Search

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent after ipilimumab exposure, which altered CD4+ T-cell gene expression, in line with ongoing T-cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemic cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses. This trial was registered at www.clinicaltrials.gov as #NCT02890329.

Large theropod dinosaurs are often reconstructed with their marginal dentition exposed because of the enormous size of their teeth and their phylogenetic association to crocodylians. We tested this hypothesis using a multiproxy approach. Regressions of skull length and tooth size for a range of theropods and extant varanid lizards confirm that complete coverage of theropod dinosaur teeth with extraoral tissues (gingiva and labial scales) is both plausible and consistent with patterns observed in living ziphodont amniotes. Analyses of dental histology from crocodylians and theropod dinosaurs, including Tyrannosaurus rex , further indicate that the most likely condition was complete coverage of the marginal dentition with extraoral tissue when the mouth was closed. This changes our perceptions about the appearance and oral configuration of these iconic predators and has broad implications for our interpretations of other terrestrial animals with large teeth.

HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate) is a short-chain polyfluorinated alkyl substance (PFAS) used in the manufacture of some types of fluorinated polymers. Like many PFAS, toxicity studies with HFPO-DA indicate the liver is the primary target of toxicity in rodents following oral exposure. Due to the structural diversity of PFAS, the mode of action (MOA) can differ between PFAS for the same target tissue. There is significant evidence for involvement of peroxisome proliferator-activated receptor alpha (PPARα) activation based on molecular and histopathological responses in the liver following HFPO-DA exposure, but other MOAs have also been hypothesized based on limited evidence. The MOA underlying the liver effects in mice exposed to HFPO-DA was assessed in the context of the Key Events (KEs) outlined in the MOA framework for PPARα activator-induced rodent hepatocarcinogenesis. The first 3 KEs (ie, PPARα activation, alteration of cell growth pathways, and perturbation of cell growth/survival) are supported by several lines of evidence from both in vitro and in vivo data available for HFPO-DA. In contrast, alternate MOAs, including cytotoxicity, PPARγ and mitochondrial dysfunction are generally not supported by the scientific literature. HFPO-DA-mediated liver effects in mice are not expected in humans as only KE 1, PPARα activation, is shared across species. PPARα-mediated gene expression in humans produces only a subset (ie, lipid modulating effects) of the responses observed in rodents. As such, the adverse effects observed in rodent livers should not be used as the basis of toxicity values for HFPO-DA for purposes of human health risk assessment.

We performed a retrospective examination of spontaneous hepatocellular carcinomas (HCCs) (primary and metastatic tumors) in 14 captive prosimians brought to the Veterinary Medical Diagnostic Laboratory in North Carolina State University over a period of 11 years (2003 to 2014) to characterize the tumors. These animals are endangered primates; a better understanding of the main fatal neoplasms is crucial. In addition to the histologic evaluation, an immunohistochemical study was also performed, using a hepatocyte marker (hepatocyte paraffin 1 [HepPar-1]) and 2 cholangiocyte markers (keratin 7 [K7] and keratin 19 [K19]), in an attempt to identify a specific profile for HCCs with metastatic behavior. Six of the 14 HCCs had pulmonary metastases. The most frequent histopathological findings were a trabecular pattern (14/14, 100%), presence of multinucleated cells (12/14, 85.7%), and foci of extramedullary hematopoiesis (9/14, 64.3%). The mitotic count was significantly higher in the metastatic HCCs ( P < .05). HepPar-1 was detected in all primary and metastatic HCCs, with a strong intensity of staining. Labeling for K7 and K19 was positive in 12 HCCs (85.7%) and 1 HCC (7.1%), respectively. Contrary to the less aggressive HCCs, most of the metastatic HCCs (5/6) expressed K7 in more than 15% of cells. The percentage of K7-positive neoplastic hepatocytes was significantly higher in metastatic HCCs. This study suggests that K7 might be a prognostically relevant marker in HCCs of captive prosimians.

