems in terms of survival following diagnosis and prognostic factors differed among cases categorized by the cut-off value of 5. KIT patterns were associated with grading systems and MC. The cohort with pattern II had a lower survival rate than those with patterns I and III. Ki67 was associated with survival when evaluated over the cut-off value of 0.018. Bax expression was associated with both grading systems. Median survival time was longer in patients with lower Bax expression level. Immunohistochemical detection of KIT, Ki67 and Bax improves histopathology in predicting the prognosis. If IHC is unavailable, reports regarding MC and values from both grading systems are the most effective, convenient and cost-effective way to provide the most reliable prognostic data and guidance for the clinicians.
Sanatın Haz ve Arzu Ötesi Potansiyeli: Jouissance
Authors: SELMANPAKOGLU Ceren 
Published: December 2023

Haz ve arzu kavramlarının temel tanımları içinde yer alan ‘istek’ kavramı, insanın varlık-eksikliği içinde kendini oldurma ve tamamlama çabasından kaynaklanmaktadır. Yaratma edimi ile yönelimlenen istek elde edildiğinde haz, yani tatmin gerçekleşir. Sanatçı, gerçekliği yansıtma tekrarından mastürbatif bir tatminle haz almaktadır. İzleyici de böylesi bir yapıtla karşılaştığında bildiği aynı simgesel yapıyı alımladığında haz almaktadır. Arzuda ise istek tamamlanamaz, yani istek devam eder. Çünkü arzu tatmin edilebilir değildir; öznenin eksiğini gidererek onun imgesel bütünlüğünün gerçekleştirilmesini sağlayacağı varsayılan imgesel objet-petit-a ile yani kayıp arzu nesnesi ile karakterize edilir. Sanatçı üretirken, izleyici de alımlarken yapıtta aktarılan ve alımlananlar ile hem tatminin sağlandığı bir haz ilişkisi hem de o hep aranan kayıp arzu nesnesi elde edilemediğinden ve edilemeyeceğinden arzu ilişkisi yürütülmektedir. Bu ikilik ortaya bir paradoks çıkarmaktadır. Bu nedenle, bir sanat yapıtında aslında bu iki kavramın da ötesinde gerçekleşen bu şey’i tarif eden üçüncü bir terimin gerekliliği ortaya çıkmıştır. Bunun için de bu araştırmada sanat, psikanaliz ve felsefe teorileri ilişkilendirilerek bir değerlendirme yapılmıştır.
Bu Şey, imgesel olarak kurgulanan yapıtın simgeselleştirilirken aktarılamayan, gösterilemeyen fark ya da eksiğin sanatçı ve izleyiciye kendi kendilerini feshetmeleri için sataşmasıdır: Buna göre, onlarda potansiyel olarak bulunan ve hem tamamlanamayan bir elde etmeyi hem de tamamlanamayışı feshetmekten duyulan coşkuyu tarif edebilen bu üçüncü terim Lacan’ın jouissance açıklamasında bulunmuştur. Yapıtın jouissance üzerinden işlemesi halinde, önce sanatçının, akabinde de izleyicinin kişiliklerinin tüm düzeylerinde gerçekliği ayrıştırma arzusunun devreye girdiği anlamına gelmektedir. Böylelikle yapıt üzerinden kendi kurmacalıklarının farkına varıp onu feshederek kendi yıkımları ile yüzleştiklerinde duydukları coşku jouissance olacaktır: Sürekli şimdi ve burada ve hiçbir yerde olmanın “etkili bozgunluğunu” bir sanat yapıtında duyumsamanın coşkusu olarak jouissance.
CORONET online risk assessment tool and Charlson comorbidity index in predicting fatalities in cancer patients with COVID-19
Authors: Rusanov A. S. , Sekacheva M. I. , Tyazhelnikov A. A. 
Published: December 2023

Purpose of the study. Сomparing and evaluating the prognostic potential of the CORONET online risk assessment tool and the Charlson Comorbidity Index in predicting mortality in cancer patients with COVID-19.Materials and methods. The results are drawn from the data of 168 case histories of cancer patients who were undergoing inpatient treatment for COVID-19 at the University Clinical Hospitals of Sechenov University between March 2020 and February 2022. The study was conducted as part of the program of the world-class research center “Digital Biodesign and Personalized Healthcare” of Sechenov University, with participation in the ESMO-CoCARE Registry project. Patients with a history of solid or hematologic malignancies were included in the study; their treatment period before the study was 5 years or less. The age ranged from 37 to 100 years, the median age was 69 years. The CORONET online risk assessment tool and the Charlson comorbidity index were used to objectify the severity of multimorbidity status and prognosis of fatal outcomes in cancer patients with COVID-19.Results. It was demonstrated that statistically significant effects on the prognosis of mortality in patients with cancer were: age, percentage of saturation on admission, treatment in intensive care units (ICU), National Early Warning Score 2 (NEWS2) distress syndrome severity scale score, computed tomography (CT) assessment of disease course severity, decreased blood albumin and platelet counts, and increased blood neutrophil counts in both categorical and immediate indicator value formats. In addition, it was determined that as the number of comorbidities increased, the probability of mortality increased significantly, odds ratio (OR) = 2.162 (CI 95 % 1.016–4.600; p = 0.045). The CORONET calculator score yields one of the highest OR values among all established statistically significant predictors,20.410 (CI 95 % 4.894–85.113; p < 0.001). For oncopathology in COVID-19 patients, the Charlson index score shows statistical significance as a predictor of mortality, OR =1.396 (CI 9 5 % 1.105–1.765; p = 0.005).Conclusion. The obtained advantages in using the CORONET online decision support tool over the Charlson comorbidity index in predicting mortality in cancer patients with COVID-19 are recognized as convincing.
Indicators of free radical oxidation in neutrophils of patients with primary and recurrent soft tissue sarcomas
Authors: Goroshinskaya I. A. , Kaplieva I. V. , Frantsiyants E. M. , Vashchenko L. N. , Lapteva T. O. , Ausheva T. V. , Nemashkalova L. A. , Kachesova P. S. , Kozel Yu. Yu. 
Published: December 2023

