Synthetic minichromosomes in plants: past, present, and promise.

The status of engineered mini-chromosomes/artificial chromosomes/synthetic chromosomes in plants is summarized. Their promise is that they provide a means to accumulate foreign genes on an independent entity other than the normal chromosomes, which would facilitate stacking of novel traits in a way that would not be linked to endogenous genes and that would facilitate transfer between lines. Centromeres in plants are epigenetic, and therefore the isolation of DNA underlying centromeres and reintroduction into plant cells will not establish a functional kinetochore, which obviates this approach for in vitro assembly of plant artificial chromosomes.

Measuring autism with the ADOS-2 using a bifactor model.

The measurement of autism characteristics can be challenging due to variability of social impairments and restricted and repetitive behaviors or interests (RRBs). Psychometrically strong measures such as the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) can improve our capacity for thorough autism assessment. The conceptualization of the ADOS-2 has been shaped by research exploring the structure of its items, which evaluate autism traits associated with social affect and RRBs.

Combining Biomarkers to Improve Diagnostic Accuracy in Detecting Diseases With Group-Tested Data.

We consider the problem of combining multiple biomarkers to improve the diagnostic accuracy of detecting a disease when only group-tested data on the disease status are available. There are several challenges in addressing this problem, including unavailable individual disease statuses, differential misclassification depending on group size and number of diseased individuals in the group, and extensive computation due to a large number of possible combinations of multiple biomarkers. To tackle these issues, we propose a pairwise model fitting approach to estimating the distribution of the optimal linear combination of biomarkers and its diagnostic accuracy under the assumption of a multivariate normal distribution.

Cancer mortality and geographic inequalities: a detailed descriptive and spatial analysis of social determinants across US counties, 2018-2021.

Objective: In the United States, cancer mortality rates continue to decline, yet geographic and racial disparities persist and are particularly evident in the Delta region, characterized by high economic distress and disease burden. We examined cancer mortality patterns by demographic groups across geographic region (Delta vs non-Delta) and investigated the influence of macro-level social determinants of health (SDoH) in cancer death.

Study Design And Methods: This observational study included cancer death records of individuals aged ≥20 years from 2018 to 2021 in the United States.

A Comparison of Statistical Methods for Studying Interactions of Chemical Mixtures.

Properly assessing the effects of environmental chemical exposures on disease risk remains a challenging problem in environmental epidemiology. Various analytic approaches have been proposed, but there are few papers that have compared the performance of different statistical methods on a single dataset. In this paper, we compare different regression-based approaches for estimating interactions between chemical mixture components using data from a case-control study on non-Hodgkin's lymphoma.

Rapid reorganization of serotonin projections and antidepressant response to 5-HT1A-biased agonist NLX-101 in fluoxetine-resistant cF1ko mice.

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) like fluoxetine remain a first-line treatment for major depression, but are effective in less than half of patients and can take 4-8 weeks to show results. In this study, we examined cF1ko mice with genetically induced upregulation of 5-HT1A autoreceptors that reduces 5-HT neuronal activity. These mice display anxiety- and depression-related behaviors that did not respond to chronic fluoxetine treatment.

CaMKIV-Mediated Phosphorylation Inactivates Freud-1/CC2D1A Repression for Calcium-Dependent 5-HT1A Receptor Gene Induction.

Calcium calmodulin-dependent protein kinase (CaMK) mediates calcium-induced neural gene activation. CaMK also inhibits the non-syndromic intellectual disability gene, Freud-1/CC2D1A, a transcriptional repressor of human serotonin-1A (5-HT1A) and dopamine-D2 receptor genes. The altered expression of these Freud-1-regulated genes is implicated in mental illnesses such as major depression and schizophrenia.

Cumulative incidence estimates for solid tumors after HCT in the CIBMTR and California Cancer Registry.

Compared with the general population, hematopoietic cell transplantation (HCT) survivors are at elevated risk for developing solid subsequent neoplasms (SNs). The Center for International Blood and Marrow Transplant Research (CIBMTR) is a key resource for quantifying solid SN incidence following HCT, but the completeness of SN ascertainment is uncertain. Within a cohort of 18 450 CIBMTR patients linked to the California Cancer Registry (CCR), we evaluated the completeness of solid SN data reported to the CIBMTR from 1991 to 2018 to understand the implications of using CIBMTR data alone or combined with CCR data to quantify the burden of solid SNs after HCT.

