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The United States does not have a federal policy offering employees paid leave. We study employer attitudes toward the Families First Coronavirus Response Act (FFCRA) federal emergency paid leave policies temporarily adopted during the COVID-19 pandemic to draw lessons for proposed permanent federal paid leave policies. We analyzed a 2021 survey of 300 San Francisco Bay Area employers to examine employers' experiences with paid sick leave (PSL) and paid family leave (PFL) policies during the COVID-19 pandemic, along with their attitudes regarding FFCRA paid leave. Most firms reported that it was not difficult to comply with or seek reimbursement for FFCRA leave. Nevertheless, most smaller firms did report difficulty in understanding policy details, and many reported being unaware of FFCRA paid leave availability. FFCRA paid leave was broadly popular among firms aware of it: 64% supported (9% opposed) the PSL provisions, and 52% supported (12% opposed) PFL. However, support for permanent extension dropped to just over 40%, despite this Bay Area sample having long familiarity with California's state paid leave policies. We conclude that federal pandemic paid leave offers a potential model that could be refined for future paid leave policies, but support is mixed., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Objectives: To understand in-facility follow-up care-seeking behavior among both people who self-managed medication abortions and those who obtained facility-managed care in low-and-middle-income countries. We explore factors that contribute to meeting individual self-reported follow-up care needs, core to person-centered care., Study Design: We conducted a qualitative, codebook thematic analysis of 67 in-depth interviews conducted with people who self-managed medication abortions or obtained facility-managed medication abortion care. We first classified individuals as having their follow-up care needs met (not seeking care when the participant felt confident that additional care was not warranted or desired or receiving care if it was desired) or not. Our a priori analytic domains came from the Anderson model of health services utilization - predisposing, enabling, or need factors (perceived and evaluated need for health services) that contributed to having follow-up care needs met or not. We also describe emergent themes within each domain., Results: Most participants (n=59, 88%) had their follow-up care needs met; half (n=33, 49%) sought follow-up care in a facility. Prior birth or abortion experiences emerged as predisposing factors for having follow-up care needs met. Having accompaniment support (from activists or hotlines who provide abortion guidance outside of clinical settings), knowing what to expect, and information sources were key enabling factors for having follow-up care needs met. Need factors included flexible follow-up care guidelines. Those who did not have their follow-up care needs met described predisposing negative health system experiences; enabling factors including health system challenges, stigma from providers, and legal risk; and need factors of required follow-up care guidelines., Conclusions: Medication abortion follow-up care experiences are diverse, and individual needs can be met both in and outside of health facilities. Understanding prior experiences, enabling accompaniment support, and considering flexible follow-up care guidelines can support meeting individual follow-up care needs, which is essential to person-centered abortion care., Implications: Follow-up care needs, essential to ensuring access to high-quality abortion services, can be met in both self-managed and in-facility medication abortion models. Policies that require follow-up care when it is not needed or desired by the person can reinforce ideas that self-managed abortion is not safe or effective, despite existing evidence., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex. We solve the structure of the seipin/Adig complex by Cryo-EM at 2.98Å overall resolution. Surprisingly, seipin can form two unique oligomers, undecamers and dodecamers. Adig selectively binds to the dodecameric seipin complex. We further find that Adig promotes seipin assembly by stabilizing and bridging adjacent seipin subunits. Functionally, Adig plays a key role in generating lipid droplets in adipocytes. In mice, inducible overexpression of Adig in adipocytes substantially increases fat mass, with enlarged lipid droplets. It also elevates thermogenesis during cold exposure. In contrast, inducible adipocyte-specific Adig knockout mice manifest aberrant lipid droplet formation in brown adipose tissues and impaired cold tolerance.

