Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation.

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

Myeloid p38 activation maintains macrophage-liver crosstalk and BAT thermogenesis through IL-12-FGF21 axis.

Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low-grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway activity in macrophages, suggesting p38 inhibition as a possible treatment for obesity comorbidities. Nevertheless, we report here that lack of p38 activation in myeloid cells worsens high-fat diet-induced obesity, diabetes, and steatosis. Deficient p38 activation increases macrophage IL-12 production, leading to inhibition of hepatic FGF21 and reduction of thermogenesis in the brown fat. The implication of FGF21 in the phenotype was confirmed by its specific deletion in hepatocytes. We also found that IL-12 correlates with liver damage in human biopsies, indicating the translational potential of our results. Our findings suggest that myeloid p38 has a dual role in inflammation and that drugs targeting IL-12 might improve the homeostatic regulation of energy balance in response to metabolic stress.

Optical thickness measurement of occluded samples by lens-less Fourier transform digital holography, thermal loading, and machine learning.

Thickness measurements of objects, especially transparent and semi-transparent objects, are essential for their characterization and identification. However, in the case of occluded objects, the optical thickness determination becomes difficult, and an indirect way must be devised. Thermal loading of the objects changes their opto-thermal properties, which will be reflected as a change in their optical thickness. The key to quantifying such occluded objects lies in collecting these opto-thermal signatures. This could be achieved by imaging the changes occurring to a probe wavefront passing through the object while it is being thermally loaded. Digital holographic interferometry is an ideal tool for observing phase changes, as it can be used to compare wavefronts recorded at different instances of time. Lens-less Fourier transform digital holographic imaging provides the phase information from a single Fourier transform of the recorded hologram and can be used to quantify occluded phase objects. Here we describe a technique for the measurement of change in optical thickness of thermally loaded occluded phase samples using lens-less Fourier transform digital holography and machine learning. The advantage of the proposed technique is that it is a single shot, lens-less imaging modality for quasi-real-time quantification of phase samples behind thin occlusions.

Improved biodistribution and enhanced immune response of subunit vaccine using a nanostructure formed by self-assembly of ascorbyl palmitate.

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response.

Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents.

This study presents the synthesis of four series of novel hybrid chalcones (20,21)a-g and (23,24)a-g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28-33)a-g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d-g, 24a-g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e-g, 33a,b,e-g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 µM and LC50 values in the range of 4.09 µM to >100 µM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25-62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 µg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.

TLR9 activation is required for cytotoxic response elicited by baculovirus capsid display.

Although the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, represents an efficient vector for vaccine development. Baculovirus surface display induces strong humoral responses against viruses and parasites. A novel strategy based on capsid display carrying foreign antigens in the AcMNPV particle further improved the immune response by eliciting CD8+ T cell activation. In this study, we analyze the intracellular mechanisms and signalling pathways involved in CD8+ T cell activation by capsid display. Our results show that baculovirus can attach to the cell surface, enter dendritic cells (DCs), transit within endocytic vesicles and escape to the cytosol for further degradation by the proteasome. We found that the availability of viral proteins, endosomal acidification, and proteasome activity are needed for efficient Major Histocompatibility Complex class-I presentation by baculovirus carrying Ovalbumin in the viral capsid. Importantly, we demonstrated with this strategy that the induction of cytotoxic T cells and IL-12 production by DCs are TLR9-dependent and STING-independent. Finally, our study shows differential intracellular processing for capsid and surface baculovirus proteins in DCs and highlights the role of different danger receptors during cytotoxic T cell priming through the capsid display delivery system, which could lead to improved baculovirus-based vaccines development.

Infectious complications associated with bronchial anastomotic dehiscence in lung transplant recipients.

