Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma.

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16 mg/ml) and sonication time (5, 10, 15 min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5 mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6 months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.

Relationship between Timed Up and Go performance and quantitative biomechanical measures of balance.

Traumatic brain injury (TBI) impairs sensory-motor functions, with debilitating consequences on postural control and balance, which persist during the chronic stages of recovery. The Timed Up and Go (TUG) test is a reliable, safe, time-efficient, and one of the most widely used clinical measures to assess gait, balance, and fall risk in TBI patients and is extensively used in inpatient and outpatient settings. Although the TUG test has been used extensively due to its ease of performance and excellent reliability, limited research has been published that investigates the relationship between TUG performance and quantitative biomechanical measures of balance. The objective of this paper was to quantify the relationship between biomechanical variables of balance and the TUG scores in individuals with chronic TBI. Regression models were constructed using six biomechanical variables to predict TUG scores. The model that conservatively removed gait speed (i.e., TUG-1/GS) gave the best results, achieving a root-mean-square error of ∼±2 s and explaining over 69% of the variability.

Correlation Between Serum and Fecal Biomarkers and Patient-Reported Outcomes in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). AIM: The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. METHODS: We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. RESULTS: 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6 years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. CONCLUSION: PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.

An aggressive interaction rapidly increases brain androgens in a male songbird during the non-breeding season.

Aggression is a crucial behavior that impacts access to limited resources in different environmental contexts. Androgens synthesized by the gonads promote aggression during the breeding season. However, aggression can be expressed during the non-breeding season, despite low androgen synthesis by the gonads. The brain can also synthesize steroids ('neurosteroids'), including androgens, which might promote aggression during the non-breeding season. Male song sparrows, Melospiza melodia, are territorial year-round and allow the study of seasonal changes in the steroid modulation of aggression. Here, we quantified steroids following a simulated territorial intrusion (STI) for 10 min in wild adult male song sparrows during the breeding and non-breeding seasons. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined 11 steroids: pregnenolone, progesterone, corticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17ß-estradiol, 17α-estradiol, estriol, and estrone. Steroids were measured in blood and 10 microdissected brain regions that regulate social behavior. In both seasons, STI increased corticosterone in the blood and brain. In the breeding season, STI had no rapid effects on androgens or estrogens. Intriguingly, in the non-breeding season, STI increased testosterone and androstenedione in several behaviorally-relevant regions, but not in the blood, where androgens remained non-detectable. Also in the non-breeding season, STI increased progesterone in the blood and specific brain regions. Overall, rapid socially modulated changes in brain steroid levels are more prominent during the non-breeding season. Brain steroid levels vary with season and social context in a region-specific manner and suggest a role for neuroandrogens in aggression during the non-breeding season.Significance Statement Steroids are important modulators of the brain and behavior. Steroids are secreted by glands into the bloodstream to exert their actions on target tissues. In addition, the brain itself can locally produce steroids ('neurosteroids'). We examined circulating and neural steroids across seasons and in response to an aggressive interaction in wild male song sparrows. Local androgen levels in the brain rapidly increase in response to an aggressive interaction in the non-breeding season, but not in the breeding season, indicating that neurosteroid production is dependent on the season and social context.

Comparing the Efficacy of Different Maintenance Intervals on Preventing Disease Recurrence in Patients with A History of Periodontal Treatment.

Background: Scheduled maintenance appointments after periodontal treatment are very much critical for the success of the treatment. This is necessary for patients seeking to prevent disease recurrence and maintain oral health. Materials and Methods: In this study, we conducted a comprehensive analysis to assess the efficacy of various maintenance intervals in preventing disease recurrence among patients with a history of periodontal treatment. We gathered data from a diverse group of patients who had undergone periodontal treatment and tracked their oral health over an extended period. Results: Our findings reveal compelling insights into the optimal maintenance intervals. Patients who attended maintenance appointments at three-month intervals showed a significant reduction in disease recurrence by 40%, compared to those at six-month intervals. Moreover, those on annual intervals experienced a disease recurrence rate of 60. Conclusion: In conclusion, our study underscores the importance of regular maintenance appointments after periodontal treatment. Patients who attend appointments every three months have a significantly lower risk of disease recurrence. These findings emphasize the need for tailored maintenance schedules to ensure long-term oral health.