Background: Rates of exclusive breastfeeding fall below recommended levels, particularly among women in paid employment. In Mexico, more than half of women are in informal employment, meaning they lack many of the protections that may support breastfeeding., Methods: In-depth interviews with 15 key informants representing government agencies (n = 6 organizations), NGOs (n = 4), international organizations (n = 2), and academia (n = 2) in Mexico. Interviews were conducted between March and June 2023. To understand and describe barriers to breastfeeding among informally employed women in Mexico according to key informants and the current and potential policies to address these barriers, we conducted a qualitative thematic analysis., Results: Current policies to promote, protect, and support breastfeeding predominantly apply to all employed women, but respondents expressed concern that they did not provide adequate protection for women in informal employment. Additional themes concerned the need for relevant programs to be institutionalized and coordinated, discussions of breastfeeding as a right, and the legal equivalence (whether true in practice or not) of formal and informal workers., Conclusions: Women employed in Mexico's informal sector face a dearth of maternity protections. According to key informants, few policies exist to promote, protect, and support breastfeeding among employed women, in general, but the economic vulnerability and challenging working conditions of women in informal employment exacerbates their situation. The lack of access to formal labor protections, such as paid maternity leave, creates a significant barrier to breastfeeding for women in the informal sector. Recommendations include short-term policies to fill gaps in social protection for informally employed women, as well as longer-term solutions such as the development of universal social protection programs and supporting formalization., (© 2024. The Author(s).)

Introduction: Even in the small number of U.S. states with paid parental leave (PPL) programs, studies have found awareness of PPL remains low and unevenly distributed among parents. Moreover, little is known about whether parents with perinatal health complications have unmet needs in obtaining information about and support for accessing parental leave during that time. This study aims to address this research gap. Given the strong evidence linking paid leave with improvements in maternal and infant health, it is critical to evaluate access among vulnerable populations., Methods: We used a multiple methods approach, including a subset of the 2016-2017 Bay Area Parental Leave Survey of Mothers (analytic sample = 1,007) and interview data from mothers who stayed at a neonatal intensive care unit in 2019 (n = 7). All participants resided at that time in California, a state that offers PPL. The independent variable for the survey analysis was a composite measure of perinatal complications, quantified as binary with a value of 1 if respondents reported experiencing any of the four complications: poor maternal mental health during or after pregnancy, premature birth, or poor infant health. Dependent variables for the survey analysis measured lack of support or information for accessing PPL. We used linear probability models to assess the relationship between perinatal complications and PPL support. Thematic analysis was conducted with the interview data to understand how perinatal complications shape the process of accessing PPL., Results: Survey results revealed that parents with perinatal complications had a lower understanding of PPL benefits and low overall support for accessing leave, including from employers, compared with parents without perinatal complications. From interviews, we learned that perinatal complications present unique challenges to parents navigating PPL. There were multiple entities involved in managing leave and providing information, such as the benefits coordinator and employers. Supervisors were reported as providers of critical emotional and financial support., Conclusions: Taken together, the findings from surveys and interviews suggest that health care and human resources personnel should be better equipped to provide information and support, particularly to those who experience perinatal complications and might struggle to complete paperwork while facing health challenges., (Copyright © 2024 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between work and health is complex and bidirectional, where work can have both health-harming and health-enhancing effects. Though employment is recognized as a social determinant of health, and clinical healthcare delivery systems are increasingly using screening tools to ask patients about social needs, little research has explored the extent to which employment-related social risk is captured in these screening tools. This study aimed to identify and characterize employment- and work-related questions in social risk screening tools that have been implemented in clinical healthcare delivery systems., Methods: We conducted a qualitative content analysis of employment-related items in screening tools that have been implemented in clinical healthcare service delivery systems. Three content areas guided data extraction and analysis: Setting, Domain, and Level of Contextualization., Results: Screening tools that asked employment-related questions were implemented in settings that were diverse in the populations served and the scope of care provided. The intent of employment-related items focused on four domains: Social Risk Factor, Social Need, Employment Exposure, and Legal Need. Most questions were found to have a low Level of Contextualization and were largely focused on identifying an individual's employment status., Conclusions: Several existing screening tools include measures of employment-related social risk, but these items do not have a clear purpose and range widely depending on the setting in which they are implemented. In order to maximize the utility of these tools, clinical healthcare delivery systems should carefully consider what domain(s) they aim to capture and how they anticipate using the screening tools to address social determinants of health., (© 2024. The Author(s).)

