Search Results (24)

This study investigates the influences of financial performance and economic determinants (inflation rate and economic growth) on financial distress (FD) in the MENA region in the context of the contagion effect theory and Minsky’s financial instability theory. This paper examines the determinants of financial distress in the MENA region from 2002 until 2020 using pooled OLS, fixed effect, and GMM panel estimation models; then the results are used to estimate the effect over the long run. The results show that the things that cause financial distress are changing a lot between countries in the MENA region. This shows how important it is to separate the effects of economic and financial factors. The results show the significance of economic growth, ROA, ROE, inflation, and stock market profitability using fixed effects. The results changed when we used GMM, concluding that economic growth, ROA, ROE, and stock market profitability were significant, while inflation was not significant. Therefore, there is a significant and negative relationship between financial distress and economic growth in GCC-MENA as well as other MENA countries. Our results can be of importance to investors and regulators. The introduction of a more stable political environment and engagement in international economic and financial markets will decrease the negative impacts of financial distress and boost economic growth and its sustainability in the MENA region. Full article

This article provides both stylized facts and estimations of the endogenous nexus of the financial fragility hypothesis (FFH) with public social spending (PSS) for a paradigmatic Eurozone member country. The sample period 1995–2022 includes three major economic crises, the global financial crisis 2007–2009, the European debt crisis 2010–2015 and the COVID-19 pandemic one in 2020–2022. Within the context of the financialization literature, this paper is founded, for the first time, as far as we know, on the “financial fragility hypothesis”, combining the effects of both Minsky’s “financial instability”, as it has been extended for open economies, and the “Eurozone fragility one”. Similar to the relevant literature, the findings show that the PSS is associated, in a long-term steady state (cointegration), with the financial fragility process, starting, firstly, from the hedge-financing structure with high profitability of firms, when PSS decreases; secondly, to hyper-speculative financing with risky options, supported by bank credit and openness, indebtedness or discretionary fiscal policy, when PSS rises; thirdly, to the hyper-speculative or even Ponzi financing structures with over-indebtedness (leverage) from the global capital market, inflated asset prices and internationalized fragility, when PSS also rises, and so on. Our conclusion validates Minsky’s famous saying, “stability breeds instability”, also in the architecturally incomplete Eurozone. Policy implications are straightforward and discussed. Full article

Following the 2008 financial crisis, Hyman Minsky’s Financial Instability Hypothesis (FIH) emerged as a prominent financial theory to explain the occurrence of business cycles in the U.S. economy. There have been many theoretical, but few empirical studies dedicated to FIH. The current literature also lacks the statistical support to confirm the necessary conditions leading to financial instability and whether FIH concepts remains applicable in the post 1980s periods. This article presents a statistical methodology to analyze the financial debt ratios related to FIH for the 1945–2023 periods through the use of nonparametric statistical analyses of ordered alternatives and a binomial test for meta-analysis. The results indicated that the conditions leading to financial instability such as debt ratios did increase prior to the onset of a recession as prescribed by FIH during the 1945–1980s era. Furthermore, such conditions also repeated prior to some recessions occurred in the 2001–2023 periods. This study provides statistical support for Minsky’s FIH theory. Full article

Background: Despite the increasing utilization of sphincter and/or organ-preservation treatment strategies, many patients with low-lying rectal cancers require abdominoperineal resection (APR), leading to permanent ostomy. Here, we aimed to characterize overall, sexual-, and bladder-related patient-reported quality of life (QOL) for individuals with low rectal cancers. We additionally aimed to explore potential differences in patient-reported outcomes between patients with and without a permanent ostomy. Methods: We distributed a comprehensive survey consisting of various patient-reported outcome measures, including the FACT-G7 survey, ICIQ MLUTS/FLUTS, IIEF-5/FSFI, and a specific questionnaire for ostomy patients. Descriptive statistics and univariate comparisons were used to compared demographics, treatments, and QOL scores between patients with and without a permanent ostomy. Results: Of the 204 patients contacted, 124 (60.8%) returned completed surveys; 22 (18%) of these had a permanent ostomy at the time of survey completion. There were 25 patients with low rectal tumors (≤5 cm from the anal verge) who did not have an ostomy at the time of survey completion, of whom 13 (52%) were managed with a non-operative approach. FACTG7 scores were numerically lower (median 20.5 vs. 22, p = 0.12) for individuals with an ostomy. Sexual function measures IIEF and FSFI were also lower (worse) for individuals with ostomies, but the results were not significantly different. MLUTS and FLUTS scores were both higher in individuals with ostomies (median 11 vs. 5, p = 0.06 and median 17 vs. 5.5, p = 0.01, respectively), suggesting worse urinary function. Patient-reported ostomy-specific challenges included gastrointestinal concerns (e.g., gas, odor, diarrhea) that may affect social activities and personal relationships. Conclusions: Despite a limited sample size, this study provides patient-centered, patient-derived data regarding long-term QOL in validated measures following treatment of low rectal cancers. Ostomies may have multidimensional negative impacts on QOL, and these findings warrant continued investigation in a prospective setting. These results may be used to inform shared decision making for individuals with low rectal cancers in both the settings of organ preservation and permanent ostomy. Full article

