Search

This paper focuses on studying the concept of walkability in Riyadh, Saudi Arabia, after the implementation of the Humanizing Neighborhoods Initiative. Al-Falah neighborhood was selected as a case study because it was one of the first neighborhoods to implement walkability strategies. By adopting a qualitative critical approach, this research collected data through a literature review and on-site observation to assess walkability in the neighborhood. Analysis of the observations highlighted the challenges and opportunities of walkability in Riyadh and the wider Gulf cities. Recommendations for promoting walkable communities in Riyadh include enhancing pedestrian infrastructure, incorporating mixed-use developments, integrating green infrastructure, implementing smart urban planning principles, and integrating public transportation systems. This paper emphasizes the importance of community engagement, preserving local identity, and involving various stakeholders to transform Riyadh into a pedestrian-friendly city that prioritizes public health and sustainability. [ABSTRACT FROM AUTHOR]

Variants in membrane trafficking proteins are known to cause rare disorders with severe symptoms. The highly conserved transport protein particle (TRAPP) complexes are key membrane trafficking regulators that are also involved in autophagy. Pathogenic genetic variants in specific TRAPP subunits are linked to neurological disorders, muscular dystrophies, and skeletal dysplasias. Characterizing these variants and their phenotypes is important for understanding the general and specialized roles of TRAPP subunits as well as for patient diagnosis. Patient-derived cells are not always available, which poses a limitation for the study of these diseases. Therefore, other systems, like the yeast Saccharomyces cerevisiae, can be used to dissect the mechanisms at the intracellular level underlying these disorders. The development of CRISPR/Cas9 technology in yeast has enabled a scar-less editing method that creates an efficient humanized yeast model. In this study, core yeast subunits were humanized by replacing them with their human orthologs, and TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC6A, and TRAPPC6B were found to successfully replace their yeast counterparts. This system was used for studying the first reported individual with an autosomal recessive disorder caused by biallelic TRAPPC1 variants, a girl with a severe neurodevelopmental disorder and myopathy. We show that the maternal variant (TRAPPC1 p.(Val121Alafs*3)) is non-functional while the paternal variant (TRAPPC1 p.(His22_Lys24del)) is conditional-lethal and affects secretion and non-selective autophagy in yeast. This parallels defects seen in fibroblasts derived from this individual which also showed membrane trafficking defects and altered Golgi morphology, all of which were rescued in the human system by wild-type TRAPPC1. This study suggests that humanized yeast can be an efficient means to study TRAPP subunit variants in the absence of human cells and can assign significance to variants of unknown significance (VUS). This study lays the foundation for characterizing further TRAPP variants through this system, rapidly contributing to disease diagnosis. [ABSTRACT FROM AUTHOR]

The cellular prion protein (PrPc) is a cell surface glycoprotein that is highly expressed in a variety of cancer tissues in addition to the nervous system, and its elevated expression is correlated to poor prognosis in many cancer patients. Our team previously found that patients with colorectal cancer (CRC) with high-level PrPc expression had significantly poorer survival than those with no or low-level PrPc expression. Mouse antibodies for PrPc inhibited tumor initiation and liver metastasis of PrPc-positive human CRC cells in mouse model experiments. PrPc is a candidate target for CRC therapy. In this study, we newly cloned a mouse anti-PrPc antibody (Clone 6) and humanized it, then affinity-matured this antibody using a CHO cell display with a peptide antigen and full-length PrPc, respectively. We obtained two humanized antibody clones with affinities toward a full-length PrPc of about 10- and 100-fold of that of the original antibody. The two humanized antibodies bound to the PrPc displayed significantly better on the cell surface than Clone 6. Used for Western blotting and immunohistochemistry, the humanized antibody with the highest affinity is superior to the two most frequently used commercial antibodies (8H4 and 3F4). The two new antibodies have the potential to be developed as useful reagents for PrPc detection and even therapeutic antibodies targeting PrPc-positive cancers. [ABSTRACT FROM AUTHOR]