INTRODUCTION: Bronchial anastomotic dehiscence (AD) is an uncommon complication following lung transplantation that carries significant morbidity and mortality. The objective of this study was to characterize fungal and bacterial infections in ADs, including whether infections following AD were associated with progression to bronchial stenosis. METHODS: This was a single-center study of 615 lung transplant recipients between 6/1/2015 and 12/31/2021. Airway complications were defined according to ISHLT consensus guidelines. RESULTS: 22 of the 615 recipients (3.6%) developed an AD. Bronchial ischemia or necrosis was common prior to dehiscence (68.1%). Fourteen (63.6%) recipients had bacterial airway infections, most commonly with Gram-negative rods, prior to dehiscence. Thirteen (59.1%) recipients had an associated pleural infection, most commonly with Candida species (30.8%). Post-dehiscence Aspergillus species were isolated in 4 recipients, 3 of which were de novo infections. Eleven had bacterial infections prior to dehiscence resolution, most commonly with Pseudomonas aeruginosa. Eleven recipients developed airway stenosis requiring dilation and/or stenting. Development of secondary infection prior to AD resolution was not associated with progression to stenosis (OR = .41, 95% CI = .05-3.30, p = .41). CONCLUSIONS: Gram-negative bacterial infections are common before and after AD. Pleural infection should be suspected in most cases. Infections prior to healing were not associated with subsequent development of airway stenosis.

Collaborative leadership in transplantation: Blending clinical, business, and regulatory roles.

Transplantation is a high-risk, high-cost treatment for end-stage diseases and is the most strictly regulated area of healthcare in the United States. Thus, achieving success for patients and the program requires skillful and collaborative leadership. Various factors, such as outcomes, volume, and financial health, may measure the success of a transplant program. Strong collaboration between clinical and administrative leaders is key to achieving and maintaining success in those three categories. Clinical leaders of adult programs, such as medical and surgical directors, bear the primary responsibility for a program's volume, outcomes, and patient safety, while administrative directors are focused on business intelligence and regulatory compliance. This paper aims to provide readers with insights into the critical role of collaborative leadership in running a successful program, with a focus on clinical, business, and regulatory perspectives.

Processing of Positive Memories Technique: Feedback From Trauma-Exposed Clients on Processing of Positive Memories Technique Components, Format, and Feasibility.

ABSTRACT: Although the majority of research and clinical interventions focused on posttraumatic stress disorder (PTSD) centers on traumatic memories, recent literature suggests the importance of considering emotionally laden memories more broadly among trauma-exposed individuals. Specifically, trauma-exposed individuals have difficulties retrieving positive and negative memories, and interventions focused on enhancing the retrieval of both traumatic and positive memories benefit overall well-being. These findings led to the development of a novel Processing of Positive Memories Technique (PPMT) for PTSD. As the next step in treatment development, PPMT was piloted among 12 trauma-exposed community members seeking therapeutic or assessment services at a university psychology clinic. In this study, we summarize participants' quantitative and qualitative feedback on the content, format, and feasibility of PPMT. Next, we outline proposed formative changes that are critical to the iterative refinement of PPMT, based on the obtained feedback to enhance its scalability, feasibility, and effectiveness. Within clinical practice, PPMT, as implemented in this study, may be feasible, and there may be potential benefits to incorporating positive memory processing using PPMT.

Dantrolene Significantly Improves Cerebral Blood Flow in a Rat Model of Hemorrhagic Vasospasms.

