bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI versus CT in the detection of brain lesions in patients with infective endocarditis before or after cardiac surgery
Authors: Vitali Paolo , Savoldi Filippo , Segati Flavia , Melazzini Luca , Zanardo Moreno , Fedeli Maria Paola , Benedek Adrienn , Di Leo Giovanni , Menicanti Lorenzo , Sardanelli Francesco
Published: October 2021

Purpose

Imaging of brain involvement in infective endocarditis can drive the clinical management of this serious condition. MRI is very sensitive, but CT is more readily available. In this retrospective study, we compared the detection rates of CT and MRI.

Methods

After Ethics Committee approval, we retrospectively reviewed a series of 20 patients (13 males, median age 64 years) who underwent both CT and MRI either before or after cardiac surgery for definite infective endocarditis. Plain CT and MRI were evaluated for acute ischemic lesions, both punctuate and large, intraparenchymal hemorrhages, cerebral microbleeds, subarachnoid hemorrhages, abscesses, microabscesses, and meningitis. Qualitative assessment and McNemar test were performed. The value of contrast-enhanced scans (MRI, n = 14; CT, n = 9) and cognitive status were also assessed.

Results

A total of 166 lesions were identified on either technique: 137 (83%) on MRI only, 4 (2%) on CT only, and 25 (15%) on both techniques (p < 0.001). For these last 25 lesions, concordance on lesion type was only 16/25 (64%). MRI detected more microbleeds and ischemic lesions, while the 4 CT-only findings were false positives. Contrast-enhanced scans identified 68 enhancing lesions, mainly abscesses and microabscesses, and allowed a better characterization for 61/117 lesions (52%) with MRI, and for 11/81 (14%) with CT. Follow-up identified mild cognitive impairment in 6/13 and dementia in 3/13 patients.

Conclusion

While CT rapidly excludes large hemorrhages in patients with infective endocarditis, MRI accurately distinguishes the whole spectrum of brain lesions, including small ischemic lesions, microbleeds, and microabscesses.
Characterization of a thermotolerant aryl-alcohol oxidase from Moesziomyces antarcticus oxidizing 5-hydroxymethyl-2-furancarboxylic acid
Authors: Lappe Alessa , Jankowski Nina , Albrecht Annemie , Koschorreck Katja
Published: October 2021

The development of enzymatic processes for the environmentally friendly production of 2,5-furandicarboxylic acid (FDCA), a renewable precursor for bioplastics, from 5-hydroxymethylfurfural (HMF) has gained increasing attention over the last years. Aryl-alcohol oxidases (AAOs) catalyze the oxidation of HMF to 5-formyl-2-furancarboxylic acid (FFCA) through 2,5-diformylfuran (DFF) and have thus been applied in enzymatic reaction cascades for the production of FDCA. AAOs are flavoproteins that oxidize a broad range of benzylic and aliphatic allylic primary alcohols to the corresponding aldehydes, and in some cases further to acids, while reducing molecular oxygen to hydrogen peroxide. These promising biocatalysts can also be used for the synthesis of flavors, fragrances, and chemical building blocks, but their industrial applicability suffers from low production yield in natural and heterologous hosts. Here we report on heterologous expression of a new aryl-alcohol oxidase, MaAAO, from Moesziomyces antarcticus at high yields in the methylotrophic yeast Pichia pastoris (recently reclassified as Komagataella phaffii). Fed-batch fermentation of recombinant P. pastoris yielded around 750 mg of active enzyme per liter of culture. Purified MaAAO was highly stable at pH 2–9 and exhibited high thermal stability with almost 95% residual activity after 48 h at 57.5 °C. MaAAO accepts a broad range of benzylic primary alcohols, aliphatic allylic alcohols, and furan derivatives like HMF as substrates and some oxidation products thereof like piperonal or perillaldehyde serve as building blocks for pharmaceuticals or show health-promoting effects. Besides this, MaAAO oxidized 5-hydroxymethyl-2-furancarboxylic acid (HMFCA) to FFCA, which has not been shown for any other AAO so far. Combining MaAAO with an unspecific peroxygenase oxidizing HMFCA to FFCA in one pot resulted in complete conversion of HMF to FDCA within 144 h. MaAAO is thus a promising biocatalyst for the production of precursors for bioplastics and bioactive compounds.

Key points

• MaAAO from M. antarcticus was expressed in P. pastoris at 750 mg/l.

• MaAAO oxidized 5-hydroxymethyl-2-furancarboxylic acid (HMFCA).