Drug development in recent years is increasingly focused on developing personalized treatments based on blocking molecules selective for therapeutic targets specifically present in individual patients. In this perspective, the specificity of therapeutic targets and blocking agents plays a crucial role. Monoclonal antibodies (mAbs) and their surrogates are increasingly used in this context thanks to their ability to bind therapeutic targets and to inhibit their activity or to transport bioactive molecules into the compartments in which the targets are expressed. Small antibody-like molecules, such as Fabs, are often used in certain clinical settings where small size and better tissue penetration are required. In the wake of this research trend, we developed a murine mAb (3D1) neutralizing the activity of Nodal, an oncofetal protein that is attracting an ever-increasing interest as a selective therapeutic target for several cancer types. Here, we report the preparation of a recombinant Fab of 3D1 that has been humanized through a computational approach starting from the sequence of the murine antibody. The Fab has been expressed in bacterial cells (1 mg/L bacterial culture), biochemically characterized in terms of stability and binding properties by circular dichroism and bio-layer interferometry techniques and tested in vitro on Nodal-positive cancer cells. [ABSTRACT FROM AUTHOR]

Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the development of the human lymphoid and myeloid lineages using a flow cytometric analysis in four humanized mouse models derived from NOD mice xenotransplanted with CD34+ fetal cord blood from a single donor. Our results showed that all murine strains sustained human immune cells within a proinflammatory environment induced by GvHD. However, the Hu-SGM3 model consistently generated higher numbers of human T cells, monocytes, dendritic cells, mast cells, and megakaryocytes, and a low number of circulating platelets showing an activated profile when compared with the other murine strains. The hu-NOG-EXL model had a similar cell development profile but a higher number of circulating platelets with an inactivated state, and the hu-NSG and hu-NCG developed low frequencies of immune cells compared with the other models. Interestingly, only the hu-SGM3 and hu-EXL models developed mast cells. In conclusion, our findings highlight the importance of selecting the appropriate humanized mouse model for specific research questions, considering the strengths and limitations of each model and the immune cell populations of interest. [ABSTRACT FROM AUTHOR]

While there is an increasing awareness regarding the culture of humanization, which is strongly needed in the healthcare environment, little knowledge has been provided in relation to accurate strategies to teach humanization skills to healthcare undergraduate students, as well as to healthcare professionals. Furthermore, the usefulness of new technologies to improve humanization skills has hardly been addressed so far in the scientific literature, including promising strategies such as Metaverse-related technologies. Presumably, this is the first systematic review focused on the efficacy of Metaverse-related technologies to increase the acquisition of humanization skills in the healthcare environment. The purpose of this study was to review the scientific studies published in the last decade to answer the following two questions: (1) are Metaverse-related technologies useful in enhancing humanization skills in the healthcare environment? (2) What are the advantages and disadvantages that should be addressed to successfully develop Metaverse-related technologies in the healthcare sector? We conducted a systematic review of the peer-reviewed literature from EBSCO, Ovid, PubMed, Scopus, and Web of Science (WOS), following the PRISMA statements and using the following keywords: "humanization + Metaverse"; "humanization + mixed reality"; "humanization + extended reality"; "humanization + augmented reality"; "humanization + virtual reality"; "humanization + app"; "humanization + telemedicine"; "humanization + digital health"; "humanization + eHealth"; "humanization + telehealth"; "humanization + web-based"; "humanization + website"; "humanization + digital"; "humanization + online"; and "humanization + internet". Studies published from 2012 to the present, written in the English language, were reviewed. A total of 505 records were obtained, of which three were selected based on the inclusion and exclusion criteria. The results will be helpful in developing new strategies to improve humanization skills in the health sphere. [ABSTRACT FROM AUTHOR]

One of the significant factors in the sustainability of education is the development of inclusive education. An inclusive educational space implies openness and accessibility of education for students, regardless of their educational needs. Inclusive education also means a partnership between students and teachers. A teacher is a living person whose socio-emotional skills and professional abilities are the basis for the sustainability of education and student development. This article is devoted to studying teachers' competence and psychological readiness at schools and higher educational institutions to work with students with special educational needs. This article includes the results of a sociological study conducted in September 2022 and is devoted to the readiness of schoolteachers and university professors for inclusive education (N = 125). The general statistical calculation was carried out based on information processing using the Vortex program version 10.0. Universities and schools are located in large administrative centers of Russian regions with a population of about a million. The relevance of this study is due to the relationship of sustainability with the ideas of inclusive education, manifested in its goal of achieving students' educational levels established by the state and the humanistic concept of equality of opportunity in the process of professional implementation and self-determination of the individual. [ABSTRACT FROM AUTHOR]

