Usability and Preliminary Efficacy of an Adaptive Supportive Care System for Patients With Cancer: Pilot Randomized Controlled Trial.

BACKGROUND: Using an iterative user-centered design process, our team developed a patient-centered adaptive supportive care system, PatientCareAnywhere, that provides comprehensive biopsychosocial screening and supportive cancer care to patients across the continuum of care adaptively. The overarching goal of PatientCareAnywhere is to improve health-related quality of life (HRQOL) and self-efficacy of patients with cancer by empowering them with self-management skills and bringing cancer care support directly to them at home. Such support is adaptive to the patient's needs and health status and coordinated across multiple sources in the forms of referrals, education, engagement of community resources, and secure social communication. OBJECTIVE: This study aims to assess the usability of the new web-based PatientCareAnywhere system and examine the preliminary efficacy of PatientCareAnywhere to improve patient-reported outcomes compared with usual care. METHODS: For phase 1, usability testing participants included patients with cancer (n=4) and caregivers (n=7) who evaluated the software prototype and provided qualitative (eg, interviews) and quantitative (eg, System Usability Scale) feedback. For phase 2, participants in the 3-month pilot randomized controlled trial were randomized to receive the PatientCareAnywhere intervention (n=36) or usual care control condition (n=36). HRQOL and cancer-relevant self-efficacy were assessed at baseline (preintervention assessment) and 12 weeks from baseline (postintervention assessment); mean differences between pre- and postintervention scores were compared between the 2 groups. RESULTS: Participants were highly satisfied with the prototype and reported above-average acceptable usability, with a mean System Usability Scale score of 84.09 (SD 10.02). Qualitative data supported the overall usability and perceived usefulness of the intervention, with a few design features (eg, "help request" function) added based on participant feedback. With regard to the randomized controlled trial, patients in the intervention group reported significant improvements in HRQOL from pre- to postintervention scores (mean difference 6.08, SD 15.26) compared with the control group (mean difference -2.95, SD 10.63; P=.01). In contrast, there was no significant between-group difference in self-efficacy (P=.09). CONCLUSIONS: Overall, PatientCareAnywhere represents a user-friendly, functional, and acceptable supportive care intervention with preliminary efficacy to improve HRQOL among patients diagnosed with cancer. Future studies are needed to further establish the efficacy of PatientCareAnywhere as well as explore strategies to enhance user engagement and investigate the optimal intensity, frequency, and use of the intervention to improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02408406; https://clinicaltrials.gov/study/NCT02408406.

Rapid and sensitive detection of genome contamination at scale with FCS-GX.

Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI's Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 min. Testing FCS-GX on artificially fragmented genomes demonstrates high sensitivity and specificity for diverse contaminant species. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination, comprising 0.16% of total bases, with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/ or https://doi.org/10.5281/zenodo.10651084 .

GenBank 2024 Update.

GenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public database that contains 25 trillion base pairs from over 3.7 billion nucleotide sequences for 557 000 formally described species. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. Recent updates include policies for including spatio-temporal metadata, clarified documentation for GenBank data processing, enhanced foreign contamination screening tools, new processes in the Submission Portal, migration of Entrez Genome and Assembly displays into NCBI Datasets, and the impending retirement of tbl2asn, replaced by table2asn.

The Power of the Heterogeneous Stock Rat Founder Strains in Modeling Metabolic Disease.

