North American Populations Research Articles

MA08.12 Semi-Sold Lung Nodule Growth Rates, Need for Treatment, and Cancer-Specific Verses All-Cause Mortality in a Large North American Population

MA08.12 Semi-Sold Lung Nodule Growth Rates, Need for Treatment, and Cancer-Specific Verses All-Cause Mortality in a Large North American Population

Midlife baseline prostate-specific antigen, velocity, and doubling time association with lethal prostate cancer and mortality.

Midlife baseline prostate-specific antigen (MB PSA), defined as a single PSA value measured between 40-59 years of age, has been proposed as a tool that can limit potential harms of PSA screening. This study aimed to examine the ability of MB PSA versus PSA doubling time (PSADT) and PSA velocity (PSAV) in assessing the likelihood of developing of lethal prostate cancer (PCa) in a diverse and contemporary North American population. Men 40-59 years old, who received their first PSA between the years 1995 and 2019, were included. For MB PSA values, the first PSA test result was included. For PSADT, the first two PSA test results were included. For PSAV, the first three PSA test results within 30 months were included. Selection criteria resulted in a total of 77,594 patients with at least two PSA test results and 11,634 patients with at least three PSA test results. Multivariable Fine-Gray regression was used to examine the impact of the value of the PSA testing methods on the development of lethal PCa (defined as death from PCa or development of metastatic disease either at diagnosis or during follow-up). Time-dependent receiver operating characteristic/area under the curve (AUC) at 5, 10, and 15 years were plotted. In the main cohort, patients were most frequently in the 50-54 age category (32.8%), had a Charlson comorbidity index of 0 (70.5%), and were White (63.2%). Of these, 9.3% had the midlife baseline PSA in the top 10th percentile, and 0.4% had a PSADT 0-6 months. Lethal PCa was diagnosed in 593 (0.8%) patients. The median (interquartile range) time to lethal PCa was 8.6 (3.2-14.9) years. In the main cohort, MB PSA and PSADT showed significant associations with the occurrence of lethal PCa, with a hazard ratio (HR) of 6.10 (95% confidence interval [CI], 4.85-7.68) and HR of 2.20 (95% CI, 1.07-4.54) for patients in the top 10th percentile MB PSA group and in the PSADT between 0 to <6 months group, respectively. In patients with three PSA results available, MB PSA and PSAV showed significant associations with the occurrence of lethal PCa, with a HR of 3.95 (95% CI, 2.29-6.79) and 3.57 (95% CI, 2.17-5.86) for patients in the top 10th percentile MB PSA group and in the in the PSAV >0.4 ng/mL/year group, respectively. PSADT and PSAV did not exhibit higher AUCs than MB PSA in assessing the likelihood of lethal PCa. Specifically, they were 0.818 and 0.708 at 10 and 15 years, respectively, for the PSADT; 0.862 and 0.756 at 10 and 15 years, respectively, for the PSAV; and 0.868 and 0.762 at 10 and 15 years, respectively, for the MB PSA (all p>.05). The study findings are that PSAV or PSADT were not superior to midlife baseline in assessing the likelihood of developing lethal PCa. This suggests that these variables may not have practical use in enhancing PSA screening strategies in a clinical setting.

Treatment outcomes in patients with papillary thyroid cancer undergoing radiofrequency ablation of metastatic lymph nodes.

