The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.

Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1. However, the mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp. in both mice and humans. Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis. We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice. Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.

Intergenerational Transmission of Ethnoracial Historical Trauma in the United States.

Throughout time, ethnoracial groups have endured a range of traumatic experiences as historically marginalized members of the United States. The consequences of these experiences have been referred to as historical trauma (HT): a collective trauma, inflicted on a group of people who share a specific identity, that has psychological, physical, and social impacts on succeeding generations. In this review, we examine the literature on HT in relation to US ethnoracial groups by defining HT, providing a background for its development, and describing critiques of the concept. We then review the literature on HT in relation to Indigenous Americans, African Americans, and Asian Americans. For each group, we address the nature of HT, the transmission of HT and its impacts, and healing strategies. We conclude with a summary of the benefits, limitations, and complexities of HT research as well as recommendations for future work in this area.

Promising Directions: A Systematic Review of Psychosocial and Behavioral Interventions with Cultural Incorporation for Advanced and Metastatic Cancer.

BACKGROUND: Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. METHOD: Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non-randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. RESULTS: Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = -0.49), and anxiety (g = -0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = -0.54), physical symptoms (g = -0.39), and depression (g = -0.38). CONCLUSION: Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure.

"No Complaining, No Crying": A Qualitative Study of the Strong Black Woman Schema in the Breast Cancer Context.

BACKGROUND: Black women have the highest mortality from breast cancer compared with other racial/ethnic groups. Black women with breast cancer also evidence compromised quality of life in some domains. Culturally relevant aspects of their experience are understudied. PURPOSE: The goal of this qualitative study was to examine the relevance of the Strong Black Woman schema in the cancer context. METHODS: Three Gatherings (i.e., culturally curated focus groups) were conducted with Black women who had been diagnosed with breast cancer and recruited from cancer-related listservs and events. A five-person team conducted reflexive thematic analysis of Gathering transcripts. RESULTS: The 37 participants ranged in age (30 to 94 years) and in diagnosis duration (2 months to 29 years). Reflexive thematic analysis yielded six themes that characterized the women's experience: historical legacy of the Strong Black Woman, navigating intersecting Strong Black Woman identities, everyday challenges encountered on the battlefield by Strong Black Women, Strong Black Woman in action during the breast cancer journey, the complexities of seeking and accepting support, and the liberated Strong Black Woman. The schema's negative consequences included the oncologic team and others expecting the participants to be strong and not to need support. Expectations to suppress emotions and continue caring for others to the neglect of the self also were evident. Positive consequences included engaging in self-advocacy in the oncologic context and redefining strength to include expressing emotions and accepting help. CONCLUSIONS: The Strong Black Woman schema is highly relevant in the breast cancer context and could be addressed in culturally centered interventions.

Compared with other racial/ethnic groups, Black American women diagnosed with breast cancer have the highest death rate and some aspects of their quality of life is lower. The authors developed Project SOAR (Speaking Our African American Realities) to shed light on the experiences of Black American women diagnosed with breast cancer. In one Project SOAR study, 37 women took part in Gatherings­small group meetings conducted in an all-Black, all-woman space­in which they talked about the relevance of the Strong Black Woman (or Black Superwoman) concept during breast cancer. Arising from a history of enslavement, the concept involves suppressing emotions, always acting strong, taking care of others while neglecting care of oneself, and declining others' support. Gathering participants ranged in age (30 to 94 years) and time elapsed since diagnosis (2 months to 29 years). Their breast cancer experiences often corresponded with the Strong Black Woman concept. For example, some medical professionals and others expected them to act strong, to keep caring for others, not to need support, and not to voice their emotions during the cancer experience. Some women redefined strength to include expressing emotions and accepting help. The authors are developing resources for Black American women breast cancer survivors.

"I'm Fighting for My Life": Exploring Interactions Between Black Women with Breast Cancer and Healthcare Providers.

Black Americans face a multitude of problems in the healthcare system, including challenges during interactions with healthcare providers. The present study examined the quality of healthcare provider-Black patient interactions in a sample of Black American women with a breast cancer diagnosis. More specifically, the study examined potential contributors to Black Americans' current healthcare experiences and lack of trust by identifying their specific negative and positive encounters in the healthcare system. Three in-person Gatherings (i.e., culturally curated focus groups; N = 37) were conducted as part of a community-academic research partnership, Project SOAR (Speaking Our African American Realities). Four themes were identified through reflexive thematic analysis: Individual and Systemic Injustice Directed at Black Breast Cancer Survivors; Protecting Myself from an Untrustworthy Medical System; Stereotypes Interfered with My Care; and Good Care Should Include Compassion, Respect, Shared Decision Making, and Tailored Support. The present findings highlight the importance of addressing systemic and individual injustice toward Black Americans in healthcare settings generally, and Black women diagnosed with breast cancer specifically.

