Analysis of Rejection, Infection and Surgical Outcomes in Type I Versus Type II Diabetic Recipients After Simultaneous Pancreas-Kidney Transplantation.

Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.

Optical orbital angular momentum analogy to the Stern-Gerlach experiment.

Symmetry breaking has been shown to reveal interesting phenomena in physical systems. A notable example is the fundamental work of Otto Stern and Walther Gerlach [Stern and Zerlach, Z. Physik9, 349 (1922)10.1007/BF01326983] nearly 100 years ago demonstrating a spin angular momentum (SAM) deflection that differed from classical theory. Here we use non-separable states of SAM and orbital angular momentum (OAM), known as vector vortex modes, to demonstrate how a classical optics analogy can be used to reveal this non-separability, reminiscent of the work carried out by Stern and Gerlach. We show that by implementing a polarization insensitive device to measure the OAM, the SAM states can be deflected to spatially resolved positions.

Interplay of Donor-Recipient Relationship and Donor Race in Living Liver Donation in the United States.

INTRODUCTION: Living liver donation improves survival of end-stage liver disease (ESLD) patients. Yet, it continues to represent a small proportion of United States (U.S.) liver transplantation with existing racial disparities. We investigated the interplay of donor-recipient relationship and donor race to understand donor subgroups with no significant increase. METHODS: We studied 4407 living liver donors in the U.S. from January 1, 2012, to December 31, 2022 (median age = 36 years, and 59% were biologically related to the recipient). We quantified the change in the number of donors per 3-year increment using negative binomial regression (incidence rate ratio [IRR]), stratified by donor-recipient relationship and race/ethnicity. RESULTS: Among biologically related donors, the observed annual number of White donors increased from 146 to 253, Hispanic donors from 18 to 53, and Black donors decreased from 11 to 10. Among unrelated donors, White donors increased from 65 to 221, Hispanic donors from 4 to 25, and Black donors from 3 to 11. For the IRR of biologically related donors aged <40 and ≥40 years, White donors increased by 18% and 22%; Hispanic donors increased by 25% and 54%; and Black donors did not change. Likewise, the IRR of unrelated donors aged <40 and ≥40 years, White donors increased by 48% and 55%; Hispanic donors increased by 52% and 65%; and Black donors did not change. CONCLUSIONS: While biologically related donors represent the majority of donors, unrelated donors have substantially risen in recent years, primarily driven by White donors. Although the rate of unrelated donations increased among Hispanic donors, the absolute number remains very small (≤25 donors/year). Interventions are needed to increase education among Hispanic and Black communities to grow unrelated living liver donations across race/ethnicity.

A new sponge from the Marjum Formation of Utah documents the Cambrian origin of the hexactinellid body plan.

Modern poriferans are classified into four classes-Calcarea, Demospongiae, Hexactinellida and Homoscleromorpha-the recognition of which in fossil specimens almost exclusively relies on spicule morphology and arrangement. Early fossil representatives of the phylum Porifera are morphologically diverse, and many of them problematically display characteristics that are incompatible with the classification scheme developed for modern taxa. Critically, hexactine spicules-a diagnostic feature of hexactinellids among modern taxa-are found in various Cambrian and Ordovician taxa that cannot be accommodated within the hexactinellid body plan. Here we describe a new poriferan from the Drumian Marjum Formation of Utah, Polygoniella turrelli gen. et sp. nov., which exhibits a unique combination of complex anatomical features for a Cambrian form, including a syconoid-like organization, a thick body wall, and a multi-layered hexactin-based skeleton. The hexactinellid-like body wall architecture of this new species supports a Cambrian origin of the hexactinellid body plan and provides valuable insights into character evolution in early glass sponges.

Localized cystic disease of the kidney: study of 14 cases and review of the literature.

