Chrysin attenuates epithelial prostatic hyperplasia in the ventral prostate of spontaneously hypertensive rats.

The aim of this study was to evaluate the effects of chrysin on the ventral prostate of spontaneously hypertensive rats (SHR). Ten-week-old male Wistar and SHR rats received 100 mg/kg/day of chrysin (TW and TSHR) or 200 µL/day of the dilution vehicle (CW and CSHR) for 70 days. After the treatment, the animals were euthanized and the prostates were dissected out, fixed, and processed for further morphological, immunohistochemical, and biochemical analyses. Blood was collected for serological analysis. Chrysin did not interfere with the blood pressure. Morphologically, the epithelial height increased in TW and decreased in TSHR. Stereology showed an increase in the epithelial and stromal relative frequency, and a decrease in the lumen of TW, whereas the epithelium in TSHR was reduced. Normal alveoli decreased, and hyperplastic alveoli had an increment in TW, whereas in TSHR normal alveoli increased and intense hyperplasia decreased. The secretion area was reduced in TW. Immunohistochemical analysis showed a smaller number of PCNA-positive cells in TW. Finally, the biochemical analysis showed a reduction in malondialdehyde, carbonylated proteins, superoxide dismutase, and catalase in TW and TSHR. We concluded that the chrysin effect is dependent on the context in which this flavonoid is employed. In normal conditions, the anabolic potential of the chrysin was favored, disrupting the morphology of the prostate. However, when used in animals predisposed to develop hyperplasia, this flavonoid attenuates the hyperplastic status, improving the morphology of the gland.

The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors.

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59-3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01-1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56-0.75) and 0.60 (0.51-0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68-0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74-0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69-0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.

Amylase and lipase levels in the metabolic syndrome and type 2 diabetes: A longitudinal study in rhesus monkeys.

Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic middle-aged humans. In the present study, we sought to determine the nature of such changes during the longitudinal progression from metabolically normal to overt type 2 diabetes mellitus (T2DM) in nonhuman primates (NHPs), a disease that appears to be the same in both pathophysiology and underlying mechanisms as that which most commonly develops in middle-aged adult humans. Amylase and lipase levels were characterized in 157 unrelated adult rhesus monkeys (Macaca mulatta); 38% developed T2DM while under study. In all monkeys, multivariable linear regression analysis revealed that amylase could be negatively predicted by % body fat (ß -0.29; p = 0.002), age (ß -0.27; p = 0.005), and HbA1c (ß -0.18; p = 0.037). Amylase levels were positively predicted by lipase levels (ß = 0.19; p = -0.024) in all NHPs included in the study. Amylase was significantly lower in NHPs with metabolic syndrome (p < 0.001), prediabetes (PreDM) (p < 0.001), and T2DM (p < 0.001) compared to metabolically normal adult NHPs. Lipase increased in NHPs with PreDM (p = 0.005) and T2DM (p = 0.04) compared to normal NHPs. This is the first longitudinal study of any species, including humans, to show the dynamics of amylase and lipase during the metabolic progression from normal to metabolic syndrome, to PreDM and then to overt T2DM. The extraordinary similarity between humans and monkeys in T2DM, in pancreatic pathophysiology and in metabolic functions give these findings high translational value.

Clinical and genomic features of Mycobacterium avium complex: a multi-national European study.

BACKGROUND: The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated. METHODS: Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort. RESULTS: Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04-0.28, p < 0.001 and OR 0.11 95% CI 0.02-0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%). CONCLUSIONS: This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.

Flowcytometric data of intermediate-large cell gastrointestinal lymphoma presenting a gross mass in 32 cats - "let them glow in the flow".

Gastrointestinal lymphoma is the most common form of lymphoma in domestic cats. Aggressive phenotypes are much less common but do bear and unfavorable prognosis. Immunophenotyping by flow cytometry (FCM) is not systematically performed in these patients, because of difficulties in the acquisition of suitable sample material from the gastrointestinal tract. A multimodal diagnostic approach is recommended to improve identification of subtypes targeting patient tailored therapeutic strategies. The aim of this prospective study was to present results of multicolor FCM immunophenotyping in surgically removed gastrointestinal mass and relate them with histopathology using the World Health Organization (WHO) classification and clonality PCR testing. Thirty-two patients were included. Eight cats (25%) had gastric, 23 (72%) had intestinal lymphoma and 1 (3%) had gastric/jejunal lymphoma. Intestinal lymphoma sites were represented by 18 small intestinal, 4 ileocaecal, 1 large intestinal. All gastric lymphomas were diffuse large B-cell lymphoma (DLBCL). Small intestinal lymphomas were 10 enteropathy associated T-cell lymphoma type I (EATL I), 2 enteropathy associated T-cell lymphoma type II (EATL II), 2 peripheral T-cell lymphoma (PTCL), 3 DLBCL and one DLBCL+EATL II. The most common small intestinal FCM T-cell phenotype was CD3+CD21- CD4-CD8-CD18+ CD5-CD79- in 7/10 EATL I and one EATL II. The most frequent FCM B-cell phenotype was CD3-CD21+ CD4-CD8-CD18+ CD5-CD79+ in 13/17 DLBCL and the DLBCL+EATL II. Clonality PCR results were positive in 87.5% (28/32) of all cases. No cross-lineage rearrangement was observed. IHC and FCM results agreed in 87.5% (28/32) of all cases. When all 3 methods were combined, consistent results were seen in 75% (24/32). This is the first demonstration of a multicolor FCM approach set in context to the gold standard histopathology and clonality testing results.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial.