Comparing the Clinical and Radiographic Outcomes of Two Different Surgical Approaches for Treating Infrabony Defects in Chronic Periodontitis Patients.

Background: Chronic periodontitis is a prevalent oral health issue, affecting a substantial portion of the population. Infrabony defects, characterized by bone loss around teeth, are a hallmark of this condition and require surgical intervention to prevent further damage and tooth loss. Two commonly used surgical approaches are open flap debridement (OFD) and guided tissue regeneration (GTR). Materials and Methods: This prospective cohort study included 60 patients with chronic periodontitis and infrabony defects. Patients were randomly assigned to either the OFD or GTR group. Clinical parameters, including probing depth (PD) and clinical attachment level (CAL), were recorded at baseline and at 6-month and 12-month follow-up appointments. Radiographic assessments were conducted using periapical radiographs. The primary outcome measures were changes in PD and CAL, while secondary outcomes included radiographic evidence of bone regeneration. Results: At the 6-month follow-up, the OFD group demonstrated an average reduction in PD of 2.4 mm (SD = 0.8) and an increase in CAL of 1.6 mm (SD = 0.5). In contrast, the GTR group showed a reduction in PD of 2.1 mm (SD = 0.7) and an increase in CAL of 1.9 mm (SD = 0.6). These differences were not statistically significant (P > 0.05). Radiographic analysis indicated a mean bone fill of 1.2 mm (SD = 0.4) in the OFD group and 1.4 mm (SD = 0.3) in the GTR group at 12 months, with no significant difference observed between the two groups (P > 0.05). Conclusion: In this study, both OFD and GTR approaches demonstrated comparable clinical and radiographic outcomes in the treatment of infrabony defects in chronic periodontitis patients.

Novel Surface Topographic Assessment of Lung Volume and Pulmonary Function Tests in Idiopathic Scoliosis: A Preliminary Study.

OBJECTIVE: Severe spinal deformity results in restrictive pulmonary disease from thoracic distortions and lung-volume limitations. Though spirometry and body plethysmography are widely accepted tests for pulmonary function tests (PFTs), they are time-consuming and require patient compliance. This study investigates whether surface topographic [surface topography (ST)] measurements of body volume difference (BVD) and torso volume difference between maximum inhale and exhale correlate to values determined on PFTs. METHODS: This study included patients with idiopathic scoliosis and thoracic/thoracolumbar curves ≥40 degrees. Patients received ST scans, clinical examinations, and EOS biplanar radiographs on the same day. PFTs were performed within 3 months of ST/radiographic analysis. Univariate linear regression analysis was used to examine relationships between BVD, PFT values, and mean curves. RESULTS: Sixteen patients (14.6 ± 2.2 y, 69% females) with idiopathic scoliosis and mean thoracic/thoracolumbar curves of 62 degrees ± 15˚ degrees (45 degrees to 93 degrees) were assessed. BVD displayed statistically high-positive positive correlations with forced vital capacity (R= 0.863, P< 0.0001), forced expiratory volume in 1 second (R= 0.870, P< 0.001), vital capacity (R= 0.802, P< 0.0001), and TLC (R= 0.831, P< 0.0001. Torso volume difference showed similarly high positive correlations to forced vital capacity, forced expiratory volume in 1 second, vital capacity, and TLC, but not residual volume. No correlations emerged between the mean thoracic/thoracolumbar curve and BVD or PFT values. CONCLUSION: This study strongly endorses further investigation into ST scanning as an alternative to traditional PFTs for assessing pulmonary volumes. The noncontact and noninvasive nature of ST scanning presents a valuable alternative method for analyzing thoracic volume, particularly beneficial for patients unable to cooperate with standard PFTs. LEVEL OF EVIDENCE: Level II-prognostic.

Advancing the Scientific Basis for Determining Death in Controlled Organ Donation After Circulatory Determination of Death.