Turnera is a genus of plants whose biological activity has been widely studied. The importance of this genus, particularly Turnera diffusa, as a source of treatment for various conditions is evidenced by the large number of new studies that have evaluated its biological activity. Accordingly, the objective of this review was to compile the information published in the last ten years concerning the biological activities reported for Turnera spp. The present work includes 92 publications that evaluate 29 bioactivities and toxicological and genotoxic information on five species of this genus. Among the pharmacological effects reported, the antioxidant, hepatoprotective, neuroprotective, hypoglycemic, and aphrodisiac activities seem more promising. Phytochemicals and standardized plant extracts could offer alternative therapeutic remedies for various diseases. Although several flavonoids, cyanogenic glycosides, monoterpenoids, triterpenoids, and fatty acids have been isolated for Turnera plants, future research should focus on the identification of the main active principles responsible for these pharmacological activities, as well as to perform clinical trials to support the laboratory results. Full article

In gastroesophageal junction (GEJ) adenocarcinoma cases, a prognosis based on ypTNM staging could be affected by preoperative therapy. Patients with esophageal adenocarcinoma and gastric adenocarcinoma who underwent preoperative therapy followed by surgical resection from 2006 through 2017 were identified in the National Cancer Database. To enable stage-by-stage OS comparisons, tumors were classified into four gross ypTNM groups: ypT1/2, N-negative; ypT1/2, N-positive; ypT3/4, N-negative; and ypT3/4, N-positive. Prognostic factors were examined, and an OS prediction nomogram was developed for patients with abdominal/lower esophageal and gastric cardia adenocarcinoma, representing GEJ cancers. We examined 25,463 patient records. When compared by gross ypTNM group, the abdominal/lower esophageal and gastric cardia adenocarcinoma groups had similar OS rates, differing from those of other esophageal or gastric cancers. Cox regression analysis of patients with GEJ cancers showed that preoperative chemoradiotherapy was associated with shorter OS than preoperative chemotherapy after adjustment for the ypTNM group (hazard ratio 1.31, 95% CI 1.24–1.39, p < 0.001), likely owing to downstaging effects. The nomogram had a concordance index of 0.833 and a time-dependent area under the curve of 0.669. OS prediction in GEJ adenocarcinoma cases should include preoperative therapy regimens. Our OS prediction nomogram provided reasonable OS prediction for patients with GEJ adenocarcinoma, and future validation is needed. Full article

(1) Background: The CT-based attenuation correction of SPECT images is essential for obtaining accurate quantitative images in cardiovascular imaging. However, there are still many SPECT cameras without associated CT scanners throughout the world, especially in developing countries. Performing additional CT scans implies troublesome planning logistics and larger radiation doses for patients, making it a suboptimal solution. Deep learning (DL) offers a revolutionary way to generate complementary images for individual patients at a large scale. Hence, we aimed to generate linear attenuation coefficient maps from SPECT emission images reconstructed without attenuation correction using deep learning. (2) Methods: A total of 384 SPECT myocardial perfusion studies that used ^99mTc-sestamibi were included. A DL model based on a 2D U-Net architecture was trained using information from 312 patients. The quality of the generated synthetic attenuation correction maps (ACMs) and reconstructed emission values were evaluated using three metrics and compared to standard-of-care data using Bland–Altman plots. Finally, a quantitative evaluation of myocardial uptake was performed, followed by a semi-quantitative evaluation of myocardial perfusion. (3) Results: In a test set of 66 test patients, the ACM quality metrics were MSSIM = 0.97 ± 0.001 and NMAE = 3.08 ± 1.26 (%), and the reconstructed emission quality metrics were MSSIM = 0.99 ± 0.003 and NMAE = 0.23 ± 0.13 (%). The 95% limits of agreement (LoAs) at the voxel level for reconstructed SPECT images were: [−9.04; 9.00]%, and for the segment level, they were [−11; 10]%. The 95% LoAs for the Summed Stress Score values between the images reconstructed were [−2.8, 3.0]. When global perfusion scores were assessed, only 2 out of 66 patients showed changes in perfusion categories. (4) Conclusion: Deep learning can generate accurate attenuation correction maps from non-attenuation-corrected cardiac SPECT images. These high-quality attenuation maps are suitable for attenuation correction in myocardial perfusion SPECT imaging and could obviate the need for additional imaging in standalone SPECT scanners. Full article