INTRODUCTION: A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg and 2 mg/kg) on MCA blood flow velocity (BFV) 7 days after the induction of CVSPs. METHODS: Vasospasms were induced by bathing the left common carotid artery with autologous whole blood. Age-matched sham rats were used as controls. BFV, mean arterial pressure (MAP), and heart rate (HR) were measured with a PeriFlux 5000 Laser Doppler System, and a CODA non-invasive blood pressure system, before and after administering the drugs. Morphometric evaluations were also performed to assess vascular alterations. RESULTS: BFV was reduced by 37% with dantrolene alone (n = 6, p ≤ 0.05) and by 27% with 2 mg/kg nimodipine (n = 6, p < 0.05), while it was not affected by 1 mg/kg nimodipine. The combination of 1 mg/kg nimodipine with dantrolene, however, decreased BFV by 35% (from 435.70 ± 21.53 to 284.30 ± 23.13 perfusion units, n = 7, p ≤ 0.05). A similar reduction (31%) was obtained with dantrolene and 2 mg/kg nimodipine (from 536.00 ± 32.61 to 367.80 ± 40.93 perfusion units, n = 6, p ≤ 0.05). Neither MAP nor HR was affected by dantrolene or nimodipine alone. The combination of dantrolene with 2 mg/kg nimodipine, however, decreased MAP and increased HR. Furthermore, 7 days after the induction of vasospasms, lumen area of the left common carotid artery decreased, whereas media thickness and the wall-to-lumen ratio increased when compared to contralateral controls. The latter finding suggests that vascular remodeling was present at this stage. CONCLUSION: Altogether, our results indicate that 2.5 mg/kg dantrolene significantly reduces BFV in the MCA without altering systemic hemodynamic parameters to a similar extent than the highest dose of nimodipine or the combination of dantrolene and the lowest dose of nimodipine. Therefore, dantrolene may provide a promising alternative to lower the risk, or partially revert, CVSP.

Barriers to access intimate partner violence services in female Romanian immigrants in Spain: A Delphi study.

Immigrant women may be at higher risk of intimate partner violence (IPV) and may seek specialized services less frequently than other populations. In Spain, Romanian origin foreigners comprise the second-highest proportion among immigrant population. This study aimed to identify, from the perspective of experts, (1) the main barriers faced by immigrant women of Romanian origin in accessing specialized services for IPV in Spain; and (2) the most useful strategies to combat these barriers. A Delphi study was conducted with a panel of 23 experts. The coefficient rWG was calculated to established agreement among participants. The results showed 58 barriers and 31 strategies with high agreement among the experts (rWG ≥ 0.80). Barriers in access to services that were considered to be highly influential included: having been in the host country for a short time; lack of language proficiency; job insecurity; difficulty with family-work reconciliation; and fear of the social consequences for help-seeking. The strategies considered most useful were: facilitating access to the job market and decent housing; promoting a social support network; translating material into Romanian; and increasing training among professionals. The findings offer guidelines for the improvement of the accessibility of specialized services to immigrant women of Romanian origin.

Phylogenomic and comparative analyses support the reclassification of several Komagataeibacter species as novel members of the Novacetimonas gen. nov. and bring new insights into the evolution of cellulose synthase genes.

The genus Komagataeibacter harbours bacteria presenting the ability to produce increased levels of crystalline nanocellulose, as well as strains used in the industrial production of fermented products and beverages. Still, most of the studies of this biotechnologically relevant genus were conducted based on limited phenotypic methodologies and taxonomical classifications. In this work, a detailed analysis of the currently described genus Komagataeibacter was conducted based on phylogenomic analysis, unveiling the phylogenomic relationships within the genus and allowing a detailed phylogenetic analysis of biotechnologically important genes such as those involved in cellulose biosynthesis (bcs genes). Phylogenomic and comparative genomic analysis revealed that several type strains formed an independent genomic group from those of other Komagataeibacter, prompting their reclassification as members of a novel genus, hereby termed Novacetimonas gen. nov. The results support the reclassification of Komagataeibacter hansenii, Komagataeibacter cocois, Komagataeibacter maltaceti and Komagataeibacter pomaceti as novel members of the genus Novacetimonas. The Novacetimonas hansenii species is the proposed representative of the novel genus. Importantly, phylogenetic analysis based on cellulose biosynthesis genes (bcsABCD, bcsAB2XYC2, bcsAB3C3, bcsAB4), showed that the evolutionary history of these genes is closely related to the strain's phylogenomic/taxonomic classification. Hence, the robust taxonomic classification of these bacteria will allow the better characterization and selection of strains for biotechnological applications.

Capsaicin 8% Dermal Patch for Neuropathic Pain in a Pain Unit.