Purpose of the study. To carry out a comparative analysis of lipid peroxidation intensity and antioxidant system indices in blood neutrophils of patients with primary and relapsed soft tissue sarcomas (STS) depending on sex and age.Patients and methods. Of the 81 patients included in the study, 48 had primary STS, 5 patients with continued growth, and 28 patients with recurrent STS. The patients were divided by sex and age; the level of lipid peroxidation products, superoxide dismutase (SOD) activity, total peroxidase activity (TPA), glutathione peroxidase (GPx) activity and reduced glutathione (RG) content in blood neutrophils were investigated by conventional spectrophotometric methods. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups: ≤ 45 years and > 45 years.Results. In donors, there was a multiple decrease in the SOD/TPA ratio with age, especially in women, and in men this was accompanied by an age-related decrease in GPx activity. In primary sarcomas in older women and in men with continued growth and recurrence, there was an increase in diene conjugates (DC). In men over 45 years of age, there was an increase in SOD, TPA, and GPx. Women of the older age group were characterized by activation of SOD and GPx, expressed in the relapsed process to a significantly greater extent than in men, and an increase in RG was observed in women. The increase in both components of the glutathione system and SOD activity was especially significant in the development of relapses in women for periods exceeding three years, which was accompanied by a decrease in DC content. Conclusions. Neutrophils are characterized by an increase in DC content in patients of both sexes in the older age group with primary and recurrent STS, with its highest content in men with continued growth and relapses. GPx activity, increased in both men and women in the older age group in all variants of STS development, may play an important role in the antioxidant protection of blood cells in STS. Thus, the most pronounced activation of GPx, accompanied by a maximum increase in reduced glutathione and activation of SOD, contributes to a decrease in the level of DC and the absence of MDA increase in women with slow development of recurrences.
Molecular and cellular aspects of the impact of secondary metabolites from common barberry and hybrid goat’s rue on the HeLa cell line
Authors: Zlatnik E. Yu. , Enin Ya. S. , Burov O. N. , Bondarenko E. S. , Sagakyants A. B. , Kutilin D. S. , Dzigunova Yu. V. , Ishonina O. G. , Shalashnaya E. V. , Ushakova N. D, 
Published: December 2023

Purpose of the study. To isolate and verify pure fractions of secondary plant metabolites contained in B. vulgaris (L.) and P. hibridus (L.), as well as to conduct a model experiment and molecular genetic study to evaluate their cytotoxic effect in vitro on the HeLa cell line.Materials and methods. The isolation and verification of all compounds used in the experiment were carried out using column chromatography and nuclear magnetic resonance methods at the Department of Natural Compounds, Faculty of Chemistry, Southern Federal University. Subsequently, an experiment was conducted using cultural and molecular methods on the HeLa cell line in three repetitions for each test compound; after incubation with them, the numbers of dead cells were counted on the automated NanoEnTek JuliFl counter, and the numbers of cells in apoptosis were measured by flow cytometry on the BD analyzer FACS Canto II. The level of copy number variation and expression of genes responsible for apoptosis were assessed by real-time PCR (RT-PCR). In total, three substances were studied, with two concentrations (4 and 12 μg/ml) and two exposures (24 and 72 hours) for each of them.Results. In the first stage of the study, we isolated and verified the berberine alkaloid extracted from the roots of B. vulgaris (L.), as well as 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one and 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde from P. hibridus (L.). The subsequent stage of the study demonstrated the maximal cellular death under the action of berberine at a 72-hour exposure. However, the RT-PCR assessment of the copy number variation and expression of the CASP8, CASP9, CASP3, BAX, BCL2, TP53 and MDM2 genes revealed the presence of apoptosis initiation in tumor cells at the molecular level under the action of all the studied compounds: both berberine and furan and azulene derivatives derived from P. hibridus (L.).Conclusion. All compounds used in the experiment exhibited a cytotoxic effect on the HeLa cell line. Berberine alkaloid showed the most pronounced cytotoxic effect on the HeLa line as recorded by all methods used in the study. Terpenoids 4-dihydroxy-2,5-dimethylfuran-3(2H)-one and 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde, when exposed to the HeLa line, caused an increase in the copy number variation and expression of the CASP9, CASP3 loci, which are among the main activators of apoptosis. They also influenced the expression of TP53 and MDM2 loci.