In silico approaches for drug repurposing in oncology: a scoping review.

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

Chronotype variability in epilepsy and clinical significance: scoping review.

PURPOSE: Chronotype, which captures a person's daily preferences for activity and sleep, is still a poorly researched area in epilepsy research. Finding common chronotype characteristics in people with epilepsy (PWE) and explaining possible effects on seizure management are the main goals. METHODS: Eleven large-scale investigations from 2010 to 2023 were examined in this scoping review. These studies included 1.167 PWE and 4.657 control subjects. RESULTS: PWE had intermediate chronotypes more often than not. Adult patients were more morning-oriented overall, while pediatric cohorts were variable. Relationships between chronotype and seizure control were limited since only two studies in adults reported this and those results conflicted. An evening-type chronotype was found to be more common in generalized epilepsy than focal. The relationship of chronotype and specific antiseizure medication (ASM) therapy was not investigated. CONCLUSIONS: The majority of PWE displayed an intermediate chronotype, but analyses based on age showed more nuanced trends, with children displaying variable patterns, adults generally tending toward morningness, and generalized epilepsy being associated with eveningness. This review underscores the importance of more research on the complex connections between epilepsy outcomes and chronotype. It emphasizes the need to study larger samples of PWE with carefully documented seizure control and ASM therapy, including dose and timing of administration to better understand the role of chronotype on epilepsy outcomes.

In vitro antimicrobial, antibiofilm photodynamic activity, and molecular dynamic simulations of tetra-cationic porphyrinmembrane interactions against foodborne microorganisms.

This manuscript presents a new report on the in vitro antimicrobial photo-inactivation of foodborne microorganisms (Salmonella spp. and Listeria monocytogenes) using tetra-cationic porphyrins. Isomeric tetra-cationic porphyrins (3MeTPyP, 4MeTPyP, 3PtTPyP, and 4PtTPyP) were tested, and antimicrobial activity assays were performed at specific photosensitizer concentrations under dark and white-light LED irradiation conditions. Among the tested bacterial strains, 4MeTPyP exhibited the highest efficiency, inhibiting bacterial growth within just 60 min at low concentrations (17.5 µM). The minimal inhibitory concentration of 4MeTPyP increased when reactive oxygen species scavengers were present, indicating the significant involvement of singlet oxygen species in the photooxidation mechanism. Furthermore, the checkerboard assay testing the association of 4MeTPyP showed an indifferent effect. Atomic force microscopy analyses and dynamic simulations were conducted to enhance our understanding of the interaction between this porphyrin and the strain's membrane.

Unraveling the rapid CO2 mineralization experiment using the Paraná flood basalts of South America.

CO2 capture and storage in geological reservoirs have the potential to significantly mitigate the effects of anthropogenic gas emissions on global climate. Here, we report the results of the first laboratory experiments of CO2 injection in continental flood basalts of South America. The results show that the analyzed basalts have a mineral assemblage, texture and composition that efficiently allows a fast carbonate precipitation that starts 72 h after injection. Based on the availability of calcium, chemical monitoring indicates an estimated CO2 storage of ~ 75%. The carbonate precipitation led to the precipitation of aragonite (75.9%), dolomite (19.6%), and calcite (4.6%).

Brazilian Psychiatric Association Consensus on the physical structure and ideal team for psychiatric emergencies services.

INTRODUCTION: An integral part of Brazil's public health system, the psychiatric emergency service (PES) has been instrumental in improving qualified support for crisis situations of mental disorders, equitable, universally accessible, and humanized. The purpose of this article is to present a systematic review and consensus about the physical area and facilities, and ideal team qualified for psychiatric emergencies services on both Brazilian settings. METHODS: The authors conducted a literature search using electronic databases such as MEDLINE (PubMed), Scielo, the Cochrane Database, and documents from the WHO, the Brazilian Ministry of Health, and others deemed relevant by experts. A total of 6839 manuscripts were found, but only 46 were selected. The analysis of article content summarizes consensus statements using the Delphi method and a series of interactive versions to provide a final report. RESULTS: Changes to PES are evaluated considering various experiences and models. The authors highlighted that The Emergency Care Network (ECN) must be coordinated with qualified management, effective implementation of integration of all health equipment's and units. PES must have adequate infrastructure; qualified staff, including a psychiatrist; sufficient consultation and observational spaces; tools and resources for differential diagnosis; training for all staff members; and communication with the health care network to facilitate referrals following patient discharge are all necessary. CONCLUSION: These standardized models need to be available to public health managers so that they can guide the installation of new services and adjust the existing ones, always looking for improvement. The authors propose requirements for PES as a model to be passed over.

