Debates on humanization of human-animal brain chimeras - are we putting the cart before the horses?

Research on human-animal chimeras have elicited alarms and prompted debates. Those involving the generation of chimeric brains, in which human brain cells become anatomically and functionally intertwined with their animal counterparts in varying ratios, either via xenografts or embryonic co-development, have been considered the most problematic. The moral issues stem from a potential for "humanization" of the animal brain, as well as speculative changes to the host animals' consciousness or sentience, with consequential alteration in the animal hosts' moral status. However, critical background knowledge appears to be missing to resolve these debates. Firstly, there is no consensus on animal sentience vis-à-vis that of humans, and no established methodology that would allow a wholesome and objective assessment of changes in animal sentience resulting from the introduction of human brain cells. Knowledge in interspecies comparative neuropsychology that could allow effective demarcation of a state of "humanization" is also lacking. Secondly, moral status as a philosophical construct has no scientific and objective points of reference. Either changes in sentience or humanization effects would remain unclear unless there are some neuroscientific research grounding. For a bioethical stance based on moral status of human-animal brain chimera to make meaningful contributions to regulatory policies, it might first need to be adequately informed by, and with its arguments constructed, in a manner that are factually in line with the science. In may be prudent for approved research projects involving the generation of human-animal brain chimera to have a mandatory component of assessing plausible changes in sentience.

Eating pigs, not Peppa Pig: The effect of identifiability on children's propensity to humanize, befriend, and consume edible animals.

This research aimed to provide experimental evidence on whether identifying an edible animal by a name and specific preferences encourages children to perceive the animal as more similar to humans, increases their willingness to befriend the animal, and makes them less willing to consume it. In two pre-registered studies involving 208 preschool children, participants were presented with pictures of pigs (Study 1) and chickens (Study 2). In the identifiability condition, one animal was depicted with individual qualities such as a name and personal preferences, while in the non-identifiability condition, animals were portrayed with characteristics representative of the entire species. The children then rated their desire to befriend and consume the animal, while in Study 2, they also rated the animal's similarity to humans. The results revealed that animal identifiability led to higher perceived similarity to humans, increased the desire to befriend it, and reduced inclination to consume the animal. These findings highlight animal identifiability's powerful and robust effect on children's attitudes toward edible animals.

Percepção de mães sobre a visitação aberta na unidade de terapia intensiva neonatal / Mothers' perception of open visitation in the neonatal intensive care unit / Percepción de las madres sobre las visitas abiertas en la unidad de cuidados intensivos neonatales

Objetivo: compreender a percepção de mães sobre a visitação aberta na unidade de terapia intensiva neonatal. Métodos: estudo descritivo, qualitativo, realizado por meio de entrevista semiestruturada e individualizada, em uma maternidade pública situada no interior de São Paulo, Brasil, em 2019. A amostra foi definida pelo método de saturação de dados e constou de 14 mães. Os dados foram submetidos a Análise de Conteúdo Temática. Resultados: elencaram-se duas categorias: evidenciando os benefícios da visitação aberta e desafios a serem superados. Os benefícios incluíram a satisfação em permanecer com o filho, participar dos cuidados, fortalecer o vínculo maternal, acompanhar a evolução do bebê, evidenciar a qualidade do cuidado e o envolvimento afetivo, redução de sentimentos negativos e visitação do pai no período noturno. Em contrapartida, os desafios incluíram a impossibilidade de permanecer com o filho, estar presente somente em horários pré-estabelecidos para receber informações de médicos, prioriza-las em relação as fornecidas pela enfermagem, receber informações parciais, ter receio em expressar as dúvidas e vivenciar sentimentos negativos. Conclusão: os achados deste estudo fornecem subsídios para que a equipe de saúde e os gestores promovam a adesão de mães à visitação aberta em unidades de terapia intensiva neonatais. (AU)