Purpose: Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group. Methods: A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes. Conclusion: This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452). Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01397-4.

Increased human papillomavirus viral load is correlated to higher severity of cervical disease and poorer clinical outcome: A systematic review.

Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer.

Exploratory screening for micro-RNA biomarkers in canine multicentric lymphoma.

Lymphoma is one of the most frequent hematopoietic tumors in dogs and shares similar features with human counterparts. MicroRNAs (miRNA, small non-coding RNAs) are pivotal in gene regulation fine tuning and cancer hallmarks are influenced by their aberrant expression. Consequently, miRNA biomarkers may assist predicting therapeutic response and clinical outcome by providing less-invasive novel diagnostics tools. The aim of this study was to detect dysregulated miRNAs in lymphomatous lymph node tissues in comparison to lymph node material or PBMCs from healthy control dogs. Potential significant differences in miRNA expression profiles between four lymphoma entities were evaluated. A customized PCR array was utilized to profile 89 canine target miRNAs. Quantification was performed using qPCR, relative expression was determined by the delta-delta Ct method, and p-values were calculated with student's t-test. In the 14 diffuse large B-cell lymphoma (DLBCL) patients, 28 and 24 different miRNAs were significantly dysregulated compared to lymph node material or PBMCs. Sixteen miRNAs occurred in both control groups, with 12 miRNAs being down- and four miRNAs being upregulated. The six peripheral T-cell lymphoma (PTCL) samples showed 24 and 25 dysregulated miRNAs when compared to the healthy controls. A combined analysis of DLBCL and PTCL samples revealed seven shared and 19 differently expressed miRNAs. Potential biomarkers in T- and B-cell lymphoma could be the miRNA-17/92 cluster and miRNA-181-family together with miRNA-34a and miRNA-150. Diagnostic utility of potential biomarkers must be validated in larger, prospective cohorts of canine lymphoma cases and in higher numbers of physiological patient material.

PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.

While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo. Consistently, PD-L1 expression marked tumor explants from cancer patients that were best infected by oncolytic viruses. Mechanistically, PD-L1 promoted a metabolic shift characterized by enhanced glycolysis rate that resulted in increased lactate production. In turn, lactate inhibited type I IFN responses. In addition to adding mechanistic insight into PD-L1 intrinsic function, our results will also help guide the numerous ongoing efforts to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.

Immunophenotype investigation in feline intestinal non-B-cell lymphoma.

Lymphoma is the most common tumour of domestic cats, developing most frequently in the small intestine. Feline small intestinal lymphoma predominantly demonstrates a T-cell immunophenotype identified by standard immunopositivity for T cells with CD3 or immunopositivity for B cells with CD20. In contrast, a wide spectrum of immunohistochemical antibodies are applied in humans to diagnose the various specific lymphoma subtypes according to the WHO classification. Our aim was to augment our knowledge of immunophenotypes in feline non-B-cell lymphomas forming macroscopic masses in the intestinal tract. We evaluated the combined immunohistochemistry and flow cytometry findings from 15 cases. Neoplastic lymphoid cells were immunopositive for CD3 in 93% (14/15), granzyme B in 87% (13/15), CD5 in 20% (3/15), CD8 in 13% (2/15), CD4 in 7% (1/15) and CD56 in 7% (1/15) of cases. Cytotoxic granules indicating a cytotoxic origin of the neoplastic cells were identified by histopathology only in 13% (2/15) and by cytology in 47% (7/15) of the cases. Without immunohistochemical labelling of the cytotoxic protein granzyme B, the cytotoxic status would have been missed in 46% (6/13) of the cytological and in 85% (11/13) of the histopathological slides. These findings suggest that more complex immunophenotyping may advance our understanding and help prognosticate small intestinal T-cell lymphoma in cats.

Preoperative cognitive performance and its association with postoperative complications in vascular surgery patients: A prospective study.