C-H borylation is a high-value transformation in the synthesis of lead candidates for the pharmaceutical industry because a wide array of downstream coupling reactions is available. However, predicting its regioselectivity, especially in drug-like molecules that may contain multiple heterocycles, is not a trivial task. Using a data set of borylation reactions from Reaxys, we explored how a language model originally trained on USPTO_500_MT, a broad-scope set of patent data, can be used to predict the C-H borylation reaction product in different modes: product generation and site reactivity classification. Our fine-tuned T5Chem multitask language model can generate the correct product in 79% of cases. It can also classify the reactive aromatic C-H bonds with 95% accuracy and 88% positive predictive value, exceeding purpose-developed graph-based neural networks.

Owing to its high natural abundance compared to the commonly used transition (precious) metals, as well as its high Lewis acidity and ability to change oxidation state, aluminium has recently been explored as the basis for a range of single-site catalysts. This paper aims to establish the ground rules for the development of a new type of cationic alkene oligomerisation catalyst containing two Al(III) ions, with the potential to act co-operatively in stereoselective assembly. Five new dimers of the type [R 2 Al(2-py')] 2 (R=Me, i Bu; py'=substituted pyridyl group) with different substituents on the Al atoms and pyridyl rings have been synthesised. The formation of the undesired cis isomers can be suppressed by the presence of substituents on the 6-position of the pyridyl ring due to steric congestion, with DFT calculations showing that the selection of the trans isomer is thermodynamically controlled. Calculations show that demethylation of the dimers [Me 2 Al(2-py')] 2 with Ph 3 C + to the cations [{MeAl(2-py')} 2 (μ-Me)] + is highly favourable and that the desired trans disposition of the 2-pyridyl ring units is influenced by steric effects. Preliminary experimental studies confirm that demethylation of [Me 2 Al(6-MeO-2-py)] 2 can be achieved using [Ph 3 C][B(C 6 F 5 ) 4 ]., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Health care providers can offer employment-related support to pregnant patients by providing information about occupational risks and benefits, discussing adjustments, and/or completing paperwork to help patients obtain accommodations or benefits, but little research has examined whether and how this support is provided., Methods: We conducted interviews with 20 adults who had been employed while pregnant within the 5 years preceding data collection. Eligible participants had low incomes, were hourly wage earners, or were employed in service or retail occupations. Applied thematic analysis was used to identify emergent themes., Results: People who had been employed while pregnant described a range of experiences during that time, including physical and psychological demands from work, lack of access to appropriate accommodations, difficulties combining breastfeeding with work, and work-related challenges accessing health care. Participants described four primary roles that health care providers played: 1) completing paperwork needed to apply for benefits or receive work modification; 2) providing information about how to mitigate employment-related risks; 3) providing referrals to social or medical services; and 4) advocating for patients to ensure receipt of accommodations, resources, and information. Strategies identified by patients that could be enacted within health care to help them better navigate the work-pregnancy interface include increasing appointment flexibility, providing information about work-related risks and benefits programs and referrals to legal support, and helping providers to understand and support their patients' individual work-related concerns., Conclusions: Health care providers have a critical role to play in supporting employed pregnant people to achieve flexibility in managing their work and to be active participants in discussions about recommended workplace accommodations., (Copyright © 2024 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