The road to xenotransplantation.

PURPOSE OF REVIEW: The aim of this study was to highlight recent progress in xenotransplantation and discuss the remaining obstacles/steps before the FDA is likely to approve a clinical trial. RECENT FINDINGS: Long-term survival of life-supporting xenografts in preclinical models has led to discussion of clinical trials of xenotransplantation. The reports of clinical cardiac xenotransplant based on compassionate use FDA approval and renal xenotransplants to brain-dead humans have led to further considerations of clinical trials. Discussions between the transplant community and the FDA have established critical next steps before a clinical trial of xenotransplants is likely to be approved. These steps include testing the clinical immunosuppression protocol and the organ from a genetically modified source animal in nonhuman primates with reproducible survival of at least 6 months. In addition, appropriate viral surveillance protocols and confirmation that the xenografts support appropriate human physiology are likely to be critical elements for FDA-approval. Finally, further studies in the human decedent model are likely to provide critical information about human immune and physiologic responses to xenografts. SUMMARY: This review highlights the current progress in nonhuman primate models and recent reports of human xenotransplantation. It also describes the remaining hurdles and currently understood FDA requirements that remain to be achieved before a clinical trial of xenotransplantation can be approved.

How discrimination experiences relate to racial/ethnic identity and mental health across first- and second-generation Vietnamese American adolescents.

OBJECTIVES: Racial/ethnic discrimination has been linked to behavioral and emotional problems in youth from marginalized groups. However, the psychological experience associated with discrimination may differ between immigrant and nonimmigrant youth. Race-based discrimination may impact an adolescent's view of their own group (private regard) and/or their sense of how others view their group (public regard). Owing to differences in racialization, immigrant adolescents may be affected differently by experiences of discrimination than their U.S.-born peers. The present study examined whether nativity moderated the paths from racial/ethnic discrimination to private and public regard to mental health problems among Vietnamese American youth. METHOD: Surveys were completed by 718 Vietnamese American 10th and 11th graders (Mage = 15.54 years, 61.4% female, 38.6% male). In this sample, 21.2% were first-generation (i.e., born outside of the United States) and 78.8% were second-generation (i.e., born in the United States with at least one parent born outside of the United States). RESULTS: Multigroup path analysis tested the direct and indirect effects of racial/ethnic discrimination on behavioral and emotional problems via private and public regard and whether associations differed for first- versus second-generation youth. Racial/ethnic discrimination was associated with lower public regard, but not private regard, for both first- and second-generation Vietnamese American youth. Public regard was negatively associated with behavioral and emotional problems only among second-generation youth. No indirect effects were significant. CONCLUSIONS: Findings suggest differences in racialized experiences, as well as opportunities to support second-generation Vietnamese American and other marginalized youth from immigrant families from the mental health impacts of discrimination. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Transitions in coping profiles after breast cancer diagnosis: implications for depressive and physical symptoms.

The objective of this study was to determine whether: (a) cancer-related coping profiles change across time; (b) coping profile transition types predict changes in depressive and physical symptoms. Latent transition analysis was conducted with repeated measures of seven cancer-related coping processes from 460 women recently diagnosed with breast cancer. In multilevel models, coping profile transition groups were entered as predictors of symptoms across 12 months. Three coping profiles emerged at study entry, with two profiles at later assessments. Forty-eight percent of women maintained high-moderate approach-oriented coping over time. Specific factors (e.g., age, acceptance of emotions) differentiated the transition groups. Women who increased and then maintained high-moderate approach-oriented coping had relatively high initial depressive symptoms that declined steeply. When cancer-related acceptance predominated, women experienced increasing physical symptoms. Distinct cancer-related coping patterns are related to the level of and change in depressive and physical symptoms longitudinally. Early intervention to increase approach-oriented coping strategies could yield favorable outcomes.

Longitudinal Relations between Emotion Restraint Values, Life Stress, and Internalizing Symptoms among Vietnamese American and European American Adolescents.