The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups. Recurrent patients had higher mean protein expression of FoxP3, MAPK-activation markers (BRAF, p38-MAPK) and PI3K/Akt activation (phospho-Akt) within the tumor regions. The TME was characterized by the higher protein expression of immune checkpoint biomarkers such as PD-1, OX40L and LAG3. For patients with recurrent SCCA, the higher mean protein expression of fibronectin was observed in the tumor and TME compartments. No significant differences in RNA expression were observed. The higher baseline expression of immune checkpoint biomarkers, together with markers of MAPK and PI3K/Akt signaling, are associated with recurrence following chemoradiation for patients with localized SCCA. These data provide a rationale towards the application of immune-based therapeutic strategies to improve curative-intent outcomes beyond conventional therapies for patients with SCCA. Full article

The targets of topical genotoxic agents are basal and stem cells of the skin. These cells may misrepair DNA lesions, resulting in deleterious mutations of tumor suppressors or oncogenes. However, the genotoxicity of many compounds has not as yet been determined and needs to be tested using a relevant skin model. To this end, we designed a new high-throughput assay for the detection of agents that create DNA damage in epidermal stem and basal cells and used it to test known DNA-damaging agents. We utilized either 2D epidermal cells or 3D skin equivalents and topically exposed them to different compounds. The Skin Immuno-CometChip assay uses arrays of microwells formed in a collagen/agarose mixture to capture single basal cells in each microwell by virtue of collagen binding to α2β1 integrin, which is present only on basal and stem cells. The presence of β1 integrin was verified by immunofluorescent labeling cells that were then subjected to an electrical field, allowing for the migration of nicked DNA out of the nucleoid in alkali, with the resulting DNA comets stained and imaged. Furthermore, using improved comet detection software allowed for the automated and rapid quantification of DNA damage. Our study indicates that we can accurately predict genotoxicity by using 3D skin cultures, as well as keratinocytes grown in 2D monolayers. Full article

The Rosenblatt’s first theorem about the omnipotence of shallow networks states that elementary perceptrons can solve any classification problem if there are no discrepancies in the training set. Minsky and Papert considered elementary perceptrons with restrictions on the neural inputs: a bounded number of connections or a relatively small diameter of the receptive field for each neuron at the hidden layer. They proved that under these constraints, an elementary perceptron cannot solve some problems, such as the connectivity of input images or the parity of pixels in them. In this note, we demonstrated Rosenblatt’s first theorem at work, showed how an elementary perceptron can solve a version of the travel maze problem, and analysed the complexity of that solution. We also constructed a deep network algorithm for the same problem. It is much more efficient. The shallow network uses an exponentially large number of neurons on the hidden layer (Rosenblatt’s A-elements), whereas for the deep network, the second-order polynomial complexity is sufficient. We demonstrated that for the same complex problem, the deep network can be much smaller and reveal a heuristic behind this effect. Full article

