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We present an algorithm for Tchakaloff-like compression of quasi-Monte Carlo volume and surface integration on an arbitrary union of balls, via non-negative least squares. We also provide the corresponding Matlab codes together with several numerical tests. [ABSTRACT FROM AUTHOR]

The pandemic of coronavirus disease 19 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), had severe repercussions for breast cancer patients. Increasing evidence indicates that SARS-CoV-2 infection may directly impact breast cancer biology, but the effects of SARS-CoV-2 on breast tumor cells are still unknown. Here, we analyzed the molecular events occurring in the MCF7, MDA-MB-231 and HCC1937 breast cancer cell lines, representative of the luminal A, basal B/claudin-low and basal A subtypes, respectively, upon SARS-CoV-2 infection. Viral replication was monitored over time, and gene expression profiling was conducted. We found that MCF7 cells were the most permissive to viral replication. Treatment of MCF7 cells with Tamoxifen reduced the SARS-CoV-2 replication rate, suggesting an involvement of the estrogen receptor in sustaining virus replication in malignant cells. Interestingly, a metagene signature based on genes upregulated by SARS-CoV-2 infection in all three cell lines distinguished a subgroup of premenopausal luminal A breast cancer patients with a poor prognosis. As SARS-CoV-2 still spreads among the population, it is essential to understand the impact of SARS-CoV-2 infection on breast cancer, particularly in premenopausal patients diagnosed with the luminal A subtype, and to assess the long-term impact of COVID-19 on breast cancer outcomes. [ABSTRACT FROM AUTHOR]

In this paper we provide a tetrahedra-free algorithm to compute low-cardinality quadrature rules with a given degree of polynomial exactness, positive weights and interior nodes on a polyhedral element with arbitrary shape. The key tools are the notion of Tchakaloff discretization set and the solution of moment-matching equations by Lawson-Hanson iterations for NonNegative Least-Squares. Several numerical tests are presented. The method is implemented in Matlab as open-source software. [ABSTRACT FROM AUTHOR]

Melanoma is characterized by high metastatic potential favored by the epithelial-to-mesenchymal transition (EMT), leading melanoma cells to exhibit a spectrum of typical EMT markers. This study aimed to analyze the expression of EMT markers in A375 and BLM melanoma cell lines cultured in 2D monolayers and 3D spheroids using morphological and molecular methods. The expression of EMT markers was strongly affected by 3D arrangement and revealed a hybrid phenotype for the two cell lines. Indeed, although E-cadherin was almost undetectable in both A375 and BLM cells, cortical actin was detected in A375 2D monolayers and 3D spheroids and was strongly expressed in BLM 3D spheroids. The mesenchymal marker N-cadherin was significantly up-regulated in A375 3D spheroids while undetectable in BLM cells, but vimentin was similarly expressed in both cell lines at the gene and protein levels. This pattern suggests that A375 cells exhibit a more undifferentiated/mesenchymal phenotype, while BLM cells have more melanocytic/differentiated characteristics. Accordingly, the Zeb1 and 2, Slug, Snail and Twist gene expression analyses showed that they were differentially expressed in 2D monolayers compared to 3D spheroids, supporting this view. Furthermore, A375 cells are characterized by a greater invasive potential, strongly influenced by 3D arrangement, compared to the BLM cell line, as evaluated by SDS-zymography and TIMPs gene expression analysis. Finally, TGF-β1, a master controller of EMT, and lysyl oxidase (LOX), involved in melanoma progression, were strongly up-regulated by 3D arrangement in the metastatic BLM cells alone, likely playing a role in the metastatic phases of melanoma progression. Overall, these findings suggest that A375 and BLM cells possess a hybrid/intermediate phenotype in relation to the expression of EMT markers. The former is characterized by a more mesenchymal/undifferentiated phenotype, while the latter shows a more melanocytic/differentiated phenotype. Our results contribute to the characterization of the role of EMT in melanoma cells and confirm that a 3D cell culture model could provide deeper insight into our understanding of the biology of melanoma. [ABSTRACT FROM AUTHOR]

Summary: A refinement of a previous asymptotic analysis of the well‐known two‐capacitor circuit is presented. It rests on some mathematical results, which allow the originally conceived regularity constraint to be replaced with a new one, not only less restrictive but also and above all simpler and easier to check. On this basis, the main time domain diagrams of the circuit with the embedding switch are presented. In addition, the solution of the circuit in the transition interval is provided, and some calculations related to the distribution side of the analysis are also reconsidered and improved. [ABSTRACT FROM AUTHOR]

The progressive reclassification of diseases has also helped in distinguishing pathologic subtypes according to their genetic cause, better establishing patients' disease risk and assessing disease severity for personalized medicine and genotype-driven therapies [[2]]. New available genetic data allow real disease prevalence to be established while defining the diseases according to their etiology and not only their phenotypes. A genome-wide association scan identified two novel loci, one around an SNP next to the I PBX1 i gene, and another within the I PCCA i gene. Recent technical breakthroughs in genotyping and bioinformatics techniques have greatly facilitated the translation of genomics into clinical care. [Extracted from the article]