Attempts to track material flows and the calculation of efficiency for material systems go hand in hand. Questions of where materials come from, where materials go to, and how much material is lost along the way are embedded in human societies. This article reviews material flows, their analysis, and progress toward material efficiency. We focus first on material flow analysis (MFA) and the three key tenets of any MFA: presentation of materials, visualization of the flow structure, and insight derived from analysis. Reviewing recent literature, we explore how each of these concepts is described, organized, and presented in MFA studies. We go on to show the role of MFA in material efficiency calculations and what-if scenario analysis for informed decision-making. We investigate the origins and motivations behind the material efficiency paradigm and the key efficiency strategies and practices developed in recent years and conclude by suggesting priorities for a future research agenda.

Introduction Erectile dysfunction (ED) affects to some degree approximately 52% of the male population aged 40–70 years. Many men do not respond to, or are precluded from using, pharmaceutical treatments for ED and are therefore advised to consider penile prostheses. Different types of penile prosthesis are available, such as inflatable penile prostheses (IPPs). IPPs consist of a pair of inflatable cylinders inserted into the corpora cavernosa (CC). During inflation/deflation of these cylinders, the CC and other surrounding tissues such as the tunica albuginea (TA) are highly impacted. Therefore, it is critical to understand the mechanics of penile tissues for successful implantation of IPPs and to reduce tissue damage induced by IPPs. Objectives We explored the importance of the biomechanics of penile tissues for successful IPP function and reviewed and summarized the most significant studies on penile biomechanics that have been reported to date. Methods We performed an extensive literature review of publications on penile biomechanics and IPP implantation. Results Indenters have been used to characterize the mechanical behavior of whole penile tissue; however, this technique applied only local deformation, which limited insights into individual tissue components. Although one reported study addressed the mechanical behavior of TA, this investigation did not consider anisotropy, and there is a notable absence of biomechanical studies on CC and CS. This lack of understanding of penile tissue biomechanics has resulted in computational models that use linear-elastic materials, despite soft tissues generally exhibiting hyperelastic behavior. Furthermore, available benchtop/synthetic models do not have tissue properties matched to those of the human penis, limiting the scope of these models for use as preclinical testbeds for IPP testing. Conclusion Improved understanding of penile tissue biomechanics would assist the development of realistic benchtop/synthetic and computational models enabling the long-term performance of IPPs to be better assessed.

Little is known about the drivers of readmission in patients undergoing Orthopaedic oncologic resection. The goal of this study was to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for primary tumors involving bone.This was a retrospective comparative cohort study of patients treated from 2008 to 2019 who underwent endoprosthetic reconstruction for a primary bone tumor or soft tissue tumor involving bone, as well as those who underwent a revision endoprosthetic reconstruction if the primary endoprosthetic reconstruction was performed for an oncologic resection. The primary outcome measure was unplanned 90-day readmission.A total of 149 patients were identified who underwent 191 surgeries were for a primary bone or soft tissue tumor. The 90-day readmission rate was 28.3%. Female gender, depression, higher tumor grade, vascular reconstruction, longer procedure duration, longer length of stay (LOS), multiple surgeries during an admission and disposition to a Skilled Nursing Facility were associated with readmission (p 0.05). In a multivariate analysis, female sex, higher tumor grade and longer procedure duration were independently associated with risk of readmission (p 0.05).Readmission rates are high following endoprosthetic reconstruction for Orthopaedic oncologic resections. Further work is necessary to help minimize unplanned readmissions.