Lymph node metastases in papillary thyroid cancer (PTC) increases recurrence risk and negatively impact survival. Traditional treatments like re-operation and radioactive iodine (RAI) have downsides. Radiofrequency ablation (RFA) is an emerging non-surgical therapeutic option, but there is seldom data on its efficacy and safety specifically for metastatic lymph nodes. We aimed to evaluate clinical outcomes of RFA applied to cervical lymph nodes in patients with PTC metastasis in North American population. This was a single-institution retrospective analysis of 68 PTC patients with lymph nodes who underwent percutaneous RFA from January 2020 to December 2022. Volume reduction ratio (VRR), changes in thyroglobulin (Tg) levels, lymph node regrowth rate, and complications were assessed. Treatment response and outcomes were analyzed. Median lymph node maximum diameter was 12.9 mm and median volume was 0.27 mL at baseline. After RFA, median VRR was 79.5% [interquartile range (IQR), 50-89.7%]. Post-RFA, Tg to an average of 0.2 ng/mL (IQR, 0-0.6 ng/mL). In the 19 patients (27.9%) with undetectable Tg after RFA, median VRR was 86% (IQR, 73-94%). Quantitative Tg decrease strongly correlated with VRR percentage (r=0.82, P<0.001). Lymph node regrowth was seen in 5 patients (7.4%) over median 18 months follow-up. Only one patient experienced transient thermal injury associated with Horner's syndrome and symptoms resolved within 1 month. In patients with PTC and metastatic cervical lymph nodes, RFA provided marked volume reduction and meaningful biochemical response without major complications. Excellent radiographic control was achieved in most patients. RFA demonstrates early promise as an emerging non-surgical therapeutic option for PTC patients with metastatic lymph nodes.

Cluster classification of a Brazilian gastric cancer cohort reveals remarkable populational differences in normal p53 rate.

Queiroz et al. showed that the application of cluster methodology for classifying gastric cancer is suitable and efficient within a Brazilian cohort, which is known for its population heterogeneity. The study highlighted the potential utilization of this method within public health services due to its low-cost, presenting a viable means to improve the diagnosis and prognosis of gastric cancer. Our Brazilian cohort with gastric cancer has a distinct distribution between mutated and normal p53. New genetic marker-based classifications improve gastric cancer diagnosis accuracy. Machine learning integration enhances predictive value in gastric cancer diagnosis. Molecular biomarkers complement clinical decisions, advancing personalized medicine. Gastric adenocarcinoma remains an aggressive disease with a poor prognosis, as evidenced by a 5-year survival rate of approximately 31%. The histological classifications already proposed do not accurately reflect the high biological heterogeneity of this neoplasm, particularly in diverse populations, and new classification systems using genetic markers have recently been proposed. Following these newly proposed models, we aimed to assess the cluster distribution in a Brazilian cohort. Furthermore, we evaluated whether the inclusion of other clinical and histological parameters could enhance the predictive value. We used a previously described four-immunohistochemistry/EBER-ISH marker to classify a cohort of 30 Brazilian patients with gastric adenocarcinoma into five different clusters and compared the distribution with other genetically diverse populations. Furthermore, we used artificial intelligence methods to evaluate whether other clinical and pathological parameters could improve the results of the methodology. Disclosing the genetic variability between populations, we observed a more balanced distribution of the aberrant/normal p53 ratio (0.6) between patients negative for the other markers tested, unlike previous studies with Asian and North American populations. In addition, decision tree analysis reinforced the efficiency of these new classifications, as the stratification accuracy was not altered with or without additional data. Our study underscores the importance of local research in characterizing diverse populations and highlights the complementary role of molecular biomarkers in personalized medicine for gastric adenocarcinoma, enhancing diagnostic accuracy and potentially improving survival rates.

From common to unreported: a real-world study of adverse events to duloxetine in the treatment of osteoarthritis

ABSTRACT Background In a review of drug guidelines published by the International Association for the Study of Osteoarthritis, it is recommended to support the conditional use of duloxetine in patients with osteoarthritis. However, there is a lack of comprehensive research on the adverse events of duloxetine for the treatment of osteoarthritis populations. Research design and methods We used the reporting odds ratio (ROR) to determine the strength of the adverse event signal. In addition, we investigated trends in the occurrence of adverse events using the Weibull shape parameter (WSP) test. Results The results showed that 50 and 14 adverse events were detected in both Asian and American populations. Four new adverse events, Mouth ulceration, femoral neck fracture, incontinence, long QT syndrome, were identified. There was a difference in the time of adverse event induction between the North American and Asian populations (p < 0.0001). The Weibull shape parameter (WSP) test showed that the incidence of AE decreased over time. Conclusion Our study contributes to an in-depth understanding of the safety of duloxetine in the treatment of osteoarthritis.