A Window of Opportunity: Radical Versus Repurposing Innovation Under Conditions of Environmental Uncertainty and Crisis.

In this article, we extend the innovation literature by examining how firms respond to crisis, specifically exogenous crises. At their early onset, crises may represent a window of opportunity for innovation, but it is not equally allocated across firms. We created a unique database of 636 biopharmaceutical firms, from 24 countries and territories, developing innovative treatments during the early outbreak of the COVID-19 crisis to study this phenomenon. We found that firms acted strategically to the shifting external environment and attempted to capitalize on the opportunity by pursuing different but complementary innovation strategies (i.e., radical versus repurposed). The successful outcome of a chosen strategy was highly dependent upon a firm's accumulated knowledge resources, which varied in degree of diversity (i.e., homogeneous versus heterogeneous). We found that firms with more focused R&D (i.e., homogeneous knowledge) developed more radical innovations, whereas firms with more diverse R&D (i.e., heterogeneous knowledge) repurposed innovations. We controlled for firm size (small versus large), firm age (startup versus mature), and country classification (developing versus emerging). We also controlled for a firm's prior knowledge and expertise in coronavirus research and found that it did not influence innovation. Our results suggest that this unique period of environmental uncertainty and crisis created a window of opportunity and a level playing field for innovation.

The Arrow Macambira (Encholirium spectabile: Bromeliaceae) as an Important Habitat for the Arthropod Fauna in Rocky Outcrops of the Brazilian Semi-Arid Region.

Bromeliads play a vital role in preserving biodiversity in the Neotropical region. To understand their impact on arthropod diversity in Brazil's semi-arid region, we studied the rupicolous bromeliad Encholirium spectabile. From 2011 to 2018, we observed the arthropod fauna in E. spectabile clumps, documenting the associated taxa, their abundance, and interactions. We also investigated how seasonality affects arthropod richness and composition during the dry and rainy seasons. Over the observation period, 15 orders and 57 arthropod families were recorded in association with E. spectabile. Insecta dominated, followed by predatory chelicerates. Eight usage categories were identified, with Shelter being the most prevalent, followed by Predators, Nesters, and Nectarivores. Significant differences in taxonomic richness were noted between rainy and dry seasons, with the rainy season exhibiting higher diversity. Seasonal variation was also observed in species composition. Clumps of E. spectabile emerged as crucial habitats for surrounding arthropod fauna. This research underscores the importance of non-phylotelm bromeliads, particularly in high abiotic stress environments like semi-arid regions. The taxonomic diversity observed aligns with findings from diverse environments, shedding light on the relevance of E. spectabile for associated arthropod fauna. These results prompt further exploration of non-phylotelm bromeliads in semi-arid settings, providing a fresh perspective on their significance in shaping arthropod communities.

Semi-arid's Unsung Heroes: Hymenoptera and the Vital Ecosystem Services Enabled by Encholirium spectabile, a Rupicolous Bromeliad in the Brazilian Semi-arid Region.