In the pursuit of improved compound identification and database search tasks, this study explores heteronuclear single quantum coherence (HSQC) spectra simulation and matching methodologies. HSQC spectra serve as unique molecular fingerprints, enabling a valuable balance of data collection time and information richness. We conducted a comprehensive evaluation of the following four HSQC simulation techniques: ACD/Labs (ACD), MestReNova (MNova), Gaussian NMR calculations (DFT), and a graph-based neural network (ML). For the latter two techniques, we developed a reconstruction logic to combine proton and carbon 1D spectra into HSQC spectra. The methodology involved the implementation of three peak-matching strategies (minimum-sum, Euclidean-distance, and Hungarian distance) combined with three padding strategies (zero-padding, peak-truncated, and nearest-neighbor double assignment). We found that coupling these strategies with a robust simulation technique facilitates the accurate identification of correct molecules from similar analogues (regio- and stereoisomers) and allows for fast and accurate large database searches. Furthermore, we demonstrated the efficacy of the best-performing methodology by rectifying the structures of a set of previously misidentified molecules. This research indicates that effective HSQC spectral simulation and matching methodologies significantly facilitate molecular structure elucidation. Furthermore, we offer a Google Colab notebook for researchers to use our methods on their own data (https://github.com/AstraZeneca/hsqc_structure_elucidation.git).

The left atrium (LA) mediates cardiopulmonary interactions. During ventricular systole, the LA functions as a compliant reservoir that is coupled to the left ventricle (LV) and offloads volume from the pulmonary vasculature. We aimed to describe LA reservoir function using phasic relationships between pulmonary artery wedge pressure (PAWP) and LA volume events. We included healthy adults (7 M/6 F, 56 ± 8 yr) who were studied at rest and during semirecumbent cycle ergometry at a target of 100 beats/min heart rate. Right heart catheterization was performed to record the PAWP and two-dimensional (2-D) echocardiography was used to measure LA and LV volumes. We manually measured A-wave, x-trough, V-wave, and y-trough PAWP beat-by-beat, as well as minimal, maximal, and precontraction biplane LA volumes. Heart rate increased by 40 ± 7 beats/min with exercise; stroke volume and cardiac output also rose. Although all phasic PAWP measurements increased with exercise, the x-V pressure pulse during LA filling doubled from 4 ± 2 to 8 ± 4 mmHg ( P = 0.001). LA minimal volume was unchanged but maximal volume increased from 39 ± 9 to 48 ± 9 mL ( P < 0.001) with exercise, and so reservoir volume increased from 24 ± 5 to 32 ± 8 mL ( P < 0.001). As such, calculated LA compliance decreased from 6.8 ± 3.4 to 4.8 ± 2.6 mL/mmHg ( P = 0.029). The product of V-wave PAWP and LA maximal volume, a surrogate for LA wall stress, increased from 486 ± 193 to 953 ± 457 mmHg·mL ( P < 0.001). In healthy older adults during submaximal exercise, the PAWP waveform shifts upward and its amplitude widens, LA filling increases, LA compliance decreases modestly, and LA wall stress may augment substantially. NEW & NOTEWORTHY We combined invasive estimates of left atrial pressure with noninvasive left atrial volume measurements made at rest and during exercise in healthy humans. Left atrial pressure and volume both increased with exercise, though the pressure increase was relatively greater, and calculated compliance decreased modestly while estimated peak wall stress nearly doubled. Our results demonstrate left atrial loading during exercise in healthy older adults and provide insight into how the left atrium mediates cardiopulmonary interactions.