The quantification of low-abundance secondary metabolites in plant extracts is an analytical problem that can be addressed by different analytical platforms, the most common being those based on chromatographic methods coupled to a high-sensitivity detection system. However, in recent years nuclear magnetic resonance (NMR) has become an analytical tool of primary choice for this type of problem because of its reliability, inherent simplicity in sample preparation, reduced analysis time, and low solvent consumption. The versatility of strategies based on quantitative NMR (qNMR), such as internal and external standards and electronic references, among others, and the need to develop validated analytical methods make it essential to compare procedures that must rigorously satisfy the analytical well-established acceptance criteria for method validation. In this work, two qNMR methods were developed for the quantification of hepatodamianol, a bioactive component of T. diffusa. The first method was based on a conventional external standard calibration, and the second one was based on the pulse length-based concentration determination (PULCON) method using the ERETIC2 module as a quantitation tool available in TopSpin software. The results show that both procedures allow the content of the analyte of interest in a complex matrix to be determined in a satisfactory way, under strict analytical criteria. In addition, ERETIC2 offers additional advantages such as a reduction in experimental time, reagent consumption, and waste generated. Full article

Background: There is a lack of predictive models to identify patients at risk of high neoadjuvant chemoradiotherapy (CRT)-related acute toxicity in rectal cancer. Patient and Methods: The CAO/ARO/AIO-04 trial was divided into a development (n = 831) and a validation (n = 405) cohort. Using a best subset selection approach, predictive models for grade 3–4 acute toxicity were calculated including clinicopathologic characteristics, pretreatment blood parameters, and baseline results of quality-of-life questionnaires and evaluated using the area under the ROC curve. The final model was internally and externally validated. Results: In the development cohort, 155 patients developed grade 3–4 toxicities due to CRT. In the final evaluation, 15 parameters were included in the logistic regression models using best-subset selection. BMI, gender, and emotional functioning remained significant for predicting toxicity, with a discrimination ability adjusted for overfitting of AUC 0.687. The odds of experiencing high-grade toxicity were 3.8 times higher in the intermediate and 6.4 times higher in the high-risk group (p < 0.001). Rates of toxicity (p = 0.001) and low treatment adherence (p = 0.007) remained significantly different in the validation cohort, whereas discrimination ability was not significantly worse (DeLong test 0.09). Conclusion: We developed and validated a predictive model for toxicity using gender, BMI, and emotional functioning. Such a model could help identify patients at risk for treatment-related high-grade toxicity to assist in treatment guidance and patient participation in shared decision making. Full article

Incentivizing businesses to lower carbon emissions and trade back excess carbon allowances paved the way for rapid growth in carbon credit ETFs. The use of carbon allowances as a hedging alternative fueled this rally further, causing a shift to speculation and forming repetitive bubbles. Speculative bubbles are born from euphoria, yet, they are relatively predictable, provided their pattern matches the log periodic power law (LPPL) with specific stylized facts. A “Minsky moment” identifies a clear speculative bubble as a signal of financial system instability, while a “Social bubble” is regarded as relatively positive, increasing in the long run, infrastructure spending and development. The aim of this paper is to investigate whether various carbon credit bubbles during the pandemic period caused financial instability or had a positive impact (“Minsky” or “Social”). Particularly, we investigate the carbon credit bubble behavior in the ETF prices of KRBN, GRN (Global Carbon Credit tracking ETFs), and the SOLCARBT index during the COVID-19 pandemic period by adopting the log-periodic power law model (LPPL) methodology, which has been widely used, over the past decade, for detecting bubbles and crashes in various markets. In conclusion, these bubbles are social and propelled by the newfound interest in carbon credit trading, for obvious reasons. Full article

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED₁₀) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED₁₀ was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted. Full article

Candida albicans is the most commonly implicated agent in invasive human fungal infections. The disease could be presented as minimal symptomatic candidemia or can be fulminant sepsis. Candidemia is associated with a high rate of mortality and high healthcare and hospitalization costs. The surveillance programs have reported the distribution of other Candida species reflecting the trends and antifungal susceptibilities. Previous studies have demonstrated that C. glabrata more frequently presents fluconazole-resistant strains. Extracts from Mexican plants have been reported with activity against pulmonary mycosis, among them Colubrina greggii. In the present study, extracts from the aerial parts (leaves, flowers, and fruits) of this plant were evaluated against clinical isolates of several species of Candida (C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis) by the broth microdilution assay. Through bioassay-guided fractionation, three antifungal glycosylated flavonoids were isolated and characterized. The isolated compounds showed antifungal activity only against C. glabrata resistant to fluconazole, and were non-toxic toward brine shrimp lethality bioassay and in vitro Vero cell line assay. The ethyl acetate and butanol extracts, as well as the fractions containing the mixture of flavonoids, were more active against Candida spp. Full article