Background Urachal remnants are a rare congenital defect resulting from failure of obliteration of a fibrous tube that connects the umbilicus to the bladder dome during embryological development. Oftentimes a urachal remnant will go undiagnosed, but occasionally a patient may present with a variety of symptoms, ultimately leading to the identification of the remnant. Given its rarity, there is very limited literature available on the management of symptomatic urachal remnants, especially in adults. Surgical resection has been the first-line management of urachal remnants for years, especially given the risk of the development of urachal adenocarcinoma secondary to recurrent infection, persistent irritation, and urinary stasis associated with some urachal remnants. Aim We present our experience in the management of symptomatic urachal remnants in adults at our institute and perform a brief literature review of the same. Methods A retrospective review of all cases who underwent surgical management of symptomatic urachal remnants between December 2015 and January 2022 was performed. Seven cases of urachal remnant excision in total were identified over the time period. Patient characteristics and perioperative parameters were analysed. Post-operative complications were measured in accordance with the Clavien-Dindo grading system. Result In total, 7 cases of urachal remnants were treated at our institute over the study period. Four patients were treated with a TURBT and 3 patients were treated with a laparoscopic partial cystectomy. There were no intraoperative complications and one post-operative complication requiring readmission for intravenous antibiotics. There was one mortality but this was not as a direct result of the operative procedure. Mean length of stay was 1.71 days. Two of patients had histologically confirmed urachal adenocarcinoma and the remaining five patients had benign histology. Each patient was seen in the outpatients department 6 weeks post-operatively for clinical review and review of histology. No further follow-up was required for the patients with benign histology given resolution of symptoms and follow-up for the malignant histology was arranged appropriately following MDM. Conclusion There is a paucity of data available on the management of urachal remnants in the adult population; however, an endoscopic or laparoscopic approach is a safe and effective method of excising symptomatic urachal remnants.

This study measures the resource efficiency of a basic oxygen steelmaking plant and develops visual maps of its resource use using raw energy and material data extracted directly from the control system. Resource efficiency is measured in units of exergy and resource flows are visualised in Sankey diagrams. Both the metric and the visuals are computed in close-to-real time scales, and are presented on a daily basis over a period of two weeks. Results show the highest level of resource efficiency (73.8%, Day 11) occurs not when energy intensity is greatest (Day 14) but instead when both energy intensity and material yields are high. Combining energy and materials into a single metric – resource efficiency – is shown to provide plant managers with a clearer picture of where interventions might deliver the greatest efficiency gains and redefines the concept of best practice.

Failure to deliver safe and high-quality food not only causes costly food crises and foodborne illnesses, but also impairs consumer confidence and the performance of cold food chains. Industry 4.0 transformation in food traceability systems i.e., the transition from manual paper-based record keeping to automatic identification and sensor technologies, holds the potential to enable improved data transmission and self-monitoring to reduce food quality issues. Selection of these technologies to meet a specific need requires a measurement on how they perform across a range of criteria. An overview of traceability technology performance rating for criteria enabling industry 4.0 in cold food chain is absent in the literature. This article presents a summary of the traceability technology criteria relevant to cold food chain industry 4.0 transformation through iterative literature review and expert validation. The selection criteria are then combined into a quantitative technology performance matrix that can help users to determine which technology is the most beneficial for a given supply chain scenario.

Useful Energy consumption is regarded as the main driver of energy system transitions. However, there are few national level estimates of useful energy consumption, mainly due to the lack of data and concerns about uncertainty. The first step to compute the useful energy consumption involves allocating primary energy to end-use conversion devices. A method is developed that employs widely available end-use energy statistics to allocate energy to conversion devices. The method includes an uncertainty analysis which is believe to increase the robustness of the results. In this paper, the method is applied to the United Kingdom in 2013. The results show that boilers are the device converting most primary energy in the UK (2.2 ±0.13 EJ) and that the consumption mix for the UK is much more equally distributed among devices compared to the global level and to China. The uncertainty analysis shows that it is difficult to rank many of the devices in terms of their primary energy consumption because the uncertainty is higher than the difference between the expected values; and that most uncertainty in the allocation is due to the uncertainty in the end use of final energy.