Background: Atrial fibrillation (AF) is a common arrhythmia characterized by uncoordinated atrial electrical activity. Lone AF occurs in the absence of traditional risk factors and is frequently observed in male endurance athletes, who face a 2- to 5-fold higher risk of AF compared with healthy, moderately active males. Our understanding of how endurance exercise contributes to the pathophysiology of lone AF remains limited. This study aimed to characterize the circulating protein fluctuations during high-intensity exercise as well as explore potential biomarkers of exercise-associated AF., Methods and Results: A prospective cohort of 12 male endurance cyclists between the ages of 40 and 65 years, 6 of whom had a history of exercise-associated AF, were recruited to participate using a convenience sampling method. The circulating proteome was subsequently analyzed using multiplex immunoassays and aptamer-based proteomics before, during, and after an acute high-intensity endurance exercise bout to assess temporality and identify potential markers of AF. The endurance exercise bout resulted in significant alterations to proteins involved in immune modulation (eg, growth/differentiation factor 15), skeletal muscle metabolism (eg, α-actinin-2), cell death (eg, histones), and inflammation (eg, interleukin-6). Subjects with AF differed from those without, displaying modulation of proteins previously known to have associations with incident AF (eg, C-reactive protein, insulin-like growth factor-1, and angiopoietin-2), and also with proteins having no previous association (eg, tapasin-related protein and α 2 -Heremans-Schmid glycoprotein)., Conclusions: These findings provide insights into the proteomic response to acute intense exercise, provide mechanistic insights into the pathophysiology behind AF in athletes, and identify targets for future study and validation.

High volume endurance training may increase the risk of paroxysmal atrial fibrillation (AF) in middle-aged athletes. Limited data are available describing the cardiovascular phenotype of middle-aged endurance athletes, or the impact of AF on atrial function and exercise performance performed in sinus rhythm. The purpose of this study was to characterize LA phasic function at rest and during exercise in athletes with paroxysmal AF, and to determine its impact on exercise performance. Fifteen endurance trained males (EA) (56 ± 5 years) without AF and 14 endurance trained males with paroxysmal AF (EA-AF) (55 ± 8 years) underwent echocardiography during cycle-ergometry at light and moderate intensities. Resting LA maximal volumes were similar between EA and EA-AF (30 ± 4 vs. 29 ± 8 ml/m2, p = 0.50), and there were no differences in atrial electromechanical delay (AEMD). During moderate intensity exercise, EA-AF had reduced LA conduit (30 ± 6 vs. 40 ± 5 ml/m2, p = 0.002) LA booster volumes (17 ± 5 vs. 21 ± 4 ml/m2, p = 0.021), and reduced LV stroke volumes (100 ± 12 vs. 117 ± 16 ml, p = 0.007). These results demonstrate that exercise testing in athletes with AF unmasks evidence of adverse functional cardiac remodelling that may contribute to impaired exercise performance. It is unclear whether these functional alterations are the consequence of AF. Reductions in LA conduit volume, LA booster volume, and LV stroke volume during exercise may be helpful in clinical management and distinguishing pathologic from physiologic remodelling., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vecchiarelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Moderate to vigorous physical activity performed regularly is cardioprotective and reduces all-cause mortality, concomitant with increased resting heart rate variability (HRV). However, there are contradictory reports regarding the effects of chronic and acute exercise on nocturnal HRV in those performing exercise well-beyond physical activity guidelines. Therefore, the purpose of this study was to compare the power spectral analysis components of HRV in middle-aged endurance athletes (EA) and recreationally active individuals (REC) and explore acute exercise effects in EA. A total of 119 EA (52, 49-57 years) and 32 REC (56, 52-60 years) were recruited to complete 24 h Holter monitoring (GE SEER 1000) in the absence of exercise. Fifty one EA (52, 49-57 years) then underwent 24 h Holter monitoring following an intense bout of endurance exercise. Power spectral HRV analysis was completed hourly and averaged to quantify morning (1000-1200 h), evening (1900-2100 h), and nocturnal (0200-0400 h) HRV. EA had greater very low frequency (VLF) and low frequency (LF) (both p  < 0.001) compared to REC. LF/high frequency (HF) was greater in EA at 0200-0400 h ( p  = 0.04). Among all participants, the change in HR and HF from 1000-1200 to 0200-0400 h was negatively correlated ( r  = -0.47, p  < 0.001). Following acute exercise in EA, only nocturnal HRV was assessed. VLF ( p  < 0.001) and HF ( p  = 0.008) decreased, while LF/HF increased ( p  = 0.02). These results suggest that in EA, both long-term and acute exercises increase nocturnal sympathovagal activity through an increase in LF and decrease in HF, respectively. Further work is required to understand the mechanism underlying reduced nocturnal HRV in middle-aged EA and the long-term health implications., Competing Interests: The authors have no competing interests to declare.