Age-Specific Cancer Mortality in the US During the COVID-19 Pandemic, March to December 2020.

Background: It is important to understand the impact of the COVID-19 pandemic on cancer death rates in 2020 in the US. We estimated whether there were larger-than-expected changes in cancer mortality rates from March to December 2020 after accounting for temporal and seasonal patterns using data from January 2011 to February 2020 by cancer type and age.

Methods: We obtained death counts and underlying causes of death by cancer type, month/year (2011-2020), and age group from the National Center for Health Statistics and population estimates from the US Census Bureau.

The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history.

Accommodating detection limits of multiple exposures in environmental mixture analyses: an overview of statistical approaches.

Background: Identifying the impact of environmental mixtures on human health is an important topic. However, such studies face challenges when exposure measurements lie below limit of detection (LOD). While various approaches for accommodating a single exposure subject to LOD have been used, their impact on mixture analysis has not been thoroughly investigated.

CUSCO: An Unobtrusive Custom Secure Audio-Visual Recording System for Ambient Assisted Living.

The ubiquity of digital technology has facilitated detailed recording of human behaviour. Ambient technology has been used to capture behaviours in a broad range of applications ranging from healthcare and monitoring to assessment of cooperative work. However, existing systems often face challenges in terms of autonomy, usability, and privacy.

Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review.

Background: The World Health Organization defines long COVID as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation." Estimations of approximately 50 million individuals suffer from long COVID, reporting low health-related quality of life. Patients develop ongoing persistent symptoms that continue for more than 12 weeks that are not explained by another alternative diagnosis.

An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort.

Background: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites.

Accounting for informative observation process in transition models of binary longitudinal outcome: Application to medical record data.

When extracting medical record data to form a retrospective cohort, investigators typically focus on a pre-specified study window, and select subjects who had hospital visits during that study window. However, such data extraction may suffer from an informative observation process, since sicker patients may have hospital visits more frequently. For example, Consecutive Pregnancy Study is a retrospective cohort study of women with multiple pregnancies in 23 Utah hospitals from 2003 to 2010, where the interest is to understand the risk factors of recurrent pregnancy outcomes, such as preterm birth.

Changes in smoking use and subsequent lung cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

Background: Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk.

Methods: We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

Conversion of the CG specific M.MpeI DNA methyltransferase into an enzyme predominantly methylating CCA and CCC sites.

We used structure guided mutagenesis and directed enzyme evolution to alter the specificity of the CG specific bacterial DNA (cytosine-5) methyltransferase M.MpeI. Methylation specificity of the M.

Chronic Desipramine Reverses Deficits in Cell Activity, Norepinephrine Innervation, and Anxiety-Depression Phenotypes in Fluoxetine-Resistant cF1ko Mice.

Selective serotonin (5-HT) reuptake inhibitors are only 30% effective for remission in subjects with major depression, and the best treatments for SSRI-resistant patients remain unclear. To model SSRI resistance, we used cF1ko mice with conditional deletion of the repressor Freud-1/CC2D1A in adult 5-HT neurons. Within weeks, this deletion leads to overexpression of 5-HT1A autoreceptors, reduced serotonergic activity, and fluoxetine-resistant anxiety-depression phenotype.

The Pediatric Proton and Photon Therapy Comparison Cohort: Study Design for a Multicenter Retrospective Cohort to Investigate Subsequent Cancers After Pediatric Radiation Therapy.

Purpose: The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially.

Asymmetric relationships and their effects on coexistence.

Species coexistence attracts wide interest in ecology. Modern coexistence theory (MCT) identifies coexistence mechanisms, one of which, storage effects, hinges on relationships between fluctuations in environmental and competitive pressures. However, such relationships are typically measured using covariance, which does not account for the possibility that environment and competition may be more related to each other when they are strong than when weak, or vice versa.

Nutritional Intake in Dichorionic Twin Pregnancies: A Descriptive Analysis of a Multisite United States Cohort.

Introduction: Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described.

Methods: In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012-2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency questionnaire during each trimester of pregnancy.