Introduction: Chemical reaction networks (CRNs) are powerful tools for describing the complex nature of cancer's onset, progression, and therapy. The main reason for their effectiveness is in the fact that these networks can be rather naturally encoded as a dynamical system whose asymptotic solution mimics the proteins' concentration profile at equilibrium. Methods and Results: This paper relies on a complex CRN previously designed for modeling colorectal cells in their G1-S transition phase and presents a mathematical method to investigate global and local effects triggered on the network by partial and complete mutations occurring mainly in its mitogenactivated protein kinase (MAPK) pathway. Further, this same approach allowed the in-silico modeling and dosage of a multi-target therapeutic intervention that utilizes MAPK as its molecular target. Discussion: Overall the results shown in this paper demonstrate how the proposed approach can be exploited as a tool for the in-silico comparison and evaluation of different targeted therapies. Future effort will be devoted to refine the model so to incorporate more biologically sound partial mutations and drug combinations. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, social listening programs across digital channels have become an integral part of health preparedness and response planning, allowing to capture and address questions, information needs, and misinformation shared by users. This study identifies key social listening trends around COVID-19 vaccines in Eastern and Southern Africa and analyses how online conversations about this issue evolved over time. Methods: A taxonomy developed and refined in collaboration with social and behaviour change teams was used to filter online conversations into nine subtopic categories. The taxonomy was applied to online content tracked in 21 countries in Eastern and Southern Africa over the period December 1, 2020—December 31, 2021. Metrics captured included volume of posts or articles and related user engagement. Qualitative analysis of content was conducted to identify key concerns, information voids and misinformation. Results: Over 300,000 articles and posts about COVID-19 vaccines shared by users or outlets geolocated in the region were analysed. These results generated over 14 million engagements on social media and digital platforms. The analysis shows how conversations about access and availability of vaccines represented the largest share of engagement over the course of the period. Conversations about vaccine effectiveness and safety represented the second and third largest share of engagement, with peaks observed in August and November 2021. Online interest in childhood vaccination increased over time as vaccine eligibility criteria expanded in some countries in the region. Conversations mentioning mandates and certificates peaked in the last quarter of 2021, as governments as private sector entities expanded vaccine requirements. Conclusions: Findings from this study show the importance of monitoring conversation trends over time and adjust social listening data collection systems to include emerging topics. The study also points to the need to consider concerns, information voids and misinformation around effectiveness and safety of vaccines in the context of overall concern for vaccine availability and access in Eastern and Southern Africa. This is fundamental to inform social and behaviour change strategies that promote vaccine demand effectively, without increasing public frustration over vaccine availability challenges and downplaying concerns around vaccine equity. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are the mammalian ortholog of Drosophila melanogaster protein Toll, originally identified for its involvement in embryonic development. In mammals, TLRs are mainly known for their ability to recognize pathogen-or damage-associated molecular patterns and, consequently, to initiate the immune response. However, it is becoming clear that TLRs can play a role also in mammal embryo development. We have previously described TLR4 and TLR7 expression in developing mouse peripheral nervous system and gastrointestinal tract. In the present study, we extended the investigation of TLR4 and TLR7 to the respiratory system and to the two main accessory organs of the digestive system, the liver and pancreas. TLR4 and TLR7 immunostaining was performed on mouse conceptuses collected at different stages, from E12 to E18. TLR4 and TLR7 immunoreactivity was evident in the embryo pancreas and liver at E12, while, in the respiratory apparatus, appeared at E14 and E17, respectively. Although further studies are required to elucidate the specific role of these TLRs in embryo development, the differential spatiotemporal TLR4 and TLR7 appearance may suggest that TLR expression in developing embryos is highly regulated for a possible their direct involvement in the formation of the organs and in the acquisition of immune-related features in preparation for the birth. [ABSTRACT FROM AUTHOR]

In this paper we propose an algorithm that computes a low cardinality PI-type (Positive weights and Interior nodes) algebraic cubature rule of degree n, with at most (n + 1) (n + 2) / 2 nodes, over curvilinear polygons defined by piecewise rational functions. Typical examples are domains whose boundary is defined piecewise by NURBS curves or by composite Bezier curves. The key tools are a relevant but overlooked theorem of 1976 by Wilhelmsen on Tchakaloff sets, a specific in-domain algorithm for such curvilinear polygons and the sparse nonnegative solution of underdetermined moment matching systems by the Lawson–Hanson Nonnegative least squares solver. Many numerical tests are performed to show the flexibility of this approach and the implemented MATLAB toolbox is freely available to the users, in particular for possible applications within FEM/VEM with NURBS-shaped curvilinear elements. [ABSTRACT FROM AUTHOR]

Over recent years, preclinical and clinical evidence has implicated myocardial inflammation (M-Infl) in the pathophysiology and phenotypes of traditionally genetic cardiomyopathies. M-Infl resembling myocarditis on imaging and histology occurs frequently as a clinical manifestation of classically genetic cardiac diseases, including dilated and arrhythmogenic cardiomyopathy. The emerging role of M-Infl in disease pathophysiology is leading to the identification of druggable targets for molecular treatment of the inflammatory process and a new paradigm in the field of cardiomyopathies. Cardiomyopathies constitute a leading cause of heart failure and arrhythmic sudden death in the young population. The aim of this review is to present, from bedside to bench, the current state of the art about the genetic basis of M-Infl in nonischemic cardiomyopathies of the dilated and arrhythmogenic spectrum in order to prompt future research towards the identification of novel mechanisms and treatment targets, with the ultimate goal of lowering disease morbidity and mortality. [ABSTRACT FROM AUTHOR]

The present study analyses the technical feasibility and economic sustainability of Moon-mined propellant transportation, storage, and distribution to final users. Two technical architectural options are considered for propellant transportation: taking fuel from the Moon or from Earth. Both architectures assume the same storage and distribution system, i.e., the use of an orbiting depot. The depot will be reachable by various types of spacecrafts for refueling. Both architectures are evaluated in terms of technical feasibility, performance and economic convenience. As the estimates of the investment, operational costs, and revenues are highly uncertain, a risk evaluation, i.e. the Monte Carlo analysis, is used to evaluate the exposure of the ventures to factors that could affect the volatility of results and lead them to fail. These analyses identify transporting propellant from the Moon as the most promising solution. • Lunar-based propellant storage and distribution through a EML 1 depot is technically feasible and economically convenient. • Montecarlo simulations indicate lower riskiness for a lunar-based propellant infrastructure compared to Earth options. • The presence of a competitive space could incentivize institutional and private investors. [ABSTRACT FROM AUTHOR]

Passivity criteria for controlled affine resistive (CAR) components are presented. First, the definitions of passive component and non‐dynamic component are recalled, as formulated in the frame of the behavioral approach (i.e., based on the concept of forwards concatenation set of an admissible process at a given time). Then, three lemmas, one theorem, and four corollaries on quadratic functions are stated and proven, which provide the mathematical tools needed. On this basis, passivity criteria for CAR components are derived, under both the standard (i.e., homogeneous, hybrid, and transmission) matrix representations and the general matrix representation. Finally, by resorting to a kind of canonic representation, two general results on the passivity of CAR components are obtained. [ABSTRACT FROM AUTHOR]

