Research increasingly recognizes that entrepreneurial activity is shaped not only by individual traits and intentions but also by external enablers—exogenous circumstances that facilitate venture creation. While prior work has emphasized technological change, regulatory shifts, and crises, relatively little attention has been given to life-course institutional arrangements. In this paper, I conceptualize parental leave as an external enabler of entrepreneurship. I argue that parental leave—particularly when paid and job-protected—creates temporally bounded institutional space that alters opportunity costs, resource configurations, and identity processes, thereby increasing the feasibility and attractiveness of entrepreneurial entry. I identify three core enabling mechanisms: (1) temporal slack facilitating opportunity experimentation, (2) income smoothing reducing perceived risk, and (3) identity work enabling career reorientation. I further outline key boundary conditions, including policy design, gender norms, and household context. By reframing parental leave from a career interruption to a potential catalyst for entrepreneurial action, this paper contributes to research on external enablers, connects entrepreneurship with work-family scholarship, and advances a more gender-attentive understanding of entrepreneurial entry.

Melatonin plays a pivotal role in the regulation of biological rhythms, beginning during prenatal development through maternal signalling and continuing postnatally via breast milk. In neonates, whose circadian systems are functionally immature, maternal melatonin serves as a critical entraining agent, facilitating the synchronisation of the sleep–wake cycle, supporting neurodevelopmental processes, and enhancing immune system maturation. Breast milk demonstrates distinct diurnal variations in melatonin concentration, alongside other bioactive components, establishing it as a vital chrononutritional medium. This rhythmic delivery is particularly significant for preterm infants, who lack sufficient endogenous melatonin production and are especially reliant on exogenous sources for circadian entrainment. Several factors, including the mode of delivery, maternal health, circadian alignment, and the handling or processing of expressed breast milk, may influence melatonin content and its bioavailability. Disruption of circadian rhythms, whether due to environmental factors such as continuous light exposure in neonatal intensive care units or desynchronised feeding schedules – can interfere with optimal physiological development. Recognising the chronobiological significance of melatonin opens new perspectives in neonatal care. Promoting feeding practices aligned with circadian principles, including time-of-day-sensitive milk administration, may support more favourable neurodevelopmental and immunological outcomes, particularly in vulnerable preterm populations. This knowledge has the potential to inform future evidence-based strategies in perinatal and neonatal clinical care.

The unique circadian clock system of fish consists of central and peripheral pacemakers that are directly regulated by light. The functioning of this clock machinery is based on cyclic changes in the expression of clock proteins that form transcriptional-translational loops. In this study, we performed an analysis of the circadian changes in Cry1, Cry2 and Clock protein levels in the nervous system, immune system and other peripheral organs of common carp. Protein-level analyses revealed that Cry1, Cry2 and Clock proteins show diurnal expression patterns in both central and peripheral tissues, with tissue-specific variations. We have shown that both Cry variants may play important roles in the clock mechanism, but their importance appears to be organ specific, with Cry2 and Cry1 likely playing important roles in central and peripheral oscillators, respectively. However, further genetic analysis will be required to clearly define the role of these proteins in the carp clock mechanism. We have found that the central oscillator function in carp is primarily performed by the retina, which is characterized by strong endogenous rhythmicity of activity. We have also observed that light availability clearly modulates the circadian clock mechanism in fish and probably indirectly other physiological functions by regulating the expression of key proteins that determine clock activity. Post-translational modifications of clock proteins, which are crucial for their functionality, affect their circadian rhythmicity.

This study explores how women entrepreneurs within a resource-constrained context of Ethiopia utilize spiritual resources and spiritual bricolage in their entrepreneurial endeavours. Drawing on 52 life-story interviews, we find that by engaging in spiritual bricolage, women entrepreneurs reconstruct the meanings of risk, resources, constraints, and legitimacy, thereby maintaining persistence in the face of adversity. We demonstrate that this entrepreneurial reframing operates as a critical connecting mechanism between spiritual bricolage and sustained entrepreneurial motivation. Further, we identify three strategies for engaging with spiritual resources that can either facilitate or hinder entrepreneurial reframing: adventurous sourcing, diligent embedding, and relational anchoring. This study advances the bricolage and entrepreneurial motivation literatures and offers practical insights for supporting women entrepreneurs in economically constrained settings.

