Rapid prediction of conformationally-dependent DFT-level descriptors using graph neural networks for carboxylic acids and alkyl amines.

Data-driven reaction discovery and development is a growing field that relies on the use of molecular descriptors to capture key information about substrates, ligands, and targets. Broad adaptation of this strategy is hindered by the associated computational cost of descriptor calculation, especially when considering conformational flexibility. Descriptor libraries can be precomputed agnostic of application to reduce the computational burden of data-driven reaction development.

Modular synthesis of aryl amines from 3-alkynyl-2-pyrones.

The synthesis of aryl amines from 3-alkynyl-2-pyrones and various amines is described. Mechanistically, the aryl amines are proposed to arise from the 3-alkynyl-2-pyrone substrates through their selective opening in a 1,6-fashion by secondary amines followed by decarboxylation and an unexpected rearrangement. The proposed mechanism is supported by quantum chemical transition-state calculations, which are consistent with the regiochemical outcome.

Win Ratio Analyses of Piperacillin-Tazobactam Versus Meropenem for Ceftriaxone-Nonsusceptible Escherichia coli or Klebsiella pneumoniae Bloodstream Infections: Post Hoc Insights From the MERINO Trial.

Background: Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance.

Trends in sleep duration in the U.S. from 2004 to 2018: A decomposition analysis.

Average sleep duration in the United States declined in recent years, and the decline may be linked with many biopsychosocial factors. We examine how a set of biopsychosocial factors have differentially contributed to the temporal trends in self-reported sleep duration across racial groups between 2004-2005 and 2017-2018. Using repeated nationally representative cross-sections from the National Health Interview Survey, we decompose the influence of biopsychosocial factors on sleep duration trends into two components.

Unified Synthesis of 2-Isocyanoallopupukeanane and 9-Isocyanopupukeanane through a "Contra-biosynthetic" Rearrangement.

Herein, we describe our synthetic efforts toward the pupukeanane natural products, in which we have completed the first enantiospecific route to 2-isocyanoallopupukeanane in 10 steps (formal synthesis), enabled by a key Pd-mediated cyclization cascade. This subsequently facilitated an unprecedented bio-inspired "contra-biosynthetic" rearrangement, providing divergent access to 9-isocyanopupukeanane in 15 steps (formal synthesis). Computational studies provide insight into the nature of this rearrangement.

An Asymmetric Aromatic Finkelstein Reaction: A Platform for Remote Diarylmethane Desymmetrization.

A first-of-its-kind enantioselective aromatic Finkelstein reaction is disclosed for the remote desymmetrization of diarylmethanes. The reaction operates through a copper-catalyzed C-I bond-forming event, and high levels of enantioselectivity are achieved through the deployment of a tailored guanidinylated peptide ligand. Strategic use of transition-metal-mediated reactions enables the chemoselective modification of the aryl iodide products; thus, the synthesis of a diverse set of otherwise difficult-to-access diarylmethanes with excellent levels of selectivity is realized from a common intermediate.

Are Changes in Somatic Health Reflected Differently in Updated Self-Ratings by Big-Five Personality Traits?

This longitudinal study tests whether the Big-Five personality traits influence the changes individuals make in self-rated health (SRH) as they adjust their initial level to account for information on concurrent changes in disease burden, activities of daily living (ADLs), and pain. A bi-variate Latent Growth Curve model was fitted to data to estimate longitudinal associations between SRH and each health measure across up-to-five repeated observations, collected from the year 2006 to 2018 from 13,096 participants in the Health and Retirement Study. Negative longitudinal associations between SRH and all three health reports were significantly stronger for those who are more conscientious.

Cost-Savings of Do Not Resuscitate Orders Among Elderly Patients With Heart Failure in the United States.

Do-not-resuscitate (DNR) orders should preclude the use of cardiopulmonary resuscitation and may be associated with patient outcomes for patients hospitalized with heart failure (HF). This study examined the association between DNR and costs, mortality, and length of stay. The study cohort was a national sample of 700 922 hospital admissions of patients aged >65 with a primary diagnosis of HF.

Strategic elements in computer-assisted retrosynthesis: A case study of the pupukeanane natural products.

Computer-assisted synthesis planning represents a growing area of research, especially for complex molecule synthesis. Here, we present a case study involving the pupukeanane natural products, which are complex, marine-derived, natural products with unique tricyclic scaffolds. Proposed routes to members of each skeletal class informed by pathways generated using the program Synthia are compared to previous syntheses of these molecules.

Treating a Global Health Crisis with a Dose of Synthetic Chemistry.

The SARS-CoV-2 pandemic has prompted scientists from many disciplines to work collaboratively toward an effective response. As academic synthetic chemists, we examine how best to contribute to this ongoing effort.

Midlife Work and Women's Long-Term Health and Mortality.

Although paid work is a well-established predictor of health, several gaps in our knowledge about the relationship between adult work patterns and later health and mortality remain, including whether these benefits persist over long periods and whether they are dependent on subjective experiences with work. We draw on more than three decades of data from the National Longitudinal Survey of Mature Women to assess how labor force participation over a period of 20 years during midlife is related to mental and physical health and mortality over the following 16-25 years. We find that consistent work earlier in life continues to predict improved health and longevity over many years as women enter late life, and this relationship does not differ between women with positive and those with negative subjective work experiences.

Women's spousal choices and a man's handshake: Evidence from a Norwegian study of cohort differences.

