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Value-based care models, such as Medicaid accountable care organizations (ACOs), have the potential to improve access to and quality of care for pregnant and postpartum Medicaid enrollees. We leveraged a natural experiment in Massachusetts to evaluate the effects of Medicaid ACOs on quality-of-care-sensitive measures and care use across the prenatal, delivery, and postpartum periods. Using all-payer claims data on Medicaid-covered live deliveries in Massachusetts, we used a difference-in-differences approach to compare measures before (the first quarter of 2016 through the fourth quarter of 2017) and after (the third quarter of 2018 through the fourth quarter of 2020) Medicaid ACO implementation among ACO and non-ACO patients. After three years of implementation, the Medicaid ACO was associated with statistically significant increases in the probability of a timely postpartum visit, postpartum depression screening, and number of all-cause office visits in the prenatal and postpartum periods, with no changes in severe maternal morbidity, preterm birth, postpartum glucose screening, or prenatal or postpartum emergency department visits. Changes in cesarean deliveries were inconclusive. Results suggest that implementing Medicaid ACOs in the thirty-eight states without them could improve maternal health care outpatient engagement, but alone it may be insufficient to improve maternal health outcomes.

Nitrogenases are the only known enzymes that reduce molecular nitrogen (N 2 ) to ammonia. Recent findings have demonstrated that nitrogenases also reduce the greenhouse gas carbon dioxide (CO 2 ), suggesting CO 2 to be a competitor of N 2 . However, the impact of omnipresent CO 2 on N 2 fixation has not been investigated to date. Here, we study the competing reduction of CO 2 and N 2 by the two nitrogenases of Rhodobacter capsulatus , the molybdenum and the iron nitrogenase. The iron nitrogenase is almost threefold more efficient in CO 2 reduction and profoundly less selective for N 2 than the molybdenum isoform under mixtures of N 2 and CO 2 . Correspondingly, the growth rate of diazotrophically grown R. capsulatus strains relying on the iron nitrogenase notably decreased after adding CO 2 . The in vivo CO 2 activity of the iron nitrogenase facilitates the light-driven extracellular accumulation of formate and methane, one-carbon substrates for other microbes, and feedstock chemicals for a circular economy.

Importance: Transitions in insurance coverage may be associated with worse health care outcomes. Little is known about insurance stability for individuals with opioid use disorder (OUD)., Objective: To examine insurance transitions among adults with newly diagnosed OUD in the 12 months after diagnosis., Design, Setting, and Participants: Longitudinal cohort study using data from the Massachusetts Public Health Data Warehouse. The cohort includes adults aged 18 to 63 years diagnosed with incident OUD between July 1, 2014, and December 31, 2014, who were enrolled in commercial insurance or Medicaid at diagnosis; individuals diagnosed after 2014 were excluded from the main analyses due to changes in the reporting of insurance claims. Data were analyzed from November 10, 2022, to May 6, 2024., Exposure: Insurance type at time of diagnosis (commercial and Medicaid)., Main Outcomes and Measures: The primary outcome was the cumulative incidence of insurance transitions in the 12 months after diagnosis. Logistic regression models were used to generate estimated probabilities of insurance transitions by insurance type and diagnosis for several characteristics including age, race and ethnicity, and whether an individual started medication for OUD (MOUD) within 30 days after diagnosis., Results: There were 20 768 individuals with newly diagnosed OUD between July 1, 2014, and December 31, 2014. Most individuals with newly diagnosed OUD were covered by Medicaid (75.4%). Those with newly diagnosed OUD were primarily male (67% in commercial insurance, 61.8% in Medicaid). In the 12 months following OUD diagnosis, 30.4% of individuals experienced an insurance transition, with adjusted models demonstrating higher transition rates among those starting with Medicaid (31.3%; 95% CI, 30.5%-32.0%) compared with commercial insurance (27.9%; 95% CI, 26.6%-29.1%). The probability of insurance transitions was generally higher for younger individuals than older individuals irrespective of insurance type, although there were notable differences by race and ethnicity., Conclusions and Relevance: This study found that nearly 1 in 3 individuals experience insurance transitions in the 12 months after OUD diagnosis. Insurance transitions may represent an important yet underrecognized factor in OUD treatment outcomes.