• Complete conversion of HMF to 2,5-furandicarboxylic acid by combining MaAAO and UPO.
Parathyroid Hormone Disturbances in Postmenopausal Women with Distal Forearm Fracture
Authors: Wihlborg Axel , Bergström Karin , Gerdhem Paul , Bergström Ingrid
Published: October 2021

Background

Primary hyperparathyroidism (PHPT) is a common endocrine disorder with a wide range of adverse effects, such as osteoporosis. Many women are not diagnosed due to asymptomatic disease or vague symptoms but are still at risk of severe adverse effects. Early identification of patients with PHPT is therefore of importance. The aim of this study was to determine PHPT prevalence among postmenopausal women with a distal forearm fracture.

Methods

Recruitment was conducted in conjunction with the occurrence of a distal forearm fracture at Karolinska University Hospital. In total, 161 postmenopausal women were included in a cross‐sectional study with repeated evaluations. Analyzes of serum calcium, ionized calcium, phosphate, parathyroid hormone (PTH), and vitamin D were performed. Diagnosis of PHPT was based on clinical evaluations and biochemical definitions of serum calcium and PTH in coherence with previous population prevalence reports.

Results

Mean age was 64.7 (9.5) years, serum calcium 2.33 (0.10) mmol/L, ionized calcium 1.25 (0.05) mmol/L and PTH 54 (26) ng/L. PTH was elevated in 32 (20%) women. In total, 11 (6.8%) women were diagnosed with PHPT; 6 with classical PHPT and 5 with mild PHPT. The prevalence of PHPT was significantly increased compared to the population prevalence of 3.4% (p = 0.022).

Conclusion

Screening postmenopausal women in conjunction with low‐energy distal forearm fracture revealed a large number of women with parathyroid disturbance. Evaluation of parathyroid hormone and calcium status in this group of patients seems beneficial.
Prevention of vascular calcification by the endogenous chromogranin A-derived mediator that inhibits osteogenic transdifferentiation
Authors: Orth-Alampour Setareh , Gayrard Nathalie , Salem Silvia , Bhargava Shruti , Jankowski Vera , Jover Bernard , Notarnicola Cécile , Noels Heidi , van der Vorst Emiel P. C. , Kuppe Christoph , Wolf Michael , Goettsch Claudia , Theelen Wendy , Bruck Heike , Fliser Danilo , Loscalzo Joseph , Wu Zhuojun , Marx Nikolaus , Zidek Walter , Argilés Àngel , Jankowski Joachim
Published: October 2021

The adrenal glands participate in cardiovascular (CV) physiology and the pathophysiology of CV diseases through their effects on sodium and water metabolism, vascular tone and cardiac function. In the present study, we identified a new adrenal compound controlling mesenchymal cell differentiation that regulates osteoblastic differentiation in the context of vascular calcification. This peptide was named the “calcification blocking factor” (CBF) due to its protective effect against vascular calcification and is released from chromogranin A via enzymatic cleavage by calpain 1 and kallikrein. CBF reduced the calcium content of cells and thoracic aortic rings under calcifying culture conditions, as well as in aortas from animals treated with vitamin D and nicotine (VDN animals). Furthermore, CBF prevented vascular smooth muscle cell (VSMC) transdifferentiation into osteoblast-like cells within the vascular wall via the sodium-dependent phosphate transporter PIT-1 and by inhibition of NF-κB activation and the subsequent BMP2/p-SMAD pathway. Pulse pressure, a marker of arterial stiffness, was significantly decreased in VDN animals treated with CBF. In line with our preclinical data, CBF concentration is significantly reduced in diseases characterized by increased calcification, as shown in patients with chronic kidney disease. In preparation for clinical translation, the active site of the native 19-AS long native CBF was identified as EGQEEEED. In conclusion, we have identified the new peptide CBF, which is secreted from the adrenal glands and might prevent vascular calcification by inhibition of osteogenic transdifferentiation. The anti-calcific effects of CBF and short active site may therefore promote the development of new tools for the prevention and/or treatment of vascular calcification.
The changing face of Irish head and neck cancer epidemiology: 20 years of data
Authors: Sexton Gerard P. , Walsh Paul , Moriarty Frank , O’Neill James Paul
Published: October 2021

Background

Head and neck cancer (HNC) is associated with significant morbidity and mortality, especially when high stage disease is present. The epidemiology and prognosis of HNC has changed considerably over the last 20 years.

Aims

This study aimed to examine the epidemiological trends in HNC patients over a prolonged period in Ireland.

Methods

We conducted a retrospective cohort study using 20 years of cancer registry data provided by the National Cancer Registry of Ireland. Baseline characteristics and survival statistics were thereby generated.

