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For over half a century, the carbazole skeleton has been the key structural motif of many biologically active compounds including natural and synthetic products. Carbazoles have taken an important part in all the existing anti-cancer drugs because of their discovery from a large variety of organisms, including bacteria, fungi, plants, and animals. In this article, we specifically explored the literature from 2012 to 2018 on the anti-tumour activities reported to carbazole derivatives and we have critically collected the most significant data. The most described carbazole anti-tumour agents were classified according to their structure, starting from the tricyclic-carbazole motif to fused tetra-, penta-, hexa- and heptacyclic carbazoles. To date, three derivatives are available on the market and approved in cancer therapy.

This paper applies an empirical model of corporate capital structure, optimal debt, and overleveraging to estimate overleveraging measured as the difference between actual and optimal debt. Estimated using a sample of the twenty largest pharmaceutical firms, covering the time span from 2000 to 2018, the model sheds light on an industry-specific default risk. The analysis presented in this paper reveals a concerning trend in the pharmaceutical industry, with corporate excess debt steadily increasing over the past two decades, particularly peaking during the 2008 crisis and after 2013. These findings underscore the critical role of excess debt in exacerbating financial instability and highlight the pharmaceutical sector’s unique challenges, including high R&D intensity and regulatory pressures. By quantifying overleveraging and linking it to financial risk, the paper offers valuable policy implications, emphasizing the need for proactive management of optimal debt levels to mitigate default risks and enhance macroeconomic resilience.

Introduction To assess the value of the Mini-Mental State Examination (MMSE)-score at baseline in predicting survival in adult primary central nervous system lymphoma (PCNSL) patients. Methods In the HOVON 105/ ALLG NHL 24 phase III study patients with newly-diagnosed PCNSL were randomized between high-dose methotrexate-based chemotherapy with or without rituximab. Data on potential (MMSE-score), and known baseline prognostic factors (age, performance status, serum LDH, cerebrospinal fluid total protein, involvement of deep brain structures, multiple cerebral lesions, and the IELSG-score) were collected prospectively. Multivariable stepwise Cox regression analyses were used to assess the prognostic value of all factors on progression-free survival (PFS) and overall survival (OS) among patients with available MMSE score at baseline. Age was analyzed as continuous variable, the MMSE-score both as a continuous and as a categorical variable. Results In univariable analysis, age, MMSE-score and whether the patient received rituximab were statistically significantly prognostic factors for PFS. Age and MMSE-score were statistically significantly associated with OS. In a multivariable analysis of the univariately significant factors only MMSE-score was independently associated with the survival endpoints, as a continuous variable (HR for PFS 1.04, 95% CI 1.01–1.08; OS 1.06 (95% CI 1.02–1.10) and as categorical variable HR (< 27 versus ≥ 27 for PFS 1.55 (1.02–2.35); OS 1.68 (1.05–2.70). In our population, performance status, serum LDH, and CSF protein level were not of prognostic value. Conclusion Neurocognitive disturbances, measured with the MMSE at baseline, are an unfavorable prognostic factor for both PFS and OS in adult PCNSL patients up to 70 years-old.

Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug’s bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets. A design of experiment (DoE) approach was used to screen different taste-masking agents and excipient blends with trained, expert sensory assessors, with quinine hydrochloride as a model bitter tastant. The taste-masking efficacy of selected prototype formulation blends was validated with naïve assessors using the highest 15 mg primaquine dose. The mean bitterness intensity rating, measured on a discrete 11-point scale, was halved from 7.04 for the unflavoured control to 2.74–3.70 for the formulation blends. Sucralose had the biggest impact on bitterness suppression and improving palatability. Two different flavouring systems have been developed, and their acceptability in paediatric patients will be assessed as part of upcoming validation field clinical trials in Africa.

This paper addresses if and how excess debt can be considered as an early warning signal for banks and takes an additional dimension by comparing the excess leverage between Islamic and conventional banks in Indonesia before, during, and after the Global Financial Crisis (GFC). To do so, this research develops an empirical model of banks' capital structure and optimal and excess debt, and it conducts an empirical analysis on the overleveraging of eleven conventional and Islamic banks in Indonesia. Results show that all banks became vulnerable to the GFC in 2007-2009 while credit build-up, i.e., overleveraging, started in 2005. However, for most of the banks in the sample, Islamic banks performed better and leveraged less prior to the GFC, which made them more resilient to the crisis.