Simple Summary: Mini-invasive surgery represents an interesting yet challenging technical evolution for treating peritoneal metastases. This retrospective study aims to present the experience of the Italian Peritoneal Surface Malignancies Oncoteam with laparoscopic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), including a detailed description of the technique and a systematic review of the literature. The study shows the feasibility and safety of laparoscopic CRS-HIPEC and its association with favorable outcomes in properly selected patients. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance in clinical practice. Performing CRS and HIPEC laparoscopically represents a challenging and intriguing technical evolution. However, the experiences are limited, and the evidence is low. This retrospective analysis was performed on patients treated with laparoscopic CRS-HIPEC within the Italian Peritoneal Surface Malignancies Oncoteam. Clinical, perioperative, and follow-up data were extracted and collected on prospectively maintained databases. We added a systematic review according to the PRISMA method for English-language articles through April 2022 using the keywords laparoscopic, hyperthermic, HIPEC, and chemotherapy. From 2016 to 2022, fourteen patients were treated with Lap-CRS-HIPEC with curative intent within the Italian centers. No conversion to open was observed. The median duration of surgery was 487.5 min. The median Peritoneal Cancer Index (PCI) was 3, and complete cytoreduction was achieved in all patients. Two patients (14.3%) had major postoperative complications, one requiring reintervention. After a median follow-up of 16.9 months, eleven patients were alive without disease (78.6%), two patients developed recurrence (14.3%), and one patient died for unrelated causes (7.1%). The literature review confirmed these results. In conclusion, current evidence shows that Lap-CRS-HIPEC is feasible, safe, and associated with a favorable outcome in selected patients. An accurate patient selection will continue to be paramount in choosing this treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal peritoneal metastases could potentially benefit from locoregional treatments such as cytoreduction combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Three recently published RCTs that have investigated HIPEC in the setting of radical or prophylactic/II^ look surgery have improved the current knowledge of the treatment of CRC PM. The current review summarizes the results of these trials, emphasizing the highlights and criticisms and focusing on the potential impact and future directions in the clinical practice of HIPEC. Oxaliplatin-based HIPEC seems ineffective in improving surgery results in patients with CRC PM. Moreover, the same oxaliplatin-based regimen is ineffective in preventing CRC PM occurrence and should be abandoned. Several ongoing trials are investigating mitomycin-based HIPEC after radical surgery or as a prevention strategy. Meanwhile, HIPEC should still be considered a therapeutic option for selected patients and offered by dedicated, experienced centers and surgical teams. HIPEC is a potentially useful locoregional treatment combined with cytoreduction in patients with peritoneal colorectal metastases. Despite being widely used in several cancer centers around the world, its role had never been investigated before the results of three important RCTs appeared on this topic. The PRODIGE 7 trial clarified the role of oxaliplatin-based HIPEC in patients treated with radical surgery. Conversely, the PROPHYLOCHIP and the COLOPEC were designed to chair the role of HIPEC in patients at high risk of developing peritoneal metastases. Although all three trials demonstrated the relative ineffectiveness of HIPEC for treating or preventing peritoneal metastases, these results are not sufficient to abandon this technique. In addition to some criticisms relating to the design of the trials and their statistical value, the oxaliplatin-based HIPEC was found to be ineffective in preventing or treating peritoneal colorectal metastases, especially in patients already treated with systemic platinum-based chemotherapy. Several studies are ongoing investigating further HIPEC drugs and regimens. The review deeply discussed all the aspects and relapses of this new evidence. [ABSTRACT FROM AUTHOR]

A classic approach to estimate individual theta‐to‐alpha transition frequency (TF) requires two electroencephalographic (EEG) recordings, one acquired in a resting state condition and one showing alpha desynchronisation due, for example, to task execution. This translates into long recording sessions that may be cumbersome in studies involving patients. Moreover, an incomplete desynchronisation of the alpha rhythm may compromise TF estimates. Here we present transfreq, a publicly available Python library that allows TF computation from resting state data by clustering the spectral profiles associated to the EEG channels based on their content in alpha and theta bands. A detailed overview of transfreq core algorithm and software architecture is provided. Its effectiveness and robustness across different experimental setups are demonstrated on a publicly available EEG data set and on in‐house recordings, including scenarios where the classic approach fails to estimate TF. We conclude with a proof of concept of the predictive power of transfreq TF as a clinical marker. Specifically, we present a scenario where transfreq TF shows a stronger correlation with the mini mental state examination score than other widely used EEG features, including individual alpha peak and median/mean frequency. The documentation of transfreq and the codes for reproducing the analysis of the article with the open‐source data set are available online at https://elisabettavallarino.github.io/transfreq/. Motivated by the results showed in this article, we believe our method will provide a robust tool for discovering markers of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

We prove that interpolation matrices for Generalized MultiQuadrics (GMQ) of order greater than one are almost surely nonsingular without polynomial addition, in any dimension and with any continuous random distribution of sampling points. We also include a new class of generalized MultiQuadrics recently proposed by Buhmann and Ortmann. [ABSTRACT FROM AUTHOR]

In this note we prove almost sure unisolvence of RBF interpolation on randomly distributed sequences by a wide class of polyharmonic splines (including Thin-Plate Splines), without polynomial addition. [ABSTRACT FROM AUTHOR]

E-cadherin, an epithelial-to-mesenchymal transition (EMT) marker, is coupled to actin cytoskeleton and distributes cell forces acting on cells. Since YAP transduces mechanical signals involving actin cytoskeleton, we aimed to investigate the relationship between YAP and mechanical cues in pancreatic ductal adenocarcinoma (PDAC) cell lines, characterized by different EMT-related phenotypes, cultured in 2D monolayers and 3D spheroids. We observed that the YAP/p-YAP ratio was reduced in HPAC and MIA PaCa-2 cell lines and remained unchanged in BxPC-3 cells when cultured in a 3D setting. CTGF and CYR61 gene expression were down-regulated in all PDAC 3D compared to 2D cultures, without any significant effect following actin cytoskeleton inhibition by Cytochalasin B (CyB) treatment. Moreover, LATS1 mRNA, indicating the activation of the Hippo pathway, was not influenced by CyB and differed in all PDAC cell lines having different EMT-related phenotype but a similar pattern of CTGF and CYR61 expression. Although the role of YAP modulation in response to mechanical cues in cancer cells remains to be completely elucidated, our results suggest that cell arrangement and phenotype can determine variable outcomes to mechanical stimuli in PDAC cells. Moreover, it is possible to speculate that YAP and Hippo pathways may act as parallel and not exclusive inputs that, converging at some points, may impact cell behavior. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most deadly and commonly diagnosed tumors worldwide. Several genes are involved in its development and progression. The most frequent mutations concern APC, KRAS, SMAD4, and TP53 genes, suggesting that CRC relies on the concomitant alteration of the related pathways. However, with classic molecular approaches, it is not easy to simultaneously analyze the interconnections between these pathways. To overcome this limitation, recently these pathways have been included in a huge chemical reaction network (CRN) describing how information sensed from the environment by growth factors is processed by healthy colorectal cells. Starting from this CRN, we propose a computational model which simulates the effects induced by single or multiple concurrent mutations on the global signaling network. The model has been tested in three scenarios. First, we have quantified the changes induced on the concentration of the proteins of the network by a mutation in APC, KRAS, SMAD4, or TP53. Second, we have computed the changes in the concentration of p53 induced by up to two concurrent mutations affecting proteins upstreams in the network. Third, we have considered a mutated cell affected by a gain of function of KRAS, and we have simulated the action of Dabrafenib, showing that the proposed model can be used to determine the most effective amount of drug to be delivered to the cell. In general, the proposed approach displays several advantages, in that it allows to quantify the alteration in the concentration of the proteins resulting from a single or multiple given mutations. Moreover, simulations of the global signaling network of CRC may be used to identify new therapeutic targets, or to disclose unexpected interactions between the involved pathways. [ABSTRACT FROM AUTHOR]

