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While innovation matters for competitiveness, it may expose firms to survival risks. Using plant-product data for Chile and discretetime hazard models, we show mat innovating plants have a lower hazard of exit. However, risk has a strong impact on the innovation-exit relationship: only innovators that retain diversified sources of revenue or face lower market risk are less likely to die. Single-product innovators are at greater risk of exiting. Exposure to technical risk does not affect exit probabilities differentially. We provide tentative evidence that singleproduct innovators have higher profits, which helps to rationalize their innovation decision despite the increased risk of exit.

Curcumin, a polyphenolic compound derived from the plant Curcuma longa L., has demonstrated a wide range of therapeutic properties, including potential anticancer effects. However, its clinical efficacy is limited due to poor bioavailability and stability. To overcome these challenges, curcumin analogs like EF-24 have been developed with improved pharmacological properties. In this study, in order to improve our understanding of EF-24’s potential mechanisms of action, we used whole-transcriptome sequencing to identify genome-wide functional impacts of EF-24 treatment in leukemia cells. These results enabled the development of a testable model system for associating druggable genes with clinical disease targets related to EF-24 treatment. To develop our model of the transcriptional response to EF-24 treatment, we used four well studied model cell lines for leukemia research, specifically the chronic myeloid leukemia (CML) cell line K-562 and acute myeloid leukemia (AML) cell lines HL-60, Kasumi-1, and THP-1. Cell viability was significantly decreased in all four of these leukemia models following EF-24 treatment as compared to untreated controls. We discovered that the genes ATF3, CLU, HSPA6, OSGIN1, ZFAND2A, and CXCL8, which are associated with reduced cell viability and proliferation, were consistently upregulated in all EF-24–treated cell lines. Further analysis of the tested cell lines revealed the activation of various signaling pathways, but notably the S100 family signaling pathway was consistently activated in all four cell lines. Our results provide critical insights into the molecular underpinnings of EF-24’s antitumor efficacy against leukemia subtypes, highlighting its multifaceted impact on signaling pathways and gene networks that regulate cell survival, proliferation, and immune responses in cell line models of myeloid leukemia subtypes.

Two novel datasets are used to estimate the effect of product standards on firms’ export decisions. The first covers all exporting firms in 42 developing countries. The second covers pesticide standards for 243 agricultural and food products in 80 importing countries over 2006–2012. The analysis shows that product standards affect significantly foreign market access. An increase in the stringency of standards in the destination country, relative to the exporting country, lowers firms’ probability of exporting, deters exporters from entering new markets, and fosters exit from existing markets. Smaller exporters are more affected in their market entry and exit decisions by the relative stringency of destination standards than larger exporters. Networks of other exporters from the same country can help overcome the negative effects of the relative stringency of destination standards on exporter entry and exit.

Background: Iron deficiency (ID) and iron deficiency anemia (IDA) are common complications of pediatric inflammatory bowel disease (IBD). Owing to questions regarding optimal iron formulation, dosage, route of administration, and safety, these complications are frequently overlooked and undertreated, negatively impacting patient development and quality of life.Purpose: To assess the safety and efficacy of iron sucrose (IS) and ferric carboxymaltose (FCM) in the treatment of ID and IDA in pediatric IBD.Methods: We retrospectively reviewed the medical records of pediatric patients with IBD treated for 10 years with IS (age <14 years) or FCM (age ≥14 years) in a single regional referral center. The Ganzoni formula was used to calculate the iron dose administered. Adverse reactions were monitored during treatment and after discharge. Efficacy was defined as a ≥2 g/dL rise in Hb or anemia resolution within 12 weeks after treatment in cases of IDA and transferrin saturation or ferritin normalization in cases of ID.Results: Sixty-three patients were treated with IV iron (41 with Crohn disease, 15 with ulcerative colitis, 7 with IBD-unclassified; median age, 14.6 years; 104 treatment courses [63 FCM, 41 IS during the 10-year study period]). Retreatment was necessary after a median 1.4 years in 26 patients (41.3%). The median activity scores of patients with recurrent ID indicated inactive disease. The treatment efficacy was 66.7% (FCM) and 67.6% (IS) in patients with IDA and 77.8% in patients with ID but without anemia. One adverse reaction (hypotension and rash) was associated with IS treatment.Conclusion: In one of the largest and longest follow-up cohorts, FCM and IS were safe and effective for correcting ID in pediatric patients with IBD. As ID recurs frequently, proactive screening and treatment are important.