Results

10,148 patients were identified. There is a growing population of young (< 50 years) and very old (> 85 years) HNC patients; 48.15% of the population was elderly (> 65 years). Oral cavity (29.8%) and laryngeal cancer (28.1%) remain the most prevalent subsites, though oral cavity cancer prevalence declined from 35.9% in 1994 to 27.5% in 2014. Oropharyngeal cancer prevalence increased from 13.6 to 22.2% over the same period. Overall 5-year survival has improved significantly to 56.8% in 2010 but there remains a disparity between the elderly and adult cohorts (42.0% vs 60.7%). 5-year survival for hypopharyngeal and oropharyngeal cancers has improved from 11.8% and 33.3% to 22.2% and 44.8%, respectively, while laryngeal and oral cavity cancer survival remains approximately stable at 58.7% and 61.5%, respectively.

Conclusion

HNC survival in Ireland has improved in line with increasing recognition of the value of multidisciplinary assessment, subspecialisation in cancer care, and targeted therapies based on tumour subsites. Survival in the elderly cohort remains poor despite increasing recognition of the challenges such cases pose.
Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia
Authors: Walther Sebastian , Lefebvre Stephanie , Conring Frauke , Gangl Nicole , Nadesalingam Niluja , Alexaki Danai , Wüthrich Florian , Rüter Maximilian , Viher Petra V. , Federspiel Andrea , Wiest Roland , Stegmayer Katharina
Published: October 2021

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.
Rehabilitation program combining physical exercise and heart rate variability biofeedback in hematologic patients: a feasibility study
Authors: Fournié Claire , Verkindt Chantal , Dalleau Georges , Bouscaren Nicolas , Mohr Catherine , Zunic Patricia , Cabrera Quentin
Published: October 2021

Purpose

Hematologic patients have a poorer health-related quality of life due to the disease and its treatments. Non-pharmacological interventions represent an opportunity in tertiary cancer prevention to manage persistent symptoms and support patients in their return to active daily living. This interventional study aimed to evaluate the feasibility of a program combining physical exercise (PE) and heart rate variability biofeedback (HRVB) in hematologic patients.

Method

Hematologic patients in remission within 6 months participated in a 12-week rehabilitation program including 24 supervised sessions of PE associated with 10 supervised sessions of HRVB and daily home-based practice of paced breathing. We assessed patient adherence, fatigue, physical function, and heart rate variability.

Results

Twenty patients were included, 17 completed the protocol and 3 dropped out due to disease progression or time constraints; no adverse events or incidents were reported. Participation rates were 85% for PE and 98% for HRVB-supervised sessions. Significant improvements of physical capacity (6-min walk test, p < 0.001; 50-foot walk test, p < 0.001), muscle strength (grip force test, p < 0.01), and flexibility (toe-touch test, p < 0.001; back scratch test, p < 0.05) were measured. Coherence ratio (p < 0.001) and low-frequency spectral density of HRV signal (p < 0.003) increased significantly, suggesting improved autonomic function. Fatigue, static balance, and other time and frequency indicators of HRV were not improved (all p > 0.05).

Conclusion

A rehabilitation program combining PE and HRVB is feasible in hematologic patients and effective on physical function. Further research with a larger sample size is needed to investigate effectiveness on patients’ autonomic functions and their impacts on symptomatology.
TEG6s Platelet Mapping assay for the estimation of plasma fibrinogen concentration during cardiovascular surgery: a single-center prospective observational study
Authors: Yamamoto Yudai , Sato Yunosuke , Takahashi Miri , Yamamoto Hiroto , Echizen Mayumi , Uchida Tokujiro
Published: October 2021

Purpose

The Activator F (ActF) test on the TEG6s Platelet Mapping assay system is a means of quantifying blood viscoelasticity caused by fibrin network formation, triggered by reptilase and factor XIII, while platelets are inhibited. This unique methodology enables the measurement of blood viscoelasticity, even in highly heparinized blood. Here, we investigated whether fibrinogen concentration could be estimated using the ActF test in blood samples obtained during cardiopulmonary bypass (CPB) and after CPB in patients undergoing cardiovascular surgery.

Methods

We performed a single-center prospective observational study at a university hospital. Forty patients aged ≥ 18 years who underwent elective cardiovascular surgery with CPB were enrolled. Blood samples were drawn after the induction of anesthesia, after declamping of the aorta during CPB, and after the reversal of heparinization using protamine (after CPB). Coagulation profiles were evaluated using the Platelet Mapping assay and standard laboratory tests.

Results

There were strong correlations between the maximal amplitude of clot strength (MA) in the ActF test and fibrinogen concentration in samples drawn during CPB (R = 0.84, 95% confidence interval [CI] 0.72–0.91; P < 0.001) and after CPB (R = 0.83, 95% CI 0.70–0.91; P < 0.001). The areas under the receiver-operating characteristic curve for the ActF MA for fibrinogen concentrations < 150 mg/dL were 0.86 (95% CI 0.73–1.0) during CPB and 0.98 (95% CI 0.94–1.0) after CPB.