The concept of Ecosystem Services (ES) recognizes the importance of natural ecosystems in supporting human well-being. Hymenoptera, a diverse group of insects including ants, bees, and wasps, play crucial roles in providing ESs. Despite their significance, the provision of ESs by Hymenoptera is often undervalued, leading to ecosystem degradation and loss of important services. This study focuses on the association between Hymenoptera and a rupicolous bromeliad species (Encholirium spectabile) and explores the ESs promoted directly and indirectly by these insects. The study area is located in the Caatinga region of Brazil, characterized by irregular rainfall and a dry season. The results show that Hymenoptera, particularly bees, ants, and wasps, provide a range of ESs including pollination, honey production, pest control, cultural symbolism, and educational value. These services are vital for plant reproduction, food production, and ecosystem functioning in both seasons; there are no differences in species richness between seasons, but rather in species composition. Understanding the importance of Hymenoptera for ESs is crucial for informing conservation and management practices to ensure the sustainability of natural ecosystems. The study highlights the need for conservation actions to protect the intricate ecological relationships between Hymenoptera and bromeliads, which indirectly support ESs by providing habitat and resources, especially during droughts when resources are scarce in the region. By recognizing the importance of bromeliads in supporting Hymenopteran communities, conservation efforts can focus on preserving these critical ecological interactions and maintaining ES provision.

A proof-of-concept study: Determining the geographical origin of Brazilwood, (Paubrasilia echinata) with the use of strontium isotopic fingerprinting.

The illicit exploitation of Brazilwood (Paubrasilia echinata) presents a significant challenge in Brazil, given its substantial value in the global production of bows for musical instruments. To address timber provenance, the use of strontium (Sr) isotope ratios as indicators of bedrock signatures has emerged as a robust tool in forensic investigations. In this study, we critically evaluate the efficacy of this approach using Sr isotope data derived from bulk soils and trees collected at two distinct sites in Brazil. Despite the statistically indistinguishable 87Sr/86Sr ratios observed in the investigated tree species, the compiled 87Sr/86Sr isotope ratios of Brazilwood from Brazilwood National Park (PNPB) and the ES Group provide valuable insights into the potential application of this method for tracing forensic timber seizures. This pilot study also addresses crucial sampling considerations. While the regional signatures exhibit clear distinctions, the limited sample sizes underscore the necessity for supplementary methods to confidently attribute timber to a specific source forest. In isolation, this method proves most effective in refuting presumed timber provenances rather than definitively confirming them. The discussion delves into the nuances of the Sr isotope data, emphasizing the importance of increasing the number of samples and exploring complementary techniques for a more comprehensive and reliable assessment of timber origin.

Surgical waiting lists and queue management in a Brazilian tertiary public hospital.

BACKGROUND: Centralized management of queues helps to reduce the surgical waiting time in the publicly funded healthcare system, but this is not a reality in the Brazilian Unified Healthcare System (BUHS). We describe the implementation of the "Patients with Surgical Indication" (PSI) in a Brazilian public tertiary hospital, the impact on waiting time, and its use in rationing oncological surgeries during the COVID-19 Pandemic. METHODS: Retrospective observational study of elective surgical requests (2016-2022) in a Brazilian general, public, tertiary university hospital. We recovered information regarding the inflows (indications), outflows and their reasons, the number of patients, and waiting time in queue. RESULTS: We enrolled 82,844 indications in the PSI (2016-2022). The waiting time (median and interquartile range) in days decreased from 98(48;168) in 2016 to 14(3;152) in 2022 (p < 0.01). The same occurred with the backlog that ranged from 6,884 in 2016 to 844 in 2022 (p < 001). During the Pandemic, there was a reduction in the number of non-oncological surgeries per month (95% confidence interval) of -10.9(-18.0;-3.8) during Phase I (January 2019-March 2020), maintenance in Phase II (April 2020-August 2021) 0.1(-10.0;10.4) and increment in Phase III (September 2021-December 2022) of 23.0(15.3;30.8). In the oncological conditions, these numbers were 0.6(-2.1;3.3) for Phase I, an increase of 3.2(0.7;5.6) in Phase II and 3.9(1,4;6,4) in Phase III. CONCLUSION: Implementing a centralized list of surgical indications and developing queue management principles proved feasible, with effective rationing. It unprecedentedly demonstrated the decrease in the median waiting time in Brazil.