Objective: Recent research has documented cultural differences in the extent and manner in which various forms of emotion regulation are linked with psychological well-being. Most of these studies, however, have been cross-sectional, nor have they directly examined the values underlying the use of emotion regulation. The present study examined emotion restraint values and their interactions with life stress in predicting internalizing symptoms across time among Vietnamese American and European American adolescents. The study focused on adolescence as a critical developmental period during which life stress and internalizing symptoms increase significantly. Method: Vietnamese American (n = 372) and European American (n = 304) adolescents' levels of emotion restraint values, internalizing symptoms, and stress were assessed at two timepoints six months apart. Results: Results indicated differential associations between emotion restraint values, stress, and symptoms over time for the two groups. For Vietnamese American adolescents, emotion restraint values did not predict depressive, anxiety, or somatic symptoms. For European American adolescents, emotion restraint values predicted higher somatic symptoms but buffered against the effects of interpersonal stress on anxiety and depressive symptoms. Conclusions: These results provide increased understanding of the role of values related to emotion restraint in shaping adolescent internalizing symptoms and responses to stress across cultural groups. Implications of the findings for guiding intervention efforts are discussed.

Perceptions of Sibling Relationships and Birth Order among Asian American and European American Emerging Adults.

Drawing from an ecological systems framework, we qualitatively explored how Confucian-heritage Asian American emerging adults compared with non-Hispanic European American emerging adults on views of sibling relationships and birth order. Thematic analysis of 48 semi-structured interviews revealed positive sibling relationship themes for both ethnocultural groups: mutual support, companionship, and appreciation; comfort from shared burden of negative parental interactions; and pride in one another. Birth-order themes were also similar across the groups. First-borns overall reported a strong pressure to be a role model to later-borns, provide sibling care, assume family responsibilities, and not expect to rely on younger siblings. Despite these similarities, Asian American first-borns were unique in taking comfort in having siblings who shared a less traditional Asian cultural perspective than their parents. They also described additional pressure from being the oldest within an immigrant family.

Myocardial ischaemia after hip and knee arthroplasty: incidence and risk factors.

PURPOSE: Because the occurrence of postoperative myocardial ischaemia (MI) predicts subsequent cardiac morbidity and mortality, we determined the prevalence of and risk factors for MI in hip and knee arthroplasty patients. METHODS: High-sensitivity cardiac troponin T (hs-cTnT) was measured on stored samples from postoperative day two in 394 hip and knee arthroplasty patients ≥ 65 years of age enrolled in the Genetics-InFormatics Trial (GIFT). RESULTS: Fifty-three (13.5 %) participants had MI, of whom only three were diagnosed clinically during their hospitalisation. The risk of MI increased with age [odds ratio (OR) 3.52 per decade, 95 % confidence interval (CI) 2.00-6.19] and diabetes (OR 2.23, 95 % CI 1.04-4.77). MI was rarer with statins (OR 0.74, 95 % CI 0.40-1.35) and more common with hypertension, coronary artery disease and tobacco use, although these were not statistically significant. CONCLUSIONS: Subclinical MI occurs frequently after arthroplasty. Diabetic and elderly patients are at highest risk.

Atypical expanded-spectrum hemifacial microsomia: a case report.

Objective : To present the case report of a patient with expanded hemifacial microsomia (HFM) that illustrates the complex interactions of these embryogenic factors and to review current theories and mechanism regarding the etiopathogenesis of HFM. Design and Method : We present the case of an African American girl who was born at full term by cesarean section and transferred to our institution for systemic malformations. Her craniofacial findings include holoprosencephaly, cleft lip and palate, low set and posteriorly rotated ears, flat midfacial features, micrognathia, left HFM with grade 1 microtia, hypoplastic mandible, and a small preauricular pharyngeal arch remnant. Systemic anomalies included ectopic kidney, atrial-septal defect, bilateral hip dysplasia, bilateral humeroradial fusion, bilateral club feet, and bilateral low-set thumbs with the right side also being triphalangeal. Genetic evaluation did not identify a molecular diagnosis or other known syndrome. Conclusions : Although vasculogenic disruption of the stapedial artery during early fetal gestation has been implicated in the etiology of HFM, the grouping and bilateral findings seen in our patient argue against this relatively simple and localized phenomenon. Instead, such diverse and widespread anomalies in the setting of expanded spectrum HFM seem to support the theory of a disorder in blastogenesis as the cause of HFM.

Clinical Factors Affecting Length of Stay After 100 Consecutive Cases of Primary Cleft Lip Repair.