Conclusion

TEG6s Platelet Mapping ActF MA values strongly correlated with plasma fibrinogen concentration in highly heparinized blood during CPB and yielded highly accurate measurements of low fibrinogen concentrations.
The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study
Authors: Ita Michael Itak , Wang Jiang Huai , Toulouse André , Lim Chris , Fanning Noel , O’Sullivan Michael , Nolan Yvonne , Kaar George Finbarr , Redmond Henry Paul
Published: October 2021

Background

Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA.

Methods

Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled.

Results

BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001).

Conclusion

We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.
Fire-fallow agriculture as a sustainable cropping system for maintaining organic carbon in Maré Loyalty Island (New Caledonia, southwest Pacific)
Authors: Leopold Audrey , Drouin Julien , Drohnu Elia , Kaplan Hélène , Wamejonengo Jacques , Bouard Severine
Published: October 2021

The Loyalty Islands are part of the French archipelago of New Caledonia in the Southwest Pacific. In these islands, Gibbsic Ferralsols (Humic) are traditionally used for fire-fallow cultivation (FFC) by the Kanak people, but the planting of perennial orchards has been encouraged over the past two decades. The impacts of this policy on soil organic carbon (SOC) are nevertheless unknown, especially in these clay-free soils in which organic matter is the main contributor to soil fertility. SOC and permanganate oxidizable organic carbon (POXC) were studied in the soils of avocado orchards, FFC, and secondary and native forests. Mean SOC stocks are particularly high, ranging between 71.9 and 194.4 MgC ha−1 in an equivalent soil mass of 2000 Mg ha−1, but they are significantly impacted by land use. Avocado farming reduced SOC stocks by about 30% compared to forest soils, even if fields were established on secondary forests that had already experienced SOC losses. In contrast, FFC did not impact them. The POXC content decreased as the degree of soil anthropization increased; however, it was less sensitive than SOC in highlighting the impacts of land use. SOC storage can be achieved through changes in agricultural practices in avocado farming, with support for farmers in transitioning from family farming to perennial cultivation and the policy management of secondary forests designed to enhance the recovery of native forests.
Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B)
Authors: Tsubata Yukari , Watanabe Kana , Saito Ryota , Nakamura Atsushi , Yoshioka Hiroshige , Morita Mami , Honda Ryoichi , Kanaji Nobuhiro , Ohizumi Satoshi , Jingu Daisuke , Nakagawa Taku , Nakazawa Kensuke , Mouri Atsuto , Takeuchi Susumu , Furuya Naoki , Akazawa Yuki , Miura Kiyotaka , Ichihara Eiki , Maemondo Makoto , Morita Satoshi , Kobayashi Kunihiko , Isobe Takeshi
Published: October 2021

Background

Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown.

Methods

Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety.

Results

Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations.

Conclusion

Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.
Simulation-based multi-criteria decision making: an interactive method with a case study on infectious disease epidemics
Authors: Dunke Fabian , Nickel Stefan
Published: October 2021

Whenever a system needs to be operated by a central decision making authority in the presence of two or more conflicting goals, methods from multi-criteria decision making can help to resolve the trade-offs between these goals. In this work, we devise an interactive simulation-based methodology for planning and deciding in complex dynamic systems subject to multiple objectives and parameter uncertainty. The outline intermittently employs simulation models and global sensitivity analysis methods in order to facilitate the acquisition of system-related knowledge throughout the iterations. Moreover, the decision maker participates in the decision making process by interactively adjusting control variables and system parameters according to a guiding analysis question posed for each iteration. As a result, the overall decision making process is backed up by sensitivity analysis results providing increased confidence in terms of reliability of considered decision alternatives. Using the efficiency concept of Pareto optimality and the sensitivity analysis method of Sobol’ sensitivity indices, the methodology is then instantiated in a case study on planning and deciding in an infectious disease epidemic situation similar to the 2020 coronavirus pandemic. Results show that the presented simulation-based methodology is capable of successfully addressing issues such as system dynamics, parameter uncertainty, and multi-criteria decision making. Hence, it represents a viable tool for supporting decision makers in situations characterized by time dynamics, uncertainty, and multiple objectives.
The Importance of Intact Senses in Mating and Social Assessments Made by Deaf Individuals
Authors: Oleszkiewicz Anna , Idziak Paulina , Rokosz Marta
Published: October 2021