Entrepreneurial ecosystems have recently emerged as a central topic on the agenda of both researchers and political leaders. As a consequence of the multiple studies published in recent times, this promising avenue of research is currently disjointed, lacking both a systematic structure and a theoretical framework. Intrinsic to entrepreneurial ecosystems, the networks established among the diverse stakeholders impact on the configuration, the evolution and the outcomes of entrepreneurial ecosystems. This study systematically analyzes 65 conceptual and empirical articles identified in the Web of Science database to explore, analyze and discussing the main trends in the literature on the topic of entrepreneurial ecosystems and networks (EEs&Ns). The analysis of bibliographic coupling of documents made possible to group the EEs&Ns literature into four clusters: (1) Context and Cooperation; (2) Established Networks; (3) Challenges to the Affirmation of Minorities; (4) Formal Structures. In turn, the analysis of keywords co-occurrence revealed the most important literature trends on this topic: (1) innovation and dynamics: actors and norms; (2) performance, knowledge, and entrepreneurship; (3) technology and firms. The systematization of these results allowed us to identify the institutional/contextual dimension, the relational dimension, and the organizational/structural dimension as the main approaches followed by the researchers on this topic. The conceptual framework advanced attests to the interdependencies among the research paths found on EEs&Ns. Finally, following the systematic literature review undertaken, we identify the promising paths and proposals for future research that may advance still further the academic understanding of EEs&Ns.

This Special Issue continues the previously published work [...]

LOX (lysyl oxidase) and lysyl oxidase like-1–4 (LOXL 1–4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (β-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source. However, novel synthetic compounds that act as LOX/LOXL2 selective inhibitors or as dual LOX/LOX-L inhibitors have been recently developed. In this review, we describe LOX enzymes and their role in promoting cancer development and metastases, with a special focus on LOXL2 and breast cancer progression. Moreover, the recent advances in the development of LOXL2 inhibitors are also addressed. Overall, this work contextualizes and explores the importance of LOXL2 inhibition as a promising novel complementary and effective therapeutic approach for breast cancer treatment.

Heart failure (HF) is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET) in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting. We employed ascending aortic stenosis (AS) inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET) or to an untrained group (AS-UN). At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65), MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels. Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state.

The type 2 diabetes mellitus (T2DM) negatively impacts patients' quality of life, affecting their physical and mental functioning as well as social relationships. Self-management is essential for T2DM control, as it involves self-care behaviors and self-efficacy, leading to better health outcomes such as better glycemic control. There are a variety of instruments in the literature capable of measuring self-management in T2DM population. Therefore, the aim of this review is to identify the available T2DM self-management instruments and evaluate their measurement properties, as well as to analyze their contents based on the international classification of functioning, disability and health. The systematic review will follow the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines, and its protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration CRD42024605840). Searches will be conducted in MEDLINE, Web of Science, Scopus, PsycINFO, Embase, and CINAHL. Additionally, a manual search will be conducted in the databases: PROQOLID, PROMIS, and Medical Outcome Trust. Studies on the development and validation of patient-reported outcome measures assessing self-management in individuals with T2DM will be included, with no restrictions on language or publication date. Data extraction will use tools recommended by COSMIN. The modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will determine the quality of the evidence. Instruments will be categorized according to COSMIN recommendations. All steps will be conducted by two independent reviewers, with a third reviewer consulted in case of discrepancies. Additionally, the content of the instruments will be analyzed and linked to the ICF. This systematic review may guide researchers and healthcare professionals to choose the most suitable instrument for their target population. Ethical approval is not required, as this study is a review of published data. The results will be disseminated through publication in peer-reviewed journals.

In the past few years, numerous studies have investigated the correlation between polyphenol intake and the prevention of several chronic diseases. Research regarding the global biological fate and bioactivity has been directed to extractable polyphenols that can be found in aqueous-organic extracts, obtained from plant-derived foods. Nevertheless, significant amounts of non-extractable polyphenols, closely associated with the plant cell wall matrix (namely with dietary fibers), are also delivered during digestion, although they are ignored in biological, nutritional, and epidemiological studies. These conjugates have gained the spotlight because they may exert their bioactivities for much longer than extractable polyphenols. Additionally, from a technological food perspective, polyphenols combined with dietary fibers have become increasingly interesting as they could be useful for the food industry to enhance technological functionalities. Non-extractable polyphenols include low molecular weight compounds such as phenolic acids and high molecular weight polymeric compounds such as proanthocyanidins and hydrolysable tannins. Studies concerning these conjugates are scarce, and usually refer to the compositional analysis of individual components rather than to the whole fraction. In this context, the knowledge and exploitation of non-extractable polyphenol-dietary fiber conjugates will be the focus of this review, aiming to access their potential nutritional and biological effect, together with their functional properties.