OBJECTIVE: To analyze the hospital course of 100 consecutive infants after primary cleft lip repair (PCLR) and identify factors related to length of stay (LOS). DESIGN: Retrospective analysis of 100 consecutive infants who were routinely admitted after PCLR. SETTING: Tertiary care center. PATIENTS: One hundred consecutive infants undergoing PCLR. Demographic and perioperative data were collected and analyzed. MAIN OUTCOME MEASURE: LOS, planned before data collection. RESULTS: Male:female ratio was 65:35. Seventy-two infants had unilateral cleft lip; syndromic association was documented in 15 patients. Mean age and weight at PCLR were 5.6 ± 4.0 months and 6.7 ± 1.3 kg, respectively. Mean duration of surgery was 2.5 ± 0.9 hours, and mean duration of general anesthesia was 3.4 ± 0.9 hours. A total of 3.3 ± 1.5 mL of intraoperative local anesthetic was used per patient. Intravenous fluids were necessary after transfer from the post-anesthesia care unit to the general ward in 98% of patients. Almost half (44%) of all patients received intravenous morphine 23 hours or more after hospital admission. Mean LOS was 35.8 ± 13.9 hours. No association was identified between patient demographic factors and LOS. Multivariate linear regression models identified significant positive correlation between LOS and duration of general anesthesia (P = .002). Greater volume of postoperative oral intake (P = .000) and higher acetaminophen dosage on the floor (P = .000) correlated with decreased LOS. CONCLUSIONS: This study identifies perioperative factors associated with LOS. Our findings question the safety of routine outpatient or short-stay observation after PCLR.

Socioeconomic Status, Stress, and Cancer-related Fatigue among Chinese American Breast Cancer Survivors: The Mediating Roles of Sleep.

Sleep-related issues may be one significant pathway through which socioeconomic disadvantages are associated with worse self-reported states in cancer. The present study examined the relationships between SES (income and education level) and two important biobehavioral factors (cancer-related fatigue and perceived stress), as well as mediation through sleep-related problems (sleep medication use, daytime dysfunction, and sleep quality) among a sample of Chinese American breast cancer survivors. 136 Chinese American breast cancer survivors completed a self-reported questionnaire. We found that relative to those with the lowest annual household income, those with the highest income have lower perceived stress. This relationship was mediated by lower sleep quality. Relative to those with a high school degree or less, those with graduate degrees have lower daytime dysfunction, and in turn lower cancer-related fatigue. Our findings point to the importance of addressing sleep-related issues, perceived stress, and cancer-related fatigue among Chinese American breast cancer survivors with low SES backgrounds.

Organ Nonutilization Following Revision to the Public Health Service Donor Risk Criteria for HIV, HCV, or HBV Transmission.

BACKGROUND: Organs from Public Health Service criteria (PHSC) donors, previously referred to as PHS infectious-risk donors, have historically been recovered but not used, traditionally referred to as "discard," at higher rates despite negligible risk to recipients. On March 1, 2021, the definition of PHSC donors narrowed to include only the subset of donors deemed to have meaningfully elevated risk in the current era of improved infectious disease testing. METHODS: Using Scientific Registry of Transplant Recipients data from May 1, 2019, to December 31, 2022, we compared rates of PHSC classification and nonutilization of PHSC organs before versus after the March 1, 2021, policy change among recovered decedents using the χ 2 tests. We performed an adjusted interrupted time series analysis to examine kidney and liver recovery/nonuse (traditionally termed "discard") and kidney, liver, lung, and heart nonutilization (nonrecovery or recovery/nonuse) prepolicy versus postpolicy. RESULTS: PHSC classification dropped sharply from 24.5% prepolicy to 15.4% postpolicy ( P  < 0.001). Before the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were comparable to non-PHSC estimates (adjusted odds ratio: kidney =  0.98 1.06 1.14 , P  = 0.14; liver =  0.85 0.92 1.01 , P  = 0.07; lung =  0.91 0.99 1.08 , P  = 0.83; heart =  0.89 0.97 1.05 , P  = 0.47); following the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were lower than non-PHSC estimates (adjusted odds ratio: kidney =  0.77 0.84 0.91 , P  < 0.001; liver =  0.77 0.84 0.92 , P  < 0.001; lung =  0.74 0.81 0.90 , P  < 0.001; heart =  0.61 0.67 0.73 , P  < 0.001). CONCLUSIONS: Even though PHSC donors under the new definition are a narrower and theoretically riskier subpopulation than under the previous classification, PHSC status appears to be associated with a reduced risk of kidney and liver recovery/nonuse and nonutilization of all organs. Although historically PHSC organs have been underused, our findings demonstrate a notable shift toward increased PHSC organ utilization.

Healthcare Professionals' Views of Supportive Care Needs for Chinese, Korean, and Vietnamese Americans with Metastatic Cancer.