RET 634 germline/gonadal mosaicism generating a second pathogenic amino acid change in multiple endocrine neoplasia type 2A.

Genetic testing for germline RET pathogenic variants, which cause the Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome, has become crucial in managing patients with medullary thyroid carcinoma (MTC). Classically, RET heterozygous missense pathogenic variants are transmitted in a Mendelian autosomal dominant pattern, of which germline/gonadal mosaicism has never been reported. We report the novel occurrence of a MEN2A patient's family in which the siblings inherited three different RET 634 genotypes: wild type (p.Cys634), p.Cys634Gly or p.Cys634Arg heterozygous pathogenic variants. We hypothesized that germline/gonadal mosaicism, derived from an inherited + early somatic mutation in the mother or a double de novo mutation during maternal embryogenesis, led to this rare event in the RET gene. Exome analysis of the proband's deceased mother's paraffin-embedded thyroid tissue confirmed the three nucleotides in the same 634 codon position. For the first time, we describe germline/gonadal mosaicism in RET, generating a second pathogenic amino acid change in the same codon causing MEN2A. Our finding shows that RET parental mosaicism, confirmed by somatic exome sequencing, might explain discrepant genotype cases in siblings with inherited cancers.

[How studies on curare contributed to the development of neurophysiological research in Brazil]. / Importance des études transnationales sur le curare dans le développement de la recherche en neurophysiologie au Brésil.

Curare is a poison obtained from different species of plants in South America, which was used in arrows by the natives. Its lethal paralyzing potential and mechanism of action began to be explored in the 19th century. In this article, we highlight the research on this poison and the fruitful exchanges between the Brazilian Emperor Dom Pedro II and the researchers João Baptista de Lacerda, Louis Couty and Alfred Vulpian who contributed to the development of experimental neurophysiology in Brazil. Vulpian found that curare does not affect the nerve itself, but acts between the nerves and the muscle, through a "ligand substance" - this Vulpian's pioneering concept is often wrongly attributed to Claude Bernard. These prestigious scientists contributed to the transnational circulation of knowledge that later yielded in the preparation of curare purified extract used for convulsive therapy and anesthesia.

Title: Importance des études transnationales sur le curare dans le développement de la recherche en neurophysiologie au Brésil. Abstract: Le curare, un poison obtenu à partir de différentes espèces de plantes en Amérique du Sud, était utilisé sur les flèches par les autochtones. Son potentiel paralysant mortel et son mécanisme d'action ont commencé à être explorés par les chercheurs au XIXe siècle. Dans cet article, nous rappelons l'historique des recherches sur ce poison et les échanges entre l'empereur brésilien Dom Pedro II et les chercheurs João Baptista de Lacerda, Louis Couty et Alfred Vulpian qui ont beaucoup contribué au développement scientifique brésilien. Vulpian a découvert que le curare n'affecte pas le nerf lui-même, mais agit entre celui-ci et le muscle, par l'intermédiaire d'une « substance de liaison ¼ ­ ce concept développé par Vulpian est souvent attribué à tort à Claude Bernard. Les travaux pionniers de ces savants prestigieux ont ultérieurement abouti à la préparation d'extrait purifié de curare, d'intérêt thérapeutique majeur pour le traitement de convulsions et pour l'anesthésie.

Chemical composition, antifungal activity, antibiofilm and citotoxicity of the essential oil of Citrus deliciosa tenore.

The leaves of Citrus deliciosa Tenore were collected in southern Brazil, dried, and subjected to the hydrodistillation process to obtain the essential oil. The extraction of essential oil yielded 0.97% ± 0.04. The chromatographic profile of this compound revealed 11 substances, being methyl N-methyl-anthranilate (75.1%), γ-terpinene (13.8%), and Limonene (7%) as major substances. The essential oil shows antifungal action against all tested yeasts, with promising action against Cryptococcus neoformans, Cryptococcus gattii, and Trichosporon asahii. This compound was also able to inhibit the biofilm production of Candida albicans, Candida glabrata, Candida parapsilosis, and T. asahii. The essential oil of tangerine showed weak antioxidant action. It did not show cytotoxicity in human mononuclear cells. It is hoped that these results may guide future studies for the production of formulations that can be used in the treatment of biofilms caused by yeasts, as well as in candidiasis, cryptococcosis, and/or trichosporonosis.