Background: Videoscopic inguinal lymphadenectomy (VIL) represents an innovative approach for patients with melanoma lymph node (LN) metastases, mainly aimed at lowering wound-related morbidity. However, long-term data on oncologic safety are still lacking. The aim of this study is to review the oncologic outcome of videoscopic groin dissection in a single institution caseload.Methods: Data were prospectively gathered on patients with inguinal melanoma metastasis who underwent VIL. Clinical data included age, race, sex, tumor histology, node counts and number of metastatic nodes. Disease-free survival and overall survival were monitored based on an institutional follow-up schedule. The study was approved by the local ethics committee (Video-SIIO II study).Results: We analyzed 48 videoscopic groin dissections performed in 50 patients (2 patients underwent bilateral VIL). Median age was 54.5 years. Female/male ratio was 15/33. Indication for surgery was positive inguinal sentinel biopsy and cytological confirmed clinical disease in 40 and 10 cases, respectively. Median LN retrieval count was 19. After a median follow-up of 28 months, groin recurrence (lymphatic basin) was observed in one single case.Conclusions: VIL for melanoma LN metastases is associated with a favorable oncologic outcome. In particular, LN yield and locoregional recurrence rate obtained with videoscopic dissection are comparable to those reported with the open technique. Prospective studies are needed to confirm these results in a larger cohort of patients. [ABSTRACT FROM AUTHOR]

A recent result obtained by means of an in vitro experiment with cancer cultured cells has configured the endoplasmic reticulum as the preferential site for the accumulation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Such a result is coherent with cell biochemistry and is made more significant by the fact that the reticular accumulation rate of FDG is dependent upon extracellular glucose availability. The objective of the present paper is to confirm in vivo the result obtained in vitro concerning the crucial role played by the endoplasmic reticulum in FDG cancer metabolism. This study utilizes data acquired by means of a Positron Emission Tomography scanner for small animals in the case of CT26 models of cancer tissues. The recorded concentration images are interpreted within the framework of a three-compartment model for FDG kinetics, which explicitly assumes that the endoplasmic reticulum is the dephosphorylation site for FDG in cancer cells. The numerical reduction of the compartmental model is performed by means of a regularized Gauss-Newton algorithm for numerical optimization. This analysis shows that the proposed three-compartment model equals the performance of a standard Sokoloff's two-compartment system in fitting the data. However, it provides estimates of some of the parameters, such as the phosphorylation rate of FDG, more consistent with prior biochemical information. These results are made more solid from a computational viewpoint by proving the identifiability and by performing a sensitivity analysis of the proposed compartment model. [ABSTRACT FROM AUTHOR]

This paper studies a system of Ordinary Differential Equations modeling a chemical reaction network and derives from it a simulation tool mimicking Loss of Function and Gain of Function mutations found in cancer cells. More specifically, from a theoretical perspective, our approach focuses on the determination of moiety conservation laws for the system and their relation with the corresponding stoichiometric surfaces. Then we show that Loss of Function mutations can be implemented in the model via modification of the initial conditions in the system, while Gain of Function mutations can be implemented by eliminating specific reactions. Finally, the model is utilized to examine in detail the G1-S phase of a colorectal cancer cell. [ABSTRACT FROM AUTHOR]

Background: 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] plays a role in calcium homeostasis but can also exert immunomodulatory effects. In lungs, characterized by a particular immunosuppressive environment primarily due to the presence of alveolar macrophages (AM), 1,25(OH)2D3 has been shown to favor the immune response against pathogens. Here, we explored the ability of aerosolized 1,25(OH)2D3 to locally promote an anti-tumor phenotype in alveolar macrophages (AM) in the treatment of lung metastases. Methods: Cytotoxicity assay has been used to assess the capability of AM, in vitro treated of not with 1,25(OH)2D3, to stimulate NK cells. Sulforhodamine B (SRB) assay has been used to assess the effect of 1,25(OH)2D3 on MC-38 and B16 tumor cells in vitro growth. 1,25(OH)2D3 was aerosolized in immunocompetent mouse models to evaluate the effect of local administration of 1,25(OH)2D3 on in vivo growth of MC-38 and B16 tumor cells within lungs and on infiltrating immune cells. Results: In vitro incubation of naïve AM with 1,25(OH)2D3 improved their ability to stimulate NK cell cytotoxicity. In vivo aerosolized 1,25(OH)2D3 significantly reduced the metastatic growth of MC-38 colon carcinoma, a tumor histotype that frequently metastasizes to lung in human. Immune infiltrate obtained from digested lungs of 1,25(OH)2D3-treated mice bearing MC-38 metastases revealed an increased expression of MHCII and CD80 on AM and an up-modulation of CD69 expression on effector cells that paralleled a strong increased ability of these cells to kill MC-38 tumor in vitro. Conclusions: Together, these data show that aerosol delivery can represent a feasible and novel approach to supplement 1,25(OH)2D3 directly to the lungs promoting the activation of local immunity against cancer. [ABSTRACT FROM AUTHOR]