Metabolic diseases are a host of complex conditions, including obesity, diabetes mellitus, and metabolic syndrome. Endocrine control systems (eg, adrenals, thyroid, gonads) are causally linked to metabolic health outcomes. N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous outbred population developed for genetic studies of complex traits. Genetic mapping studies in adult HS rats identified loci associated with cardiometabolic risks, such as glucose intolerance, insulin resistance, and increased body mass index. This study determined underappreciated metabolic health traits and the associated endocrine glands within available substrains of the HS rat founders. We hypothesize that the genetic diversity of the HS rat founder strains causes a range of endocrine health conditions contributing to the diversity of cardiometabolic disease risks. ACI/EurMcwi, BN/NHsdMcwi, BUF/MnaMcwi, F344/StmMcwi, M520/NRrrcMcwi, and WKY/NCrl rats of both sexes were studied from birth until 13 weeks of age. Birth weight was recorded, body weight was measured weekly, metabolic characteristics were assessed, and blood and tissues were collected. Our data show wide variation in endocrine traits and metabolic health states in ACI, BN, BUF, F344, M520, and WKY rat strains. This is the first report to compare birth weight, resting metabolic rate, endocrine gland weight, hypothalamic-pituitary-thyroid axis hormones, and brown adipose tissue weight in these rat strains. Importantly, this work unveils new potential for the HS rat population to model early life adversity and adrenal and thyroid pathophysiology. The HS population likely inherited risk alleles for these strain-specific traits, making the HS rat a powerful model to investigate interventions on endocrine and metabolic health.

Anxiety, Depression, and Coping Strategies during Chemotherapy Treatment: A Comparison of Older and Younger Adults with Advanced Cancer in Brazil.

We sought to examine differences in anxiety, depression and coping strategies among younger (<64-year old) and older (≥65-year old) patients. Patients were assessed at baseline (T1), mid-point (T2) and on the last day of treatment (T3) using the Hospital Anxiety and Depression Scale and the Ways of Coping. A linear mixed modeling approach was used. The study included 200 patients (gender: 70% women; diagnosis: 30% breast, 22% hematological, 18% gastrointestinal; disease stage: 60% advanced). Older patients who used an emotion-focused coping strategy had a greater decrease in anxiety at T3 compared to those that used problem-focused coping (p = .002).

Training to Transition: Using Simulation-Based Training to Improve Resident Physician Confidence in Hospital Discharges.

Introduction: Hospital discharge is a highly critical and complex process that is prone to medical errors, poor communication, and ineffective synchronization of transitional teams. Improving safety during postacute care transitions has become a national focus. Simulation-based training is an underutilized method of instruction for medical resident transitions of care education. Methods: As an integral part of a transitions curriculum, 36 PGY 1 residents from internal medicine and transitional year residency programs underwent a discharge simulation utilizing a trained simulated participant (SP) and a lay caregiver. The objective of the training was to implement a simulation-based education intervention to improve transition practices and discharge communication in graduate medical education. A faculty observer used a case-specific discharge rubric to standardize feedback to the resident and observed the resident navigate the electronic medical record (EMR) for discharge orders. Pretest and posttest surveys assessing resident attitudes and confidence regarding specific areas of the discharge process were distributed to all participating residents for completion. Results: Thirty-six internal medicine and transitional year residents (100%) completed an observed discharge simulation with an SP and a separate encounter with the EMR discharge navigator. All 36 residents (100%) completed the pretest survey, and 23 (63%) completed the postsurvey evaluation. Postsurvey results showed residents agreed (92%, p < .05) that the simulation increased their confidence in safely discharging a patient. Discussion: Simulation encounters are an effective adjunct to postacute care transition education.

Impact of the metabolic syndrome on prevalence and survival in motor neuron disease: a retrospective case series.

Metabolic dysfunction is an important factor in the pathogenesis of motor neuron disease, but its prevalence and association with survival in this disorder is unknown. We hypothesized that patients with motor neuron disease would show a higher prevalence of metabolic syndrome compared to the general New Zealand population, and that metabolic syndrome would be associated with worsened survival. We undertook a retrospective analysis in 109 motor neuron disease patients diagnosed and treated at Waikato Hospital from 2013 to 2020. Demographic, clinical, and laboratory data were collected. Survival was defined as the date of initial symptom onset to the date of death. Of 104 eligible patients, 34 patients (33%) had metabolic syndrome (33% of Europeans, 46% of Maori). Mean survival in motor neuron disease patients with metabolic syndrome was significantly reduced compared to patients without metabolic syndrome (38 vs. 61 months, P = 0.044), with a 5-year survival rate of 21% for the former and 38% for the latter (P = 0.012). Compared with the general New Zealand population, metabolic syndrome is highly prevalent amongst motor neuron disease patients in the Waikato region and it is associated with worsened survival. Metabolic dysfunction may be a key factor underlying the pathogenesis of motor neuron disease.