In this study, we explore how women who are both mothers and entrepreneurs construct their subject position as mothers in the presence of dominant discourses. Based on multiple interviews with 15 participants, our findings indicate that women engage in doing and undoing motherhood. Although undoing one's motherhood is related to negotiating one's position vis-& agrave;-vis social norms and expectations, doing motherhood is related to the construction of new discourses. We illustrate how a norm-breaking motherhood discourse emerges through processes of gender abating and coalescing. In this discourse, child-rearing is not a woman's primary responsibility but is shared between the parents, and the public and private spheres-work and family-coalesce. A good mother is constructed as an individual who can pursue her passions and realize her dreams and who focuses on her relationship with her child through her work as an entrepreneur while mastering desirable attitudes and values in life. We also find that entrepreneurship can be a vehicle for escaping normative assumptions about motherhood and crafting one's "project of the self."

In this chapter, the authors argue that entrepreneurship education (EE) as currently conceived, does little to eradicate gender inequality – rather, its focus on the individual and its neglect of structural impediments and measures tend to reinforce this inequality. The authors discuss why this happens and suggest ways forward. The authors believe the most positive action would be to employ legislation and public policy to change gendered structures and practices which would lead to changes in gendered norms. However, the relationship between norms and structures is mutual. Structural change can only be achieved if existing norms are questioned and this should be the first step toward changing discriminatory structures. The authors argue that in this context EE must include norm critical education. The authors provide some practical examples related to the context of EE.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that is secreted mostly by immune cells such as neutrophils, macrophages, and dendritic cells. Its production is stimulated in response to inflammation. The concentrations of NGAL can be measured in plasma, urine, and biological fluids such as peritoneal effluent. NGAL is known mainly as a biomarker of acute kidney injury and is released after tubular damage and during renal regeneration processes. NGAL is also elevated in chronic kidney disease and dialysis patients. It may play a role as a predictor of the progression of renal function decreases with complications and mortality due to kidney failure. NGAL is also useful in the diagnostic processes of cardiovascular diseases. It is highly expressed in injured heart tissue and atherosclerostic plaque; its serum concentrations correlate with the severity of heart failure and coronary artery disease. NGAL increases inflammatory states and its levels rise in arterial hypertension, obesity, diabetes, and metabolic complications such as insulin resistance, and is also involved in carcinogenesis. In this review, we present the current knowledge on NGAL and its involvement in different pathologies, especially its role in renal and cardiovascular diseases.

Discovering synthetic lethal (SL) gene partners of cancer genes is an important step in developing cancer therapies. However, identification of SL interactions is challenging, due to a large number of possible gene pairs, inherent noise and confounding factors in the observed signal. To discover robust SL interactions, we devised SLIDE-VIP, a novel framework combining eight statistical tests, including a new patient data-based test iSurvLRT. SLIDE-VIP leverages multi-omics data from four different sources: gene inactivation cell line screens, cancer patient data, drug screens and gene pathways. We applied SLIDE-VIP to discover SL interactions between genes involved in DNA damage repair, chromatin remodeling and cell cycle, and their potentially druggable partners. The top 883 ranking SL candidates had strong evidence in cell line and patient data, 250-fold reducing the initial space of 200K pairs. Drug screen and pathway tests provided additional corroboration and insights into these interactions. We rediscovered well-known SL pairs such as RB1 and E2F3 or PRKDC and ATM, and in addition, proposed strong novel SL candidates such as PTEN and PIK3CB. In summary, SLIDE-VIP opens the door to the discovery of SL interactions with clinical potential. All analysis and visualizations are available via the online SLIDE-VIP WebApp.

Malignant hypertension (MH) is a state which can rapidly progress to multi-organ failure. It can develop in the course of both primary and secondary type of hypertension. In our study, we present a case of a 36-year-old man diagnosed with renal failure and MH complicated with retinopathy. As the secondary nature of the condition was suspected extensive diagnostics has been conducted. In spite of excluding plenty of pathologies, the underlying cause remained unknown. Eventually, the renal biopsy has been performed, leading to a diagnosis of IgA nephropathy. However, symptoms and course of the disease has not been typical. Nevertheless, IgA nephropathy should be considered as a possible cause of secondary hypertension as well as malignant hypertension. The diagnosis is not easy and a crucial role is played by renal biopsy.