Vast numbers of microorganisms inhabit the mammalian gastrointestinal tract in a complex community referred to as the gut microbiome. An individual's microbiome may be impacted by genetics, diet, and various environmental factors, and has been associated with many health states and diseases, though specific explanations are lacking. While these communities are well-studied in human populations, non-human primates (NHPs), in particular zoo-resident or captive NHPs, offer distinct advantages to increasing our understanding of factors that influence gut microbiome composition. Here, we characterize the gut microbiome composition of a phylogenetically diverse cohort of NHPs residing in the same urban zoo. We show that despite overlapping and controlled environmental contexts, gut microbiomes are still distinguished between NHP host species. However, when comparing the zoo cohort to wild NHPs, we show that captivity status strongly distinguishes zoo-resident NHPs from their wild counterparts, regardless of host phylogeny. Microbial orders unique to captive NHPs include taxa commonly present in human gut microbiomes. Together, these results demonstrate that differences between NHP species are strongly associated with gut microbiome composition and diversity, suggesting that species-specific approaches should be considered when investigating environmental factors' influence on gut microbiome composition. [ABSTRACT FROM AUTHOR]

Today, migration has become one of the main challenges for humanity. In the last ten years, the percentage of displaced people gradually increased, mainly from the southern hemisphere to the north, in search for better living conditions and, in many cases, forced by risks and instability in their countries of origin. The COVID-19 pandemic, far from minimizing migrations, further exacerbated these processes. In light of this situation, some states passed immigration laws that protect their citizens on one hand, but which violate the fundamental rights of migrants on the other. This article aims to determine the main reasons behind the alarming process of migrant dehumanization. We will verify how these national and supranational laws and decisions represent a move towards securitization through a strategic or adiaphoric process, and how ethics and morals are not at the core of these policies. With these decisions, the suffering and death of migrants generates attitudes of indifference among citizens, who often accept and normalize its occurrence. We suggest revising these public policies on migration from the framework of the ethics of Levinasian alterity and Kantian hospitality. [ABSTRACT FROM AUTHOR]

At 420 million years, the variable domain of New Antigen Receptors or VNARs are undoubtedly the oldest (and smallest) antigen binding single domains identified in the vertebrate kingdom. Their role as an integral part of the adaptive immune system of sharks has been well established and has served to provide a greater understanding of the evolution of humoral immunity; their cellular components and processes as well as the underlying genetic organization and molecular control mechanisms. Intriguingly, unlike the variable domain of the camelid heavy chain antibodies or VHH, VNARs do not conform to all of the characteristic properties of classical antibodies with an ancestral origin that clearly distinguishes them from true immunoglobulin antibodies. However, this uniqueness of their origin only adds to their potential as next generation therapeutic biologics with their structural and functional attributes and commercial freedom all enhancing their profile and current success. In fact their small size, remarkable stability, molecular flexibility and solubility, together with their high affinity and selectivity for target, all reinforce the potential of these domains as drug candidates. The purpose of this review is to provide an overview of the existing basic biology of these unique domains, to highlight the drug-like properties of VNARs and describe current progress in their journey towards the clinic. [ABSTRACT FROM AUTHOR]

Targeted therapies for the treatment of cancer, but also inflammation and autoimmune diseases will reduce major side effects accompanied with conventional treatment modalities. The immunotoxin concept uses bacterial or plant toxins, coupled to antibodies or natural ligands targeting cancer cells. Initially, immunotoxins suffered from drawbacks like nonspecific cytotoxicity. Even the third generation of immunotoxins comprised of truncated antibodies and modified effector molecules experienced clinical set-backs due to immune responses. Long-term treatment of cancer and non-lifethreatening chronic inflammatory diseases requires their complete 'humanization'. This lead to evaluating human cytolytic fusion proteins (hCFPs), based on human apoptosisinducing proteins. Lacking an endogenous translocation domain dramatically reduces the cell-death inducing capacity of such proteins. Here, we report on optimizing hCFPs, based on the anti-CD64 single chain variable fragment H22(scFv), specifically eliminating CD64+ macrophages and malignant progenitor cells. We replaced the bacterial toxin in H22(scFv)-ETA' with the pro-apoptotic human granzyme B or angiogenin. Translocation was promoted by a sophisticated adapter containing a membrane transfer peptide (MTD) flanked by endosomal and cytosolic cleavable peptides, thus achieving in vitro cytotoxic activity comparable to bacterial immunotoxins. We demonstrate for the first time that optimized hCFPs, based on granzyme B or angiogenin, can compete with classical ETA-based immunotoxins. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose proliferative effects can contribute to the development of many types of solid tumors when overexpressed. For this reason, EGFR inhibitors such as cetuximab can play an important role in treating cancers such as colorectal cancer and head and neck cancer. Cetuximab is a chimeric monoclonal antibody containing mouse variable regions that bind to EGFR and prevent it from signaling. Although cetuximab has been used clinically since 2004 to successfully control solid tumors, advances in protein engineering have created the opportunity to address some of its shortcomings. In particular, the presence of mouse sequences could contribute to immunogenicity in the form of anti-cetuximab antibodies, and an occupied glycosylation site in FR3 can contribute to hypersensitivity reactions and product heterogeneity. Using simple framework graft or sequence-/structure-guided approaches, cetuximab was humanized onto 11 new frameworks. In addition to increasing humanness and removing the VH glycosylation site, dynamic light scattering revealed increases in stability, and bio-layer interferometry confirmed minimal changes in binding affinity, with patterns emerging across the humanization method. This work demonstrates the potential to improve the biophysical and clinical properties of first-generation protein therapeutics and highlights the advantages of computationally guided engineering. [ABSTRACT FROM AUTHOR]