Differences of biopsychosocial distress and requests for psychological assistance between Asian American and non-Hispanic White oncology patients.

OBJECTIVE: The purpose of this study was to compare Asian American (AA) to non-Hispanic White (NHW) cancer patients regarding biopsychosocial distress and requests for psychological assistance. METHODS: This retrospective study included 5627 eligible patients, newly diagnosed with cancer, who completed the 30-item SupportScreen® survey of biopsychosocial distress. The top 10 sources of high distress were assessed. Distress domains (Emotional, Physical/Functional, and Practical) were examined by race/ethnicity. Requests for psychological assistance were also explored by ethnic groups. RESULTS: Overall, the top 10 sources of high distress were similar between groups and approximately half consisted of concerns regarding physical symptoms. All patients preferred "talking" as their method of receiving assistance for these items. Ratings of emotional, practical, and physical/functional distress were similar between AA and NHW patients. However, AAs (vs. NHWs) requested more assistance regarding physical/functional and practical distress. No difference was observed between these two groups regarding requests for emotional support. CONCLUSIONS: Overall, our study suggests that healthcare providers should be aware of the physical and practical needs of AA cancer patients and provide culturally sensitive care that addresses these needs.

Rapid and sensitive detection of genome contamination at scale with FCS-GX.

Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI's Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1-10 minutes. Testing FCS-GX on artificially fragmented genomes demonstrates sensitivity >95% for diverse contaminant species and specificity >99.93%. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination (0.16% of total bases), with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/.

Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure.

Environmental bisphenol compounds like bisphenol F (BPF) are endocrine-disrupting chemicals (EDCs) affecting adipose and classical endocrine systems. Genetic factors that influence EDC exposure outcomes are poorly understood and are unaccounted variables that may contribute to the large range of reported outcomes in the human population. We previously demonstrated that BPF exposure increased body growth and adiposity in male N/NIH heterogeneous stock (HS) rats, a genetically heterogeneous outbred population. We hypothesize that the founder strains of the HS rat exhibit EDC effects that were strain- and sex-dependent. Weanling littermate pairs of male and female ACI, BN, BUF, F344, M520, and WKY rats randomly received either vehicle (0.1% EtOH) or 1.125 mg BPF/l in 0.1% EtOH for 10 weeks in drinking water. Body weight and fluid intake were measured weekly, metabolic parameters were assessed, and blood and tissues were collected. BPF increased thyroid weight in ACI males, thymus and kidney weight in BUF females, adrenal weight in WKY males, and possibly increased pituitary weight in BN males. BUF females also developed a disruption in activity and metabolic rate with BPF exposure. These sex- and strain-specific exposure outcomes illustrate that HS rat founders possess diverse bisphenol-exposure risk alleles and suggest that BPF exposure may intensify inherent organ system dysfunction existing in the HS rat founders. We propose that the HS rat will be an invaluable model for dissecting gene EDC interactions on health.

Sleep Quality and Disability for Custodial Grandparents Caregivers in the Southern United States.

Sleep quality amongst caregivers with disability may have been compounded by the COVID-19 pandemic. We evaluated differences in sleep quality amongst custodial grandparents from a southern state that were identified through state-based Kinship Care support groups coordinators and online. Participants (N = 102) completed the Pittsburgh Sleep Quality Index and self-reported disability statuses. Gamma tests showed a strong negative relationship between disability and sleep duration indicating fewer hours of sleep, higher use of sleep medication and greater sleep disturbances. Disability is not significantly related to sleep latency, sleep efficiency, and daytime dysfunction. T-tests showed no strength of relationship between disability and overall sleep quality. During the first year of the COVID-19 pandemic, custodial grandparents with disability had greater issues with their sleep quality than those without disability. Sleep, as it pertains to its overall preponderant role in maintaining good health, should be examined amongst custodial grandparent caregivers and those with disability.

Collection and curation of prokaryotic genome assemblies from type strains at NCBI.