Objective: understand the perception of mothers about open visitation in the neonatal intensive care unit. Methods: descriptive, qualitative study, carried out through semi-structured and individualized interviews, in a public maternity hospital located in the interior of São Paulo, Brazil, in 2019. The sample was defined by the data saturation method and consisted of 14 mothers. Data were submitted to Thematic Content Analysis. Results: two categories were listed: showing the benefits of open visitation and challenges to be overcome. The benefits included the satisfaction of staying with the child, participating in care, strengthening the maternal bond, monitoring the baby's evolution, showing the quality of care and affective involvement, reducing negative feelings and visiting the father at night. On the other hand, the challenges included the impossibility of staying with the child, being present only at preestablished times to receive information from doctors, prioritizing it in relation to that provided by nurses, receiving partial information, being afraid to express doubts and experience negative feelings. Conclusion: the findings of this study provide support for the health team and managers to promote the adherence of mothers to open visitation in neonatal intensive care units. (AU)

Objetivo: comprender la percepción de las madres sobre la visita abierta en la unidad de cuidados intensivos neonatales. Métodos: estudio descriptivo, cualitativo, realizado a través de entrevistas semiestructuradas e individualizadas, en una maternidad pública ubicada en el interior de São Paulo, Brasil, en 2019. La muestra fue definida por el método de saturación de datos y estuvo conformada por 14 madres. Los datos se enviaron a Análisis de contenido temático. Resultados: se enumeraron dos categorías: mostrando los beneficios de la visita abierta y los desafíos a superar. Los beneficios incluyeron la satisfacción de quedarse con el niño, participar en los cuidados, fortalecer el vínculo materno, monitorear la evolución del bebé, mostrar la calidad del cuidado y el involucramiento afectivo, reducir los sentimientos negativos y visitar al padre por la noche. Por otro lado, los desafíos incluían la imposibilidad de quedarse con el niño, estar presente solo en horarios preestablecidos para recibir información de los médicos, priorizarla en relación a la brindada por enfermeras, recibir información parcial, tener miedo a expresar dudas y experimentar sentimientos negativos. Conclusión: los hallazgos de este estudio brindan apoyo al equipo de salud y gerentes para promover la adherencia de las madres a la visita abierta en las unidades de cuidados intensivos neonatales. básico sobre las conductas frente a los accidentes, a pesar de desconocieren el flujo de atención del servicio. (AU)

Prospects for the computational humanization of antibodies and nanobodies.

To be viable therapeutics, antibodies must be tolerated by the human immune system. Rational approaches to reduce the risk of unwanted immunogenicity involve maximizing the 'humanness' of the candidate drug. However, despite the emergence of new discovery technologies, many of which start from entirely human gene fragments, most antibody therapeutics continue to be derived from non-human sources with concomitant humanization to increase their human compatibility. Early experimental humanization strategies that focus on CDR loop grafting onto human frameworks have been critical to the dominance of this discovery route but do not consider the context of each antibody sequence, impacting their success rate. Other challenges include the simultaneous optimization of other drug-like properties alongside humanness and the humanization of fundamentally non-human modalities such as nanobodies. Significant efforts have been made to develop in silico methodologies able to address these issues, most recently incorporating machine learning techniques. Here, we outline these recent advancements in antibody and nanobody humanization, focusing on computational strategies that make use of the increasing volume of sequence and structural data available and the validation of these tools. We highlight that structural distinctions between antibodies and nanobodies make the application of antibody-focused in silico tools to nanobody humanization non-trivial. Furthermore, we discuss the effects of humanizing mutations on other essential drug-like properties such as binding affinity and developability, and methods that aim to tackle this multi-parameter optimization problem.

Preclinical development of humanized monoclonal antibodies against CD169 as a broad antiviral therapeutic strategy.

New therapies to treat or prevent viral infections are essential, as recently observed during the COVID-19 pandemic. Here, we propose a therapeutic strategy based on monoclonal antibodies that block the specific interaction between the host receptor Siglec-1/CD169 and gangliosides embedded in the viral envelope. Antibodies are an excellent option for treating infectious diseases based on their high specificity, strong targeting affinity, and relatively low toxicity. Through a process of humanization, we optimized monoclonal antibodies to eliminate sequence liabilities and performed biophysical characterization. We demonstrated that they maintain their ability to block viral entry into myeloid cells. These molecular improvements during the discovery stage are key if we are to maximize efforts to develop new therapeutic strategies. Humanized monoclonal antibodies targeting CD169 provide new opportunities in the treatment of infections caused by ganglioside-containing enveloped viruses, which pose a constant threat to human health. In contrast with current neutralizing antibodies that bind antigens on the infectious particle, our antibodies can prevent several types of enveloped viruses interacting with host cells because they target the host CD169 protein, thus becoming a potential pan-antiviral therapy.