Infective endocarditis (IE) is an inflammatory disease involving a proliferative-destructive processes, usually of streptococcal or staphylococcal etiology. It may also be caused by the physiological flora of the oral cavity, mainly gram-negative bacteria from the HACEK group. IE typically develops in damaged areas of the endocardium. Bacterial vegetations are found in majority on valves but they may be as well visualised in blood vessels, ventricles, on mechanical valves, electrodes and intracardiac catheters. Risk factors for endocarditis concern the growing population of adults with congenital heart disease and patients with frequent healthcare contact for other comorbidities, also patients who are immunocompromised, treated with hemodialysis or use intravenous drugs. The diagnosis of IE is made by the use of transthoracic or transesophageal echocardiography, also other imaging techniques are used. Blood cultures also should be taken. However, it was estimated that approximately 10% of patients have cultures and serologic tests negative for IE. In our study we present a case of a 51-year-old man with end-stage renal disease treated with peritoneal dialysis for 3 weeks prior to hospital admission with an acute infection of unknown origin. Infective endocarditis was suspected based on echocardiography examination. In this case PET-CT (positron emission tomography/computed tomography) was performed for verification. Its result as well as sterile blood cultures did not fully confirm the diagnosis of IE. Despite the access to highly specialized diagnostic methods and broad spectrum antibiotics the diagnosis and treatment were not easy. This story of patient’s disease can be the confirmation that IE is heterogeneous in etiology, clinical manifestations, and course.

Melatonin is a neurohormone that is mainly secreted by the pineal gland. It coordinates the work of the superior biological clock and consequently affects many processes in the human body. Disorders of the waking and sleeping period result in nervous system imbalance and generate metabolic and endocrine derangements. The purpose of this review is to provide information regarding the potential benefits of melatonin use, particularly in kidney diseases. The impact on the cardiovascular system, diabetes, and homeostasis causes melatonin to be indirectly connected to kidney function and quality of life in people with chronic kidney disease. Moreover, there are numerous reports showing that melatonin plays a role as an antioxidant, free radical scavenger, and cytoprotective agent. This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress occur, regardless of the mechanism. The administration of melatonin has a renoprotective effect and inhibits the progression of complications connected to renal failure. It is very important that exogenous melatonin supplementation is well tolerated and that the number of side effects caused by this type of treatment is low.

This article explores why an increasing number of Swedish mothers are becoming entrepreneurs; this choice appears counterintuitive given the prevailing social welfare system prioritizes the rights of employed women. Using an interpretative stance, we analyzed the life stories of 18 Swedish mothers who created new ventures while caring for young children. The value of the time afforded by parental leave policies was identified as vital to the business creation process. Hence, we argue that time is a critical entrepreneurship-relevant resource; this is illustrated by the positive effect of the Swedish welfare system upon entrepreneurship entry and the timing of this decision.

In both mammals and fish, the circadian system is composed of oscillators that function at the cellular, tissue, and system levels and show the cyclic expression of clock genes. The organization and functioning of the biological clock in fish has not yet been characterized in detail, therefore, in the present study, an extensive analysis of the rhythmic expression of the main components of the biological clock in the central and peripheral organs of common carp was performed. The diurnal changes in clock gene expression were determined with respect to the subjective light cycle in fish exposed to constant light or darkness. It was found that the pattern of expression of clock, bmal, per and cry genes in carp was highest in the brain, pituitary gland, and retina. The peak clock and bmal expression was phase aligned with the lights off, whereas both per genes show similar phasing with acrophase close to light onset. The expression of cry genes varied depending on the type of tissue and the subtype of gene. The diurnal changes in the expression of clock genes demonstrates that, in particular, the expression of the clock in the retina shows endogenous oscillations independent of the influence of light. The data suggest that in carp, the time-varying expression of individual genes allows for a diverse and tissue-specific response to secure oscillations with variable phase and period.

The paper conceptualizes how social entrepreneurs construct their prosocial motivation through a person-centered approach. The study examines seven social entrepreneurs who actively own and manage their businesses in Sweden. Gioia methodology was adopted to analyze social entrepreneurs’ life stories and the interview data with their close relations to understand how they construct prosocial motivation in social entrepreneurship. Based on grounded theory-building and constructive perspectives, this study contributes in a few ways. First, it departs from the subjective viewpoint of social entrepreneurs taking a lived experience approach to their prosocial motivation. Secondly, we elaborate on the relationship between meaning in life, time orientation, and the adopted perspective to wellbeing in social entrepreneurship setting. Showing that finding meaning in life results in both long-term orientation and a more eudaimonic view of own wellbeing, whereas experiencing meaning void contributes to entrepreneurs taking a short-time perspective and focusing more on hedonic wellbeing, the feeling of being happy.