We present an ℓ 2 2 + ℓ 1 -regularized discrete least squares approximation over general regions under assumptions of hyperinterpolation, named hybrid hyperinterpolation. Hybrid hyperinterpolation, using a soft thresholding operator and a filter function to shrink the Fourier coefficients approximated by a high-order quadrature rule of a given continuous function with respect to some orthonormal basis, is a combination of Lasso and filtered hyperinterpolations. Hybrid hyperinterpolation inherits features of them to deal with noisy data once the regularization parameter and the filter function are well chosen. We derive L 2 errors in theoretical analysis for hybrid hyperinterpolation to approximate continuous functions with noise data on sampling points. Numerical examples illustrate the theoretical results and show that well chosen regularization parameters can enhance the approximation quality over the unit-sphere and the union of disks. [ABSTRACT FROM AUTHOR]

Summary: The notion of topologically fractionable circuit components is defined and discussed using the paradigm of the behavioral approach. It sheds new light on the well‐known (but often badly grasped) distinction between multi‐terminal components and multi‐ports, because it places the matter into a much more general and meaningful framework. For the sake of completeness, the notion of electrically fractionable circuit components is also defined and discussed. [ABSTRACT FROM AUTHOR]

Introduction: The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal and appendix cancer at risk of peritoneal seeding is an appealing strategy to prevent peritoneal metastases. Here, we present the technical details and postoperative outcomes of laparoscopic HIPEC performed with prophylactic intent in three patients with low‐grade appendiceal neoplasm (LAMN) considered at risk of peritoneal recurrence. Materials and Surgical Technique: Three patients with LAMN previously treated outside our department were selected for second‐look laparoscopic exploration and HIPEC. The study received institutional review board approval. A Hasson trocar was inserted around the umbilicus. Four additional 10‐mm trocars were inserted—one each in the left and right upper and lower quadrants. After full abdominal exploration, laparoscopic cytoreductive surgery was performed. Perfusion catheters were inserted through the four lateral trocars in the abdominal quadrants. HIPEC was performed with mitomycin 12 mg/m2 and cisplatin 90 mg/m2 for 60 minutes at a target temperature of 41.0°C. The postoperative course was uneventful, except for an episode of fluid leak due to dural tear (treated with supine bed rest for 48 hours and resulting in no adverse sequelae). The median length of hospital stay was 11 days. After a median follow‐up of 36 months, all patients were asymptomatic with no evidence of recurrence. Discussion: Laparoscopic HIPEC for LAMN at risk of peritoneal recurrence appeared to be feasible, safe, and associated with a favorable postoperative outcome. More studies with larger samples of patients and with a standardized design are needed to better analyze the oncological value of this approach. [ABSTRACT FROM AUTHOR]

Purpose: The use of central venous catheters with peripheral insertion (PICC) has increased rapidly in recent years, particularly in cancer patients. The benefits provided may occasionally be affected by relevant complications, such as infections and thrombotic events, especially in neuro-oncological patients. To date, the risk of PICC-related complications in this subset of patients is unknown, as is tolerability. As a primary objective, this study aimed to collect complications related to PICCs in primary neuro-oncological patients. As a secondary objective, the study aimed to evaluate PICC tolerability.Methods: Neuro-oncological patients with PICCs that were placed as part of normal clinical practice at IRCCS Neurologico C. Besta were consecutively enrolled in the study. PICC-related complications were recorded immediately (during the procedure), early (within 1 week after PICC insertion), and late (1-3-5 months after PICC placement). At the same time points, all patients were also evaluated for tolerability through interviews with semi-structured, open-ended questions.Results: Sixty patients were enrolled (41 males and 19 females, with a median age of 56.2 years). Excluding loss to follow-up, 33/49 patients developed at least one complication related to the PICC. Immediate complications mainly included hematoma (8), accidental arterial puncture (4), and primary malpositioning (3). Regarding early and late complications, 3 device-related infections, 8 thrombotic events, and 20 mechanical complications were registered. Semi-structured interviews revealed an overall positive experience with the device. The most negative impact was on hygiene habits, with 34 patients becoming caregiver-dependent. Over time, almost all patients became used to the device and perceived greater security during chemotherapy. A strongly negative issue was the difficulty of relying on competently trained healthcare personnel in outpatient setting.Conclusion: The results showed a nonnegligible increased thromboembolic risk in neuro-oncological patients with PICCs, almost double that in historical oncological populations. It is essential to extend the study to a greater number of patients to achieve reliable results and to identify patients at high risk. The device seems to be positively accepted by the majority of patients, without affecting activities of daily living. [ABSTRACT FROM AUTHOR]

The 50th anniversary of the first human landing on the Moon has revived the interest of space agencies and private companies on the Earth only natural satellite. Mining the Moon has become the topics of interest to the entire space community. This paper will address the following questions: (i) is space resource utilization by solely private markets sustainable, and (ii) if not, what type of public-private partnership are important/appropriate to enable the development of a private-sector market. • A business model based on private-public partnership results in net present value maximization. • A private business model points to negative NPV. • Montecarlo simulations for private-public partnership indicate very low probabilities of negative NPVs. • Hence, government-prospecting missions are needed prior to private exploration missions. [ABSTRACT FROM AUTHOR]

We compute low-cardinality algebraic cubature formulas on convex or concave polygonal elements with a circular edge, by subdivision into circular quadrangles, blending formulas via subperiodic trigonometric Gaussian quadrature and final compression via Caratheodory–Tchakaloff subsampling of discrete measures. We also discuss applications to the VEM (Virtual Element Method) in computational mechanics problems. [ABSTRACT FROM AUTHOR]

We present an instrument for the measurement of total ozone reactivity – the reciprocal of the chemical lifetime of ozone (O3) – in the troposphere. The Total Ozone Reactivity System (TORS) was developed with the objective to study the role of biogenic volatile organic compounds (BVOCs) as chemical sinks of tropospheric ozone. The instrument was extensively characterized and tested in the laboratory using individual BVOCs and small plants (lemon thyme, Thymus citriodorus) in a Teflon bag and proved able to measure reactivities corresponding to >4.5×10-5 s-1 (at 5 min averaging time), with an estimated total uncertainty of ∼ 32%. Such reactivities correspond to > 20 ppb of α -pinene or > 150 ppb of isoprene in isolation – larger than typical ambient levels but observable in environmental chamber and enclosure experiments as well as in BVOC-rich environments. The functionality of TORS was demonstrated in quasi-ambient conditions with a deployment in a horticultural glasshouse containing a range of aromatic plants. The measurements of total ozone reactivity made in the glasshouse showed a clear diurnal pattern, following the emissions of BVOCs, and are consistent with mixing ratios of tens of parts per billion of monoterpenes and several parts per billion of sesquiterpenes. [ABSTRACT FROM AUTHOR]