In controlled organ donation after circulatory determination of death (cDCDD), accurate and timely death determination is critical, yet knowledge gaps persist. Further research to improve the science of defining and determining death by circulatory criteria is therefore warranted. In a workshop sponsored by the National Heart, Lung, and Blood Institute, experts identified research opportunities pertaining to scientific, conceptual, and ethical understandings of DCDD and associated technologies. This article identifies a research strategy to inform the biomedical definition of death, the criteria for its determination, and circulatory death determination in cDCDD. Highlighting knowledge gaps, we propose that further research is needed to inform the observation period following cessation of circulation in pediatric and neonatal populations, the temporal relationship between the cessation of brain and circulatory function after the withdrawal of life-sustaining measures in all patient populations, and the minimal pulse pressures that sustain brain blood flow, perfusion, activity, and function. Additionally, accurate predictive tools to estimate time to asystole following the withdrawal of treatment and alternative monitoring modalities to establish the cessation of circulatory, brainstem, and brain function are needed. The physiologic and conceptual implications of postmortem interventions that resume circulation in cDCDD donors likewise demand attention to inform organ recovery practices. Finally, because jurisdictionally variable definitions of death and the criteria for its determination may impede collaborative research efforts, further work is required to achieve consensus on the physiologic and conceptual rationale for defining and determining death after circulatory arrest.

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme.

Over the past two decades, the gold standard of glioblastoma multiforme (GBM) treatment is unchanged and adjunctive therapy has offered little to prolong both quality and quantity of life. To improve pharmacotherapy for GBM, galectins are being studied provided their positive correlation with the malignancy and disease severity. Despite the use of galectin inhibitors and literature displaying the ability of the lectin proteins to decrease tumor burden and decrease mortality within various malignancies, galectin inhibitors have not been studied for GBM therapy. Interestingly, anti-galectin siRNA delivered in nanoparticle capsules, assisting in blood brain barrier penetrance, is well studied for GBM, and has demonstrated a remarkable ability to attenuate both galectin and tumor count. Provided that the two therapies have an analogous anti-galectin effect, it is hypothesized that galectin inhibitors encapsuled within nanoparticles will likely have a similar anti-galectin effect in GBM cells and further correlate to a repressed tumor burden.

The electrostatic landscape of MHC-peptide binding revealed using inception networks.

Predictive modeling of macromolecular recognition and protein-protein complementarity represents one of the cornerstones of biophysical sciences. However, such models are often hindered by the combinatorial complexity of interactions at the molecular interfaces. Exemplary of this problem is peptide presentation by the highly polymorphic major histocompatibility complex class I (MHC-I) molecule, a principal component of immune recognition. We developed human leukocyte antigen (HLA)-Inception, a deep biophysical convolutional neural network, which integrates molecular electrostatics to capture non-bonded interactions for predicting peptide binding motifs across 5,821 MHC-I alleles. These predictions of generated motifs correlate strongly with experimental peptide binding and presentation data. Beyond molecular interactions, the study demonstrates the application of predicted motifs in analyzing MHC-I allele associations with HIV disease progression and patient response to immune checkpoint inhibitors. A record of this paper's transparent peer review process is included in the supplemental information.

Implementation of a high-resolution, high-contrast magnetic resonance imaging protocol with extended delayed phases for peritoneal mesothelioma.

Background: Imaging of peritoneal malignancies using conventional cross-sectional imaging is challenging, but accurate assessment of peritoneal disease burden could guide better selection for definitive surgery. Here we demonstrate feasibility of high-resolution, high-contrast magnetic resonance imaging (MRI) of peritoneal mesothelioma and explore optimal timing for delayed post-contrast imaging. Methods: Prospective data from inpatients with malignant peritoneal mesothelioma (MPM), imaged with a novel MRI protocol, were analyzed. The new sequences augmenting the clinical protocol were (I) pre-contrast coronal high-resolution T2-weighted single-shot fast spin echo (COR hr T2w SSH FSE) of abdomen and pelvis; and (II) post-contrast coronal high-resolution three-dimensional (3D) T1-weighted modified Dixon (COR hr T1w mDIXON) of abdomen, acquired at five delay times, up to 20 min after administration of a double dose of contrast agent. Quantitative analysis of contrast enhancement was performed using linear regression applied to normalized signal in lesion regions of interest (ROIs). Qualitative analysis was performed by three blinded radiologists. Results: MRI exams from 14 participants (age: mean ± standard deviation, 60±12 years; 71% male) were analyzed. The rate of lesion contrast enhancement was strongly correlated with tumor grade (cumulative nuclear score) (r=-0.65, P<0.02), with 'early' delayed phase (12 min post-contrast) and 'late' delayed phase (19 min post-contrast) performing better for higher grade and lower grade tumors, respectively, in agreement with qualitative scoring of image contrast. Conclusions: High-resolution, high-contrast MRI with extended post-contrast imaging is a viable modality for imaging peritoneal mesothelioma. Multiple, extended (up to 20 min post-contrast) delayed phases are necessary for optimal imaging of peritoneal mesothelioma, depending on the grade of disease.