The supportive care needs of people with metastatic cancer, particularly Asian Americans, are understudied. Distinct psychosocial support needs may exist across ethnocultural groups with Confucian-heritage values and norms. Cultural factors may shape how adults approach their oncologic care. This qualitative study represents the perspectives of 15 experienced healthcare professionals about the supportive care needs of Chinese-, Korean-, and Vietnamese-heritage (CKV) adults with metastatic solid cancers. Reflexive thematic analysis was conducted with transcripts from three semi-structured focus groups and five parallel-format individual interviews. Inductive coding and iterative theme development resulted in four themes describing the types of needs (basic, care-related, mental health, relational trust) that should be met for CKV patients with metastatic cancer, which may fall through the gaps when the healthcare system and patient's differing cultural contexts collide. In conclusion, greater involvement of psychosocial care specialists with cultural expertise is essential to promote patients' and families' well-being, prevent care disparities, and better support the healthcare team. Systemic changes that increase workforce diversity, reduce language and insurance barriers, and allow healthcare professionals to build relational trust with patients, are needed to improve quality of life for CKV patients with metastatic cancer.

Supportive Care Needs in Chinese, Vietnamese, and Korean Americans With Metastatic Cancer: Mixed Methods Protocol for the DAWN Study.

BACKGROUND: Asian Americans with metastatic cancer are an understudied population. The Describing Asian American Well-Being and Needs in Cancer (DAWN) Study was designed to understand the supportive care needs of Chinese-, Vietnamese-, and Korean-descent (CVK) patients with metastatic cancer. OBJECTIVE: This study aims to present the DAWN Study protocol involving a primarily qualitative, convergent, mixed methods study from multiple perspectives (patients or survivors, caregivers, and health care professionals). METHODS: CVK Americans diagnosed with solid-tumor metastatic cancer and their caregivers were recruited nationwide through various means (registries, community outreach newsletters, newspapers, radio advertisements, etc). Potentially eligible individuals were screened and consented on the web or through a phone interview. The study survey and interview for patients or survivors and caregivers were provided in English, traditional/simplified Chinese and Cantonese/Mandarin, Vietnamese, and Korean, and examined factors related to facing metastatic cancer, including quality of life, cultural values, coping, and cancer-related symptoms. Community-based organizations assisted in recruiting participants, developing and translating study materials, and connecting the team to individuals for conducting interviews in Asian languages. Health care professionals who have experience working with CVK patients or survivors with metastatic solid cancer were recruited through referrals from the DAWN Study community advisory board and were interviewed to understand unmet supportive care needs. RESULTS: Recruitment began in November 2020; data collection was completed in October 2022. A total of 66 patients or survivors, 13 caregivers, and 15 health care professionals completed all portions of the study. We completed data management in December 2023 and will submit results for patients or survivors and caregivers to publication outlets in 2024. CONCLUSIONS: Future findings related to this protocol will describe and understand the supportive care needs of CVK patients or survivors with metastatic cancer and will help develop culturally appropriate psychosocial interventions that target known predictors of unmet supportive care needs in Chinese, Vietnamese, and Korean Americans with metastatic cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50032.

Cellular dynamics in pig-to-human kidney xenotransplantation.

BACKGROUND: Xenotransplantation of genetically engineered porcine organs has the potential to address the challenge of organ donor shortage. Two cases of porcine-to-human kidney xenotransplantation were performed, yet the physiological effects on the xenografts and the recipients' immune responses remain largely uncharacterized. METHODS: We performed single-cell RNA sequencing (scRNA-seq) and longitudinal RNA-seq analyses of the porcine kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal scRNA-seq of the peripheral blood mononuclear cells (PBMCs) to detect recipient immune responses across time. FINDINGS: Although no hyperacute rejection signals were detected, scRNA-seq analyses of the xenografts found evidence of endothelial cell and immune response activation, indicating early signs of antibody-mediated rejection. Tracing the cells' species origin, we found human immune cell infiltration in both xenografts. Human transcripts in the longitudinal bulk RNA-seq revealed that human immune cell infiltration and the activation of interferon-gamma-induced chemokine expression occurred by 12 and 48 h post-xenotransplantation, respectively. Concordantly, longitudinal scRNA-seq of PBMCs also revealed two phases of the recipients' immune responses at 12 and 48-53 h. Lastly, we observed global expression signatures of xenotransplantation-associated kidney tissue damage in the xenografts. Surprisingly, we detected a rapid increase of proliferative cells in both xenografts, indicating the activation of the porcine tissue repair program. CONCLUSIONS: Longitudinal and single-cell transcriptomic analyses of porcine kidneys and the recipient's PBMCs revealed time-resolved cellular dynamics of xenograft-recipient interactions during xenotransplantation. These cues can be leveraged for designing gene edits and immunosuppression regimens to optimize xenotransplantation outcomes. FUNDING: This work was supported by NIH RM1HG009491 and DP5OD033430.