Congenital heart diseases (CHDs) represent one of the most common types of congenital abnormalities. More than 90% of children with critical heart defects achieve adulthood due to improvements in medical and surgical treatments. Nonetheless, survivors are at risk for neurodevelopmental disorders that may lead also to language impairments. The current study analyzed the linguistic profiles of a group of school-aged children treated surgically for CHD. Fifteen Children with CHDs (7 girls and 8 boys; mean age = 9.31 with SD = 2.10), without intellectual disability (i.e., IQ>70), who underwent cardiac surgery on cardiopulmonary bypass (CPB), were administered a selection of tests from the language assessment tool BVL 4–12. Their performance was compared with that of 15 healthy children matched for age and gender. As a result, children with CHDs scored significantly lower than healthy peers on tasks tapping lexical and grammatical processing as well as the episodic buffer component of working memory. Interestingly, the two groups did not differ on tasks assessing their lexical repertoire and phonological discrimination abilities. These findings are discussed in light of current theories of cognitive development and functioning. [ABSTRACT FROM AUTHOR]

AtChem is an open-source zero-dimensional box model for atmospheric chemistry. Any general set of chemical reactions can be used with AtChem, but the model was designed specifically for use with the Master Chemical Mechanism (MCM, http://mcm.york.ac.uk/ , last access: 16 January 2020). AtChem was initially developed within the EUROCHAMP project as a web application (AtChem-online, https://atchem.leeds.ac.uk/webapp/ , last access: 16 January 2020) for modelling environmental chamber experiments; it was recently upgraded and further developed into a stand-alone offline version (AtChem2), which allows the user to run complex and long simulations, such as those needed for modelling of intensive field campaigns, as well as to perform batch model runs for sensitivity studies. AtChem is installed, set up and configured using semi-automated scripts and simple text configuration files, making it easy to use even for inexperienced users. A key feature of AtChem is that it can easily be constrained to observational data which may have different timescales, thus retaining all the information contained in the observations. Implementation of a continuous integration workflow, coupled with a comprehensive suite of tests and version control software, makes the AtChem code base robust, reliable and traceable. The AtChem2 code and documentation are available at https://github.com/AtChem/ (last access: 16 January 2020) under the open-source MIT License. [ABSTRACT FROM AUTHOR]

AtChem is an open source zero-dimensional box-model for atmospheric chemistry. Any general set of chemical reactions can be used with AtChem, but the model was designed specifically for use with the Master Chemical Mechanism (MCM, http://mcm.york.ac.uk/). AtChem was initially developed within the EUROCHAMP project as a web application (AtChem-online, https://atchem.leeds.ac.uk/webapp/) for modelling environmental chamber experiments; it was recently upgraded and further developed into a standalone offline version (AtChem2) which allows the user to run complex and long simulations, such as those needed for modelling of intensive field campaigns, as well as to perform batch model runs for sensitivity studies. AtChem is installed, set up and configured using semi-automated scripts and simple text configuration files, making it easy to use even for non-experienced users. A key feature of AtChem is that it can easily be constrained to observational data which may have different timescales, thus retaining all the information contained in the observations. Implementation of a continuous integration workflow, coupled with a comprehensive suite of tests and version control software, makes the AtChem codebase robust, reliable and traceable. The AtChem2 code and documentation are available at https://github.com/AtChem/, under the open source MIT license. [ABSTRACT FROM AUTHOR]

We present an instrument for the measurement of total ozone reactivity (RO3), i.e. the reciprocal of the chemical lifetime of ozone (O3) in the troposphere. The Total Ozone Reactivity System (TORS) was developed with the objective to study the role of biogenic organic compounds (BVOCs) as chemical sinks of tropospheric ozone. The instrument was extensively characterized and tested in the laboratory using individual compounds and small plants (lemonthyme, Thymus citriodorus) in a Teflon bag and proved able to measure reactivities corresponding to > 4.5 × 10−5 s−1, corresponding to 20 ppb of α-pinene or 150 ppb of isoprene in isolation – larger than typical ambient levels but consistent with levels commonly found in environmental chamber and enclosure experiments. The functionality of TORS was demonstrated in quasi-ambient conditions with a deployment in a horticultural glasshouse containing a range of aromatic plants. The measurements of total ozone reactivity made in the glasshouse showed a clear diurnal pattern, following the emissions of BVOCs, and is consistent with mixing ratios of tens ppb of monoterpenes and several ppb of sesquiterpenes. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic hematoma is a rare but possible complication of ERCP. We describe the case of a 75-year old man with a large, 8 × 12 cm, sub-capsular and intra-parenchymal hematoma post ERCP, affecting the right liver segments and treated conservatively.Areas Covered: A review of literature has been performed, highlighting two possible mechanisms: hematoma may occur as the result of accidental laceration of a small intrahepatic vessel by the guidewire, whereas the other hypothesis posits that the hepatic damage is secondary to traction on the biliary system exerted by the balloon. We speculate that in case of anomalies of the biliary tree, the incidence of this complication is higher than expected.Expert Commentary: In case of hepatic hematoma post ERCP, a conservative approach should always be considered before proceeding to interventional radiologic procedures or to surgical therapy. [ABSTRACT FROM AUTHOR]

Caloric restriction mimetics (CRMs), compounds that mimic the biochemical effects of nutrient deprivation, administered via systemic route promote antitumor effects through the induction of autophagy and the modulation of the immune microenvironment; however, collateral effects due to metabolic changes and the possible weight loss might potentially limit their administration at long term. Here, we investigated in mice local administration of CRMs via aerosol to reduce metastasis implantation in the lung, whose physiologic immunosuppressive status favors tumor growth. Hydroxycitrate, spermidine, and alpha-lipoic acid, CRMs that target different metabolic enzymes, administered by aerosol, strongly reduced implantation of intravenously injected B16 melanoma cells without overt signs of toxicity, such as weight loss and changes in lung structure. Cytofluorimetric analysis of lung immune infiltrates revealed a significant increase of alveolar macrophages and CD103+ dendritic cells in mice treated with CRMs that paralleled an increased recruitment and activation of both CD3 T lymphocytes and NK cells. These effects were associated with the upregulation of genes related to M1 phenotype, as IL-12 and STAT-1, and to the decrease of M2 genes, as IL-10 and STAT-6, in adherent fraction of lung immune infiltrate, as revealed by real-time PCR analysis. Thus, in this proof-of-principle study, we highlight the antitumor effect of CRM aerosol delivery as a new and noninvasive therapeutic approach to locally modulate immunosurveillance at the tumor site in the lung. [ABSTRACT FROM AUTHOR]