Hepatic ciliated foregut remnants or cysts are congenital abnormalities resulting from retention of embryonic ciliated foregut within the liver. These structures are rarely reported in the human medical literature and have not been reported in the veterinary literature previously, to our knowledge. We describe here a case of an 8-wk-old male French Bulldog with a congenital patent hepatic ciliated foregut remnant resulting in an umbilicobiliary sinus tract. The dog also had concurrent gallbladder agenesis. The patient had yellow fluid discharging from the umbilicus, mimicking a patent urachus. Surgical exploration, removal, and histology provided a conclusive diagnosis of a hepatic foregut remnant and therapeutic resolution of the clinical signs. The histologic appearance of a hepatic foregut remnant is classical, namely a duct composed of 4 layers: an inner ciliated epithelial lining, loose connective tissue, smooth muscle, and a fibrous capsule., None

Background & Aims Hepatitis A virus (HAV) is a common cause of enterically transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections. However, the overall contribution of T cells to the control of HAV and the pathogenesis of hepatitis A is unclear and has been impeded by a historic lack of small animal models. Methods Ifnar1-/- mice are highly permissive for HAV and develop pathogenesis that recapitulates many features of hepatitis A. Using this model, we identified HAV-specific CD8+ and CD4+ T cells by epitope mapping, and then used tetramers and functional assays to quantify T cells in the liver at multiple times after infection. We assessed the relationships between HAV-specific T cell frequency, viral RNA amounts, and liver pathogenesis. Results A large population of virus-specific T cells accumulated within the livers of Ifnar1-/- mice during the first 1-2 weeks of infection and persisted over time. HAV replication was enhanced and liver disease exacerbated when mice were depleted of T cells. Conversely, immunization with a peptide vaccine increased virus-specific CD8+ T cell frequencies in the liver, reduced viral RNA abundance, and lessened liver injury. Conclusion These data show that T cells protect against HAV-mediated liver injury and can be targeted to improve liver health. Lay summary Hepatitis A virus is a leading cause of acute viral hepatitis worldwide. T cells were thought to contribute to liver injury during acute infection. We now show that virus-specific T cells protect against infection and limit liver injury.

Objective To describe and illustrate a novel technique of uretero-ileal anastomosis for use in urinary diversion – the Pull-through Anastomosis of Ureter To Enteric Conduit (PAUTEC). A second objective was to evaluate the surgical outcomes of the PAUTEC anastomosis. Materials and Methods Our novel anastomotic technique was described step-by-step and visually depicted with illustrations and the accompanying narrated video. Additionally, to evaluate safety and efficacy, a retrospective review of a prospectively maintained database was performed. Patients who underwent radical cystectomy alone or during pelvic exenteration, with ileal conduit diversion incorporating PAUTEC, 2016-2020 with ≥6 months follow-up were included. Surgical outcomes and renal function were analysed. Results PAUTEC anastomosis was performed on 43 ureters in 23 patients. Mean age was 66 years [50-80] and 21 of 23 patients were male. One patient had a conservatively-managed small urine leak. No ureteric strictures have been identified to date. Mean serum creatinine was 1.15 mg/dL [0.69-2.08] (102umol/L, range 61-184 umol/L) preoperatively, and 1.09 mg/dL [0.61-2.59] (96.3 umol/L, range 54-229 umol/L) at follow-up, demonstrating no significant change (P= .26, paired t-test). Mean follow-up was 15 months [6-44]. Conclusion A PAUTEC technique of uretero-ileal anastomosis is feasible and technically straightforward, with satisfactory outcomes observed to date.

Maternal anti-respiratory syncytial virus (RSV) antibodies protect neonates from RSV disease throughout first weeks of life. Previous studies of maternal immunization in cotton rats showed that a single immunization during pregnancy of RSV-primed dams with virus-like particles (VLPs) assembled with pre-fusion F protein and the wild type G protein boosted their RSV serum antibody concentration and protected pups early in life against RSV challenge. We extended these findings by evaluating responses to RSV infection in litters from two consecutive pregnancies of immunized dams. Using an RSV-primed population of VLP-vaccinated and unvaccinated dams, we defined correlations between dams' and litters' RSV neutralizing antibodies (NA); between litters' NA and protection; and between litter's NA and their lung expression of selected cytokines, of a first or of a second pregnancy. Lung pathology was also evaluated. We found positive correlation between the NA titers in the dams at delivery and the NA in their first and second litters and negative correlations between the litters' NA and protection from RSV challenge. Vaccination of dams modulated the mRNA expression for IFNγ and IL-6 and lung pathology in the first and in the second litter at different times after birth, even in the absence of detectable NA. Maternal RSV vaccination enhanced the levels of antibodies transferred to offspring and their protection from challenge. Importantly, maternal vaccination also impacted the immunological and inflammatory response of the offspring's lungs well into maturity, and after the antiviral effect of maternally transferred NA waned or was no longer detectable.