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia., (© 2024. The Author(s).)

During Drosophila oogenesis, the Oskar (OSK) RNA binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here, we identify mechanisms that subsequently regulate germ plasm assembly in the early embryo. We show that the Smaug (SMG) RBP is transported into the germ plasm of the early embryo where it accumulates in the germ granules. SMG binds to and represses translation of the osk messenger RNA (mRNA) as well as the bruno 1 ( bru1 ) mRNA, which encodes an RBP that we show promotes germ plasm production. Loss of SMG or mutation of SMG's binding sites in the osk or bru1 mRNA results in excess translation of these transcripts in the germ plasm, accumulation of excess germ plasm, and budding of excess primordial germ cells (PGCs). Therefore, SMG triggers a posttranscriptional regulatory pathway that attenuates the amount of germ plasm in embryos to modulate the number of PGCs.

Microbes can be found in abundance many kilometers underground. While microbial metabolic capabilities have been examined across different geochemical settings, it remains unclear how changes in subsurface niches affect microbial needs to sense and respond to their environment. To address this question, we examined how microbial extracellular sensor systems vary with environmental conditions across metagenomes at different Deep Mine Microbial Observatory (DeMMO) subsurface sites. Because two-component systems (TCSs) directly sense extracellular conditions and convert this information into intracellular biochemical responses, we expected that this sensor family would vary across isolated oligotrophic subterranean environments that differ in abiotic and biotic conditions. TCSs were found at all six subsurface sites, the service water control, and the surface site, with an average of 0.88 sensor histidine kinases (HKs) per 100 genes across all sites. Abundance was greater in subsurface fracture fluids compared with surface-derived fluids, and candidate phyla radiation (CPR) bacteria presented the lowest HK frequencies. Measures of microbial diversity, such as the Shannon diversity index, revealed that HK abundance is inversely correlated with microbial diversity ( r 2 = 0.81). Among the geochemical parameters measured, HK frequency correlated most strongly with variance in dissolved organic carbon ( r 2 = 0.82). Taken together, these results implicate the abiotic and biotic properties of an ecological niche as drivers of sensor needs, and they suggest that microbes in environments with large fluctuations in organic nutrients (e.g., lacustrine, terrestrial, and coastal ecosystems) may require greater TCS diversity than ecosystems with low nutrients (e.g., open ocean).IMPORTANCEThe ability to detect extracellular environmental conditions is a fundamental property of all life forms. Because microbial two-component sensor systems convert information about extracellular conditions into biochemical information that controls their behaviors, we evaluated how two-component sensor systems evolved within the deep Earth across multiple sites where abiotic and biotic properties vary. We show that these sensor systems remain abundant in microbial consortia at all subterranean sampling sites and observe correlations between sensor system abundances and abiotic (dissolved organic carbon variation) and biotic (consortia diversity) properties. These results suggest that multiple environmental properties may drive sensor protein evolution and highlight the need for further studies of metagenomic and geochemical data in parallel to understand the drivers of microbial sensor evolution., Competing Interests: The authors declare no conflict of interest.

Preserving insurance coverage in the wake of pandemic-related job loss was a priority in early 2020. To this end, the Families First Coronavirus Response Act implemented a continuous coverage policy in Medicaid to shore up access to health insurance. Prior to the pandemic, Medicaid enrollees experienced frequent coverage disruptions, known as "churning." The effect of the continuous coverage policy on churning during the COVID-19 public health emergency (PHE) is unknown. We performed a difference-in-differences analysis of nonelderly Medicaid enrollees using longitudinal national survey data to compare a 2019-2020 cohort exposed to the policy with a control cohort in 2018-2019. We found that the policy led to reduced transitions to uninsurance among adults, although not among children. The policy prevented over 300 000 transitions to uninsurance each month. However, disenrollment from Medicaid persisted at a low rate, despite the continuous coverage policy. As the PHE unwinds, policymakers should consider long-term continuous coverage policies to minimize churning in Medicaid., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials.

Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients mostly including unaffected siblings (SIB) with neurotypical controls (NC) at the same age stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R 2 varied from 0.02 to 0.05). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlates with genetic risk for SCZ and is detectable with MRI in young participants.

Rationale: Incidental radiographic findings are common, and primary care providers (PCPs) are often charged with the conducting or initiating an appropriate evaluation. Clinical guidelines are available for management of common 'incidentalomas' including lung and adrenal nodules, but guidelines-adherent evaluations are not always performed; for example, in the setting of incidental adrenal masses (IAMs), recent literature suggests that an evidence-based evaluation occurs in <25% of patients for whom it is warranted-a quality and safety concern., Aims and Objectives: The objective of this study was to examine whether point-of-care access to concise clinical guidelines would promote appropriate evaluations of two common incidentalomas: IAMs and lung nodules., Method: This study was a survey-based, single-blinded, randomized experiment of decision-making within clinical vignettes. Respondents were PCPs in a variety of clinical practice settings, and half were randomly assigned to surveys that included concise clinical guidelines while the other half served as controls without access to guidelines. Scenarios involved patients with IAMs and lung nodules, and the scenarios included both higher-risk and lower-risk lesions. Our primary analysis examined safe versus inappropriate clinical decisions, while a secondary analysis compared guidelines-concordant versus guidelines-discordant responses., Results: For both the higher-risk IAM and higher-risk lung nodule scenarios, safe answer choices were selected at a similar rate by respondents regardless of whether they had access to guidelines or not. However, for the lower risk scenarios, inappropriate answer choices were chosen substantially more frequently by respondents without access to guidelines compared to those with the guidelines (lung: 29.3% vs. 4.5%, p = 0.003, adrenal: 31.6% vs. 7.0%, p = 0.01). There was less variation in the secondary analysis., Conclusion: Survey respondents were significantly more likely to make safe management decisions in lower-risk clinical scenarios when clinical guidelines were available. Point-of-care access to clinical guidelines for incidentalomas is an intervention that may reduce management errors and improve patient safety., (© 2023 John Wiley & Sons Ltd.)