Humanized oncology nursing care in a person with gastric cancer: A case report.

Cancer impacts the person's physical health, psychosocial and spiritual wellbeing. The humanization of care is an essential element to achieve integral wellbeing of the individual. The aim of this article is to present a clinical case, using the nursing process with the NANDA, NOC and NIC taxonomies, and based on the principles of Watson's theory of humanized care. The participant is a 45-year-old woman with gastric cancer in palliative stage. The assessment was performed using Gordon's functional patterns and the Watson Caritas Patient Score scale to evaluate the care received previously in the health system. Eight nursing diagnoses were identified, prioritizing 3 diagnoses using the clinical reasoning web (decisional conflict, anxiety, and ineffective self-management of health). Expected outcomes and nursing interventions were planned and implemented through moments of care using health education through tele-nursing and the intentional use of Caritas processes of care in the transpersonal relationship. The results were evaluated with the scales of the indicators and anxiety was also evaluated with the Beck Anxiety Inventory. Health education in oncology nursing contributed to improve informed decision making, reducing anxiety and providing emotional support to facilitate self-management of health. The participant perceived as humanized care throughout the sessions, reflected in the final evaluation with the Watson Caritas Patient Score scale.

Cultural adaptation and validation of the caring behaviors assessment tool into Spanish.

BACKGROUND: The aim of the research was to translate, culturally adapt and validate the Caring Behaviors Assessment (CBA) tool in Spain, ensuring its appropriateness in the Spanish cultural context. METHODS: Three-phase cross-cultural adaptation and validation study. Phase 1 involved the transculturation process, which included translation of the CBA tool from English to Spanish, back-translation, and refinement of the translated tool based on pilot testing and linguistic and cultural adjustments. Phase 2 involved training research assistants to ensure standardized administration of the instrument. Phase 3 involved administering the transculturally-adapted tool to a non-probabilistic sample of 402 adults who had been hospitalized within the previous 6 months. Statistical analyses were conducted to assess the consistency of the item-scale, demographic differences, validity of the tool, and the importance of various caring behaviors within the Spanish cultural context. R statistical software version 4.3.3 and psych package version 2.4.1 were used for statistical analyses. RESULTS: The overall internal consistency of the CBA tool was high, indicating its reliability for assessing caring behaviors. The subscales within the instrument also demonstrated high internal consistency. Descriptive analysis revealed that Spanish participants prioritized technical and cognitive aspects of care over emotional and existential dimensions. CONCLUSIONS: The new version of the tool proved to be valid, reliable and culturally situated, which will facilitate the provision of objective and reliable data on patients beliefs about what is essential in terms of care behaviors in Spain.

A Humanized Patient-Derived Xenograft Model for Pancreatic Cancer.

Pancreatic cancer is associated with a high mortality rate, and there are still very few effective treatment options. Patient-derived xenografts have proven to be invaluable preclinical disease models to study cancer biology and facilitate testing of novel therapeutics. However, the severely immune-deficient mice used to generate standard models lack any functional immune system, thereby limiting their utility as a tool to investigate the tumor-immune cell interface. This chapter will outline a method for establishment of "humanized" patient-derived xenografts, which are reconstituted with human immune cells to imitate the immune-rich microenvironment of pancreatic cancer.

A murine model of DC-SIGN humanization exhibits increased susceptibility against SARS-CoV-2.

To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus.

Humanization of a mouse anti-human complement C6 monoclonal antibody as a potential therapeutic for certain complement-mediated diseases.

The assembly of tissue-damaging membrane attack complexes (MACs; C5b-9) is a major mechanism by which excessive complement activation causes diseases. We previously developed a mouse anti-human C6 monoclonal antibody (mAb) 1C9 that selectively inhibits the assembly of MACs in human and non-human primates. In this project, we found that 1C9 also cross-reacted with rat and guinea pig C6, and determined its binding domains on C6 using different truncated C6 proteins. We then humanized the anti-C6 mAb by molecular modeling and complementarity-determining region grafting. After screening a library of 276 humanized variants with different combinations of humanized light and heavy chains in biophysical assays, we identified clone 3713 with the best developability profile, and an increased affinity against C6 when compared with the parental 1C9 mAb. This humanized 3713 mAb inhibited human, monkey, and rat complement-mediated hemolysis in vitro, and more importantly, it significantly reduced complement-mediated hemolysis in vivo in rats. These results demonstrated the successful humanization of the anti-C6 mAb and suggested that the humanized 3713 mAb could be further developed as a new therapeutic that selectively targets MAC for certain complement-mediated pathological conditions.