Analysing the pedigree to identify undesirable losses of genetic diversity and to prioritize management decisions in captive breeding: a case study.

When prevention of species extinction is the priority, captive breeding is a key component in conservation programmes, allowing the recording of pedigree information in studbooks. The genealogical information registered in Cuvier's gazelle studbook between 1975 and 2023 was analysed to (a) assess if the implemented mating policy was successful in preserving the genetic background of the founders (1 male:3 females) in the present population, and b) improve future management and breeding decisions. Although the maternal contribution of one founder female was lost and the mean inbreeding of the total live population was high (0.305 ± 0.095), the breeding policy applied produced better results than expected from a population starting from four founders. It was successful in keeping the individual increase in inbreeding low (0.047 ± 0.021), and, notably, the inbreeding tended to decrease during the last three decades of the breeding programme, ensuring the viability of this highly inbred population. Historical dissemination of individuals among the zoos of Europe and North America caused population structuring and genetic differentiation of the live North American population. However, it did not risk the viability of the captive population. The average relatedness coefficients allowed the identification of individuals with underrepresented genotypes, which is relevant to plan future mating guidelines to keep the founders' representation balanced in the next generations. This study highlights the importance of keeping long-term pedigree information to monitor changes in the genetic diversity of captive populations, which is crucial to implement optimal mating decisions and assuring their long-term viability within an ex situ conservation programme.

Impacts of paternal latitudinal origin on herbivore response strategies in Lythrum salicaria

Plants have evolved different strategies to withstand and respond to herbivore stress. The two main strategies plants employ under herbivore stress are known as tolerance and induced resistance. Tolerance is the ability to maintain high fitness despite experiencing high levels of herbivore damage. While induced resistance typically involves changing the concentrations of internal secondary metabolites as a response to initial herbivory and to prevent further damage. These strategies can lead to fitness differences between populations that vary by latitudinal origin. Previous studies have focused on the occurrence of herbivore response in general, whereas this study will make a direct comparison between response types and their fitness implications. Our study investigates whether eastern North American populations of Lythrum salicaria respond differently to herbivore stress. F1 crosses between L. salicaria individuals with different parental latitudinal ranges were grown in a common garden under two experimental herbivory treatments (pesticide sprayed vs. no pesticide) at the Queen’s University Biological Station. To identify differences in herbivore tolerance, we measured plant growth and development over 13 weeks and quantified herbivore damage, caused by the biocontrol beetle Galerucella calmariensis. A 48-hour feeding assay was then conducted to identify differences in herbivore resistance between populations. This assay provided beetles with a choice between young and old L. salicaria leaves from each experimental treatment. Our preliminary analysis of the feeding assay showed differences in leaf damage between parental lines. The initial analysis also showed that older leaves generally experienced more damage than younger leaves over the course of the 48-hour period. These results indicate population differences in herbivory stress response and differences in stress response effectiveness that varies with plant age. This experiment showed that L. salicaria individuals have varying degrees of herbivore stress response and effectiveness. However, further analysis that includes reproductive outputs and developmental differences will be completed to clearly identify the type of strategies L. salicaria populations with different parental latitudinal origins employ in response to herbivore damage.

Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries

Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Is gender primacy universal?