BACKGROUND: Cognitive impairment affects nearly half of vascular surgery patients, but its association with postoperative outcomes remains poorly understood. This study explores the link between preoperative cognitive performance and postoperative complications, including postoperative delirium, in vascular surgery patients. METHODS: A prospective cohort study was conducted on vascular surgery patients aged ≥65. Preoperative cognitive performance was assessed using the Montreal Cognitive Assessment, and postoperative complications were evaluated using the Comprehensive Complication Index. The association was analyzed through multivariable logistic regression. RESULTS: Among 110 patients (18.2 â€‹% female, mean age 73.8 â€‹± â€‹5.7 years), cognitive impairment was evident in 48.2 â€‹%. Of the participants, 29 (26.3 â€‹%) experienced postoperative complications, among which 11 (10 â€‹%) experienced postoperative delirium. The adjusted odds ratio for the association between cognitive performance and postoperative complications was 1.19 (95 â€‹% CI 1.02-1.38; p â€‹= â€‹0.02). CONCLUSION: Worse preoperative cognitive performance correlated with increased odds of postoperative complications and postoperative delirium in vascular surgery patients.

A corpus of GA4GH Phenopackets: case-level phenotyping for genomic diagnostics and discovery.

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present phenopacket-store. Version 0.1.12 of phenopacket-store includes 4916 phenopackets representing 277 Mendelian and chromosomal diseases associated with 236 genes, and 2872 unique pathogenic alleles curated from 605 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

Losing sleep influences dietary intake in children: a longitudinal compositional analysis of a randomised crossover trial.

BACKGROUND: Although inadequate sleep increases the risk of obesity in children, the mechanisms remain unclear. The aims of this study were to assess how sleep loss influenced dietary intake in children while accounting for corresponding changes in sedentary time and physical activity; and to investigate how changes in time use related to dietary intake. METHODS: A randomized crossover trial in 105 healthy children (8-12 years) with normal sleep (~ 8-11 h/night) compared sleep extension (asked to turn lights off one hour earlier than usual for one week) and sleep restriction (turn lights off one hour later) conditions, separated by a washout week. 24-h time-use behaviors (sleep, wake after sleep onset, physical activity, sedentary time) were assessed using waist-worn actigraphy and dietary intake using two multiple-pass diet recalls during each intervention week. Longitudinal compositional analysis was undertaken with mixed effects regression models using isometric log ratios of time use variables as exposures and dietary variables as outcomes, and participant as a random effect. RESULTS: Eighty three children (10.2 years, 53% female, 62% healthy weight) had 47.9 (SD 30.1) minutes less sleep during the restriction week but were also awake for 8.5 (21.4) minutes less at night. They spent this extra time awake in the day being more sedentary (+ 31 min) and more active (+ 21 min light physical activity, + 4 min MVPA). After adjusting for all changes in 24-h time use, losing 48 min of sleep was associated with consuming significantly more energy (262 kJ, 95% CI:55,470), all of which was from non-core foods (314 kJ; 43, 638). Increases in sedentary time were related to increased energy intake from non-core foods (177 kJ; 25, 329) whereas increases in MVPA were associated with higher intake from core foods (72 kJ; 7,136). Changes in diet were greater in female participants. CONCLUSION: Loss of sleep was associated with increased energy intake, especially of non-core foods, independent of changes in sedentary time and physical activity. Interventions focusing on improving sleep may be beneficial for improving dietary intake and weight status in children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTR ACTRN12618001671257, Registered 10th Oct 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367587&isReview=true.

Preparing for future pandemics: frailty associates with mortality in hospitalised older people during the entire COVID-19 pandemic, a Dutch multicentre cohort study.

PURPOSE: Viral mutations and improved prevention or treatment options may have changed the association of frailty with mortality throughout the COVID-19 pandemic. We investigated how associations of frailty with in-hospital mortality changed throughout the pandemic in older people hospitalised for COVID-19. METHODS: The COVID-OLD study included COVID-19 patients aged ≥ 70 years hospitalised during the first (early 2020), second (late 2020), third (late 2021) or fourth wave (early 2022). Based on the clinical frailty scale, patients were categorised as fit (1-3), pre-frail (4-5) or frail (6-9). Associations of frailty with in-hospital mortality were assessed with pairwise comparisons with fit as reference category and modelled using binary logistic regression adjusted for age and sex. RESULTS: This study included 2362 patients (mean age 79.7 years, 60% men). In the first wave, in-hospital mortality was 46% in patients with frailty and 27% in fit patients. In-hospital mortality decreased in each subsequent wave to 25% in patients with frailty and 11% in fit patients in the fourth wave. After adjustments, an overall higher risk of in-hospital mortality was found in frail (OR 2.26, 95% CI: 1.66-3.07) and pre-frail (OR 1.73, 95% CI: 1.27-2.35) patients compared to fit patients, which did not change over time (p for interaction = 0.74). CONCLUSIONS: Frailty remained associated with a higher risk of in-hospital mortality throughout the entire COVID-19 pandemic, although overall in-hospital mortality rates decreased. Frailty therefore remains a relevant risk factor in all stages of a pandemic and is important to consider in prevention and treatment guidelines for future pandemics.

The complete sequence and comparative analysis of ape sex chromosomes.

Apes possess two sex chromosomes-the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements-owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.

Tool use promotes dental health.

Using tools increases foraging success in sea otters and protects their teeth from damage.