Dehumanization in intensive care units and standard wards: A survey for a comparative cross-sectional study.

OBJECTIVES: Dehumanization refers to the practice of treating patients as objects rather than individuals with dignity and respect. METHODS: This study explores dehumanization in healthcare, specifically mechanistic dehumanization and self-dehumanization, which can result in poor care and negative outcomes. A cross-sectional observational study was conducted using a dehumanization questionnaire given to 324 nurses in various departments. The study took place at ANONYMIZED, from September to November 2022. The questionnaire analyzed emotions like anger, impatience, and apathy, identified as key dehumanizing factors. RESULTS: Results indicated that these emotions were prevalent in nurses' perceptions of patients. Interestingly, while Intensive Care nurses often involved families in patient care, leading to higher satisfaction, ward department nurses sometimes viewed patient or family relationships as obstacles. Despite this, 66 % of nurses reported satisfaction with the care provided, while 12 % were indifferent. CONCLUSIONS: The study concludes that the root of dehumanization lies in nurses' inability to feel emotions, the impersonality of care, and the sterility of assistance, leading to self-dehumanization. To combat this, the study suggests strengthening nursing autonomy and education and fostering a positive work environment. The way nurses perceive themselves directly impacts their treatment of patients.

The Humanization and Maturation of an Anti-PrPc Antibody.

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.

Humanized mouse models for anti-cancer therapy.

Patient-derived xenograft (PDX) models are the golden standard for preclinical oncology as they can recapitulate the genotypic and phenotypic complexity of human tumors, thus enabling the development of effective therapeutic strategies. PDX models are typically established in immunocompromised animals that allow efficient growth of the xenografted tumor. Given the recent success of immune therapies in different tumors however, the establishment of humanized PDX models is critical to evaluate immune oncology drugs and/or combinations thereof. Here, we describe the detailed methods to obtain humanized PDX models for anti-cancer therapy testing.

Parents' and nurses' affective perception of a pictorial intervention in a pediatric hospital environment: Quasi-experimental design pre-post-testing.

BACKGROUND/AIM: The humanization of the hospital environment of pediatric departments represents an area of research and intervention on improving the quality of life for hospitalized patients, but also that one of relatives and health professionals. The aim of the study was to test, in a sample of nurses and hospitalized children's parents, whether the pictorial intervention impacted the perceptions of affective qualities of hospital environment. METHODS: This quasi-experimental design study investigated the effects of a pictorial humanization intervention which consisted of some naturalistic and colorful illustrations in the corridor of two pediatric wards of an Italian hospital. A total of 425 parents of hospitalized children and 80 nurses were asked to complete the Italian version of the "Scale of measurement of the affective qualities of places" in two different moments: 1) before the pictorial intervention and 2) three months after its implementation. RESULTS: For all participants (parents and nurses), results showed a significant effect of pictorial intervention with the four positive dimensions investigated (Relaxing, Exciting, Pleasant, and Stimulating) reporting higher scores after being performed it, and with the four negative dimensions (Distressing, Gloomy, Unpleasant, Sleepy) showing lower scores. CONCLUSIONS: Data suggest that the pictorial intervention could be particularly useful to create more welcoming hospital environments, reducing distress levels from hospitalized patients, but also of relatives and healthcare professionals. IMPLICATIONS TO PRACTICE: Pictorial interventions improve the emotional atmosphere in pediatric healthcare settings. Integrating visual elements related to care and healing enhances user experience, creating a more welcoming environment.