Emerging evidence suggests that gender is a defining feature of personhood. Studies show that gender is the primary social category individuals use to perceive humanness and the social category most strongly related to seeing someone-or something-as human. However, the universality of gender's primacy in social perception and its precedence over other social categories like race and age have been debated. We examined the primacy of gender perception in the Mayangna community of Nicaragua, a population with minimal exposure to Western influences, to test whether the primacy of gender categorization in humanization is more likely to be a culturally specific construct or a cross-cultural and potentially universal phenomenon. Consistent with findings from North American populations [A. E. Martin, M. F. Mason, J. Pers. Soc. Psychol. 123, 292-315 (2022)], the Mayangna ascribed gender to nonhuman objects more strongly than any other social category-including age, race, sexual orientation, disability, and religion-and gender was the only social category that uniquely predicted perceived humanness (i.e., the extent to which a nonhuman entity was seen as "human"). This pattern persisted even in the most isolated subgroup of the sample, who had no exposure to Western culture or media. The present results thus suggest that gender's primacy in social cognition is a widely generalizable, and potentially universal, phenomenon.

Assortative mating and the dark triad: Evidence from the UK, Fiji, and meta-analytic review

The ‘dark triad’ represents the socially aversive personality traits of Machiavellianism, subclinical narcissism (henceforth, ‘narcissim’), and subclinical psychopathy (henceforth, ‘psychopathy’). There is evidence of assortative mating suggesting romantic partners are more similar than chance for these traits at the start of relationships (initial assortment) and not becoming alike with time (convergence), that people seek out partners to whom they are similar (active assortment), and that partner resemblance is not explained by social stratification processes (social homogamy). As the literature relates primarily to Eastern European and North American populations, we present studies from the UK (N = 104 couples) and Fiji (N = 99 couples). These showed significant positive assortment for each dark triad trait (other than psychopathy in the Fijian sample), and suggest the effects are explained by initial and active assortment and not by convergence or social homogamy. We also submitted the literature to meta-analytic review (Machiavellianism: k = 10, N = 1302; narcissism: k = 14, N = 1645; psychopathy: k = 13, N = 1989) and observed positive within-couple correlations of small (narcissism, psychopathy) to medium (Machiavellianism) effect size for each of the dark triad traits.

Does introduced European Phragmites australis experience belowground microbial enemy release in North America?

AbstractEscape from native range enemies can give invasive species a competitive edge according to the enemy‐release hypothesis. While more commonly associated with predators and herbivores, release from belowground microbial antagonists has been recently demonstrated to benefit invasive plants. Biogeographic variation in dominance and comparisons of soil communities suggest that invasive European Phragmites australis may have also benefitted from belowground enemy release in North America (NA). Here we examine the effects of native range (Europe) versus introduced range (NA) soil communities on European and North American P. australis using a reciprocal inoculation seedling growth experiment. Contrary to the enemy‐release hypothesis, we found that North American P. australis was sensitive to soil community origin in that the seedlings grown in European soil communities had higher total biomass than seedlings grown in North American soil communities. This pattern was not observed in the European P. australis seedlings which had similar biomass when grown with North American or European soil communities. Notably, North American P. australis had higher biomass than European P. australis regardless of which soil community it was grown in, suggesting a growth–defense tradeoff. Though the relative abundance of mutualists and pathogens composition did not differ between the two ranges, an indicator analysis revealed that mutualistic fungi and bacteria were key components of European soil communities but not in North American communities. Interestingly, North American soil communities had lower β diversity than European communities suggesting higher levels of community conservation among North American populations. This research represents the first evidence of growth–defense trade‐offs in North American P. australis and offers a novel mechanism in understanding the invasion of P. australis in NA.

New insights on the chromosomal inversion thermal adaptation in insects: American populations of Drosophila subobscura

AbstractDrosophila subobscura is an excellent model species for testing genetic variation in thermal adaptation due to its rich inversion chromosomal polymorphism. In Palearctic populations, the inversions of this species can be classified as “cold”, “warm” or “nonthermal” adapted. Based on this classification the Chromosomal Thermal Index (CTI) was developed, which allows measuring the thermal adaptation of populations and monitoring changes over time. Here, we aim to use this index in American colonizing populations of D. subobscura for the first time to obtain new information on the species thermal adaptation. Thus, thermal adapted inversions (“cold” and “warm”) were defined for the American continent and CTI was computed in South American (1981 and 1999 samples) and North American (1985 and 2004 samples) populations of D. subobscura. In general, both American populations showed an inverse relationship between CTI values and latitude, with CTI values decreasing when latitude increases. When comparing populations sampled in different years, an increase in CTI values was detected in four out of six temporal comparisons (only one was significant) of South America (1981 and 1999) and in six out of seven populations of North America (1985 and 2004). A global analysis using a one‐way repeated measures anova of CTI values in both American hemispheres showed a trend of increase for “warm” adapted inversions in Chile and North America, but this increase was only significant for the latter. Overall, these results are in agreement with global warming expectations, although natural selection acted differently in the colonized hemispheres.