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A"-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications. [ABSTRACT FROM AUTHOR]

Background: obstetric violence is still far too invisible; the word "violence" generates rejection and obstetric violence is complex to define and typify, as it is a subjective experience. It has been widely analyzed from legal, sociological, and clinical perspectives, but not equally so from the bioethical point of view. This article sets out to take a more in-depth look at the experiences of midwives in order to describe the ethical perspectives of obstetric violence. We intend to describe the effects that malpractice and violence within obstetric care have on American and European bioethical principles., Methodology: A qualitative methodology of the phenomenological tradition was used: 24 midwives participated in three focus groups., Results and Discussion: four categories were arrived at; they are "the maleficence of forgetting my vulnerability", "beneficence requires respect for my integrity and dignity", "my autonomy is being removed from me" and "a problem of social justice towards us, women"., Conclusion: obstetric violence infringes on the main bioethical principles (non-maleficence, beneficence, autonomy, justice, vulnerability, dignity, and integrity). Beyond whether it is called violence or not, what matters from an ethical perspective is that, as long as women have such negative experiences during pregnancy and childbirth, obstetric care needs better humanizing.

Several hundred genes have been identified to contribute to epilepsy—the disease affecting 65 million people worldwide. One of these genes is GNAO1 encoding Gαo, the major neuronal α-subunit of heterotrimeric G proteins. An avalanche of dominant de novo mutations in GNAO1 have been recently described in paediatric epileptic patients, suffering, in addition to epilepsy, from motor dysfunction and developmental delay. Although occurring in amino acids conserved from humans to Drosophila, these mutations and their functional consequences have only been poorly analysed at the biochemical or neuronal levels. Adequate animal models to study the molecular aetiology of GNAO1 encephalopathies have also so far been lacking. As the first step towards modeling the disease in Drosophila, we here describe the humanization of the Gαo locus in the fruit fly. A two-step CRISPR/Cas9-mediated replacement was conducted, first substituting the coding exons 2–3 of Gαo with respective human GNAO1 sequences. At the next step, the remaining exons 4–7 were similarly replaced, keeping intact the gene Cyp49a1 embedded in between, as well as the non-coding exons, exon 1 and the surrounding regulatory sequences. The resulting flies, homozygous for the humanized GNAO1 loci, are viable and fertile without any visible phenotypes; their body weight, locomotion, and longevity are also normal. Human Gαo-specific antibodies confirm the endogenous-level expression of the humanized Gαo, which fully replaces the Drosophila functions. The genetic model we established will make it easy to incorporate encephalopathic GNAO1 mutations and will permit intensive investigations into the molecular aetiology of the human disease through the powerful toolkit of Drosophila genetics. [ABSTRACT FROM AUTHOR]

Envenoming due to Loxosceles spider bites still remains a neglected disease of particular medical concern in the Americas. To date, there is no consensus for the treatment of envenomed patients, yet horse polyclonal antivenoms are usually infused to patients with identified severe medical conditions. It is widely known that venom proteins in the 30–35 kDa range with sphingomyelinase D (SMasesD) activity, reproduce most of the toxic effects observed in loxoscelism. Hence, we believe that monoclonal antibody fragments targeting such toxins might pose an alternative safe and effective treatment. In the present study, starting from the monoclonal antibody LimAb7, previously shown to target SMasesD from the venom of L. intermedia and neutralize its dermonecrotic activity, we designed humanized antibody V-domains, then produced and purified as recombinant single-chain antibody fragments (scFvs). These molecules were characterized in terms of humanness, structural stability, antigen-binding activity, and venom-neutralizing potential. Throughout this process, we identified some blocking points that can impact the Abs antigen-binding activity and neutralizing capacity. In silico analysis of the antigen/antibody amino acid interactions also contributed to a better understanding of the antibody's neutralization mechanism and led to reformatting the humanized antibody fragment which, ultimately, recovered the functional characteristics for efficient in vitro venom neutralization. [ABSTRACT FROM AUTHOR]