Localized cystic disease of the kidney (LCDK) is rare without hereditary background and does not progress. It can mimic neoplastic process, leading to unnecessary surgical intervention. We present 14 patients [male-to-female 9:5; mean age 50.3 years (range: 3-79)] with LCDK in a multinational cohort. Flank pain (n=5) and incidental lesions (n=4) were common. All cases were unilateral (9 right, 5 left), and contralateral kidneys were mostly normal (n=11). No family history was present, and none had extrarenal solid organ cysts. Radical and partial nephrectomies were performed in 9 and 5 cases, respectively. All lesions were multilocular, ranging from 1.8 - 20cm. 2 cases had diffuse renal involvement. Cystic septa contained nonneoplastic elements including renal tubules and glomeruli without primitive epithelial cellular elements, blastema, or immature stromal cells. In addition, we also comprehensively reviewed 75 previously reported cases. Conclusions. LCDK should be considered in the differential of cystic kidney lesions.

PET Imaging Using 89Zr Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention (EPR) in Prostate Cancer.

The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors, and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET-imaging surrogate may benefit EPR-mediated therapeutic drug delivery. We developed two 89Zr-radiolabeled nanocarriers based on 4-armed-starPEG40kDa with or without talazoparib (TLZ), a potent PARPi, as surrogates for the PEG-TLZ4 therapeutic scaffold. For PET imaging, PEG-DFB4 and PEG-DFB1-TLZ3 were radiolabeled with 89Zr by replacing one or all four TLZ on PEG-TLZ4 with deferoxamine B (DFB). The radiolabeled nanodrugs [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 were tested in vivo in prostate cancer subcutaneous xenografts (22Rv1, LTL-545, and LTL-610) and 22Rv1 metastatic models. Their EPR-mediated tumoral uptake and penetration was compared to CT26, a known EPR-high MicroPET/CT images, organ biodistribution, and calculated kinetic parameters showed high uptake in CT26 and LTL-545, moderate to low uptake in LTL-610 and 22Rv1. MicroPET/CT and high-resolution autoradiographic images showed nanocarrier penetration into highly permeable CT26, but heterogeneous peripheral accumulation was observed in LTL-545, LTL-610, and 22Rv1 subcutaneous xenografts and metastatic tumors. CD31 staining of tumor sections showed homogenous vascular development in CT26 tumors and heterogeneity in other xenografts. Both [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 showed similar accumulation and distribution in subcutaneous and metastatic tumor models. Both nanocarriers can measure tumor model passive uptake heterogeneity. Although heterogeneous, prostate cancer xenografts had low EPR. These starPEG nanocarriers could be used as PET imaging surrogates to predict drug delivery and efficacy.

Humoral Immunity and Antibody Responses against Diphtheria, Tetanus, and Pneumococcus after Immune Effector Cell Therapies: A Prospective Study.

Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients' response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanus, and pneumococcus were measured before IECT, at 1 month, and 3-6 months after. Eligible patients were vaccinated after IECT. In non-seroprotected patients, we discontinued testing. Before IECT, most patients had seroprotective antibody levels against tetanus (68/69, 99%) and diphtheria (65/69, 94%), but fewer did against pneumococcus (24/67, 36%). After IECT, all patients had seroprotective antibody levels for tetanus at 1 month (68/68) and 3-6 months (56/56). For diphtheria, 65/65 patients (100%) had seroprotective antibody levels at 1 month, and 48/53 (91%) did at 3-6 months. For pneumococcus, seroprotective antibody levels were identified in 91% (21/23) of patients at 1 month and 79% (15/19) at 3-6 months following IECT. Fifteen patients received a pneumococcal vaccine after IECT, but none achieved seroprotective response. One patient received the tetanus-diphtheria vaccine and had a seroprotective antibody response. Because some patients experience loss of immunity after IECT, studies evaluating vaccination strategies post-IECT are needed.

MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a p53-R270H Mouse Model.

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment are understood. MYC, an oncogene, is amongst the most amplified genes in high-grade serous ovarian cancer (HGSOC), but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant-negative mutant p53-R270H with a fallopian tube epithelium (FTE)-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 14.5 months. Histopathologic examination of mice revealed HGSOC characteristics, including nuclear p53 and nuclear MYC in clusters of cells within the FTE and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the FTE. Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy-number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate that the Myc and Trp53-R270H transgenes were able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology-directed repair mutations. Histologic and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the FTE. SIGNIFICANCE: Mouse models using transgenes which generate spontaneous cancers are essential tools to examine the etiology of human diseases. Here, the first Myc-driven spontaneous model is described as a valid HGSOC model. Surprisingly, aspects of uterine serous carcinoma were also observed in this model.

