Boltzmann's Concept of Reality

In this article we describe and analyze the concept of reality developed by the Austrian theoretical physicist Ludwig Boltzmann. It is our thesis that Boltzmann was fully aware that reality could, and actually was, described by different points of view. In spite of this, Boltzmann did not renounce the idea that reality is real. We also discuss his main motivations to be strongly involved with philosophy of science, as well as further developments made by Boltzmann himself of his main philosophical ideas, namely scientific theories as images of Nature and its consequences. We end the paper with a discussion about the modernity of Boltzmann's philosophy of science.Comment: 13 pages, pdf only. To appear in the book on Ludwig Boltzmann scientific philosophy, published by Nova Science. Edited by A. Eftekhar

Dogmatism and Theoretical Pluralism in Modern Cosmology

This work discusses the presence of a dogmatic tendency within modern cosmology, and some ideas capable of neutralizing its negative influence. It is verified that warnings about the dangers of dogmatic thinking in cosmology can be found as early as the 1930's, and we discuss the modern appearance of "scientific dogmatism". The solution proposed to counteract such an influence, which is capable of neutralizing this dogmatic tendency, has its origins in the philosophical thinking of the Austrian physicist Ludwig Boltzmann (1844-1906). In particular we use his two main epistemological theses, scientific theories as representations of nature and theoretical pluralism, to show that once they are embodied in the research practice of modern cosmology, there is no longer any reason for dogmatic behaviours.Comment: 14 pages; LaTeX sourc

Temperature distribution of a Fast-Field Cycling Nuclear Magnetic Resonance relaxometer's electromagnet with reduced volume

The temperature distribution of a Fast Field Cycling (FFC) Nuclear Magnetic Resonance (NMR) electromagnet plays an important role in the operation of this type of apparatus. The designed electromagnet presents a reduced volume and is iron and copper based, fulfilling the technical requirements for the magnetic field. With this solution, it is possible to increase the overall performance in comparison with former similar FFC relaxometers. Electromagnet's simulation results evaluating the temperature distribution, heating effects and cooling requirements are presented.info:eu-repo/semantics/publishedVersio

The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies

The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.info:eu-repo/semantics/publishedVersio

Artificial intelligence (AI) in rare diseases: is the future brighter?

The amount of data collected and managed in (bio)medicine is ever-increasing. Thus, there is a need to rapidly and efficiently collect, analyze, and characterize all this information. Artificial intelligence (AI), with an emphasis on deep learning, holds great promise in this area and is already being successfully applied to basic research, diagnosis, drug discovery, and clinical trials. Rare diseases (RDs), which are severely underrepresented in basic and clinical research, can particularly benefit from AI technologies. Of the more than 7000 RDs described worldwide, only 5% have a treatment. The ability of AI technologies to integrate and analyze data from different sources (e.g., multi-omics, patient registries, and so on) can be used to overcome RDs' challenges (e.g., low diagnostic rates, reduced number of patients, geographical dispersion, and so on). Ultimately, RDs' AI-mediated knowledge could significantly boost therapy development. Presently, there are AI approaches being used in RDs and this review aims to collect and summarize these advances. A section dedicated to congenital disorders of glycosylation (CDG), a particular group of orphan RDs that can serve as a potential study model for other common diseases and RDs, has also been included.info:eu-repo/semantics/publishedVersio

Nonketotic Hyperglycinemia: A Report of Two Infants Treated with Dextromethorphan and Sodium Benzoate

A hiperglicinémia não cetótica é um erro inato da degradação da glicina, resultando na sua excessiva acumulação nos tecidos corporais, designadamente no sistema nervoso central. Trata-se de uma doença muito grave e uma das terapêuticas recentemente propostas consiste na associação do dextrometorfano com o benzoato de sódio em altas doses. Admite-se a possibilidade de o dextrometorfano bloquear o complexo-canal receptor de N-metil-D-aspartato, implicado na toxicidade da hiperglicinémia ao nível do cérebro e de o benzoato reduzir os níveis de glicina, pela sua conjugação e eliminação como hipurato. Relatamos dois casos clínicos de crianças com hiperglicinémia não cetótita, actualmente com mais de 15 meses de idade, as quais foram medicadas com dextrometorfano e benzoato de sódio desde as primeiras semanas após o parto. Não obstante se ter verificado sobrevivência para além do período neonatal e aquisição de autonomia respiratória, a evolução neurológica, até à data, não tem sido satisfatória, porventura devido ao atraso no início da terapêutica

