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Institutional ownership, free float, and systematic risk
No full textThis study investigates how institutional ownership (IO) and free float (FF) jointly affect firms’systematic risks. It contends that larger institutional stakes increase the dollar imbalance subject tocommon flows, whereas a greater tradable float broadens the set of funds that can tradesynchronously. Both channels should increase the stock market beta. Using a cross-section of12,655 non-financial firms from 93 countries, unconditional, downside (β−), and upside (β+) capitalasset pricing model betas over two-, three-, and five-year windows are analysed. The resultsconfirm that IO and FF are positively and significantly associated with unconditional and downsidebetas. These relationships remain robust after controlling for firm size, valuation, profitability,leverage, liquidity, and industry fixed effects, indicating that the ownership and tradability chan-nels explain systematic risk beyond standard fundamentals. The impact of IO is pronounced forupside beta. Two-stage least squares regressions corroborate the baseline results while addressingendogeneity concerns. Additional tests show that the IO effect is concentrated in advancedeconomies, while the FF effect remains robust across geography, development status, and firmsize. This study evinces the trading flow hypothesis that ownership concentration and tradabilityare the additive drivers of systematic risk
zAvatar-test—a functional precision model to personalize ovarian cancer treatments: Results from a co-clinical study
No full textIn ovarian cancer, 80% of patients relapse after first-line therapy. In recurrent cases, oncologists lack reliable tests to guide chemotherapy choices, creating an unmet clinical need. Here, we develop the ovarian cancer zebrafish Avatar-test, a functional in vivo model using patient tumor cells implanted in zebrafish embryos to predict treatment responses. We present the largest observational study (32 patients), where the zAvatar-test achieves 91% accuracy in predicting patient outcomes. Patients with a zAvatar-sensitive-test correlate with longer progression-free survival (17 vs. 6 months). Tumors in zAvatars are dynamic, with human-host cell interactions, and higher metastatic potential in poor-prognosis cases. Finally, as a proof of concept, we demonstrate that venetoclax has the potential to sensitize multidrug-resistant tumors. Altogether, this clinical study demonstrates that the zAvatar-test may help clinicians personalize treatments for ovarian cancer patients. We are now conducting a multicentric randomized clinical trial to evaluate the zAvatar-test as a companion tool in clinical oncology.PTDC/BTM-SAL/3796/202
Revisiting relative humidity: conceptual ambiguities and applicability conditions
No full textThe state of moist air significantly impacts human comfort, human health, preservation of goods and food, and many processes. At a given pressure, it is usually defined by one pair of independent variables, one invariably the dry bulb temperature, and the other the humidity ratio, the relative humidity, or the specific enthalpy. Relative humidity is a widely referred to and used concept. However, there is no consensus on its definition. The different definitions in literature are not clear enough, and are prone to misleading and questionable numerical values. This is especially relevant for high temperatures when using psychrometric charts, online calculators, simulation tools, software of measuring systems, and home-made routines or numerical tools. This work aims to highlight how and why the concept of relative humidity needs to be clearly and uniquely defined, and why care is needed concerning its applicability conditions. Additionally to the given explanations, mathematical expressions are used to do that more clearly and accurately. The main key issues raised in this paper are related to the consideration, and use of relative humidity when moist air temperature exceeds the water saturation temperature corresponding to the prevailing total pressure.LA/P/0079/202
Biomarkers for predicting malignant transformation of premalignant lesions of the larynx: a systematic review
No full textBackground/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts
Advanced nanotherapeutic strategies transforming diabetic wound healing
No full textDue to their high recurrence rates and slow healing, diabetic wounds are becoming a greater public health concern [Citation1]. Each year, 1.6 million cases of diabetic wounds occur in the United States alone, affecting approximately 18.6 million people worldwide [Citation2]. Because of poor cellular regeneration, increased inflammation, and reduced angiogenesis, traditional treatments like debridement, antibiotics, and dressings usually do not work [Citation3]. To overcome the limitations of traditional treatments, there is now a significant demand for advanced therapeutic modalities that promise accurate, efficient, and rapid healing processes [Citation4]. These include microneedles (MNs), exosomes, tetrahedral framework nucleic acids (tFNAs), three-dimensional scaffolds, gene therapy, oxygen-releasing biomaterials, phototherapies, and nanozymes.UID/04326/2025; UID/PRR/04326/202
Beyond the rhetoric of “sustainable aviation”: a counterfactual confrontation