Objective: We used the newly developed Abortion Care Quality Tool (ACQTool) to compare client-reported quality of medication abortion care by source (facility-managed vs pharmacy-sourced self-managed abortion (SMA)) in Bangladesh., Methods: We leveraged exit and 30-day follow-up surveys collected to develop and validate the ACQTool collected at nongovernmental organisation (NGO)-supported or -operated facilities in the public and private sector and pharmacies from three districts in Bangladesh. We used bivariate statistics to compare 18 client-reported quality indicators grouped in six domains and eight abortion outcomes, by source (facility vs pharmacy). We used multivariable logistic regression to identify factors associated with selected quality indicators and outcomes (abortion affordability, information provision, and knowing what to do for an adverse event), controlling for client sociodemographic characteristics., Results: Of 550 abortion clients, 146 (26.5%) received a facility-managed medication abortion and 404 (73.5%) had a pharmacy-sourced SMA. Clients reported higher quality in facilities for five indicators, and higher in pharmacies for two indicators; the remaining 11 indicators were not different by source. Compared with facility-based clients, pharmacy clients had higher odds of reporting that the cost of abortion was affordable (adjusted odds ratio (aOR) 3.55; 95% CI 2.27 to 5.58) but lower odds of reporting high information provision (aOR 0.14; 95% CI 0.09 to 0.23). Seven of eight abortion outcomes showed no differences; pharmacy clients had lower odds of knowing what to do if an adverse event occurred (aOR 0.45; 95% CI 0.23 to 0.82)., Conclusions: In Bangladesh, there is no difference in client-reported quality of medication abortion care between health facilities and pharmacies for the majority of quality and outcome indicators. However, information provision and preparedness were higher quality at facilities, while pharmacies were more affordable., Competing Interests: Competing interests: BGD’s institution receives research funding from Organon and the Office of Population Affairs (OPA) on which she is Principal Investigator, and she is a member of the Board of Directors of the Society of Family Planning (SFP) and a Deputy Editor on Contraception. She has received an honorarium from the American College of Obstetrics and Gynecology (ACOG) for committee work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Machine Learning (ML) is increasingly applied to fill data gaps in assessments to quantify impacts associated with chemical emissions and chemicals in products. However, the systematic application of ML-based approaches to fill chemical data gaps is still limited, and their potential for addressing a wide range of chemicals is unknown. We prioritized chemical-related parameters for chemical toxicity characterization to inform ML model development based on two criteria: (1) each parameter's relevance to robustly characterize chemical toxicity described by the uncertainty in characterization results attributable to each parameter and (2) the potential for ML-based approaches to predict parameter values for a wide range of chemicals described by the availability of chemicals with measured parameter data. We prioritized 13 out of 38 parameters for developing ML-based approaches, while flagging another nine with critical data gaps. For all prioritized parameters, we performed a chemical space analysis to assess further the potential for ML-based approaches to predict data for diverse chemicals considering the structural diversity of available measured data, showing that ML-based approaches can potentially predict 8-46% of marketed chemicals based on 1-10% with available measured data. Our results can systematically inform future ML model development efforts to address data gaps in chemical toxicity characterization.