Both high grip strength and being married independently relate to better functional capacity and health at older ages, but the combined effect of marital status and strength have not been investigated. Especially at older ages, declining strength can have adverse health and social consequences, where having a spouse could potentially help with everyday support and alleviate some of the negative effects of sarcopenia. We investigate how grip strength relates to being married among two cohorts of 59-71 year olds (born 1923-35 and 1936-48) in the Norwegian city of Tromsø, controlling for a broad set of health variables and sociodemographic characteristics.

Integrating Metal-Catalyzed C-H and C-O Functionalization To Achieve Sterically Controlled Regioselectivity in Arene Acylation.

One major goal of organometallic chemists is the direct functionalization of the bonds most recurrent in organic molecules: C-H, C-C, C-O, and C-N. An even grander challenge is C-C bond formation when both precursors are of this category. Parallel to this is the synthetic goal of achieving reaction selectivity that contrasts with conventional methods.

Multigenerational Attainments, Race, and Mortality Risk among Silent Generation Women.

This study extends health disparities research by examining racial differences in the relationships between multigenerational attainments and mortality risk among "Silent Generation" women. An emerging literature suggests that the socioeconomic attainments of adjacent generations, one's parents and adult children, provide an array of life-extending resources in old age. Prior research, however, has demonstrated neither how multigenerational resources are implicated in women's longevity nor how racial disparities faced by Silent Generation women may differentially structure the relationships between socioeconomic attainments and mortality.

Race Differences in Linking Family Formation Transitions to Women's Mortality.

We examine how the timing and sequencing of first marriage and childbirth are related to mortality for a cohort of 4,988 white and black women born between 1922 and 1937 from the National Longitudinal Survey of Mature Women. We use Cox proportional hazard models to estimate race differences in the association between family formation transitions and mortality. Although we find no relationships between marital histories and longevity, we do find that having children, the timing of first birth, and the sequencing of childbirth and marriage are associated with mortality.

Depression in later life: A closer look at the gender gap.

Gender differences in depressive symptoms have been extensively documented, with women reporting a higher number of depressive symptoms than men. However, studies offer different explanations for why such a gap exists. The goal of the current paper is to analyze how much of the observed gender gap in depression may be attributed to (1) compositional versus (2) reporting differences or (3) differences in reactivity to adversities.

The Long-Term Effects of Caregiving on Women's Health and Mortality.

Caregivers experience numerous mental and physical health effects from the stress of providing care, but we know little about whether these problems persist in the long term and whether long-term effects differ across caregiving contexts. Using the National Longitudinal Survey of Mature Women, we examine the relationship between caregiving and long-term patterns of depressive symptoms, functional limitations, and mortality. We also explore the health effects of caregiving in-home versus out-of-home and by caregiver/care-recipient relationship.

Clarifying hierarchical age-period-cohort models: A rejoinder to Bell and Jones.

Previously, Reither et al. (2015) demonstrated that hierarchical age-period-cohort (HAPC) models perform well when basic assumptions are satisfied. To contest this finding, Bell and Jones (2015) invent a data generating process (DGP) that borrows age, period and cohort effects from different equations in Reither et al.

The Longevity Legacy of World War II: The Intersection of GI Status and Mortality.

Purpose Of The Study: We examine hypotheses involving the potential health advantages of selection into military service and the potential health disadvantages associated with the experience of military service by comparing later-life mortality rates for veterans and nonveterans as well as among veterans based on their cohort of reentry into civilian life.

Design And Methods: We use data on 3,453 men, including 1,496 veterans from the older men cohort of the National Longitudinal Surveys to estimate Cox proportional hazard mortality models. We distinguish between veterans and nonveterans and further classify veterans by age at exit while incorporating measures associated with military selection, health behaviors, and socioeconomic status.

Health insurance instability among older immigrants: region of origin disparities in coverage.

Objectives: We provide a detailed analysis of how the dynamics of health insurance coverage (HIC) at older ages differs among Latino, Asian, and European immigrants in the United States.

Method: Using Survey of Income and Program Participation data from the 2004 and 2008 panels, we estimate discrete-time event history models to examine first and second transitions into and out of HIC, highlighting substantial differences in hazard rates among immigrants aged 50-64 from Asia, Latin America, and Europe.

Results: We find that the likelihood of having HIC at first observation and the rates of gaining and losing coverage within a relatively short time frame are least favorable for older Latino immigrants, although immigrants from all three regions are at a disadvantage relative to native-born non-Hispanic Whites.

How health conditions translate into self-ratings: a comparative study of older adults across Europe.

Using data from the Survey of Health, Ageing and Retirement in Europe, we examine how respondents translate morbidity and disability into self-rated health (SRH), how national populations differ in SRH, and how normative and person-specific reporting styles shape SRH. We construct proxy variables that allow us to specify cultural differences in reporting styles and individual differences in relative rating behavior. Using generalized logistic regression, we find that both of these dimensions of subjectivity are related to SRH; however, their inclusion does not significantly alter the connection between SRH and the set of disease and disability indicators.

Another health insurance gap: gaining and losing coverage among natives and immigrants at older ages.

As the immigrant population grows older and larger, limitations on access to health insurance may create a new subgroup of people who remain outside or on the margin of coverage. Using the Survey of Income and Program Participation (SIPP) data from the 2004 and 2008 panels, we address the health insurance gap between foreign-born and native-born adults among those aged 50-64 and the 65 and older, two sub-populations that have received relatively little attention in past research. We argue that current practices leave a significant minority of older foreign-born residents inconsistently covered or without any insurance.