Encuesta nacional sobre cambios en las políticas de comunicación, visitas y cuidados al final de la vida en las unidades de cuidados intensivos durante las diferentes olas de la pandemia de COVID-19 (estudio COVIFAUCI) / National survey on changes in visitation, communication and end-of-life care policies in intensive care units through the different COVID-19 pandemic's waves (COVIFAUCI study)

Introducción La pandemia derivada de la infección por SARS-CoV-2 propició cambios en los cuidados tanto a familiares como a pacientes de cuidados intensivos durante las diferentes olas de incidencia del virus. La línea de humanización seguida por la mayoría de los hospitales se vio gravemente afectada por las restricciones aplicadas. Como objetivo, planteamos conocer las modificaciones experimentadas durante las diferentes olas de la pandemia por SARS-CoV-2 en España respecto a la política de visitas a los pacientes en UCI, el acompañamiento al final de la vida, y el uso de las nuevas tecnologías de la comunicación entre familiares, pacientes y profesionales. Métodos Estudio descriptivo transversal multicéntrico mediante encuesta a las UCI españolas desde febrero a abril de 2022. Se realizaron métodos de análisis estadísticos a los resultados según lo apropiado. El estudio fue avalado por la Sociedad Española de Enfermería Intensiva y Unidades Coronarias. Resultados Respondieron un 29% de las unidades contactadas. Los minutos de visita diarios de los familiares se redujeron drásticamente de 135 (87,5-255) a 45 (25-60) en el 21,2% de las unidades que permitían su acceso, mejorando levemente con el paso de las olas. En el caso de duelo, la permisividad fue mayor, aumentando el uso de las nuevas tecnologías para la comunicación paciente-familia en el caso del 96,5% de las unidades. Conclusiones Las familias de los pacientes ingresados en UCI durante las diferentes olas de la pandemia por COVID-19 han experimentado restricciones en las visitas y cambio de la presencialidad por técnicas virtuales de comunicación. Los tiempos de acceso se redujeron a niveles mínimos durante la primera ola, recuperándose con el avance de la pandemia pero sin llegar nunca a los niveles iniciales... (AU)

Introduction The pandemic derived from the SARS-CoV-2 infection led to changes in care for both relatives and intensive care patients during the different waves of incidence of the virus. The line of humanization followed by the majority of the hospitals was seriously affected by the restrictions applied. As an objective, we propose to know the modifications suffered during the different waves of the SARS-CoV-2 pandemic in Spain regarding the policy of visits to patients in the ICU, monitoring at the end of life, and the use of new technologies of communication between family members, patients and professionals. Methods Multicenter cross-sectional descriptive study through a survey of Spanish ICUs from February to April 2022. Statistical analysis methods were performed on the results as appropriate. The study was endorsed by the Spanish Society of Intensive Nursing and Coronary Units. Results Twenty-nine percent of the units contacted responded. The daily visiting minutes of relatives dropped drastically from 135 (87.5-255) to 45 (25-60) in the 21.2% of units that allowed their access, improving slightly with the passing of the waves. In the case of bereavement, the permissiveness was greater, increasing the use of new technologies for patient-family communication in the case of 96.5% of the units. Conclusions The family of patients admitted to the ICU during the different waves of the COVID-19 pandemic have suffered restrictions on visits and a change from face-to-face to virtual communication techniques. Access times were reduced to minimum levels during the first wave, recovering with the advance of the pandemic but never reaching initial levels. Despite the implemented solutions and virtual communication, efforts should be directed towards improving the protocols for the humanization of healthcare that allow caring for families and patients whatever the healthcare context. (AU)

Engineering a human P2X2 receptor with altered ligand selectivity in yeast.

P2X receptors are a family of ligand gated ion channels found in a range of eukaryotic species including humans but are not naturally present in the yeast Saccharomyces cerevisiae. We demonstrate the first recombinant expression and functional gating of the P2X2 receptor in baker's yeast. We leverage the yeast host for facile genetic screens of mutant P2X2 by performing site saturation mutagenesis at residues of interest, including SNPs implicated in deafness and at residues involved in native binding. Deep mutational analysis and rounds of genetic engineering yield mutant P2X2 F303Y A304W, which has altered ligand selectivity toward the ATP analog AMP-PNP. The F303Y A304W variant shows over 100-fold increased intracellular calcium amplitudes with AMP-PNP compared to the WT receptor and has a much lower desensitization rate. Since AMP-PNP does not naturally activate P2X receptors, the F303Y A304W P2X2 may be a starting point for downstream applications in chemogenetic cellular control. Interestingly, the A304W mutation selectively destabilizes the desensitized state, which may provide a mechanistic basis for receptor opening with suboptimal agonists. The yeast system represents an inexpensive, scalable platform for ion channel characterization and engineering by circumventing the more expensive and time-consuming methodologies involving mammalian hosts.