Background: Access to paid family and medical leave (PFML), including leave to care for a seriously ill loved one or recover from one's own serious illness, conveys health and economic benefits for workers and their families. However, without a national PFML policy, access to paid leave remains limited and unequal. Previous work documenting inequitable access by socioeconomic status and race/ethnicity primarily focuses on parental leave, measures theoretical access to paid leave rather than actual leave uptake, and lacks an accounting for why workers of color and women may have less access to PFML. We extend this literature by looking at leave-taking for medical needs or caregiving among a high-risk population during the COVID-19 pandemic., Methods: We draw on data from 2595 service-sector workers surveyed by the Shift Project in 2020 and 2021 to estimate inequities in leave uptake among workers who experienced qualifying events. We then estimate the relative importance of worker demographic characteristics, qualifying event types (medical vs. caregiving leave), proxies for access to state and employer PFML policies, job characteristics, and ultimately within-firm differences to these gaps., Results: Overall, one-fifth of workers reported sufficient leave. Women are significantly more likely than men to report insufficient or no leave. Hispanic and Black workers are more likely to take insufficient or no leave, respectively, but these differences were attenuated when controlling for covariates., Conclusions: The dearth of PFML laws leaves women and workers of color without access to leave that is paid and of sufficient duration when facing a qualifying event., (© 2023 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

The selectivity in a group of oxazaborolidinium ion-catalysed reactions between aldehyde and diazo compounds cannot be explained using transition state theory. VRAI-selectivity, developed to predict the outcome of dynamically controlled reactions, can account for both the chemo- and the stereo-selectivity in these reactions, which are controlled by reaction dynamics. Subtle modifications to the substrate or catalyst substituents alter the potential energy surface, leading to changes in predominant reaction pathways and altering the barriers to the major product when reaction dynamics are considered. In addition, this study suggests an explanation for the mysterious inversion of enantioselectivity resulting from the inclusion of an ortho i PrO group in the catalyst., Competing Interests: There are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

CONFPASS ( Conf ormer P rioritizations and A naly s i s for DFT re-optimizations) has been developed to extract dihedral angle descriptors from conformational searching outputs, perform clustering, and return a priority list for density functional theory (DFT) re-optimizations. Evaluations were conducted with DFT data of the conformers for 150 structurally diverse molecules, most of which are flexible. CONFPASS gives a confidence estimate that the global minimum structure has been found, and based on our dataset, we can have 90% confidence after optimizing half of the FF structures. Re-optimizing conformers in order of the FF energy often generates duplicate results; using CONFPASS, the duplication rate is reduced by a factor of 2 for the first 30% of the re-optimizations, which include the global minimum structure about 80% of the time.

The epigenetic modification 5-methylcytosine plays a vital role in development, cell specific gene expression and disease states. The selective chemical modification of the 5-methylcytosine methyl group is challenging. Currently, no such chemistry exists. Direct functionalisation of 5-methylcytosine would improve the detection and study of this epigenetic feature. We report a xanthone-photosensitised process that introduces a 4-pyridine modification at a C(sp 3 )-H bond in the methyl group of 5-methylcytosine. We propose a reaction mechanism for this type of reaction based on density functional calculations and apply transition state analysis to rationalise differences in observed reaction efficiencies between cyanopyridine derivatives. The reaction is initiated by single electron oxidation of 5-methylcytosine followed by deprotonation to generate the methyl group radical. Cross coupling of the methyl radical with 4-cyanopyridine installs a 4-pyridine label at 5-methylcytosine. We demonstrate use of the pyridination reaction to enrich 5-methylcytosine-containing ribonucleic acid., Competing Interests: S.B. is an advisor and shareholder of Biomodal Ltd. (formerly called Cambridge Epigenetix Ltd.), Inflex Ltd. and Elyx Ltd. A patent application has been filed based on some of the work described in this manuscript., (© 2023 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.)