Discovering synthetic lethal (SL) gene partners of cancer genes is an important step in developing cancer therapies. However, identification of SL interactions is challenging, due to a large number of possible gene pairs, inherent noise and confounding factors in the observed signal. To discover robust SL interactions, we devised SLIDE-VIP, a novel framework combining eight statistical tests, including a new patient data-based test iSurvLRT. SLIDE-VIP leverages multi-omics data from four different sources: gene inactivation cell line screens, cancer patient data, drug screens and gene pathways. We applied SLIDE-VIP to discover SL interactions between genes involved in DNA damage repair, chromatin remodeling and cell cycle, and their potentially druggable partners. The top 883 ranking SL candidates had strong evidence in cell line and patient data, 250-fold reducing the initial space of 200K pairs. Drug screen and pathway tests provided additional corroboration and insights into these interactions. We rediscovered well-known SL pairs such as RB1 and E2F3 or PRKDC and ATM, and in addition, proposed strong novel SL candidates such as PTEN and PIK3CB. In summary, SLIDE-VIP opens the door to the discovery of SL interactions with clinical potential. All analysis and visualizations are available via the online SLIDE-VIP WebApp.

Copy number alterations constitute important phenomena in tumor evolution. Whole genome single-cell sequencing gives insight into copy number profiles of individual cells, but is highly noisy. Here, we propose CONET, a probabilistic model for joint inference of the evolutionary tree on copy number events and copy number calling. CONET employs an efficient, regularized MCMC procedure to search the space of possible model structures and parameters. We introduce a range of model priors and penalties for efficient regularization. CONET reveals copy number evolution in two breast cancer samples, and outperforms other methods in tree reconstruction, breakpoint identification and copy number calling.

Abstract The concept of synthetic lethality (SL) has made a pivotal impact for the development of the anti-cancer drug olaparib, the first approved agent targeting the DNA Damage Response (DDR). Typically, SL is described as the interaction of two genes, whereby simultaneous inactivation of both genes results in cell death whereas loss of one gene can be tolerated. Given the importance of SL to develop highly selective anti-cancer therapeutics, large efforts have been undertaken to identify these interactions, both experimentally and computationally. Here, we present a novel computational framework harnessing large-scale cell line gene inactivation screens (DepMap, Project Score), as well as patient data (TCGA), to discover known and novel SL gene pairs. Overall, we implemented six statistical tests considering gene dependency scores, genomic profiles, gene expression and patient survival as parameters. We further utilized data from public drug screening consortia to validate our top-ranking pairs. We applied our framework to a defined target space covering genes relating to DDR, chromatin binding, cell cycle and druggable genes (overall > 2.5 M. pairs were tested). When focusing on SL partners for three DDR genes with promising inhibitors in early clinical development: ATM, ATR and DNA-PK; we noticed that chromatin modifiers were enriched in the top ranking pairs. In particular, SL interactions were predicted with histone (de)methylases, histone (de)acetyltransferases and members of SWI/SNF family. For instance, we observed that loss of function mutations in several members of the KMT2 family, also known as MLL family, would render cancers cells more dependent on ATR or ATM. Similarly, drug sensitivity was increased for selected DDR inhibitors in cell lines with KMT2 mutations. Members of the KMT2 family play essential roles in transcription, but have recently also been shown to be recruited to DNA damage sites and may be mediators for PARP inhibitor sensitivity. The KMT2 family is frequently mutated in several cancers types such as endometrial and bladder, thus underpinning their suitability as potential selection biomarkers as well as relevance to cancer. Furthermore, we observed that patients with mutations in EP300, a histone lysine acetyl transferase, exhibited an increase in ATR expression which may comprise a compensatory mechanism. In addition, patients with ATR and EP300 double mutation tend to have a better probability of survival, suggesting decreased tumor fitness. In summary, we present a modular framework to predict SL gene pairs to a defined target space. Here, we focused on discovering novel SL relationships for the key DDR regulators ATM, ATR and DNA-PK. Our results provide not only new biomarker hypotheses for further validation, but also suggest that cancers with a high mutation rate in chromatin modifying genes may be efficiently targeted by DDRi. Citation Format: Anna M. Coenen-Stass, Magda Markowska, Magdalena Budzinska-Zaniewska, Krzysztof Kolmus, Ewa Szczurek, Eike Staub. A novel computational framework predicts synthetic lethal interactions between key regulators of the DNA damage response and chromatin modifiers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1918.

In this research, we ask why and how some women start or grow a business after initiating divorce, while others will not. Grounded on an in-depth study of 24 women who experienced divorce in a patriarchal society, we develop a framework that identifies two pathways. The first pathway is followed by those women who felt trapped in their marriage and engaged in entrepreneurial activities as part of an overall process of self-discovery and self-development that enabled them to search for and find new sources of meanings, while the second pathway is followed by those women who felt discontent with their marriage, remarried but did not engage in entrepreneurship. Our emergent theoretical framework explains the importance of entrepreneurship to attain eudaimonic well-being following an adversity, thereby expanding the scope of entrepreneurship research.