Social perception is a multimodal process involving vision and audition as central input sources for human social cognitive processes. However, it remains unclear how profoundly deaf people assess others in the context of mating and social interaction. The current study explored the relative importance of different sensory modalities (vision, smell, and touch) in assessments of opposite- and same-sex strangers. We focused on potential sensory compensation processes in mate selection (i.e., increased importance of the intact senses in forming impressions of an opposite-sex stranger as a potential partner). A total of 74 deaf individuals and 100 normally hearing controls were included in the study sample. We found diminished importance of vision and smell in deaf participants compared with controls for opposite- and same-sex strangers, and increased importance of touch for the assessment of same-sex strangers. The results suggested that deaf people rely less on visual and olfactory cues in mating and social assessments, highlighting a possible role of sign language in shaping interpersonal tactile experience in non-romantic relationships.
Scattering efficiencies measurements of soft protons at grazing incidence from an Athena Silicon Pore Optics sample
Authors: Amato Roberta , Diebold Sebastian , Guzman Alejandro , Perinati Emanuele , Tenzer Chris , Santangelo Andrea , Mineo Teresa
Published: October 2021

Soft protons are a potential threat for X-ray missions using grazing incidence optics, as once focused onto the detectors they can contribute to increase the background and possibly induce radiation damage as well. The assessment of these undesired effects is especially relevant for the future ESA X-ray mission Athena, due to its large collecting area. To prevent degradation of the instrumental performance, which ultimately could compromise some of the scientific goals of the mission, the adoption of ad-hoc magnetic diverters is envisaged. Dedicated laboratory measurements are fundamental to understand the mechanisms of proton forward scattering, validate the application of the existing physical models to the Athena case and support the design of the diverters. In this paper we report on scattering efficiency measurements of soft protons impinging at grazing incidence onto a Silicon Pore Optics sample, conducted in the framework of the EXACRAD project. Measurements were taken at two different energies, $\sim $
∼
470 keV and $\sim $
∼
170 keV, and at four different scattering angles between 0.6∘ and 1.2∘. The results are generally consistent with previous measurements conducted on eROSITA mirror samples, and as expected the peak of the scattering efficiency is found around the angle of specular reflection.
Review of applications and challenges of quantitative systems pharmacology modeling and machine learning for heart failure
Authors: Cheng Limei , Qiu Yuchi , Schmidt Brian J. , Wei Guo-Wei
Published: October 2021

Quantitative systems pharmacology (QSP) is an important approach in pharmaceutical research and development that facilitates in silico generation of quantitative mechanistic hypotheses and enables in silico trials. As demonstrated by applications from numerous industry groups and interest from regulatory authorities, QSP is becoming an increasingly critical component in clinical drug development. With rapidly evolving computational tools and methods, QSP modeling has achieved important progress in pharmaceutical research and development, including for heart failure (HF). However, various challenges exist in the QSP modeling and clinical characterization of HF. Machine/deep learning (ML/DL) methods have had success in a wide variety of fields and disciplines. They provide data-driven approaches in HF diagnosis and modeling, and offer a novel strategy to inform QSP model development and calibration. The combination of ML/DL and QSP modeling becomes an emergent direction in the understanding of HF and clinical development new therapies. In this work, we review the current status and achievement in QSP and ML/DL for HF, and discuss remaining challenges and future perspectives in the field.
Success factors of initial coin offerings
Authors: Belitski Maksim , Boreiko Dmitri
Published: October 2021

This study furthers recent research on Initial Coin Offerings (ICO) in understanding the set of characteristics that drive ICO performance and reduce information asymmetry. Using data on 166 ICOs and more than 300,000 contribution addresses that sent funds to ICOs in Bitcoins or in Ether between 2013 and 2017, we examined the effect of ICO characteristics on ICO performance. We found that three boundary conditions predict ICO fundraising amount, number of investors, hard cap achievement and token ranking. These are registering ICO and publishing project’s code on GitHub, obtaining VC or Business angel financing before the campaign or during presale, and finally, publishing the whitepaper before the campaign’s start. Other factors such as serial investors, presale of tokens, bonus sales and funders' ownership share explain ICO performance. We offer implications for ICO investors and policymakers.
Kasteleyn Theorem, Geometric Signatures and KP-II Divisors on Planar Bipartite Networks in the Disk
Authors: Abenda Simonetta
Published: October 2021