The Dinosaur Park Formation (DPF) of Alberta, Canada, has produced one of the most diverse dinosaur faunas, with the record favouring large-bodied taxa, in terms of number and completeness of skeletons. Although small theropods are well documented in the assemblage, taxonomic assessments are frequently based on isolated, fragmentary skeletal elements. Here we reassess DPF theropod biodiversity using morphological comparisons, high-resolution biostratigraphy, and morphometric analyses, with a focus on specimens/taxa originally described from isolated material. In addition to clarifying taxic diversity, we test whether DPF theropods preserve faunal zonation/turnover patterns similar to those previously documented for megaherbivores. Frontal bones referred to a therizinosaur (cf. Erlikosaurus), representing among the only skeletal record of the group from the Campanian–Maastrichtian (83–66 Ma) fossil record of North America, plot most closely to troodontids in morphospace, distinct from non-DPF therizinosaurs, a placement supported by a suite of troodontid anatomical frontal characters. Postcranial material referred to cf. Erlikosaurus in North America is also reviewed and found most similar in morphology to caenagnathids, rather than therizinosaurs. Among troodontids, we document considerable morphospace and biostratigraphic overlap between Stenonychosaurus and the recently described Latenivenatrix, as well as a variable distribution of putatively autapomorphic characters, calling the validity of the latter taxon into question. Biostratigraphically, there are no broad-scale patterns of faunal zonation similar to those previously documented in ornithischians from the DPF, with many theropods ranging throughout much of the formation and overlapping extensively, possibly reflecting a lack of sensitivity to environmental changes, or other cryptic ecological or evolutionary factors.

Chemical products, such as plastics, solvents, and fertilizers, are essential for supporting modern lifestyles. Yet, producing, using and disposing of chemicals creates adverse environmental impacts which threaten the industry's license to operate. This study presents seven planet compatible pathways towards 2050 employing demand-side and supply-side interventions with total investment costs of US$1.2-3.7 billion. Resource efficiency and circularity interventions reduce global chemicals demand by 23–33% and are critical for mitigating risks associated with using fossil feedstocks and carbon capture and sequestration, and constraints on available biogenic and recyclate feedstocks. Replacing fossil feedstocks with biogenic/air-capture sources, shifting carbon destinations from atmosphere to ground, and electrifying/decarbonizing energy supply for production technologies, could enable net negative emissions of 200 MtCO2eq yr-1, while still delivering essential chemical-based services to society.

Despite excellent vaccines, resurgent outbreaks of hepatitis A have caused thousands of hospitalizations and hundreds of deaths within the United States in recent years. There is no effective antiviral therapy for hepatitis A, and many aspects of the hepatitis A virus (HAV) replication cycle remain to be elucidated. Replication requires the zinc finger protein ZCCHC14 and noncanonical TENT4 poly(A) polymerases with which it associates, but the underlying mechanism is unknown. Here, we show that ZCCHC14 and TENT4A/B are required for viral RNA synthesis following translation of the viral genome in infected cells. Cross-linking immunoprecipitation sequencing (CLIP-seq) experiments revealed that ZCCHC14 binds a small stem-loop in the HAV 5′ untranslated RNA possessing a Smaug recognition-like pentaloop to which it recruits TENT4. TENT4 polymerases lengthen and stabilize the 3′ poly(A) tails of some cellular and viral mRNAs, but the chemical inhibition of TENT4A/B with the dihydroquinolizinone RG7834 had no impact on the length of the HAV 3′ poly(A) tail, stability of HAV RNA, or cap-independent translation of the viral genome. By contrast, RG7834 inhibited the incorporation of 5-ethynyl uridine into nascent HAV RNA, indicating that TENT4A/B function in viral RNA synthesis. Consistent with potent in vitro antiviral activity against HAV (IC 50 6.11 nM), orally administered RG7834 completely blocked HAV infection in Ifnar1 −/− mice, and sharply reduced serum alanine aminotransferase activities, hepatocyte apoptosis, and intrahepatic inflammatory cell infiltrates in mice with acute hepatitis A. These results reveal requirements for ZCCHC14-TENT4A/B in hepatovirus RNA synthesis, and suggest that TENT4A/B inhibitors may be useful for preventing or treating hepatitis A in humans.