Impact of Prostate-Specific Antigen Screening Pattern on Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White Men: A Large, Urban Health System Cohort Analysis.

Randomized studies assessing the effect of PSA screening on mortality in non-Hispanic Black (NHB) men are lacking. We aimed to assess the association between PSA screening and survival among NHB men in comparison to non-Hispanic White (NHW) men in a racially diverse real-world North American population. The study cohort included 6378 men who self-identified as NHB or NHW and were diagnosed with prostate cancer (PCa). Patients received PSA screening and subsequent PCa treatment and follow-up at our institution. Patients were sorted based on PSA testing intensity for the 5 years prior to diagnosis, as follows: never, some (<1 test/y), and annual testing (1 test/y). The primary outcome was risk of prostate cancer-specific mortality (PCSM). Competing risk cumulative incidence curves estimated PCSM rates. Competing risk regression analyses examined the impact of PSA testing on PCSM. An interaction term was incorporated to assess the impact of race on the outcome. Median (IQR) age and PSA at diagnosis were 67 (60-73) years and 5.8 (4.4-9.6) ng/mL, respectively, and 2929 (46%) men were NHB (Kruskal-Wallis P values < .001). Annual PSA testing was more frequent in NHW (5%) than in NHB (3%) men (χ2 P value < .001). On cumulative incidence analysis, in the never, some, and annual PSA testing groups, the 10-year PCSM was respectively 12.3%, 5.8%, and 4.6% in NHW and 18.5%, 7%, and 1.2% in NHB patients (Gray's test P values < .001). At competing risk regression, PSA screening rate was associated with more favorable PCSM rates (HR: 0.47; 95% CI 0.33-0.68; P < .001). The interaction term for race did not show statistical significance (P = .2). PSA testing was associated with a reduced risk of PCSM in both NHB and NHW men diagnosed with PCa. Additionally, the positive impact of the screening rate seemed to be independent of race.

Parkinson's disease variant detection and disclosure: PD GENEration, a North American study.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease.

Baseline Association between Healthy Eating Index-2015 and Health-Related Quality of Life in Breast Cancer Patients Enrolled in a Randomized Trial.

Health-related quality of life (HRQoL) represents one of the most concerning aspects for cancer patients. The Healthy Eating Index (HEI) is an a priori diet quality index directly associated with health outcomes and HRQoL in cancer survivors in North American populations. We evaluated, in a Mediterranean population, the baseline associations between HEI-2015 and HRQoL in 492 women with breast cancer recruited in a DEDiCa lifestyle trial. Dietary data were obtained from 7-day food records; HRQoL was assessed through the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) and the C30 Summary Score (SumSc). Analysis of variance and multivariable linear and log-gamma regression models were performed. Mean and standard deviation for HEI-2015 score was 68.8 ± 11.2; SumSc was 81.5 ± 12.9. Women with lower HEI-2015 score had higher BMI, were more frequently exposed to tobacco smoke and had fewer years of education. Patients with a HEI-2015 score greater than 68.7 (median value) showed a significant increase in SumSc of 4% (p = 0.02). HEI-2015 components also associated with SumSc were beans and greens (β = 1.04; p = 0.02). Weak associations were found for total vegetables and saturated fats. Higher diet quality in breast cancer survivors was associated with higher overall HRQoL in this cross-sectional analysis.