Maximal minors of Kasteleyn sign matrices on planar bipartite graphs in the disk count dimer configurations with prescribed boundary conditions, and the weighted version of such matrices provides a natural parametrization of the totally non–negative part of real Grassmannians (Postnikov et al. J. Algebr. Combin. 30(2), 173–191, 2009; Lam J. Lond. Math. Soc. (2) 92(3), 633–656, 2015; Lam 2016; Speyer 2016; Affolter et al. 2019). In this paper we provide a geometric interpretation of such variant of Kasteleyn theorem: a signature is Kasteleyn if and only if it is geometric in the sense of Abenda and Grinevich (2019). We apply this geometric characterization to explicitly solve the associated system of relations and provide a new proof that the parametrization of positroid cells induced by Kasteleyn weighted matrices coincides with that of Postnikov boundary measurement map. Finally we use Kasteleyn system of relations to associate algebraic geometric data to KP multi-soliton solutions. Indeed the KP wave function solves such system of relations at the nodes of the spectral curve if the dual graph of the latter represents the soliton data. Therefore the construction of the divisor is automatically invariant, and finally it coincides with that in Abenda and Grinevich (Sel. Math. New Ser. 25(3), 43, 2019; Abenda and Grinevich 2020) for the present class of graphs.
How to compute invariant manifolds and their reduced dynamics in high-dimensional finite element models
Authors: Jain Shobhit , Haller George
Published: October 2021

Invariant manifolds are important constructs for the quantitative and qualitative understanding of nonlinear phenomena in dynamical systems. In nonlinear damped mechanical systems, for instance, spectral submanifolds have emerged as useful tools for the computation of forced response curves, backbone curves, detached resonance curves (isolas) via exact reduced-order models. For conservative nonlinear mechanical systems, Lyapunov subcenter manifolds and their reduced dynamics provide a way to identify nonlinear amplitude–frequency relationships in the form of conservative backbone curves. Despite these powerful predictions offered by invariant manifolds, their use has largely been limited to low-dimensional academic examples. This is because several challenges render their computation unfeasible for realistic engineering structures described by finite element models. In this work, we address these computational challenges and develop methods for computing invariant manifolds and their reduced dynamics in very high-dimensional nonlinear systems arising from spatial discretization of the governing partial differential equations. We illustrate our computational algorithms on finite element models of mechanical structures that range from a simple beam containing tens of degrees of freedom to an aircraft wing containing more than a hundred–thousand degrees of freedom.
Computational Social Science for Nonprofit Studies: Developing a Toolbox and Knowledge Base for the Field
Authors: Ma Ji , Ebeid Islam Akef , de Wit Arjen , Xu Meiying , Yang Yongzheng , Bekkers René , Wiepking Pamala
Published: October 2021

How can computational social science (CSS) methods be applied in nonprofit and philanthropic studies? This paper summarizes and explains a range of relevant CSS methods from a research design perspective and highlights key applications in our field. We define CSS as a set of computationally intensive empirical methods for data management, concept representation, data analysis, and visualization. What makes the computational methods “social” is that the purpose of using these methods is to serve quantitative, qualitative, and mixed-methods social science research, such that theorization can have a solid ground. We illustrate the promise of CSS in our field by using it to construct the largest and most comprehensive database of scholarly references in our field, the Knowledge Infrastructure of Nonprofit and Philanthropic Studies (KINPS). Furthermore, we show that through the application of CSS in constructing and analyzing KINPS, we can better understand and facilitate the intellectual growth of our field. We conclude the article with cautions for using CSS and suggestions for future studies implementing CSS and KINPS.
Call to action: cardiologists should promote influenza vaccination
Authors: Habib G. L. , Yousuf H. , Narula J. , Hofstra L.
Published: October 2021

The COVID-19 pandemic has spurred clinical and scientific interest in the cardiology community because of the significantly enhanced vulnerability of patients with underlying cardiac diseases. COVID-19 vaccination is therefore of vital importance to the patients we see in our clinics and hospitals every day and should be promoted by the medical community, especially cardiologists. In view of vaccine-preventable diseases, the association between influenza and cardiovascular complications has been widely investigated. Several studies have found a substantially elevated risk of hospital admission for acute myocardial infarction in the first 7 days after laboratory-confirmed influenza, with incidence ratios ranging from 6.05–8.89. The effectiveness of the influenza vaccine to protect against acute myocardial infarction is about 29%. This effectiveness is comparable to or even better than that of existing secondary preventive therapies, such as statins (prevention rate approximately 36%), antihypertensives (prevention rate approximately 15–18%), and smoking cessation (prevention rate approximately 26%). As the influenza season is rapidly approaching, this Point of View article serves as a call to action: Cardiologists should promote influenza vaccination and actively advice their patients to get the seasonal influenza vaccination.
Financialisation reinforced: the dual legacy of the covid pandemic
Authors: Lysandrou Photis , Ranjbaran Taimaz
Published: October 2021