Encuesta nacional sobre cambios en las políticas de comunicación, visitas y cuidados al final de la vida en las unidades de cuidados intensivos durante las diferentes olas de la pandemia de COVID-19 (estudio COVIFAUCI) / National survey on changes in visitation, communication and end-of-life care policies in intensive care units through the different COVID-19 pandemic's waves (COVIFAUCI study)

Introducción La pandemia derivada de la infección por SARS-CoV-2 propició cambios en los cuidados tanto a familiares como a pacientes de cuidados intensivos durante las diferentes olas de incidencia del virus. La línea de humanización seguida por la mayoría de los hospitales se vio gravemente afectada por las restricciones aplicadas. Como objetivo, planteamos conocer las modificaciones experimentadas durante las diferentes olas de la pandemia por SARS-CoV-2 en España respecto a la política de visitas a los pacientes en UCI, el acompañamiento al final de la vida, y el uso de las nuevas tecnologías de la comunicación entre familiares, pacientes y profesionales. Métodos Estudio descriptivo transversal multicéntrico mediante encuesta a las UCI españolas desde febrero a abril de 2022. Se realizaron métodos de análisis estadísticos a los resultados según lo apropiado. El estudio fue avalado por la Sociedad Española de Enfermería Intensiva y Unidades Coronarias. Resultados Respondieron un 29% de las unidades contactadas. Los minutos de visita diarios de los familiares se redujeron drásticamente de 135 (87,5-255) a 45 (25-60) en el 21,2% de las unidades que permitían su acceso, mejorando levemente con el paso de las olas. En el caso de duelo, la permisividad fue mayor, aumentando el uso de las nuevas tecnologías para la comunicación paciente-familia en el caso del 96,5% de las unidades. Conclusiones Las familias de los pacientes ingresados en UCI durante las diferentes olas de la pandemia por COVID-19 han experimentado restricciones en las visitas y cambio de la presencialidad por técnicas virtuales de comunicación. Los tiempos de acceso se redujeron a niveles mínimos durante la primera ola, recuperándose con el avance de la pandemia pero sin llegar nunca a los niveles iniciales... (AU)

Introduction The pandemic derived from the SARS-CoV-2 infection led to changes in care for both relatives and intensive care patients during the different waves of incidence of the virus. The line of humanization followed by the majority of the hospitals was seriously affected by the restrictions applied. As an objective, we propose to know the modifications suffered during the different waves of the SARS-CoV-2 pandemic in Spain regarding the policy of visits to patients in the ICU, monitoring at the end of life, and the use of new technologies of communication between family members, patients and professionals. Methods Multicenter cross-sectional descriptive study through a survey of Spanish ICUs from February to April 2022. Statistical analysis methods were performed on the results as appropriate. The study was endorsed by the Spanish Society of Intensive Nursing and Coronary Units. Results Twenty-nine percent of the units contacted responded. The daily visiting minutes of relatives dropped drastically from 135 (87.5-255) to 45 (25-60) in the 21.2% of units that allowed their access, improving slightly with the passing of the waves. In the case of bereavement, the permissiveness was greater, increasing the use of new technologies for patient-family communication in the case of 96.5% of the units. Conclusions The family of patients admitted to the ICU during the different waves of the COVID-19 pandemic have suffered restrictions on visits and a change from face-to-face to virtual communication techniques. Access times were reduced to minimum levels during the first wave, recovering with the advance of the pandemic but never reaching initial levels. Despite the implemented solutions and virtual communication, efforts should be directed towards improving the protocols for the humanization of healthcare that allow caring for families and patients whatever the healthcare context. (AU)

Perceptions and Expectations of Youth Regarding the Respect for Their Rights in the Hospital.