This study examines how first-generation immigrants in the United States plan for retirement, report income, and engage with the Social Security system. The analysis combines an original anonymous survey of 120 first-generation immigrants with descriptive, correlational, and illustrative aggregate evidence constructed from Social Security Administration, Census Bureau, and related institutional data for 2013-2023. The survey results show three consistent patterns. First, retirement knowledge is limited: most respondents do not understand how Social Security benefits are calculated, yet a large majority would attend retirement-planning workshops. Second, financial behavior is shaped by legal status and labor-market formality. Tax filing rates are high overall, but underreporting incentives are stronger among respondents paid in cash and among groups facing legal or administrative uncertainty. Third, family obligations materially affect long-term planning. Many respondents prioritize supporting relatives over retirement savings, and women report lower earnings despite comparable English proficiency and, in this sample, higher educational attainment. Over 2013-2023, Social Security program income and program cost rose alongside the immigrant population, but this aggregate exercise is illustrative only, is not causal, and cannot identify immigrants' net fiscal impact on the system. The paper's main contribution is therefore behavioral: it shows how limited knowledge, payment formality, and family obligations shape retirement planning within a non-representative regional sample of first-generation immigrants.

It is generally argued that Islamic banks are safer than conventional banks. The prime reason is that their product structure is essentially asset-backed financing, while conventional banks rely heavily on leveraging, which was considered one of the main causes of the 2008 global financial crisis. This paper examines the riskiness of Islamic and conventional banks during the 2008 global crisis by measuring overleveraging, defined as the difference between actual and optimal debt. This research conducted empirical analysis on the overleveraging of 20 banks (10 conventional and 10 Islamic banks) from five different countries, namely, Bahrain, Kuwait, Malaysia, the United States, and the United Kingdom. The analysis is double-folded: on the one hand, the results in this paper suggest that excess debt, rather than the mere holding of debt, was the reason behind the severe financial meltdown in 2007-2009; on the other hand, this paper shows that Islamic banks, in most of the countries in context, performed better during the recent crisis, but were subject to the second-round effect of the global crisis around the years of 2011-2013.

The normal umbilical cord is a crucial component during pregnancy, but sometimes it could become compromised due to some abnormalities such as excessive long umbilical cord, and though they usually end up with a healthy baby, they may lead to severe consequences. Excessive long umbilical cords are found in 4% of pregnancies and represent a risk factor for nuchal cords and true knots. We report a case of a 37-year-old Syrian pregnant woman who presented to the hospital at 37 weeks of gestation asking for a C-section for a fear of ambiguous ultrasound findings that have been interpreted as fetal malformation. At delivery, a healthy baby was born with a 150-cm umbilical cord, a true knot, and double-looped nuchal cords; the formation of the loops and the knot had been attributed to the elongated cord. Besides, ultrasound imaging could sometimes be deceptive and lead to unnecessary interventions; therefore, cord anomalies should always be kept in mind because they do not always represent a justification for a C-section.

We develop an empirical model of bank capital structure to study the impact of large oil shocks on overleveraging of banks which presents severe challenges for banks’ balance sheet management. The measure of overleveraging builds on the Stein (2012) model by adding a jump-diffusion component that captures the jump size and intensity of predictors such as oil prices and political instability. Overleveraging is derived and estimated for a sample of six banks in three oil-producing countries and Western countries using the Markov Chain Monte Carlo (MCMC) method, for the years 2006–2016. The estimation of the optimal debt shows that most of the banks in this context had a high optimal debt around 2008, overlapping with the oil price shock. In addition, most of the predictors, namely oil prices and political instability factors proxied by terrorism, political corruption, and military expenses, regularly appeared in volatility and jump intensity factors.

This paper presents a theoretical model of bank leveraging based on Stein (2011, 2012) and Brunnermeier and Sannikov (2014). The paper offers an analytical review of the literature on bank leveraging and focuses on the adverse effects of excessive leverage and the vulnerabilities and credit contractions that can subsequently occur. Moreover, this paper solves the optimal control problem of the model with a finite time decision horizon to present an analysis of the dynamics of net worth and optimal or sustainable leverage, including a discussion of periods of high and low interest rates. The study shows that overleveraging and optimal debt move in opposite directions. Furthermore, a literature review on bank leverage and monetary policy is presented followed by an analysis of the link between credit growth, GDP growth, and overleveraging in five countries. The findings show that periods of low credit growth are accompanied by periods of low GDP growth because constrained credit limits investments as well as consumption in many cases.