The public sequence databases are entrusted with the dual responsibility of providing an accessible archive to all submitters and supporting data reliability and its re-use to all users. Genomes from type materials can act as an unambiguous reference for a taxonomic name and play an important role in comparative genomics, especially for taxon verification or reclassification. The National Center for Biotechnology Information (NCBI) collects and curates information on prokaryotic type strains and genomes from type strains. The average nucleotide identity (ANI)-based quality control processes introduced at NCBI to verify the genomes from type strains and improve related sequence records are detailed here. Using the curated genomes from type strains as reference, the taxonomy of over 1.1 million GenBank genomes were verified and the taxonomy of over 7000 new submissions before acceptance to GenBank and over 1800 existing genomes in GenBank were reclassified.

GenBank 2023 update.

GenBank® (https://www.ncbi.nlm.nih.gov/genbank/) is a comprehensive, public database that contains 19.6 trillion base pairs from over 2.9 billion nucleotide sequences for 504 000 formally described species. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. Recent updates include resources for data from the SARS-CoV-2 virus, NCBI Datasets, BLAST ClusteredNR, the Submission Portal, table2asn, a Foreign Contamination Screening tool and BioSample.

Differences in the intrinsic chondrogenic potential of human mesenchymal stromal cells and iPSC-derived multipotent cells.

BACKGROUND: Human multipotent progenitor cells (hiMPCs) created from induced pluripotent stem cells (iPSCs) represent a new cell source for cartilage regeneration. In most studies, bone morphogenetic proteins (BMPs) are needed to enhance transforming growth factor-ß (TGFß)-induced hiMPC chondrogenesis. In contrast, TGFß alone is sufficient to result in robust chondrogenesis of human primary mesenchymal stromal cells (hMSCs). Currently, the mechanism underlying this difference between hiMPCs and hMSCs has not been fully understood. METHODS: In this study, we first tested different growth factors alone or in combination in stimulating hiMPC chondrogenesis, with a special focus on chondrocytic hypertrophy. The reparative capacity of hiMPCs-derived cartilage was assessed in an osteochondral defect model created in rats. hMSCs isolated from bone marrow were included in all studies as the control. Lastly, a mechanistic study was conducted to understand why hiMPCs and hMSCs behave differently in responding to TGFß. RESULTS: Chondrogenic medium supplemented with TGFß3 and BMP6 led to robust in vitro cartilage formation from hiMPCs with minimal hypertrophy. Cartilage tissue generated from this new method was resistant to osteogenic transition upon subcutaneous implantation and resulted in a hyaline cartilage-like regeneration in osteochondral defects in rats. Interestingly, TGFß3 induced phosphorylation of both Smad2/3 and Smad1/5 in hMSCs, but only activated Smad2/3 in hiMPCs. Supplementing BMP6 activated Smad1/5 and significantly enhanced TGFß's compacity in inducing hiMPC chondrogenesis. The chondro-promoting function of BMP6 was abolished by the treatment of a BMP pathway inhibitor. CONCLUSIONS: This study describes a robust method to generate chondrocytes from hiMPCs with low hypertrophy for hyaline cartilage repair, as well as elucidates the difference between hMSCs and hiMPCs in response to TGFß. Our results also indicated the importance of activating both Smad2/3 and Smad1/5 in the initiation of chondrogenesis.

The impact of COVID-19 on access to canine integrative medical care in Michigan, USA, and Ontario and British Columbia, Canada.