AIMS: Pain units manage approximately 20% of the patients with neuropathic pain, usually presenting with severe uncontrolled pain associated with substantial impairment of quality-of-life and disability. We aimed to analyze the experience with the capsaicin 8% dermal patch for managing patients with neuropathic pain in a pain unit. DESIGN: This was a post-authorization observational and retrospective study conducted at a single pain unit on patients with peripheral neuropathic pain under routine clinical care. METHODS: Diagnosis of neuropathic pain was based on the Douleur Neuropathique 4 (DN4) questionnaire. Evaluations included pain intensity according to a visual analog scale and the quality-of-life as evaluated with the European Quality of Life-5 Dimensions (EQ-5D). RESULTS: We included 66 patients with neuropathic pain lasting for a median of 24 months. The most frequent diagnosis was iatrogenic neuropathic pain (47%) and two thirds of patients exhibited extreme pain or discomfort. Pain intensity was reduced significantly from a mean (standard deviation [SD]) of 7.20 (1.95) at baseline to 6.02 (2.77) at month 3, leading to a mean change from baseline of 1.19 (95% confidence interval [CI], 0.59 to 1.78; p < .001; Cohen's d 0.49). The extent of the pain area was also significantly reduced from a median (interquartile range [IQR]) of 169.5 cm2 (69.3-299.9) at baseline to 121.2 cm2 (35.4-183.9) at month 3 (p < .001). There was an improvement in most dimensions of quality-of-life, especially regarding "usual activities," "pain/discomfort," and "anxiety/depression." Tolerability was consistent with the known profile. CONCLUSIONS: Our results suggest that the capsaicin 8% dermal patch is a useful and well-tolerated treatment option for managing peripheral neuropathic pain in pain units.

Floral Microbes Suppress Growth of Monilinia laxa with Minimal Effects on Honey Bee Feeding.

Management of Monilinia laxa, the causal agent of brown rot blossom blight in almond (Prunus dulcis), relies heavily on the use of chemical fungicides during bloom. However, chemical fungicides can have nontarget effects on beneficial arthropods, including pollinators, and select for resistance in the pathogen of concern. Almond yield is heavily reliant on successful pollination by healthy honey bees (Apis mellifera); thus, identifying sustainable, effective, and pollinator-friendly control methods for blossom blight during bloom is desirable. Flower-inhabiting microbes could provide a natural, sustainable form of biocontrol for M. laxa, while potentially minimizing costly nontarget effects on almond pollinators and the services they provide. As pollinators are sensitive to floral microbes and their associated taste and scent cues, assessing effects of prospective biocontrol species on pollinator attraction is also necessary. Here, our objective was to isolate and identify potential biocontrol microbes from an array of agricultural and natural flowering hosts and test their efficacy in suppressing M. laxa growth in culture. Out of an initial 287 bacterial and fungal isolates identified, 56 were screened using a dual culture plate assay. Most strains reduced M. laxa growth in vitro. Ten particularly effective candidate microbes were further screened for their effect on honey bee feeding. Of the 10, nine were found to both strongly suppress M. laxa growth in culture and not reduce honey bee feeding. These promising results suggest a number of strong candidates for augmentative microbial biocontrol of brown rot blossom blight in almond with potentially minimal effects on honey bee pollination.

Data Analysis and Filter Optimization for Pulse-Amplitude Measurement: A Case Study on High-Resolution X-ray Spectroscopy.

In this study, we present a procedure to optimize a set of finite impulse response filter (FIR) coefficients for digital pulse-amplitude measurement. Such an optimized filter is designed using an adapted digital penalized least mean square (DPLMS) method. The effectiveness of the procedure is demonstrated using a dataset from a case study on high-resolution X-ray spectroscopy based on single-photon detection and energy measurements. The energy resolutions of the Kα and Kß lines of the Manganese energy spectrum have been improved by approximately 20%, compared to the reference values obtained by fitting individual photon pulses with the corresponding mathematical model.

A Simplified Correlation Index for Fast Real-Time Pulse Shape Recognition.