Objective: Accumulating evidence demonstrates that gender affirming hormone therapy (GAHT) improves mental health outcomes in transgender persons. Data specific to the risks associated with GAHT for transgender persons continue to emerge, allowing for improvements in understanding, predicting, and mitigating adverse outcomes while informing discussion about desired effects. Of particular concern is the risk of venous thromboembolism (VTE) in the context of both longitudinal GAHT and the perioperative setting. Combining what is known about the risk of VTE in cisgender individuals on hormone therapy (HT) with the evidence for transgender persons receiving HT allows for an informed approach to assess underlying risk and improve care in the transgender community., Observations: Hormone formulation, dosing, route, and duration of therapy can impact thromboembolic risk, with transdermal estrogen formulations having the lowest risk. There are no existing risk scores for VTE that consider HT as a possible risk factor. Risk assessment for recurrent VTE and bleeding tendencies using current scores may be helpful when assessing individual risk. Gender affirming surgeries present unique perioperative concerns, and certain procedures include a high likelihood that patients will be on exogenous estrogens at the time of surgery, potentially increasing thromboembolic risk., Conclusions and Relevance: Withholding GAHT due to potential adverse events may cause negative impacts for individual patients. Providers should be knowledgeable about the management of HT in transgender individuals of all ages, as well as in the perioperative setting, to avoid periods in which transgender individuals are off GAHT. Treatment decisions for both anticoagulation and HT should be individualized and tailored to patients' overall goals and desired outcomes, given that the physical and mental health benefits of gender affirming care may outweigh the risk of VTE., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Importance: Physician work hours are an underexplored facet of the physician workforce that can inform policy for the rapidly changing health care labor market., Objective: To examine trends in individual physician work hours and their contribution to clinical workforce changes over a 20-year period., Design, Setting, and Participants: This cross-sectional study focused on active US physicians between January 2001 and December 2021 who were included in the Current Population Survey. Outcomes for physicians, advanced practice professionals (APPs), and nonphysician holders of doctoral degrees were compared, and generalized linear models were used to estimate differences in time trends for weekly work hours across subgroups., Main Outcomes and Measures: Physician and APP workforce size, defined as the number of active clinicians, 3-year moving averages of weekly work hours by individual physicians, and weekly hours contributed by the physician and APP workforce per 100 000 US residents., Results: A total of 87 297 monthly surveys of physicians from 17 599 unique households were included in the analysis. The number of active physicians grew 32.9% from 2001 to 2021, peaking in 2019 at 989 684, then falling 6.7% to 923 419 by 2021, with disproportionate loss of physicians in rural areas. Average weekly work hours for individual physicians declined by 7.6% (95% CI, -9.1% to -6.1%), from 52.6 to 48.6 hours per week from 2001 to 2021. The downward trend was driven by decreasing hours among male physicians, particularly fathers (11.9% decline in work hours), rural physicians (-9.7%), and physicians aged 45 to 54 years (-9.8%). Physician mothers were the only examined subgroup to experience a statistically significant increase in work hours (3.0%). Total weekly hours contributed by the physician workforce per 10 000 US residents increased by 7.0%, from 13 006 hours in 2001 to 2003 to 13 920 hours in 2019 to 2021, compared with 16.6% growth in the US population over that time period. Weekly hours contributed by the APP workforce per 100 000 US residents grew 71.2% from 2010 through 2012 to 2019 through 2021., Conclusions and Relevance: This cross-sectional study showed that physician work hours consistently declined in the past 20 years, such that physician workforce hours per capita lagged behind US population growth. This trend was offset by rapid growth in hours contributed by the APP workforce. The gap in physician work hours between men and women narrowed considerably, with diverging potential implications for gender equity. Increasing physician retirement combined with a drop in active physicians during the COVID-19 pandemic may further slow growth in physician workforce hours per capita in the US.

Aging is associated with a progressive decrease in skeletal muscle mass, strength and power and impairment of physical function. Serum testosterone concentrations in men decrease with advancing age due to defects at all levels of the hypothalamic-pituitary-testicular axis. Testosterone administration increases skeletal muscle mass, strength and power in older men with low or low normal testosterone levels, but the effects on performance-based measures of physical function have been inconsistent. Adequately powered randomized trials are needed to determine the long-term safety and efficacy of testosterone in improving physical function and quality of life in older adults with functional limitations., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Total and free testosterone levels decline in men with advancing age due to defects at all levels of the hypothalamic-pituitary-testicular axis. Testosterone treatment of older men with low testosterone levels is associated with improvements in sexual activity, sexual desire, and erectile function; lean body mass, muscle strength, and stair climbing power, and self-reported mobility; areal and volumetric bone mineral density, and estimated bone strength; depressive symptoms; and anemia. Long-term risks of cardiovascular events and prostate cancer during testosterone treatment remain unknown. Testosterone treatment may be offered on an individualized basis to older men with unequivocally low testosterone levels and symptoms or conditions associated with testosterone deficiency after consideration of potential benefits and risks, burden of symptoms, and patient's values., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The Affordable Care Act takes a "patchwork" approach to expanding coverage: Medicaid covers individuals with incomes 138% of the federal poverty level (FPL) in expansion states, while subsidized Marketplace insurance is available to those above this income cutoff., Objective: To characterize the magnitude of churning between Medicaid and Marketplace coverage and to examine the impact of the 138% FPL income cutoff on stability of coverage., Design: We measured the incidence of transitions between Medicaid and Marketplace coverage. Then, we used a differences-in-differences framework to compare insurance churning in Medicaid expansion and non-expansion states, before and after the ACA, among adults with incomes 100-200% of poverty., Participants: Non-elderly adult respondents of the Medical Expenditure Panel Survey 2010-2018 MAIN MEASURES: The annual proportion of adults who (1) transitioned between Medicaid and Marketplace coverage; (2) experienced any coverage disruption., Key Results: One million U.S. adults transitioned between Medicaid and Marketplace coverage annually. The 138% FPL cutoff in expansion states was not associated with an increase in insurance churning among individuals with incomes close to the cutoff., Conclusions: Transitions between Medicaid and Marketplace insurance are uncommon-far lower than pre-ACA analyses predicted. The 138% income cutoff does not to contribute significantly to insurance disruptions., (© 2022. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes., (© 2022. The Author(s).)