A new model based on artificial intelligence to screening preterm birth.

OBJECTIVE: The objective of this study is to create a new screening for spontaneous preterm birth (sPTB) based on artificial intelligence (AI). METHODS: This study included 524 singleton pregnancies from 18th to 24th-week gestation after transvaginal ultrasound cervical length (CL) analyzes for screening sPTB < 35 weeks. AI model was created based on the stacking-based ensemble learning method (SBELM) by the neural network, gathering CL < 25 mm, multivariate unadjusted logistic regression (LR), and the best AI algorithm. Receiver Operating Characteristics (ROC) curve to predict sPTB < 35 weeks and area under the curve (AUC), sensitivity, specificity, accuracy, predictive positive and negative values were performed to evaluate CL < 25 mm, LR, the best algorithms of AI and SBELM. RESULTS: The most relevant variables presented by LR were cervical funneling, index straight CL/internal angle inside the cervix (≤ 0.200), previous PTB < 37 weeks, previous curettage, no antibiotic treatment during pregnancy, and weight (≤ 58 kg), no smoking, and CL < 30.9 mm. Fixing 10% of false positive rate, CL < 25 mm and SBELM present, respectively: AUC of 0.318 and 0.808; sensitivity of 33.3% and 47,3%; specificity of 91.8 and 92.8%; positive predictive value of 23.1 and 32.7%; negative predictive value of 94.9 and 96.0%. This machine learning presented high statistical significance when compared to CL < 25 mm after T-test (p < .00001). CONCLUSION: AI applied to clinical and ultrasonographic variables could be a viable option for screening of sPTB < 35 weeks, improving the performance of short cervix, with a low false-positive rate.

An eosimiid primate of South Asian affinities in the Paleogene of Western Amazonia and the origin of New World monkeys.

Recent fossil discoveries in Western Amazonia revealed that two distinct anthropoid primate clades of African origin colonized South America near the Eocene/Oligocene transition (ca. 34 Ma). Here, we describe a diminutive fossil primate from Brazilian Amazonia and suggest that, surprisingly, a third clade of anthropoids was involved in the Paleogene colonization of South America by primates. This new taxon, Ashaninkacebus simpsoni gen. et sp. nov., has strong dental affinities with Asian African stem anthropoids: the Eosimiiformes. Morphology-based phylogenetic analyses of early Old World anthropoids and extinct and extant New World monkeys (platyrrhines) support relationships of both Ashaninkacebus and Amamria (late middle Eocene, North Africa) to the South Asian Eosimiidae. Afro-Arabia, then a mega island, played the role of a biogeographic stopover between South Asia and South America for anthropoid primates and hystricognathous rodents. The earliest primates from South America bear little adaptive resemblance to later Oligocene-early Miocene platyrrhine monkeys, and the scarcity of available paleontological data precludes elucidating firmly their affinities with or within Platyrrhini. Nonetheless, these data shed light on some of their life history traits, revealing a particularly small body size and a diet consisting primarily of insects and possibly fruit, which would have increased their chances of survival on a natural floating island during this extraordinary over-water trip to South America from Africa. Divergence-time estimates between Old and New World taxa indicate that the transatlantic dispersal(s) could source in the intense flooding events associated with the late middle Eocene climatic optimum (ca. 40.5 Ma) in Western Africa.