Cancer survivors manage their new status using a multitude of coping mechanisms. Coping strategies vary by individual, but are also socioculturally mediated. Scarce evidence on coping strategies adopted by Hispanic male cancer survivors (HMCS) is available to date. The purpose of this study was to explore the reaction to diagnosis and subsequent coping strategies employed by HMCS. Data were gathered through focus groups (n = 18), cognitive interviews (n = 12), and phone interviews (n = 84). Coping strategies included positive attitudes, humor, optimism and social support, use of home remedies, lifestyle changes, and faith. Findings are consistent with research on non-cancer-related coping showing that HMCS use active coping strategies, such as religion and support from family and friends. The analysis of existing strategies and needs points to the need to develop evidence-based psychosocial services that build on strengths and coping behaviors already employed by HMCS. [ABSTRACT FROM AUTHOR]

• Describes how the choice of ROI extraction method affects the estimation of MEG resting state functional connectivity. • Measures how ROI-based extraction strategies vary across two connectivity measures (ciPLV, PLV) and frequency bands (theta, alpha, beta) in real and simulated data. • Defines the reliability of extraction methods and how it varies according to the size of the ROI. • Finally, it provides practical recommendations for future studies and applications. Magnetoencephalography and electroencephalography (M/EEG) seed-based connectivity analysis typically requires regions of interest (ROI)-based extraction of measures. M/EEG ROI-derived source activity can be treated in different ways. For instance, it is possible to average each ROI's time series prior to calculating connectivity measures. Alternatively one can compute connectivity maps for each element of the ROI, prior to dimensionality reduction to obtain a single map. The impact of these different strategies on connectivity estimation is still unclear. Here, we address this question within a large MEG resting state cohort (N=113) and simulated data. We consider 68 ROIs (Desikan-Kiliany atlas), two measures of connectivity (phase locking value-PLV, and its imaginary counterpart- ciPLV), and three frequency bands (theta 4-8 Hz, alpha 9-12 Hz, beta 15-30 Hz). We consider four extraction methods: (i) mean, or (ii) PCA of the activity within the ROI before computing connectivity, (iii) average, or (iv) maximum connectivity after computing connectivity for each element of the seed. Connectivity outputs from these extraction strategies are then compared with hierarchical clustering, followed by direct contrasts across extraction methods. Finally, the results are validated by using a set of realistic simulations. We show that ROI-based connectivity maps vary remarkably across strategies in both connectivity magnitude and spatial distribution. Dimensionality reduction procedures conducted after computing connectivity are more similar to each-other, while PCA before approach is the most dissimilar to other approaches. Although differences across methods are consistent across frequency bands, they are influenced by the connectivity metric and ROI size. Greater differences were observed for ciPLV than PLV, and in larger ROIs. Realistic simulations confirmed that after aggregation procedures are generally more accurate but have lower specificity (higher rate of false positive connections). Although computationally demanding, after dimensionality reduction strategies should be preferred when higher sensitivity is desired. Given the remarkable differences across aggregation procedures, caution is warranted in comparing results across studies applying different extraction methods. [ABSTRACT FROM AUTHOR]

Abstract In this paper of numerical nature, we test the Lebesgue constant of several available point sets on the disk Ω and propose new ones that enjoy low Lebesgue constant. Furthermore we extend some results in Cuyt (2012), analyzing the case of Bos arrays whose radii are nonnegative Gauss–Gegenbauer–Lobatto nodes with exponent α , noticing that the optimal α still allows to achieve point sets on Ω with low Lebesgue constant Λ n for degrees n ≤ 30. Next we introduce an algorithm that through optimization determines point sets with the best known Lebesgue constants for n ≤ 25. Finally, we determine theoretically a point set with the best Lebesgue constant for the case n = 1. [ABSTRACT FROM AUTHOR]

Summary: The available active power of a circuit component under AC operation is defined from the behavioral point of view. Then, the complete investigation of the N‐port AC Thévenin source is carried out using the simplest tools of linear algebra. Finally, the diagrams (normalized active power delivered and efficiency vs normalized current) pertaining to the one‐port AC Thévenin source with finite available active power are presented, in case of both real and complex parameters values. The available active power of a circuit component under AC operation is defined from the behavioral point of view. Then, the complete investigation of the N‐port AC Thévenin source is carried out using the simplest tools of linear algebra. Finally, the diagrams (normalized active power delivered and efficiency vs normalized current) pertaining to the one‐port AC Thévenin source are presented, in case of both real and complex parameters values. [ABSTRACT FROM AUTHOR]

By discrete trigonometric norming inequalities on subintervals of the period, we construct norming meshes with optimal cardinality growth for algebraic polynomials on sections of sphere, ball and torus. [ABSTRACT FROM AUTHOR]

Introduction: This randomized, controlled, Phase III non-inferiority clinical trial aimed to determine whether herbal therapy with Canephron® N (BNO 1045) is non-inferior to fosfomycin trometamol (FT) in treating acute lower uncomplicated urinary tract infections (uUTIs). Materials and Methods: Women aged 18–70 years with typical symptoms of newly diagnosed acute lower uUTIs were randomized to BNO 1045 (n = 325) or FT (n = 334), with corresponding matched placebo. The primary endpoint was the proportion of patients who received additional antibiotics (ABs) to treat uUTIs between Days 1 and 38 ±3. Results: Between Days 1 and 38, 238 (83.5%) patients in the BNO 1045 group and 272 (89.8%) patients in the FT group received no additional ABs. At a 15% non-inferiority margin, BNO 1045 was non-inferior to FT in treating uUTIs (non-AB rate difference: –6.26%; 95% CI –11.99 to –0.53%; 2-sided p = 0.0014). Adverse event rates were similar between groups, with higher rates of gastrointestinal disorders in the FT group and pyelonephritis in the BNO 1045 group. During the trial, no patient died or discontinued due to a treatment-related adverse event. Conclusions: BNO 1045 has the potential to reduce outpatient use of ABs for uUTIs and thus may have a significant impact on antimicrobial stewardship strategies. Trial registration: NCT02639520, EudraCT number 2013-004529-99. [ABSTRACT FROM AUTHOR]