The circulating concentrations of total and free testosterone vary substantially in people over time due to biologic factors as well as due to measurement variation. Accurate measurement of total and free testosterone is essential for making the diagnosis of androgen disorders. Total testosterone should ideally be measured in a fasting state in the morning using a reliable assay, such as liquid chromatography tandem mass spectrometry, in a laboratory that is certified by an accuracy-based benchmark. Free testosterone levels should be measured in men in whom alterations in binding protein concentrations are suspected or in whom total testosterone levels are only slightly above or slightly below the lower limit of the normal male range for testosterone., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to concerns about the risk of infectious exposures during the coronavirus disease 2019 (COVID-19) pandemic, the uptake of telemedicine has increased rapidly, aided by increased acceptance by clinicians and patients and a reduction in regulatory and reimbursement hurdles. The increased access to telemedicine may have benefits beyond the reduction in contagious risk, especially for vulnerable populations. By breaking down some of the common barriers to care for vulnerable populations, the broad implementation of telemedicine may help reduce some inequities in health care access, but telemedicine does raise other challenges that need to be considered and addressed. One vulnerable group that can benefit from telemedicine is transgender and gender nonbinary (TGNB) individuals, who have less access to both gender-affirming and general medical care due to the consequences of stigma, discrimination, and marginalization. Telemedicine allows TGNB individuals to access clinical expertise even if it is not available locally, and without the expense of travel and without the concern for exposure to discrimination and mistreatment. However, lack of access to or expertise in navigating the required technology, lack of a safe and confidential space to access care, and an unpredictable regulatory and reimbursement environment remain hurdles for harvesting the full benefits of telemedicine., Competing Interests: No competing financial interests exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Background: Incidental adrenal masses (IAMs) are common. Primary care providers (PCPs) are frequently responsible for incidentaloma evaluations. We evaluated whether PCPs view this paradigm effective, barriers faced, and strategies to optimize care delivery., Methods: This is a sequential explanatory study, comprised of surveys followed by focus groups of PCPs. Because lung nodules are another type of common incidental finding, we compared PCP views on management of lung nodules to their views on IAMs., Results: For IAMs, 22.3% of PCPs "always refer" to specialists, but for lung nodules this was 11.5% (p = 0.026). For lung nodules, the most significant barrier was insufficient time/support to longitudinally follow results (69%), but for IAMs it was uncertainty about which tests to order (68%). Fear of litigation was equal (lung = 22.5%, IAMs = 21.3%). Consistent themes regarding the "ideal" system included specific recommendations in radiology reports; automation of orders for follow-up tests; longitudinal tracking tools; streamlined consultations; and decision guides embedded within the electronic health record., Conclusions: Respondents are more comfortable with lung nodules than IAMs. Management of "incidentalomas" is within their scope of practice, but the current system can be optimized., (Copyright © 2021 Elsevier Inc. All rights reserved.)