Solvent Minimized Synthesis of Amides by Reactive Extrusion.

Herein, we report on the translation of a small scale ball-milled amidation protocol into a large scale continuous reactive extrusion process. Critical components to the successful translation were: a) understanding how the different operating parameters of a twin-screw extruder should be harnessed to control prolonged continuous operation, and b) consideration of the physical form of the input materials. The amidation reaction is applied to 36 amides spanning a variety of physical form combinations (liquid-liquid, solid-liquid and solid-solid). Following this learning process, we have developed an understanding for the translation of each physical form combination and demonstrated a 7-hour reactive extrusion process for the synthesis of an amide on 500 gram scale (1.3 mols of product).

Editors' Note: 2024 Annual Report Regarding JAACAP's Antiracist Journey.

In 2020, we wrote to you about our dedication and vision for JAACAP "to be antiracist at every level."1 Over the last 4 years we have pursued initiatives "to reshape the Journal to pursue this vision."2-4 In this article, we provide an update on these goals and initiatives (Figure 1). These initiatives include both scientific journals in the JAACAP family, JAACAP and JAACAP Open. Through this work we aspire to be a leader among mental health journals in our intentional pursuit of antiracist policies and practices.

The W2024 database of the water isotopologue H 2 16 O .

The rovibrational spectrum of the water molecule is the crown jewel of high-resolution molecular spectroscopy. While its significance in numerous scientific and engineering applications and the challenges behind its interpretation have been well known, the extensive experimental analysis performed for this molecule, from the microwave to the ultraviolet, is admirable. To determine empirical energy levels for H 2 16 O , this study utilizes an improved version of the MARVEL (Measured Active Rotational-Vibrational Energy Levels) scheme, which now takes into account multiplet constraints and first-principles energy-level splittings. This analysis delivers 19027 empirical energy values, with individual uncertainties and confidence intervals, utilizing 309 290 transition wavenumbers collected from 189 (mostly experimental) data sources. Relying on these empirical, as well as some computed, energies and first-principles intensities, an extensive composite line list, named CW2024, has been assembled. The CW2024 dataset is compared to lines in the canonical HITRAN 2020 spectroscopic database, providing guidance for future experimental investigations.

The anabolic response to a ground beef patty and soy-based meat alternative: a randomized controlled trial.

BACKGROUND: Soy-based meat alternatives (SBMA) are becoming increasingly popular, but it is unclear if they have the same anabolic effect on skeletal muscle as animal meat. OBJECTIVES: We aimed to compare the stimulation of skeletal muscle protein synthesis by consumption of 1 or two 4 oz patties of SBMA with 4 oz (80% protein/20% fat) beef. METHODS: The study design was a randomized controlled trial. Participants were aged 18-40 y of age and in good general health with a body mass index (kg/m2) between 20 and 32. Stable isotope tracer methods were used (L-[ring-2H5] phenylalanine, [U-13C9-15N]- tyrosine, and L-[ring-2H4] tyrosine) to quantify the response of muscle protein fractional synthetic rate (FSR) to consumption of a single beef (4 oz), single SBMA (4 oz), or two 4 oz SBMA patties (8 oz). Whole-body rates of protein synthesis, breakdown, and net balance, as well as plasma essential amino acid concentrations, were also measured. RESULTS: The increase above basal in muscle protein FSR following consumption of the 4 oz beef patty (0.020 ± 0.016%/h) was significantly greater than the increase following consumption of 4 oz SBMA (P = 0.021; 0.003 ± 0.010%/h) but not 8 oz SBMA (P = 0.454; 0.013 ± 0.016%/h). The maximal essential amino acid concentration was significantly correlated (P = 0.046; r = 0.411) with the change in muscle FSR from the basal to the postprandial period. In addition, the change in muscle FSR from the basal to postprandial period was significantly correlated (P = 0.046; r = 0.412) with the corresponding change in whole-body protein synthesis. CONCLUSIONS: Consumption of a 4 oz beef patty stimulates muscle and whole-body protein synthesis >4 oz SBMA patty and similarly to 8 oz of SBMA. This trial was registered at clinicaltrials.gov as NCT05197140.