Implementation of the Targeted Axillary Dissection Procedure in Clinically Node-Positive Breast Cancer: A Retrospective Analysis.

BACKGROUND: The targeted axillary dissection (TAD) procedure is used in clinically positive lymph node (cN+) breast cancer to assess whether pathological complete response (pCR) is achieved after neoadjuvant systemic therapy (NST) to decide on de-escalation of axillary lymph node dissection (ALND). In this study, we review the implementation of the TAD procedure in a large regional breast cancer center. METHODS: All TAD procedures between 2016 and 2022 were reviewed. The TAD procedure consists of marking pre-NST the largest suspected metastatic lymph node(s) using a radioactive I-125 seed. During surgery, the marked node was excised together with a sentinel node procedure. Axillary therapy (ALND, axillary radiotherapy, or nothing) recommendations were based on the amount of suspected positive axillary lymph nodes (ALNs < 4 or ≥ 4) pre-NST and if pCR was achieved after NST. RESULTS: A total of 312 TAD procedures were successfully performed in 309 patients. In 134 (43%) cases, pCR of the TAD lymph nodes were achieved. Per treatment protocol, 43 cases (14%) did not receive any axillary treatment, 218 cases (70%) received adjuvant axillary radiotherapy, and 51 cases (16%) underwent an ALND. During a median follow-up of 2.8 years, 46 patients (14%) developed recurrence, of which 11 patients (3.5%) had axillary recurrence. CONCLUSIONS: Introduction of the TAD procedure has resulted in a reduction of 84% of previously indicated ALNDs. Moreover, 18% of cases did not receive adjuvant axillary radiotherapy. These data show that implementation of de-escalation axillary treatment with the TAD procedure appeared to be successful.

COVID-19-related work absenteeism and associated lost productivity cost in Germany: a population-based study.

OBJECTIVE: To estimate COVID-19 absenteeism and indirect costs, by care setting. METHODS: A population-based retrospective cohort study using data from the German Statutory Health Insurance (SHI) database to define outpatient (April 2020-December 2021) and hospitalized (April 2020-October 2022) cohorts of employed working-aged individuals. RESULTS: In the outpatient cohort (n = 369,220) median absenteeism duration and associated cost was 10.0 (IQR: 5.0, 15.0) days and €1,061 (530, 1,591), respectively. In the hospitalized cohort (n = 20,687), median absenteeism and associated cost was 15.0 (7.0, 32.0) days and €1,591 (743, 3,394), respectively. Stratified analyses showed greater absenteeism in older workers, those at risk and those with severe disease. CONCLUSIONS: The hospitalized cohort had longer absenteeism resulting in higher productivity loss. Being older, at risk of severe COVID-19 and higher disease severity during hospitalization were important drivers of higher absenteeism duration.

Sex-specific patterns of donor-derived cell-free DNA in heart transplant rejection: An analysis from the Genomic Research Alliance for Transplantation (GRAfT).

BACKGROUND: Noninvasive methods for surveillance of acute rejection are increasingly used in heart transplantation (HT), including donor-derived cell-free DNA (dd-cfDNA). As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in the performance of dd-cfDNA for the detection of acute rejection. The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in male and female transplant recipients. METHODS: Patients enrolled in the Genomic Research Alliance for Transplantation who were ≥18 years at the time of HT were included. Rejection was defined by endomyocardial biopsy with acute cellular rejection (ACR) grade ≥2R and/or antibody-mediated rejection ≥ pAMR 1. dd-cfDNA was quantitated using shotgun sequencing. Median dd-cfDNA levels were compared between sexes during quiescence and rejection. The performance of dd-cfDNA by sex was assessed using area under the receiver operator characteristic (AUROC) curve. Allograft injury was defined as dd-cfDNA ≥0.25%. RESULTS: One hundred fifty-one unique patients (49 female, 32%) were included in the analysis with 1,119 available dd-cfDNA measurements. Baseline characteristics including demographics and comorbidities were not significantly different between sexes. During quiescence, there were no significant sex differences in median dd-cfDNA level (0.04% [IQR 0.00, 0.16] in females vs 0.03% [IQR 0.00, 0.12] in males, p = 0.22). There were no significant sex differences in median dd-cfDNA for ACR (0.33% [0.21, 0.36] in females vs 0.32% [0.21, 1.10] in males, p = 0.57). Overall, median dd-cfDNA levels were higher in antibody-mediated rejection (AMR) than ACR but did not significantly differ by sex (0.50% [IQR 0.18, 0.82] in females vs 0.63% [IQR 0.32, 1.95] in males, p = 0.51). Elevated dd-cfDNA detected ACR/AMR with an AUROC of 0.83 in females and 0.89 in males, p-value for comparison = 0.16. CONCLUSIONS: There were no significant sex differences in dd-cfDNA levels during quiescence and rejection. Performance characteristics were similar, suggesting similar diagnostic thresholds can be used in men and women for rejection surveillance.