No full textAmid evidence of rising emissions, the aviation industry continues to promote demand growth while offering long-term sustainability reassurances communicated as “facts.” Using counterfactual analysis, this paper examines how industry rhetoric constructs and defends these discursive strategies. Drawing on a content analysis of 211 sources – including airline websites, industry reports, and manufacturer statements – the study identifies seven discursive strategies. The findings reveal a novel theoretical mechanism, “future soothing”: projecting technological salvation into a perpetually deferred future to ease public concern and postpone regulation. By transforming delay into the illusion of progress, discourses operate as rhetorical governance, sustaining growth under the guise of climate responsibility. The paper contributes to scholarship on the temporal politics of sustainability, showing how appeals to the future enable inaction in the present and illustrating how rhetoric, temporality, and power intertwine in shaping societal responses to climate change. Breaking aviation’s “cycle of blame” requires policymaker action.UID/04020/202
Gravitational waves from two scalar fields unifying the dark sector with inflation
No full textWe investigate the gravitational-wave background predicted by a two-scalar-field cosmological model that aims to unify primordial inflation with the dark sector, namely late-time dark energy and dark matter, in a single and self-consistent theoretical framework. The model is constructed from an action inspired by several extensions of general relativity and string-inspired scenarios and features a non-minimal interaction between the two scalar fields, while both remain minimally coupled to gravity. In this context, we derive the gravitational-wave energy spectrum over wavelengths ranging from today’s Hubble horizon to those at the end of inflation. We employ the continuous Bogoliubov coefficient formalism, originally introduced to describe particle creation in an expanding Universe, in analogy to the well-established mechanism of gravitational particle production and, in particular, generalized to gravitons. Using this method, which enables an accurate description of graviton creation across all cosmological epochs, we find that inflation provides the dominant gravitational-wave contribution, while subdominant features arise at the inflation-radiation, radiation-matter, and matter-dark energy transitions, i.e., epochs naturally encoded inside our scalar field picture. The resulting energy density spectrum is thus compared with the sensitivity curves of the planned nextgeneration ground- and space-based gravitational-wave observatories. The comparison identifies frequency bands where the predicted signal could be probed, providing those windows associated with potentially detectable signals, bounded by our analyses. Consequences of our recipe are thus compared with numerical outcomes and the corresponding physical properties discussed in detail.UID/04106/2025; UID/PRR/04106/202
Evaluation of high-pressure processing (HPP) in european seabass (Dicentrarchus labrax) allergenicity
No full textDespite fresh fish being a valuable source of essential nutrients in the human diet, they are highly perishable compared to other food sources and they are among the major allergenic food products. It has been estimated that allergies provoked by fish proteins are on the rise (up to 0.9% of the USA adult population is affected). Moreover, novel food processing technologies, such as High-Pressure processing (HPP), are being implemented as a means to extend the shelf-life of perishable food and reduce waste, but their impact on food allergenicity is not well known. Allergens are often proteins found in common foods, and food processing may lead to the exposure or loss of IgE epitopes, potentially increasing or decreasing the allergenic potential, respectively. Around 12 important allergenic proteins in different fish species (seabass is not reported) have been identified and registered in 2023 in the WHO/IUIS allergen nomenclature sub-committee database but few studies have explored how they change under processing conditions. This study explored the effect of HPP (300, 450, 600 MPa for 2 and 5 min, 1 and 12 days of refrigerated storage) on the allergens present in the soluble sarcoplasmic fraction of white muscle from European seabass (Dicentrarchus labrax), one of the most consumed species in the Mediterranean. Proteome analysis showed a significant decrease in protein solubility (p < 0.05), and alteration in the proteome profile between control and processed samples, in a pressure-dependent manner. Four sarcoplasmic proteins were tested by Western blot as promising biomarkers of fish that has undergone HPP (allergenic proteins and/or processing biomarkers), three of them (FBP2, Aldolase A, Tropomyosin, (p < 0.05)) were sensitive to pressure intensity. The allergenicity of unpressurized seabass was investigated by Western blot using human blood serum or plasma from patients with fish allergies (n = 16) or non-allergic controls (n = 3), resulting in the detection of 9 IgE immunoreactive protein bands in seabass extracts. Although 7 individual IgE reactive protein bands changed after HP processing, the total detectability and thus the total allergenicity of the processed fish was not significantly affected by HPP. Finally, two isoforms of a major fish allergen, β-parvalbumin, were successfully been purified from seabass in their native forms. These isoforms exhibited divergent IgE reactivity and were both affected by HPP (p < 0.05). In summary, our results strongly contribute to characterise seabass allergic potential so it can be registered in the public database listing allergenic fishes. Furthermore, although HPP changed the muscle proteome it did not dramatically change the intrinsic allergenicity, as measured by IgE