Differentiating clinical characteristics of perianal inflammatory bowel disease from perianal hidradenitis suppurativa.

BACKGROUND: Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas. METHODS: We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD. RESULTS: A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife-cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral. CONCLUSIONS: The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome.

Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration.

Injury is common in the life of organisms. Because the extent of damage cannot be predicted, injured organisms must determine how much tissue needs to be restored. Although it is known that amputation position affects the regeneration speed of appendages, mechanisms conveying positional information remain unclear. We investigated tissue dynamics in regenerating caudal fins of the African killifish (Nothobranchius furzeri) and found position-specific, differential spatial distribution modulation, persistence, and magnitude of proliferation. Single-cell RNA sequencing revealed a transient regeneration-activated cell state (TRACS) in the basal epidermis that is amplified to match a given amputation position and expresses components and modifiers of the extracellular matrix (ECM). Notably, CRISPR-Cas9-mediated deletion of the ECM modifier sequestosome 1 (sqstm1) increased the regenerative capacity of distal injuries, suggesting that regeneration growth rate can be uncoupled from amputation position. We propose that basal epidermis TRACS transduce positional information to the regenerating blastema by remodeling the ECM.

Green spaces provide substantial but unequal urban cooling globally.

Climate warming disproportionately impacts countries in the Global South by increasing extreme heat exposure. However, geographic disparities in adaptation capacity are unclear. Here, we assess global inequality in green spaces, which urban residents critically rely on to mitigate outdoor heat stress. We use remote sensing data to quantify daytime cooling by urban greenery in the warm seasons across the ~500 largest cities globally. We show a striking contrast, with Global South cities having ~70% of the cooling capacity of cities in the Global North (2.5 ± 1.0 °C vs. 3.6 ± 1.7 °C). A similar gap occurs for the cooling adaptation benefits received by an average resident in these cities (2.2 ± 0.9 °C vs. 3.4 ± 1.7 °C). This cooling adaptation inequality is due to discrepancies in green space quantity and quality between cities in the Global North and South, shaped by socioeconomic and natural factors. Our analyses further suggest a vast potential for enhancing cooling adaptation while reducing global inequality.

Inflammation-induced epigenetic imprinting regulates intestinal stem cells.

It remains unknown whether and how intestinal stem cells (ISCs) adapt to inflammatory exposure and whether the adaptation leaves scars that will affect their subsequent regeneration. We investigated the consequences of inflammation on Lgr5+ ISCs in well-defined clinically relevant models of acute gastrointestinal graft-versus-host disease (GI GVHD). Utilizing single-cell transcriptomics, as well as organoid, metabolic, epigenomic, and in vivo models, we found that Lgr5+ ISCs undergo metabolic changes that lead to the accumulation of succinate, which reprograms their epigenome. These changes reduced the ability of ISCs to differentiate and regenerate ex vivo in serial organoid cultures and also in vivo following serial transplantation. Furthermore, ISCs demonstrated a reduced capacity for in vivo regeneration despite resolution of the initial inflammatory exposure, demonstrating the persistence of the maladaptive impact induced by the inflammatory encounter. Thus, inflammation imprints the epigenome of ISCs in a manner that persists and affects their sensitivity to adapt to future stress or challenges.

Methane fluxes in tidal marshes of the conterminous United States.