A Protocol for Evaluating Digital Technology for Monitoring Sleep and Circadian Rhythms in Older People and People Living with Dementia in the Community.

Sleep and circadian rhythm disturbance are predictors of poor physical and mental health, including dementia. Long-term digital technology-enabled monitoring of sleep and circadian rhythms in the community has great potential for early diagnosis, monitoring of disease progression, and assessing the effectiveness of interventions. Before novel digital technology-based monitoring can be implemented at scale, its performance and acceptability need to be evaluated and compared to gold-standard methodology in relevant populations. Here, we describe our protocol for the evaluation of novel sleep and circadian technology which we have applied in cognitively intact older adults and are currently using in people living with dementia (PLWD). In this protocol, we test a range of technologies simultaneously at home (7-14 days) and subsequently in a clinical research facility in which gold standard methodology for assessing sleep and circadian physiology is implemented. We emphasize the importance of assessing both nocturnal and diurnal sleep (naps), valid markers of circadian physiology, and that evaluation of technology is best achieved in protocols in which sleep is mildly disturbed and in populations that are relevant to the intended use-case. We provide details on the design, implementation, challenges, and advantages of this protocol, along with examples of datasets.

Knowledge gaps in heart and lung donation after the circulatory determination of death: Report of a workshop of the National Heart, Lung, and Blood Institute.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.

Directing the migration of serum-free, ex vivo-expanded Vγ9Vδ2 T cells.

Vγ9Vδ2 T cells represent a promising cancer therapy platform because the implementation of allogenic, off-the-shelf product candidates is possible. However, intravenous administration of human Vγ9Vδ2 T cells manufactured under good manufacturing practice (GMP)-compliant, serum-free conditions are not tested easily in most mouse models, mainly because they lack the ability to migrate from the blood to tissues or tumors. We demonstrate that these T cells do not migrate from the circulation to the mouse bone marrow (BM), the site of many malignancies. Thus, there is a need to better characterize human γδ T-cell migration in vivo and develop strategies to direct these cells to in vivo sites of therapeutic interest. To better understand the migration of these cells and possibly influence their migration, NSG mice were conditioned with agents to clear BM cellular compartments, i.e., busulfan or total body irradiation (TBI), or promote T-cell migration to inflamed BM, i.e., incomplete Freund's adjuvant (IFA), prior to administering γδ T cells. Conditioning with TBI, unlike busulfan or IFA, increases the percentage and number of γδ T cells accumulating in the mouse BM, and cells in the peripheral blood (PB) and BM display identical surface protein profiles. To better understand the mechanism by which cells migrate to the BM, mice were conditioned with TBI and administered γδ T cells or tracker-stained red blood cells. The mechanism by which γδ T cells enter the BM after radiation is passive migration from the circulation, not homing. We tested if these ex vivo-expanded cells can migrate based on chemokine expression patterns and showed that it is possible to initiate homing by utilizing highly expressed chemokine receptors on the expanded γδ T cells. γδ T cells highly express CCR2, which provides chemokine attraction to C-C motif chemokine ligand 2 (CCL2)-expressing cells. IFNγ-primed mesenchymal stromal cells (MSCs) (γMSCs) express CCL2, and we developed in vitro and in vivo models to test γδ T-cell homing to CCL2-expressing cells. Using an established neuroblastoma NSG mouse model, we show that intratumorally-injected γMSCs increase the homing of γδ T cells to this tumor. These studies provide insight into the migration of serum-free, ex vivo-expanded Vγ9Vδ2 T cells in NSG mice, which is critical to understanding the fundamental properties of these cells.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.