Application of hyperthermia for cancer treatment: Synthesis and characterization of magnetic nanoparticles and their internalization on tumor cell lines

FEDER funds through the COMPETE 2020 Program under the project number POCI-01-0145-FEDER-007688. This work was also funded by the Scientific merit prize Santander-Totta - Lisbon New University - "Antibody engineering for breast cancer therapy" 2013. Catarina I. P. Chaparro also acknowledges the financial support from Liga Portuguesa Contra o Cancro (LPCC)/Pfizer 2017.Truncated sialylated O-glycans, such as cell-surface carbohydrate antigen sialyl-Tn (STn) are overexpressed by several cancer types, but not by the respective normal tissues. STn expression is associated with oncogenesis and metastatic ability of cancer cells, with reduced overall survival and lack of response to chemotherapy. Advances in nanomedicine have resulted in rapid development of biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with considerable potential in cancer treatment. Therefore, in this study SPIONs coated with oleic acid (OA) or dimercaptosuccinic acid (DMSA) were developed and characterized for internalization in two breast cancer cell lines: cell line expressing the STn antigen and the corresponding control. SPIONs with an average diameter of 8 nm showed superparamagnetic behavior and high potential to be used as magnetic hyperthermia agents. OA and DMSA coating provided high stability of SPIONs in physiological conditions while not changing their main properties. NPs internalization studies showed a higher accumulation of DMSA coated NPs in the breast cancer MDA-MB-231 WT cell line. In MDA-MB-231 cell line expressing STn both coated NPs showed a similar accumulation. Therefore, STn antigen can act as a receptor capable of detecting and covalently bind to the molecules present on NPs surface and induce their cellular uptake by endocytosis.publishersversionpublishe

Stakeholders’ views on drug development: the congenital disorders of glycosylation community perspective

Background Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic. The main aim of this study was to understand current and steer future CDG drug development and approval by collecting and analysing the views and experiences of the CDG community, encompassing professionals and families. An electronic (e-)survey was developed and distributed to achieve this goal. Results A total of 128 respondents (46 CDG professionals and 82 family members), mainly from Europe and the USA, participated in this study. Most professionals (95.0%) were relatively familiar with drug development and approval processes, while CDG families revealed low familiarity levels, with 8.5% admitting to never having heard about drug development. However, both stakeholder groups agreed that patients and families make significant contributions to drug development and approval. Regarding their perceptions of and experiences with specific drug development and approval tools, namely biobanks, disease models, patient registries, natural history studies (NHS) and clinical trials (CT), the CDG community stakeholders described low use and participation, as well as variable familiarity. Additionally, CDG professionals and families shared conflicting views about CT patient engagement and related information sharing. Families reported lower levels of involvement in CT design (25.0% declared ever being involved) and information (60.0% stated having been informed) compared to professionals (60.0% and 85.7%, respectively). These contrasting perceptions were further extended to their insights and experiences with patient-centric research. Finally, the CDG community (67.4% of professionals and 54.0% of families) reported a positive vision of artificial intelligence (AI) as a drug development tool. Nevertheless, despite the high AI awareness among CDG families (76.8%), professionals described limited AI use in their research (23.9%). Conclusions This community-centric study sheds new light on CDG drug development and approval. It identifies educational, communication and research gaps and opportunities for CDG professionals and families that could improve and accelerate CDG therapy development