Despite efforts to promote good care, many institutionalized older adults (IOA) experience elevated neglectful conditions and reduced person-centered care approaches. Based on the job demand-control model, this study aimed to analyze the relationship between nursing home professionals' personal and organizational factors and good care provided to institutionalized older people. Data was collected through a self-administered survey completed by 208 nursing home staff members. Three dimensions of personal factors (i.e., personal accomplishment, depersonalization, and negative old age stereotypes) were significant predictors of good care. Depersonalization and negative old age stereotypes were negatively associated with IOA, and both good care and personal accomplishment were positively associated with good care in nursing homes. Only one work-related factor (i.e., management support) was positively associated with good care. Personal factors may play a significant role in good care. Management support offers a promising mechanism to promote good care among nursing home professionals. The findings support the need to change the focus on entirely completing care tasks to providing good care of residents in nursing homes that promotes management support, personal accomplishment, personalization and positive old age consideration, attitudes, and behaviors. Policies and interventions should be developed to address in a more humanized way.

Humanization of nursing is related to certain social and moral variables. Moral sensitivity, empathy, and prosocial behavior help understand a situation and make decisions that benefit the patient. The objective of this study is to find out how these variables are related, and define the differences in moral sensitivity, empathy, and prosocial behavior in humanization of nursing. We also analyzed the mediating role of empathy in the relationship between moral sensitivity and prosocial behavior. The sample was made up of 330 Spanish nurses aged 22 to 56, who completed the HUMAS Scale and adapted versions of the Basic Empathy Scale, the Moral Sensitivity Questionnaire, and the Prosocial Behavior Scale. Descriptive analyses, bivariate correlations and multiple mediation models were calculated. The results found significantly different mean scores between all the groups in responsibility and moral strength, cognitive empathy, and prosocial behavior, and in moral burden, the differences were in the high-humanization-score group compared to the low-score group. Furthermore, the mediation models showed the mediating effect of cognitive empathy between the responsibility, strength, and moral burden factors on prosocial behavior, but not of affective empathy. The study concluded that humanization in nursing is closely related to moral sensitivity, cognitive empathy, and prosocial behavior. This facilitates a helping, caring, and understanding attitude toward patient needs, but without the affective flooding that affective empathy can lead to.

Introduction: The approach and use of the term "humanization" is very much present in healthcare. However, instruments for measuring the concept of the humanization of care are yet to be designed and developed., Objective: The main objective of this study was to evaluate and validate the Healthcare Professional Humanization Scale (HUMAS) for nursing professionals., Method: The sample was made up of 338 adults, who were nurses working at health centers and hospitals, and aged between 22 and 56., Results: The results of the analyses confirm that the Healthcare Professional Humanization Scale (HUMAS) has an adequate construct validity and reliability, and defines the humanization of care as a multidimensional construct, made up of five factors: Affection, Self-efficacy, Emotional understanding, Optimistic disposition and Sociability., Conclusions: The new HUMAS scale may be an easily administered and coded instrument for approaching the humanization of care, not only in research, but also in practice.

Health information and communication are key elements that allow patients and family members to make decisions about end-of-life care and guarantee a death with dignity. Objective : To understand caregivers' experiences regarding health information and communication during the illness and death of family members. Methods : This qualitative study was conducted in Andalusia based on the paradigm of hermeneutic phenomenology. Participants were caregivers who had accompanied a family member at the end of life for over 2 months and less than 2 years. Five nominal groups and five discussion groups were established, and 41 in-depth interviews with 123 participants were conducted. Atlas.ti 7.0 software was used to analyze the discourses. A comprehensive reading was carried out along with a second reading. The most relevant units of meaning were identified, and the categories were extracted. The categories were then grouped in dimensions and, finally, the contents of each dimension were interpreted and described given the appropriate clarifications. Results : Four dimensions of the dying process emerged: differences in caregivers' perceptions of information and communication, a conspiracy of silence, consequences of the absence or presence of information, and the need for a culture change. Conclusions : Poor management of health information and communication at the end of life increased the suffering and discomfort of patients and their families. The culture of denying and avoiding death is still present today. A change in education about death would better enable health professionals to care for patients at the end of life.