This paper examines the impact of the covid pandemic on the financialisation process, here viewed as the growing domination of the world’s bond and equity markets over the world’s product markets. Two major arguments are advanced. The first is that the pandemic has reinforced the functionality of financial market scale, which is that its continuing growth signifies nothing other than that government and corporate organisations are colonising the future to cope with the rising financial pressures of the present. The second argument is that the pandemic has also accentuated one of the more notable dysfunctional aspects of the continuing growth of financial market scale, which is its enforcement of a core-periphery divide between the advanced and emerging market economies that occupy the global financial system. The paper concludes with some policy implications of the analysis that includes the call for a global wealth tax.
Advocating for Preservation
Authors: Banks Kimball M. , Snortland J. Signe
Published: October 2021

Over the past few years our body politic has become increasingly polarized: Republicans versus Democrats, conservatives versus liberals. That polarization filters down to governmental actions, policies, and decisions, evidenced in disagreements over regulation versus deregulation and fossil fuels versus renewable energy. Such polarization—whether legislative, administrative, or judicial and whether at the federal, state, or tribal level—can and does impact the management of our archaeological resources and the way cultural resource management is practiced in the United States. Given that most archaeologists in the United States are employed in cultural resource management, these actions affect their employment. Consequently, it is more critical than ever that archaeologists become cultural resource management and historic preservation advocates. This article discusses the whys and hows of preservation advocacy. Active, science-based advocacy by preservationists can engage governmental decision-makers to give due consideration to cultural resources and their management when making decisions or drafting and voting on legislation. Although the discussion focuses on advocacy at the federal level, the observations and suggestions are applicable at the state and local level.
Geometric-control formulation and averaging analysis of the unsteady aerodynamics of a wing with oscillatory controls
Authors: Taha Haithem E. , Pla Olea Laura , Khalifa Nabil , Gonzalez Cody , Rezaei Amir S.
Published: October 2021

Differential-geometric-control theory represents a mathematically elegant combination of differential geometry and control theory. Practically, it allows exploitation of nonlinear interactions between various inputs for the generation of forces in non-intuitive directions. Since its early developments in the 1970s, the geometric-control theory has not been duly exploited in the area of fluid mechanics. In this paper, we show the potential of geometric-control theory in the analysis of fluid flows, exemplifying it as a heuristic analysis tool for discovery of symmetry-breaking and unconventional force-generation mechanisms. In particular, we formulate the wing unsteady aerodynamics problem in a geometric-control framework. To achieve this goal, we develop a reduced-order model for the unsteady flow over a pitching–plunging wing that is (i) rich enough to capture the main physical aspects (e.g. nonlinearity of the flow dynamics at large angles of attack and high frequencies) and (ii) efficient and compact enough to be amenable to the analytic tools of geometric nonlinear control theory. We then combine tools from geometric-control theory and averaging to analyse the developed reduced-order dynamical model, which reveals regimes for lift and thrust enhancement mechanisms. The unsteady Reynolds-averaged Navier–Stokes equations are simulated to validate the theoretical findings and scrutinize the underlying physics behind these enhancement mechanisms.
Verifying non-isomorphism of groups
Authors: MacHale Des
Published: October 2021

The concept of isomorphism is central to group theory, indeed to all of abstract algebra. Two groups {G, *} and {H, ο}are said to be isomorphic to each other if there exists a set bijection α from G onto H, such that
$$\left( {a\;*\;b} \right)\alpha = \left( a \right)\alpha \; \circ \;(b)\alpha $$
for all a, b ∈ G. This can be illustrated by what
is usually known as a commutative diagram:
India and overseas Indians in Ceylon and Burma, 1946–1965: Experiments in post-imperial sovereignty
Authors: Khan Raphaëlle , Sherman Taylor C.
Published: October 2021

Despite the existence of a large Indian diaspora, there has been relatively little scholarly attention paid to India's relations with overseas Indians after its independence in 1947. The common narrative is that India abruptly cut ties with overseas Indians at independence, as it adhered to territorially based understandings of sovereignty and citizenship. Re-examining India's relations with Indian communities in Ceylon and Burma between the 1940s and the 1960s, this article demonstrates that, despite its rhetoric, independent India did not renounce responsibility for its diaspora. Instead, because of pre-existing social connections that spanned the former British empire, the Government of India faced regular demands to assist overseas Indians, and it responded on several fronts. To understand this continued engagement with overseas Indians, this article introduces the idea of ‘post-imperial sovereignty'. This type of sovereignty was layered, as imperial sovereignty had been, but was also concerned with advancing norms designed to protect minority communities across the world. India’s strategy to argue for these norms was simultaneously multilateral, regional, and bilateral. It sought to use the United Nations, the Commonwealth, and the 1947 Asian Relations Conference to secure rights for overseas Indians. As those attempts failed, India negotiated claims for citizenship with governments in Burma and Ceylon, and shaped the institutions and language through which Indians voiced demands for their rights in these countries. Indian expressions of sovereignty beyond the space of the nation-state, therefore, impacted on practices of citizenship, even during the process of de-recognition in Asia.
Exploring the alignment between the bottom-up and top-down objectives of a landscape-scale conservation initiative
Authors: Mc Culloch-Jones Samantha , Novellie Peter , Roux Dirk J , Currie Bianca
Published: October 2021