ST3Gal.I sialyltransferase relevance in bladder cancer tissues and cell lines

<p>Abstract</p> <p>Background</p> <p>The T antigen is a tumor-associated structure whose sialylated form (the sialyl-T antigen) involves the altered expression of sialyltransferases and has been related with worse prognosis. Since little or no information is available on this subject, we investigated the regulation of the sialyltransferases, able to sialylate the T antigen, in bladder cancer progression.</p> <p>Methods</p> <p>Matched samples of urothelium and tumor tissue, and four bladder cancer cell lines were screened for: <it>ST3Gal.I</it>, <it>ST3Gal.II </it>and <it>ST3Gal.IV </it>mRNA level by real-time PCR. Sialyl-T antigen was detected by dot blot and flow cytometry using peanut lectin. Sialyltransferase activity was measured against the T antigen in the cell lines.</p> <p>Results</p> <p>In nonmuscle-invasive bladder cancers, <it>ST3Gal.I </it>mRNA levels were significantly higher than corresponding urothelium (p < 0.001) and this increase was twice more pronounced in cancers with tendency for recurrence. In muscle-invasive cancers and matching urothelium, <it>ST3Gal.I </it>mRNA levels were as elevated as nonmuscle-invasive cancers. Both non-malignant bladder tumors and corresponding urothelium showed <it>ST3Gal.I </it>mRNA levels lower than all the other specimen groups. A good correlation was observed in bladder cancer cell lines between the <it>ST3Gal.I </it>mRNA level, the ST activity (r = 0.99; p = 0.001) and sialyl-T antigen expression, demonstrating that sialylation of T antigen is attributable to ST3Gal.I. The expression of sialyl-T antigens was found in patients' bladder tumors and urothelium, although without a marked relationship with mRNA level. The two <it>ST3Gal.I </it>transcript variants were also equally expressed, independently of cell phenotype or malignancy.</p> <p>Conclusion</p> <p>ST3Gal.I plays the major role in the sialylation of the T antigen in bladder cancer. The overexpression of <it>ST3Gal.I </it>seems to be part of the initial oncogenic transformation of bladder and can be considered when predicting cancer progression and recurrence.</p

listening to what matters for the patients and health professionals

Funding Information: The authors would like to acknowledge the members of the medical and patient committees for the input, advice and experiences shared for the guidance of this study. Namely, to AM, SP, JP, LR, MC, RF, TR and JB for being part of the patient committee and to JJ, EM, LB, DCo, DCa, CTL, RA, CL and AE for integrating the medical committee. We also want to acknowledge the volunteers from the NOVA Sci & Tech Volunteer program that helped with the organisation of this project. Funding Information: This work was supported by the CDG & Allies—Professionals and Patient Associations International Network (CDG&Allies-PPAIN) and by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the Project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO, the Project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB C.P. and R.F. were funded by Fundação para a Ciência e Tecnologia with the Grants SFRH/BD/138647/2018 and (SFRH/BD/124326/2016) respectively. Publisher Copyright: © 2022, The Author(s).Background: Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most common CDG is phosphomannomutase 2 (PMM2)-CDG which often has a severe clinical presentation and life-limiting consequences. There are no approved therapies for this condition. Also, there are no validated disease-specific quality of life (QoL) scales to assess the heterogeneous clinical burden of PMM2-CDG which presents a challenge for the assessment of the disease severity and the impact of a certain treatment on the course of the disease. Aim and methods: This study aimed to identify the most impactful clinical signs and symptoms of PMM2-CDG, and specific patient and observer reported outcome measures (PROMs and ObsROMs, respectively) that can adequately measure such impact on patients’ QoL. The most burdensome signs and symptoms were identified through input from the CDG community using a survey targeting PMM2-CDG families and experts, followed by family interviews to understand the real burden of these symptoms in daily life. The list of signs and symptoms was then verified and refined by patient representatives and medical experts in the field. Finally, a literature search for PROMs and ObsROMs used in other rare or common diseases with similar signs and symptoms to those of PMM2-CDG was performed. Results: Twenty-four signs/symptoms were identified as the most impactful throughout PMM2-CDG patients’ lifetime. We found 239 articles that included tools to measure those community-selected PMM2-CDG symptoms. Among them, we identified 80 QoL scales that address those signs and symptoms and, subsequently, their psychometric quality was analysed. These scales could be applied directly to the PMM2-CDG population or adapted to create the first PMM2-CDG-specific QoL questionnaire. Conclusion: Identifying the impactful clinical manifestations of PMM2-CDG, along with the collection of PROMs/ObsROMs assessing QoL using a creative and community-centric methodology are the first step towards the development of a new, tailored, and specific PMM2-CDG QoL questionnaire. These findings can be used to fill a gap in PMM2-CDG clinical development. Importantly, this methodology is transferable to other CDG and rare diseases with multiple signs and symptoms.publishersversionpublishe