CRISPR-Cas9 and Cas12a target site richness reflects genomic diversity in natural populations of Anopheles gambiae and Aedes aegypti mosquitoes

Due to limitations in conventional disease vector control strategies including the rise of insecticide resistance in natural populations of mosquitoes, genetic control strategies using CRISPR gene drive systems have been under serious consideration. The identification of CRISPR target sites in mosquito populations is a key aspect for developing efficient genetic vector control strategies. While genome-wide Cas9 target sites have been explored in mosquitoes, a precise evaluation of target sites focused on coding sequence (CDS) is lacking. Additionally, target site polymorphisms have not been characterized for other nucleases such as Cas12a, which require a different DNA recognition site (PAM) and would expand the accessibility of mosquito genomes for genetic engineering. We undertook a comprehensive analysis of potential target sites for both Cas9 and Cas12a nucleases within the genomes of natural populations of Anopheles gambiae and Aedes aegypti from multiple continents. We demonstrate that using two nucleases increases the number of targets per gene. Also, we identified differences in nucleotide diversity between North American and African Aedes populations, impacting the abundance of good target sites with a minimal degree of polymorphisms that can affect the binding of gRNA. Lastly, we screened for gRNAs targeting sex-determination genes that could be widely applicable for developing field genetic control strategies. Overall, this work highlights the utility of employing both Cas9 and Cas12a nucleases and underscores the importance of designing universal genetic strategies adaptable to diverse mosquito populations.

One-year post-acute COVID-19 syndrome and mortality in South Korea: a nationwide matched cohort study using claims data.

Current understanding of post-COVID-19 syndrome in South Korea is primarily based on survey studies or research targeting specific patient groups, such as those hospitalized. Moreover, the majority of relevant studies have been conducted in European and North American populations, which may limit their applicability to the South Korean context. To address this gap, our study explores the one-year outcomes of COVID-19, focusing on the potential post-acute syndrome and all-cause mortality in South Korea. This retrospective cohort study used nationwide claims data in South Korea, including adults aged >18 with records between January 20, 2020, and February 25, 2021. Patients were classified into COVID-19 and non-COVID-19 groups and matched 1:1 based on propensity scores. Primary outcomes were 12-month post-acute COVID-19 syndrome and all-cause mortality. The study involved 34,802 matched patients. The COVID-19 group had significantly elevated risks of coagulopathies (OR = 2.70 [2.24, 3.28]; p < 0.001), chronic lower respiratory diseases (OR = 1.96 [1.80, 2.14]; p < 0.001), symptoms of the circulatory and respiratory systems (OR = 1.91 [1.80, 2.04]; p < 0.001), mood disorders (OR = 1.67 [1.51, 1.86]; p < 0.001), cardiac diseases (OR = 1.39 [1.21, 1.59]; p < 0.001), and symptoms of cognition, perception, emotional state, and behavior (OR = 1.15 [1.04, 1.27]; p = 0.005). All-cause mortality was higher in the COVID-19 group during the 6 months (OR = 1.34 [1.06, 1.69]; p = 0.015), but gradually decreased, reaching an OR of 0.996 ([0.83, 1.19]; p = 0.964) at 1 year. In South Korea, the 12-month post-acute COVID-19 syndrome includes coagulopathies, respiratory issues, mood disorders, and cardiac diseases. The risk of all-cause mortality post-COVID-19 is heightened for up to 6 months, then significantly decreases and resolves within a year.