Neurophysiology in between the interests of Dom Pedro II of Brazil, and Charles Brown-Séquard (Historical Note) / Neurofisiologia entre os interesses de Dom Pedro II do Brasil e Charles Brown-Séquard (Nota Histórica)

This article presents our historical research regarding Charles Brown-Séquard, a famous scientist with important contributions to the medical field, in particular for neurology, and endocrinology, and his relationship with Dom Pedro II, the second and last Brazilian Emperor, and an enlightened ruler. The Emperor contacted several illustrious personages in support of State policy, such as for the development of experimental physiology at the Imperial Museum of Natural History, but also for personal purposes given his health problems and those of the Empress. Charles Brown-Séquard and his pilgrimage between different worlds as a physician and physiologist are presented until his definitive establishment in Paris, where he replaces Claude Bernard in the chair of experimental medicine at the Collège de France. Jacques-Arsene d'Arsonval took over after this chair, and together with Brown-Séquard, he electrophysiologically examined the Emperor's diabetic peripheral neuropathy. In this article, the Emperor´s relationship with Brown-Séquard was studied mainly from the correspondence sent to Dom Pedro II and retrieved from the Imperial Museum in Petrópolis, Brazil, and from the accounts of his meetings that included scientific sessions and clinical consultations. This article can be used to understand the progress of knowledge in the field of neurology/clinical neurophysiology, the tracking of emerging ideas in the field of science in the past and the threat to the credibility of researchers.

Este artigo apresenta nossa pesquisa histórica a respeito de Charles Brown-Séquard, famoso cientista com importantes contribuições para a área médica, em especial para a neurologia e endocrinologia, e sua relação com Dom Pedro II, segundo e último Imperador brasileiro, e governante esclarecido. O Imperador contactou várias personalidades ilustres no apoio à política de Estado, como para o desenvolvimento da fisiologia experimental no Museu Imperial de História Natural, mas também para fins pessoais dados os seus problemas de saúde e os da Imperatriz. Charles Brown-Séquard e sua peregrinação entre diferentes mundos como médico e fisiologista são apresentados até seu estabelecimento definitivo em Paris, onde substitui Claude Bernard na cadeira de medicina experimental no Collège de France. Jacques-Arsene d'Arsonval assumiu após esta cadeira e, juntamente com Brown-Séquard, examinou eletrofisiologicamente a neuropatia periférica diabética do imperador. Neste artigo, a relação do Imperador com BrownSéquard foi estudada principalmente a partir da correspondência enviada a Dom Pedro II e recuperada no Museu Imperial de Petrópolis, Brasil, e dos relatos de seus encontros que incluíam sessões científicas e consultas clínicas . Este artigo pode ser usado para entender o progresso do conhecimento no campo da neurologia/neurofisiologia clínica, o rastreamento de ideias emergentes no campo da ciência no passado e a ameaça à credibilidade dos pesquisadores.

A U.S. National Study of Family Resilience During the COVID-19 Pandemic.

The COVID-19 pandemic has significantly disrupted the lives of children and their caregivers. Recent research has examined the impact of the pandemic on child and caregiver functioning but there is a paucity of work examining the impact of the pandemic on the broader family system. The current study examined family resilience during the COVID-19 pandemic across three aims: Aim 1 tested whether meaning, control, and emotion systems form a unitary family adaption factor, Aim 2 evaluated a concurrent model of family resilience, and Aim 3 examined whether parent gender and vaccination status moderated paths in the final model. A nationally representative sample of U.S. parents (N = 796; 51.8% fathers, M age = 38.87 years, 60.3% Non-Hispanic White) completed a cross-sectional survey about themselves and one child (5-16 years old) between February-April 2021, including measures of COVID-19 family risk and protective factors, pre-existing family health vulnerabilities, race, COVID-19 stressors, and family adaptation. Confirmatory Factor Analysis demonstrated that the meaning (i.e., family making meaning of COVID-19), control (i.e., stability in routines), and emotional (i.e., family support) facets of family adaptation are unique but related. A path model revealed that there were concurrent effects from COVID-19 exposure, pre-existing vulnerabilities, and racial diversity status to the family protective, vulnerability, and adaptation variables. Additionally, parent COVID-19 vaccination status altered the association between pre-existing family health vulnerabilities and the family protective factor. Overall, results underscore the importance of examining pre-existing and concurrent risk and protective factors for family resilience during a stressful, global, and far-reaching event.