immunoreactivity, of the European seabass fillets.Apesar do peixe fresco ser uma fonte valiosa de nutrientes essenciais na dieta humana, este alimento é altamente perecível em comparação com outras fontes alimentares. Além disso, está entre os principais produtos alimentares considerados alergénicos e estima-se que as alergias alimentares provocadas pelas proteínas do peixe estão a aumentar (até 0,9% da população adulta dos EUA está a ser afetada). Novas tecnologias de processamento de alimentos, como o processamento por alta pressão (High pressure processing, HPP), estão a ser implementadas como um meio de prolongar a vida útil destes alimentos perecíveis e reduzir o desperdício alimentar, mas o seu impacto real na alergenicidade alimentar não é ainda bem conhecido. Os alergénios são frequentemente proteínas comuns nos alimentos e o processamento pode levar à exposição ou ocultação de epítopos de IgE (imunoglobulina E), que podem aumentar ou diminuir o potencial alergénico do alimento. Cerca de 12 proteínas alergénicas identificadas em diferentes espécies de peixes (não reportado em robalo, Dicentrarchus labrax) estão registadas na base de dados do subcomité de nomenclatura de alergénios da OMS/IUIS (até 2023), mas poucos estudos têm explorado o impacto das novas tecnologias de processamento nos alergénios e menos se têm reportado ao robalo. Este estudo explorou o efeito do HPP (300, 450, 600 MPa por 2 e 5 min. e armazenamento refrigerado durante 1 e 12 dias) sobre os alérgenos presentes na fração sarcoplasmática solúvel do músculo branco e filetes de robalo europeu (Dicentrarchus labrax), uma das espécies de peixe mais consumida na região Mediterrânica. A análise da solubilidade e do perfil do proteoma revelou uma diminuição significativa da solubilidade proteica (p < 0,05) e alteração no perfil do proteoma entre amostras controlo e processadas por HP, de maneira dependente da intensidade da pressão. Quatro proteínas sarcoplasmáticas foram testadas por Western blot como biomarcadores de processamento por HP (proteínas alergénicas e/ou biomarcadores de processamento) e três delas FBP2, Aldolase A, Tropomiosina mostraram ser sensíveis à intensidade de pressão (p < 0,05). A alergenicidade ao robalo não pressurizado foi investigada por Western blot utilizando soro e plasma humano de pacientes alérgicos a peixes (n=16) ou não (n=3), resultando na deteção de 9 bandas de proteínas imunorreativas a IgE. Embora 7 bandas individuais de proteínas reativas à IgE tenham apresentado alterações na detetabilidade após o processamento por HP, a alergenicidade total ao produto não foi significativamente afetada pelo processamento. Duas isoformas do principal alérgeno de peixes, a β-parvalbumina (β-Parv), foram purificadas com sucesso e na forma nativa a partir da fração sarcoplasmática do músculo branco de filetes de robalo e demonstraram reatividade diferencial para a IgE (p < 0.05). Em resumo, os nossos resultados contribuem fortemente para colocar o robalo na lista da base de dados pública de peixes com potencial de alergenicidade e, apesar do efeito das alterações no proteoma, o processamento por HP parece não alterar a alergenicidade intrínseca dos filetes de robalo europeu
Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.
No full textAlzheimer's disease and Parkinson's disease are the two most prevalent neurodegenerative disorders worldwide, both characterized by progressive neuronal loss. Despite distinct pathophysiological features, they share cellular dysfunctions such as abnormal protein aggregation, oxidative stress, and neuroinflammation, research into which might be beneficial for developing novel therapeutic strategies that could tackle both conditions. This review highlights the emerging role of the gasotransmitters nitric oxide, carbon monoxide and hydrogen sulfide as modulators of adult neurogenesis and neuroprotection in Alzheimer's disease and Parkinson's disease. We have gathered recent evidence demonstrating that these endogenous gases exert anti-inflammatory, antioxidant, and anti-apoptotic effects, and, critically, promote neurogenesis - suggesting a dual neuroprotective and neuroregenerative therapeutic potential. The unique physicochemical features of these gasotransmitters, including their ability to cross the blood-brain barrier and diffuse rapidly throughout the neural tissue, further support their suitability as candidates for innovative neuroregenerative treatments. While clinical translation remains challenging, harnessing the neurogenic and neuroprotective actions of these gasotransmitters may offer transformative avenues for addressing the increasing burden of Alzheimer's disease and Parkinson's disease
Earliest evidence for intentional cremation of human remains in Africa
No full textHuman cremation on an open pyre demands intensive labor, communal resources, and sensory exposures. We report the earliest evidence for intentional cremation in Africa, the oldest in situ adult pyre in the world, and one of only a few associated with hunter-gatherers. A large cremation feature at Hora 1 in Malawi dates to similar to 9500 years ago and contains the remains of a small, gracile adult with evidence for perimortem defleshing and postcremation manipulation. Subsequent revisiting of the site to build fires in the same place provided additional pyrotechnological spectacles. High-resolution, multiproxy reconstruction of the ritual associated with cremation and its subsequent deposition demonstrates complex mortuary practices among ancient African foraging groups with substantial social investment and use of natural landscape features as persistent mortuary monuments