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10 -5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

We propose a novel optimization framework that integrates imaging and genetics data for simultaneous biomarker identification and disease classification. The generative component of our model uses a dictionary learning framework to project the imaging and genetic data into a shared low dimensional space. We have coupled both the data modalities by tying the linear projection coefficients to the same latent space. The discriminative component of our model uses logistic regression on the projection vectors for disease diagnosis. This prediction task implicitly guides our framework to find interpretable biomarkers that are substantially different between a healthy and disease population. We exploit the interconnectedness of different brain regions by incorporating a graph regularization penalty into the joint objective function. We also use a group sparsity penalty to find a representative set of genetic basis vectors that span a low dimensional space where subjects are easily separable between patients and controls. We have evaluated our model on a population study of schizophrenia that includes two task fMRI paradigms and single nucleotide polymorphism (SNP) data. Using ten-fold cross validation, we compare our generative-discriminative framework with canonical correlation analysis (CCA) of imaging and genetics data, parallel independent component analysis (pICA) of imaging and genetics data, random forest (RF) classification, and a linear support vector machine (SVM). We also quantify the reproducibility of the imaging and genetics biomarkers via subsampling. Our framework achieves higher class prediction accuracy and identifies robust biomarkers. Moreover, the implicated brain regions and genetic variants underlie the well documented deficits in schizophrenia., (Copyright © 2021. Published by Elsevier Inc.)

Human serum albumin (HSA) acts as a carrier for testosterone, other sex hormones, fatty acids, and drugs. However, the dynamics of testosterone's binding to HSA and the structure of its binding sites remain incompletely understood. Here, we characterize the dynamics of testosterone's binding to HSA and the stoichiometry and structural location of the binding sites using 2-dimensional nuclear magnetic resonance (2D NMR), fluorescence spectroscopy, 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt partitioning, and equilibrium dialysis, complemented by molecular modeling. 2D NMR studies showed that testosterone competitively displaced 18-[13C]-oleic acid from at least 3 known fatty acid binding sites on HSA that also bind many drugs. Binding isotherms of testosterone's binding to HSA generated using fluorescence spectroscopy and equilibrium dialysis were nonlinear and the apparent dissociation constant varied with different concentrations of testosterone and HSA. The binding isotherms neither conformed to a linear binding model with 1:1 stoichiometry nor to 2 independent binding sites; the binding isotherms were most consistent with 2 or more allosterically coupled binding sites. Molecular dynamics studies revealed that testosterone's binding to fatty acid binding site 3 on HSA was associated with conformational changes at site 6, indicating that residues in in these 2 distinct binding sites are allosterically coupled. There are multiple, allosterically coupled binding sites for testosterone on HSA. Testosterone shares these binding sites on HSA with free fatty acids, which could displace testosterone from HSA under various physiological states or disease conditions, affecting its bioavailability., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Coverage disruptions and coverage loss occur frequently among Medicaid enrollees and are associated with delayed health care access and reduced medication adherence. Little is known about the effect on churning of the expansion of eligibility for Medicaid under the Affordable Care Act (ACA), which had the potential to reduce coverage disruptions as a result of increased outreach and more generous income eligibility criteria. We used a difference-in-differences framework to compare rates of coverage disruption in expansion versus nonexpansion states, and in subgroups of states that used alternative expansion strategies. We found that among low-income Medicaid beneficiaries ages 19-64, disruption in coverage decreased 4.3 percentage points in the post-ACA period in expansion states compared to nonexpansion states, and there was a similar decrease in the share of people who experienced a period without any insurance. Men, people of color, and those without chronic illnesses experienced the largest improvements in coverage continuity. Coverage disruptions declined in both traditional expansion states and those that used Section 1115 waivers for expansion. Our quasi-experimental study provides the first nationwide evidence that Medicaid expansion led to decreased rates of coverage disruption. We estimate that half a million fewer adults experienced an episode of churning annually.

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Background: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects., Methods: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects., Results: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects., Conclusions: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)