OBJECTIVE: To determine the effects of the COVID-19 associated restrictions on the ability of owners in Michigan (MI), USA versus Ontario (ON) and British Columbia (BC), Canada, to obtain care for their chronically painful dogs. STUDY DESIGN: Cross-sectional survey. POPULATION: A total of 90 owners met the inclusion criteria for the study. METHODS: An anonymous electronic survey was distributed to owners at four veterinary integrative medicine (IM) clinics during July and August 2020. Two clinics in MI and one each in ON and BC were recruited. Owners were asked about availability of IM care preceding and during COVID-19 restrictions and their opinions of the impact of COVID-19 on their dog's health. The survey asked where owners sought care for their dogs, types of chronic conditions treated, therapeutic modalities used, and if owners had a medical background. Comparisons were made within and between groups. Thematic analysis, Fisher's exact test, chi-square analyses, McNemar's and Wilcoxon signed-rank tests for paired comparisons were performed (p < 0.05). RESULTS: During COVID-19 restrictions, access to IM care was better for dogs in ON and BC than in MI (p < 0.001). The negative effect of the pandemic restrictions to IM care on quality of life was perceived greater by owners in MI than those in ON and BC (p < 0.001). The owners' medical backgrounds had no effect on attempts to access care during this time (p = 0.76). CONCLUSIONS AND CLINICAL RELEVANCE: The results suggest that a widespread disease in humans had an adverse impact on animal welfare. Providers of veterinary care should use this experience to establish protocols to ensure continuity of care for chronically painful animals in the event of a similar situation in the future.

Potential Methods of Targeting Cellular Aging Hallmarks to Reverse Osteoarthritic Phenotype of Chondrocytes.

Osteoarthritis (OA) is a chronic degenerative joint disease that causes pain, physical disability, and life quality impairment. The pathophysiology of OA remains largely unclear, and currently no FDA-approved disease-modifying OA drugs (DMOADs) are available. As has been acknowledged, aging is the primary independent risk factor for OA, but the mechanisms underlying such a connection are not fully understood. In this review, we first revisit the changes in OA chondrocytes from the perspective of cellular hallmarks of aging. It is concluded that OA chondrocytes share many alterations similar to cellular aging. Next, based on the findings from studies on other cell types and diseases, we propose methods that can potentially reverse osteoarthritic phenotype of chondrocytes back to a healthier state. Lastly, current challenges and future perspectives are summarized.

Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models.

BACKGROUND: Traumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models. METHODS: Engineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-ß3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1ß, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed. RESULTS: Cell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1ß treatment. CONCLUSIONS: Traumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs.

Needs of Grandparents Raising Grandchildren: A Qualitative Study.

This study identified custodial grandparents' perception of sources of stress that may affect their health and better understand their needs. Findings from this qualitative study are based on thematic analysis of interviews with 10 custodial grandparents. The following themes emerged: 1) grandparents' stress from perceived lack of readiness to care for grandchildren; 2) need for effective communication between and among family members; 3) sufficiency of financial and legal resources; 4) access to community resources, and 5) raising grandchildren reenergizes and revitalizes grandparents' physical and mental health. These findings provide insight into the stressful aspects of the role of raising grandchildren. Understanding stressors affecting custodial grandparents and their grandchildren will help school nurses, social workers, teachers, school administrators and other professionals collaborate to address their challenges.

Body Composition and Metabolic Changes in a Lyon Hypertensive Congenic Rat and Identification of Ercc6l2 as a Positional Candidate Gene.

Central obesity is genetically complex, and its exponential increase in the last decades have made it a critical public health issue. The Lyon Hypertensive (LH) rat is a well-characterized hypertensive model that also exhibits spontaneous and profound differences in body weight and adiposity, relative to its metabolically healthy control, the Lyon Normotensive (LN) rat. The mechanisms underlying the body weight differences between these strains are not well-understood, thus a congenic model (LH17LNa) was developed where a portion of the proximal arm of LN chromosome 17 is introgressed on the LH genomic background to assess the contribution of LN alleles on obesity features. Male and female LH17LNa rats were studied, but male congenics did not significantly differ from LH in this study. Female LH17LNa rats exhibited decreases in total body growth, as well as major alterations to their body composition and adiposity. The LH17LNa female rats also showed decreases in metabolic rate, and a reduction in food intake. The increased adiposity in the female LH17LNa rats was specific to abdominal white adipose tissue, and this phenomenon was further explained by significant hypertrophy in those adipocytes, with no evidence of adipocyte hyperplasia. Sequencing of the parental strains identified a novel frameshift mutation in the candidate gene Ercc6l2, which is involved in transcription-coupled DNA repair, and is implicated in premature aging. The discovery of the significance of Ercc6l2 in the context of female-specific adipocyte biology could represent a novel role of DNA repair failure syndromes in obesity pathogenesis.