Globally, there is a trend towards conserving biodiversity by promoting co-management with multiple stakeholders at landscape scales. Environmental policies emphasize stakeholder engagement in decision-making, yet landscape conservation is typically a bureaucratic–scientific endeavour. Building trusting relationships with stakeholders is key to negotiations that minimize trade-offs and maximize synergies. Incorporating shared stakeholder objectives improves co-management, as they act as incentives for participation and trust development. We explored the degree of alignment between the bottom-up stakeholder objectives and top-down management objectives of a landscape-scale conservation initiative on the West Coast of South Africa. We categorized stakeholders into six affiliations representing governmental, private and community organizations, and using a social-ecological inventory we identified ten shared objectives. Of these objectives, three were shared between all affiliations, namely biodiversity conservation, socioeconomic development and coordination of the landscape approach. The first two aligned with the top-down landscape management objectives and the latter did not. The importance of coordinating landscape approaches in multi-stakeholder landscape-scale initiatives is crucial to long-term success, and we recommend that it be formally included as a landscape management objective. Exploring the alignment between bottom-up and top-down objectives can highlight overlooked functions of co-management and can reduce the transaction costs of sustaining conservation efforts in the long term.
Validating a risk assessment tool in United Kingdom and Irish paediatric cardiac catheterisation practice
Authors: O’Callaghan Barry , Shepherd Emma , Taliotis Demetris , Bentham James , Kenny Damien , Smith Benjamin , Franco Salvador Rodriguez , Morgan Gareth J.
Published: October 2021

Background:

No established risk prediction tool exists in United Kingdom and Irish Paediatric Cardiology practice for patients undergoing cardiac catheterisation. The Catheterisation RISk score for Paediatrics is used primarily in North American practice to assess risk prior to cardiac catheterisation. Validating the utility and transferability of such a tool in practice provides the opportunity to employ an already established risk assessment tool in everyday practice.

Aims:

To ascertain whether the Catheterisation RISk score for Paediatrics assessment tool can accurately predict complications within United Kingdom and Irish congenital catheterisation practice.

Methods:

Clinical and procedural data including National Institute for Cardiovascular Outcomes Research derived outcome data from 1500 patients across five large congenital cardiology centres in the United Kingdom and Ireland were retrospectively collected. Catheterisation RISk score for Paediatrics were then calculated for each case and compared with the observed procedural outcomes. Chi-square analysis was used to determine the relationship between observed and predicted events.

Results:

Ninety-eight (6.6%) patients in this study experienced a significant complication as qualified by National Institute for Cardiovascular Outcomes Research classification. 4% experienced a moderate complication, 2.3% experienced a major complication and 0.3% experienced a catastrophic complication resulting in death. Calculated Catheterisation RISk score for Paediatrics scores correlated well with all observed adverse events for paediatric patients across all CRISP categories. The association was also transferable to adult congenital heart disease patients in lower Catheterisation RISk score for Paediatrics categories (CRISP 1–3).

Conclusion:

The Catheterisation RISk score for Paediatrics score accurately predicts significant complications in congenital catheterisation practice in the United Kingdom and Ireland. Our data validated the Catheterisation RISk score for Paediatrics assessment tool in five congenital centres using National Institute for Cardiovascular Outcomes Research-derived outcome data.
John Locke, Toleration, and Samuel Parker's A Discourse of Ecclesiastical Politie (1669): A New Manuscript
Authors: Walmsley J. C. , Waldmann Felix
Published: October 2021

The following article prints a new manuscript by John Locke: a commentary on A Discourse of Ecclesiastical Politie (1669) by Samuel Parker (1640–88), the religious controversialist. Locke's interest in Parker's work has been known to scholars since 1954, when notes by Locke of roughly one thousand words were purchased by the Bodleian Library. The article reports the discovery of an unknown portion of this commentary: a manuscript of roughly three thousand words in the University of North Carolina at Chapel Hill. The article transcribes the manuscript, reconstructs its provenance, and reexamines Locke's engagement with Parker's Discourse. This engagement occurred in the period following Locke's composition of the first recensions of his Essay Concerning Toleration (1667–8), as Locke contemplated a refutation of Parker's ecclesiology. The discovered manuscript provides the first evidence of Locke's commitment to the principle that minimalistic theism would suffice for peaceable coexistence in any civil society.