Methane (CH4) is a potent greenhouse gas (GHG) with atmospheric concentrations that have nearly tripled since pre-industrial times. Wetlands account for a large share of global CH4 emissions, yet the magnitude and factors controlling CH4 fluxes in tidal wetlands remain uncertain. We synthesized CH4 flux data from 100 chamber and 9 eddy covariance (EC) sites across tidal marshes in the conterminous United States to assess controlling factors and improve predictions of CH4 emissions. This effort included creating an open-source database of chamber-based GHG fluxes (https://doi.org/10.25573/serc.14227085). Annual fluxes across chamber and EC sites averaged 26 ± 53 g CH4 m-2 year-1, with a median of 3.9 g CH4 m-2 year-1, and only 25% of sites exceeding 18 g CH4 m-2 year-1. The highest fluxes were observed at fresh-oligohaline sites with daily maximum temperature normals (MATmax) above 25.6°C. These were followed by frequently inundated low and mid-fresh-oligohaline marshes with MATmax ≤25.6°C, and mesohaline sites with MATmax >19°C. Quantile regressions of paired chamber CH4 flux and porewater biogeochemistry revealed that the 90th percentile of fluxes fell below 5 ± 3 nmol m-2 s-1 at sulfate concentrations >4.7 ± 0.6 mM, porewater salinity >21 ± 2 psu, or surface water salinity >15 ± 3 psu. Across sites, salinity was the dominant predictor of annual CH4 fluxes, while within sites, temperature, gross primary productivity (GPP), and tidal height controlled variability at diel and seasonal scales. At the diel scale, GPP preceded temperature in importance for predicting CH4 flux changes, while the opposite was observed at the seasonal scale. Water levels influenced the timing and pathway of diel CH4 fluxes, with pulsed releases of stored CH4 at low to rising tide. This study provides data and methods to improve tidal marsh CH4 emission estimates, support blue carbon assessments, and refine national and global GHG inventories.

Parental feeding in the dinosaur Lufengosaurus revealed through multidisciplinary comparisons with altricial and precocious birds.

Previous studies arguing for parental care in dinosaurs have been primarily based on fossil accumulations of adults and hatchlings, perinatal and post-hatchlings in nests and nest areas, and evidence of brooding, the majority of which date to the Late Cretaceous. Similarly, the general body proportions of preserved embryonic skeletons of the much older Early Jurassic Massospondylus have been used to suggest that hatchlings were unable to forage for themselves. Here, we approach the question of parental care in dinosaurs by using a combined morphological, chemical, and biomechanical approach to compare early embryonic and hatchling bones of the Early Jurassic sauropodomorph Lufengosaurus with those of extant avian taxa with known levels of parental care. We compare femora, the main weight-bearing limb bone, at various embryonic and post-embryonic stages in a precocious and an altricial extant avian dinosaur with those of embryonic and hatchling Lufengosaurus, and find that the rate and degree of bone development in Lufengosaurus is closer to that of the highly altricial Columba (pigeon) than the precocious Gallus (chicken), providing strong support for the hypothesis that Lufengosaurus was fully altricial. We suggest that the limb bones of Lufengosaurus hatchlings were not strong enough to forage for themselves and would likely need parental feeding.

Robotic parastomal hernia repair: A single-center cohort study.

Parastomal hernia is a common occurrence following stoma construction, necessitating surgical intervention in symptomatic cases. This study presents a comprehensive analysis of Robotic-Assisted Parastomal Hernia Repair (r-PSHR), utilizing the Da Vinci Xi™ Surgical System. Retrospective analysis was conducted on patients undergoing r-PSHR at a high-volume center. Surgical variables, complications, and recurrence rates were assessed. The primary technique involved a modified Sugarbaker intraperitoneal onlay mesh. Eighty-six patients underwent r-PSHR, predominantly females (59.3%), with mean age 60.8 years. Mean BMI was 31.0. Most patients were classified as ASA 2 (31.4%) or ASA 3 (65.1), with 64.6% having no prior PSH repair. Index procedures primarily involved laparoscopic colonic resections (27.8%) and open abdominoperineal resections (27.8%). Parastomal hernias were mainly associated with end ileostomy (50%) and end colostomy (47.7%). A hybrid modification was required in 22.1% of cases, with only one conversion to open repair. Mean operative time was 257 min. Thirty-day morbidity was 40.7% and includes ileus (24.4%), deep surgical-site infections (7.0%), acute kidney injury (5.8%), and sepsis (5.8%). Grade IIIB complications occurred in 5.8% of cases. Thirty-day readmissions were observed in 19.8% of cases. There were five cases (5.8%) of recurrence within 15 months post-surgery. This study highlights the effectiveness of r-PSHR in managing parastomal hernia. R-PSHR shows promising outcomes with an acceptable post-operative occurrence profile and a favorable recurrence rate.