Increased prevalence of valgus constitutional alignment subtypes in a South African arthritic population group using the coronal plane alignment of the knee (CPAK) classification

BackgroundKnee alignment philosophies and patient specific models to improve patient reported outcomes are gaining increasing attention. The coronal plane alignment of the knee (CPAK) classification describes nine knee phenotypes and then proposes surgical alignment strategies to achieve constitutional alignment. The CPAK classification has been validated in Australian, European, Asian and North American population groups. To date no African data has been analyzed using CPAK. MethodsA total of 344 arthritic patients (608 knees) with appropriate long leg radiographs were classified based on the CPAK type. Measurements included mechanical hip-knee-angle(mHKA), medial proximal tibial angle (mMPTA) and lateral distal femoral angle (mLDFA) and the derived calculations of joint line obliquity (JLO) and arithmetic hip-knee-angle (aHKA). ResultsThe sample population was 77.9% (n = 268) female with a mean age of 68.4 ± 9.2 years. The most common CPAK types in order were type 3 (n = 174; 28.6%), type 2 (n = 155; 25.5%), type 1 (n = 94; 15.5%) and type 6 (n = 80; 13.2%). The most common limb alignment types were valgus (CPAK types 3,6,9; 41.8%). ConclusionThis study, which investigated arthritic patients from a single institution in South Africa, shows a divergence of CPAK phenotypic knee patterns relative to other international studies, with much higher proportions of valgus phenotypes (3 and 6). This regional difference should be further investigated in other South African and African population samples and used to adapt the surgical strategies employed by local surgeons.

Across two continents: The genomic basis of environmental adaptation in house mice (Mus musculus domesticus) from the Americas.

Replicated clines across environmental gradients can be strong evidence of adaptation. House mice (Mus musculus domesticus) were introduced to the Americas by European colonizers and are now widely distributed from Tierra del Fuego to Alaska. Multiple aspects of climate, such as temperature, vary predictably across latitude in the Americas. Past studies of North American populations across latitudinal gradients provided evidence of environmental adaptation in traits related to body size, metabolism, and behavior and identified candidate genes using selection scans. Here, we investigate genomic signals of environmental adaptation on a second continent, South America, and ask whether there is evidence of parallel adaptation across multiple latitudinal transects in the Americas. We first identified loci across the genome showing signatures of selection related to climatic variation in mice sampled across a latitudinal transect in South America, accounting for neutral population structure. Consistent with previous results, most candidate SNPs were in putatively regulatory regions. Genes that contained the most extreme outliers relate to traits such as body weight or size, metabolism, immunity, fat, eye function, and the cardiovascular system. We then compared these results with the results of analyses of published data from two transects in North America. While most candidate genes were unique to individual transects, we found significant overlap among candidate genes identified independently in the three transects. These genes are diverse, with functions relating to metabolism, immunity, cardiac function, and circadian rhythm, among others. We also found parallel shifts in allele frequency in candidate genes across latitudinal gradients. Finally, combining data from all three transects, we identified several genes associated with variation in body weight. Overall, our results provide strong evidence of shared responses to selection and identify genes that likely underlie recent environmental adaptation in house mice across North and South America.

Evolution of "invasion syndrome" in invasive goldenrod is not constrained by genetic trade-offs.

A suite of plant traits is thought to make weed populations highly invasive, including vigorous growth and reproduction, superior competitive ability, and high dispersal ability. Using a breeding design and a common garden experiment, we tested whether such an "invasion syndrome" has evolved in an invasive range of Solidago altissima, and whether the evolution is likely to be genetically constrained. We found an overall shift in invasive phenotypes between native North American and invasive Japanese populations. The invasive populations were taller and produced more leaves, suggesting a superior ability to exploit limited resources. The populations also produced more allelopathic compounds that can suppress competitor growth. Finally, invasive populations produced more seeds, which are smaller and are released from a greater height, indicating a potential for superior dispersal ability than the native populations. Quantitative genetics analyses found a large amount of additive genetic variation in most focal traits across native and invasive populations, with no systematic differences in its magnitude between the ranges. Genetic covariances among three traits representing invasion strategies (leaf mass, polyacetylene concentration and seed size) were small. The R metric, which measures the effect of genetic covariances on the rate of adaptation, indicated that the covariance neither constrains nor accelerates concerted evolution of these traits. The results suggest that the invasion syndrome in S. altissima has evolved in the novel range due to ample additive genetic variation, and relatively free from genetic trade-offs.