Information obtained from children themselves regarding the characteristics of the ideal hospital that ensure well-being during a hospital stay is scarce. Here, we report the opinions, perceptions, and expectations of 700 children and adolescents about their experiences, assessed through a mixed-method research approach with age-appropriate questionnaires, three open-ended questions, and an analysis of optional pictorial and textual narratives. Most children indicated that, while they acknowledged the expertise of hospital staff, they also noted several shortcomings, e.g., insufficiently understandable medical information as well as emotional and cognitive support. The continuity of schooling and the right to suffer as little as possible were also critical issues. Adolescents valued in particular the quality of care and services provided, the hospital's adherence to equality and non-discrimination rights, and protection systems but negatively perceived several aspects related to play and participation. Significant differences in the co-occurrences of the most frequently used text terms with the keywords "hospital" and "child/adolescent" between age groups highlight variations in the way patients perceive and articulate their experiences within the hospital setting depending on the cognitive processes linked to age. In drawings, prevailing attention was placed on the physical context of the hospital room, with figures expressing mostly negative emotions. Specifically, in this regard, the main emotion in children was sadness, and, in adolescents, it was fear. Overall, these insights are pivotal in the context of our research objectives as they shed light on the nuanced preferences, needs, and perspectives of children and adolescents during their hospital stays. Recognizing the identified shortcomings, we propose recommendations emphasizing the improvement of medical communication clarity, enhancement of emotional and cognitive support, and the improvement of programs to avoid instructional gaps during hospital stays. Addressing these specific needs is critical for a more comprehensive approach to pediatric healthcare provision.

Structure- and machine learning-guided engineering demonstrate that a non-canonical disulfide in an anti-PD-1 rabbit antibody does not impede antibody developability.

Rabbits produce robust antibody responses and have unique features in their antibody repertoire that make them an attractive alternative to rodents for in vivo discovery. However, the frequent occurrence of a non-canonical disulfide bond between complementarity-determining region (CDR) H1 (C35a) and CDRH2 (C50) is often seen as a liability for therapeutic antibody development, despite limited reports of its effect on antibody binding, function, and stability. Here, we describe the discovery and humanization of a human-mouse cross-reactive anti-programmed cell death 1 (PD-1) monoclonal rabbit antibody, termed h1340.CC, which possesses this non-canonical disulfide bond. Initial removal of the non-canonical disulfide resulted in a loss of PD-1 affinity and cross-reactivity, which led us to explore protein engineering approaches to recover these. First, guided by the sequence of a related clone and the crystal structure of h1340.CC in complex with PD-1, we generated variant h1340.SA.LV with a potency and cross-reactivity similar to h1340.CC, but only partially recovered affinity. Side-by-side developability assessment of both h1340.CC and h1340.SA.LV indicate that they possess similar, favorable properties. Next, and prompted by recent developments in machine learning (ML)-guided protein engineering, we used an unbiased ML- and structure-guided approach to rapidly and efficiently generate a different variant with recovered affinity. Our case study thus indicates that, while the non-canonical inter-CDR disulfide bond found in rabbit antibodies does not necessarily constitute an obstacle to therapeutic antibody development, combining structure- and ML-guided approaches can provide a fast and efficient way to improve antibody properties and remove potential liabilities.

The Italian Validation of the Healthcare Professional Humanization Scale for Nursing.

Purpose: The Healthcare Professional Humanization Scale (HUMAS) is a measure of the evaluation of the humanization of care in nursing professions. Despite being validated for the Spanish language, there still needed validation in Italian, which seems essential considering the cultural differences. Aim: We aimed to test the validity and reliability of the HUMAS with an Italian sample of registered nurses. Methods: The present study used cross-sectional data from 300 nurses that completed the survey. The study's main phases were (a) construction of the Italian version; (b) testing and analyzing the psychometric properties of the scale. The exploratory factor analysis and the Content Validity Index (CVI) were performed. Cronbach's alpha and test-retest were used to determine the reliability. Findings: The final Italian version of HUMAS (HUMAS-I) comprised 19 items grouped into five correlated latent factors, accounting for 68.4% of the variance. Additionally, it exhibited a satisfactory Cronbach's alpha for each latent component and an average CVI for the entire scale of 0.68. Conclusions: The HUMAS-I shows acceptable psychometric proprieties as the original Spanish version. Therefore, it could be an advantageous instrument for use in nursing practice and research.