Introduction: Penile cancer is a rare malignancy, with a European-wide annual incidence rate of 1/100 000 males. Approximately one-third of cases are attributable to human papillomavirus (HPV) infection. p16INK4a is a recognized surrogate marker for HPV infection in penile cancer. University Hospital Waterford (UHW) is the national referral center for penile cancer in Ireland. We report the prevalence of HPV infection and histological characteristics of an Irish penile cancer cohort using p16INK4a as a surrogate marker. Methods: Patients who attended UHW for penile cancer surgery between June 2015 and November 2020 were entered into a prospectively maintained database. Clinical, histopathological, and outcome data were collected. Results: Over the study period, 70 patients with a histological diagnosis of penile squamous cell carcinoma had staining for p16INK4a, of whom 64% were positive. p16INK4a positive patients were significantly younger at diagnosis, with a mean age of 61±15 years compared to 68±12 (p

OBJECTIVES Liquid medication dosing errors are common in pediatrics. Our outpatient clinic identified gaps in caregiver education based on a 2015 American Academy of Pediatrics policy statement on prescribing liquid medications. This quality improvement (QI) initiative sought to improve caregiver’s understanding of liquid acetaminophen administration at the 2-month well-child visit from 30% to 70% over a 32-month period. METHODS A resident-led interdisciplinary QI team performed sequential interventions to improve our outcome measure: the percentage of caregivers with an adequate understanding of 4 essential components of liquid acetaminophen administration (name, indication, dose, and frequency). Outcome data were collected via a 4-item verbal assessment of caregiver’s understanding by nursing staff, with correct answers to all items considered adequate understanding. Process measures (medications prescribed and education provided), and balancing measures (anticipatory guidance items discussed) were gathered via electronic health record review. Shewhart “P” charts and established rules for detecting special cause variation were used to analyze data. Scatter plots assessed the association between the provision of syringes and caregiver understanding of medication administration. RESULTS In 636 caregivers, overall understanding of medication use improved from 39.8% to 74%. Knowledge of accurate dosage improved from 50.9% to 76.8%. Correlation between syringe provision and caregiver understanding was strong (R = .84). CONCLUSIONS Resident-led QI improved caregiver’s understanding of liquid acetaminophen administration in infants. The most impactful interventions were implementation of English and Spanish pictograms and provision of dose-demarcated oral syringes, coupled with teach-back. Future interventions will examine generalizability to other medications and expansion to other services.

It is well established that environmental exposures can modify the profile of heritable factors in an individual's germ cells, ultimately affecting the inheritance of phenotypes in descendants. Similar to exposures, an ancestor's genotype can also affect the inheritance of phenotypes across generations, sometimes in offspring who do not inherit the genetic aberration. This can occur via a variety of prenatal, in utero, or postnatal mechanisms. In this review, we discuss the evidence for this process in mammals, with a focus on examples that are potentially mediated through the germline, while also considering alternate routes of inheritance. Noninherited ancestral genotypes may influence descendant's disease risk to a much greater extent than currently appreciated, and focused evaluation of this phenomenon may reveal novel mechanisms of inheritance. Summary sentence This is a review of the evidence that non-inherited ancestral alleles can influence the phenotypes of descendants via a variety of mechanisms including germline, in utero, and postnatal processes. Graphical Abstract