Measurements of nitryl chloride (ClNO2) and its precursors (O3, NO2, particulate chloride) were made in 2014–2016 at three contrasting locations in the United Kingdom: Leicester, Penlee Point and Weybourne. ClNO2 was observed at all sites and in every season, with the highest concentrations between 00:00 and 04:00 GMT. The median nocturnal concentration of ClNO2 ranged between the detection limit (4.2 ppt) and 139 ppt. A clear seasonal cycle, with maxima in spring and winter, and significant differences between locations in the same season were observed. The main source of particulate chloride was sea salt aerosol (including at Leicester, ∼200 km from the coast). In general, ClNO2 levels were controlled by the concentrations of O3 and NO2, rather than by the uptake and reaction of N2O5 with particulate chloride. Under these conditions, the seasonality and geographical distribution of ClNO2 can be explained in terms of O3‐limited and NO2‐limited regimes affecting the formation of the N2O5 precursor. A global version of the GEOS‐Chem model at medium resolution (2° × 2.5°) was not able to fully capture the observed seasonality of ClNO2, mostly because the model overestimated the concentrations of the precursors, particularly of nocturnal O3. A higher‐resolution (0.25° × 0.3125°) version of GEOS‐Chem showed better agreement with the observations, although it still overestimated ClNO2 concentrations during summer. [ABSTRACT FROM AUTHOR]

Purpose: Aim of the study is to assess the reliability and correlation with surgical peritoneal cancer index (PCI) of combined PET/CT and ceCT scans (PET/ceCT) performed in a session in patients with peritoneal carcinomatosis candidates for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC).Methods: We retrospectively analyzed data collected from 27 patients with different types of peritoneal carcinomatosis candidates to CS + HIPEC who underwent FDG PET/ceCT in a single session. Two nuclear medicine physicians and two radiologists independently and blindly evaluated PET/CT and ceCT imaging, respectively. In the case of discordance, the consensus was reached by a discussion between the specialists. Moreover, the combined images were evaluated by all the specialists in consensus. The PCIs obtained from surgical look, PET/CT, ceCT, and PET/ceCT were compared with each other. The coefficients of correlation (r) were calculated. The study was conducted after approval of local ethics committee.Results: Surgical PCI was available in 21 patients. The coefficient of correlation between PCI of PET/CT and surgery was 0.528, while it resulted higher between PET/ceCT and surgery (r = 0.878), very similar to ceCT and surgery (r = 0.876). The r coefficient between surgical PCI and PET/CT was higher in patients with a non-mucinous cancer (n = 12) than the counterpart (0.601 vs. 0.303) and the addition of ceCT significantly increases the correlation (r = 0.863), which is anyway similar to ceCT alone (r = 0.856).Conclusions: PET/ceCT as single examination is more accurate than PET/CT but not than ceCT alone for the definition of PCI in a selected group of patients candidates to CS + HIPEC. [ABSTRACT FROM AUTHOR]

We prove a.s. (almost sure) unisolvency of interpolation by continuous random sampling with respect to any given density, in spaces of multivariate a.e. (almost everywhere) analytic functions. Examples are given concerning polynomial and RBF approximation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate clinical characteristics, quality of life (QoL) and effectiveness in patients with menstrual cycle disorders (MCDs) including abnormal uterine bleeding, dysmenorrhea and mastodynia/mastalgia related to premenstrual syndrome taking the Vitex agnus-castus (VAC) products Cyclodynon® or Mastodynon® in a real-world setting. Methods: A single-center retrospective longitudinal cohort study (3 ± 1 months), using data obtained from healthcare data archive and telephone interviews. The main study variables were changes in bleeding, menstrual pain, breast tenderness and patients' QoL. Results: Data from 1700 women with a mean age of 30.2 years (± 6.3) were analyzed. The most common MCDs were dysmenorrhea (43.8%) and mastodynia/mastalgia (21.1%). Three-month treatment with VAC extract substantially decreased the percentage of patients with irregular cycle (from 9.1% to 0.1%) and breast tenderness (from 39.9% to 0.8%). Improvement in bleeding intensity, frequency and menstrual pain was experienced by 83.4%, 79.2%, and 85.2% of the patients, respectively. When analyzed by disease category, these parameters improved in almost all dysmenorrhea patients, while they improved to a lesser extent in mastodynia/mastalgia patients. QoL improved in all aspects, but was reported by a higher proportion of dysmenorrhea patients compared to mastodynia/mastalgia patients. Treatment was overall well tolerated with a favorable safety profile. Conclusion: These real-world data demonstrate the effectiveness of the VAC-containing products Cyclodynon® and Mastodynon® in the three-month treatment of MCDs, with a pronounced improvement in key disease symptoms and QoL. Intriguingly, while QoL was generally greatly improved, the response to VAC therapy varied depending on the type of underlying MCD. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that territorial borders continue to have an impact on research collaboration in Europe. Knowledge of national research structural contexts is therefore crucial to the promotion of Europe-wide policies for research funding. Nevertheless, studies assessing and comparing research systems remain scarce. This paper aims to further the knowledge on national research landscapes in Europe, focusing on non-communicable disease (NCD) research in Italy and Germany.Methods: To capture the architecture of country-specific research funding systems, a three-fold strategy was adopted. First, a literature review was conducted to determine a list of key public, voluntary/private non-profit and commercial research funding organisations (RFOs). Second, an electronic survey was administered qualifying RFOs. Finally, survey results were integrated with semi-structured interviews with key opinion leaders in NCD research. Three major dimensions of interest were investigated - funding mechanisms, funding patterns and expectations regarding outputs.Results: The number of RFOs in Italy is four times larger than that in Germany and the Italian research system has more project funding instruments than the German system. Regarding the funding patterns towards NCD areas, in both countries, respiratory disease research resulted as the lowest funded, whereas cancer research was the target of most funding streams. The most reported expected outputs of funded research activity were scholarly publication of articles and reports.Conclusions: This cross-country comparison on the Italian and German research funding structures revealed substantial differences between the two systems. The current system is prone to duplicated research efforts, popular funding for some diseases and intransparency of research results. Future research will require addressing the need for better coordination of research funding efforts, even more so if European research efforts are to play a greater role. [ABSTRACT FROM AUTHOR]