A simplified correlation index is proposed to be used in real-time pulse shape recognition systems. This index is similar to the classic Pearson's correlation coefficient, but it can be efficiently implemented in FPGA devices with far fewer logic resources and excellent performance. Numerical simulations with synthetic data and comparisons with the Pearson's correlation show the suitability of the proposed index in applications such as the discrimination and counting of pulses with a predefined shape. Superior performance is evident in signal-to-noise ratio scenarios close to unity. FPGA implementation of Person's method and the proposed correlation index have been successfully tested and the main results are summarized.

Na+/K+- and Mg2+-ATPases and Their Interaction with AMPA, NMDA and D2 Dopamine Receptors in an Animal Model of Febrile Seizures.

Febrile seizures (FS) are one of the most common seizure disorders in childhood which are classified into short and prolonged, depending on their duration. Short FS are usually considered as benign. However, epidemiological studies have shown an association between prolonged FS and temporal lobe epilepsy. The development of animal models of FS has been very useful to investigate the mechanisms and the consequences of FS. One of the most used, the "hair dryer model", has revealed that prolonged FS may lead to temporal lobe epilepsy by altering neuronal function. Several pieces of evidence suggest that Na+/ K+-ATPase and Mg2+-ATPase may play a role in this epileptogenic process. In this work, we found that hyperthermia-induced seizures (HIS) significantly increased the activity of Na+/ K+-ATPase and Mg2+-ATPase five and twenty days after hyperthermic insult, respectively. These effects were diminished in response to AMPA, D2 dopamine A1 and A2A receptors activation, respectively. Furthermore, HIS also significantly increased the protein level of the AMPA subunit GluR1. Altogether, the increased Na+/ K+-ATPase and Mg2+-ATPase agree well with the presence of protective mechanisms. However, the reduction in ATPase activities in the presence of NMDA and AMPA suggest an increased propensity for epileptic events in adults.

RNA-Seq, Bioinformatic Identification of Potential MicroRNA-like Small RNAs in the Edible Mushroom Agaricus bisporus and Experimental Approach for Their Validation.

Although genomes from many edible mushrooms are sequenced, studies on fungal micro RNAs (miRNAs) are scarce. Most of the bioinformatic tools are designed for plants or animals, but the processing and expression of fungal miRNAs share similarities and differences with both kingdoms. Moreover, since mushroom species such as Agaricus bisporus (A. bisporus, white button mushroom) are frequently consumed as food, controversial discussions are still evaluating whether their miRNAs might or might not be assimilated, perhaps within extracellular vesicles (i.e., exosomes). Therefore, the A. bisporus RNA-seq was studied in order to identify potential de novo miRNA-like small RNAs (milRNAs) that might allow their later detection in diet. Results pointed to 1 already known and 37 de novo milRNAs. Three milRNAs were selected for RT-qPCR experiments. Precursors and mature milRNAs were found in the edible parts (caps and stipes), validating the predictions carried out in silico. When their potential gene targets were investigated, results pointed that most were involved in primary and secondary metabolic regulation. However, when the human transcriptome is used as the target, the results suggest that they might interfere with important biological processes related with cancer, infection and neurodegenerative diseases.

Managing connective tissue disease: how to select and facilitate successful transplantation.

PURPOSE OF REVIEW: Lung transplant (LTx) evaluation and selection of candidates with connective tissue disease (CTD) remains controversial and varies between centers, and the optimal candidate selection is still controversial. RECENT FINDINGS: Recent United States and European publications have reported reasonable short-term and long-term LTx outcomes in patients with CTD to other lung fibrosis patients without CTD. This article discusses the recently published International Society for Heart and Lung Transplantation (ISHLT) consensus document recommendations to evaluate and select CTD candidates, the importance of early referral, posttransplant management, and the involvement of a multidisciplinary team. SUMMARY: Future standardized practices among centers adapting the 2021 ISHLT consensus recommendations to evaluate and select CTD candidates will allow risk stratification, determine the best candidates, and facilitate the most successful long-term LTx outcomes.