Purpose: Time spent closer to maximal effort during exercise is a potent stimulus for cardiorespiratory adaptations. The primary purpose was to determine which high-intensity interval exercise (HIIE) protocol provided the greatest physiological stimulus by comparing time spent ≥ 90% peak oxygen consumption (V̇O 2 peak) and heart rate reserve (HRR) in patients with coronary artery disease (CAD) in response to 3 HIIE protocols and the exercise standard of care, moderate-intensity continuous exercise (MICE). A secondary purpose was to assess protocol preference., Methods: Fifteen patients with CAD (6 females, 67 ± 6 years) underwent measurements of V̇O 2 and heart rate during MICE and three HIIE protocols all performed on a treadmill. The HIIE protocols included one with long intervals (4 × 4-min), short intervals (10 × 1-min), and an adapted version of the 4 × 4 [Toronto Rehabilitation Institute Protocol, (TRIP)]. Time spent ≥ 90% V̇O 2 peak and HRR were compared., Results: Time spent ≥ 90% V̇O 2 peak was higher during 4 × 4 (6.3 ± 8.4 min) vs. MICE (1.7 ± 3.9 min; P = 0.001), while time spent ≥ 90% HRR was higher during 4 × 4 (6.0 ± 5.3 min) vs. MICE (0.1 ± 0.2 min; P < 0.001) and 10 × 1 (0.7 ± 0.8 min; P = 0.016). TRIP had similar responses as 10 × 1 and MICE. The 10 × 1 was the most preferred protocol and the 4 × 4 was the least preferred protocol., Conclusion: Longer intervals (4 × 4) provided the greatest physiological stimulus compared to the exercise standard of care and shorter intervals. However, this protocol was least preferred which may impact exercise adherence. Although the physiological stimulus is important to maximize training adaptations, exercise preferences and attitudes should be considered., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Computational reaction prediction has become a ubiquitous task in chemistry due to the potential value accurate predictions can bring to chemists. Boronic acids are widely used in industry; however, understanding how to avoid the protodeboronation side reaction remains a challenge. We have developed an algorithm for in silico prediction of the rate of protodeboronation of boronic acids. A general mechanistic model devised through kinetic studies of protodeboronation was found in the literature and forms the foundation on which the algorithm presented in this work is built. Protodeboronation proceeds through 7 distinct pathways, though for any particular boronic acid, only a subset of mechanistic pathways are active. The rate of each active mechanistic pathway is linearly correlated with its characteristic energy difference, which in turn can be determined using Density Functional Theory. We validated the algorithm using leave-one-out cross-validation on a data set of 50 boronic acids and made a further 50 rate predictions on academically and industrially important boronic acids out of sample. We believe this work will provide great assistance to chemists performing reactions that feature boronic acids, such as Suzuki-Miyaura and Chan-Evans-Lam couplings.

Vibrational circular dichroism (VCD) spectroscopy can generate the data required for the assignment of absolute configuration, but the spectra are hard to interpret. We have recorded VCD data for thirty pairs of small organic compounds and we use this database to validate a method for the automated analysis of VCD spectra and the assignment of absolute configuration: the Cai•factor (Configuration: absolute information). The analysis of the data demonstrates that the procedure is a reliable and time-efficient method for determination of absolute configuration, which gives both the assignment and a measure of confidence in the outcome, even when the spectra are imperfect. The majority of molecules tested have a high confidence score and all of these have the correct assignment., (© 2023. The Author(s).)

Background: Paid family leave and working conditions are components of employment quality-a key social determinant of health across the life course, particularly during pregnancy. Increased research on prenatal social risk screening has not extended to employment quality. The objective of this systematic review was to identify prenatal screening practices and interventions in health care settings that address employment and working conditions as social risk factors among pregnant adults and to describe their properties and key findings., Method: We searched MEDLINE, PsychINFO, SocINDEX, EMBASE, and the SIREN Evidence and Resource Library for studies published through February 14, 2022. We selected multiple search terms related to four domains: (1) employment or working conditions; (2) screening; (3) health care settings; and (4) pregnancy or maternal health., Results: Of the 2317 unique titles and abstracts that were potentially relevant, eight articles met all inclusion criteria and focused on pregnant populations. The content of identified screening practices varied substantially, highlighting the multiple ways employment is conceptualized as a potential risk factor. Few studies included multidimensional measures of employment to assess working conditions, which may be particularly relevant during pregnancy., Conclusions: Our review suggests that screening for employment as a social risk factor does not regularly occur in prenatal care. Although pragmatic properties of the screening tools we assessed are promising, tools seldom examine the multidimensional nature of work. Understanding the principal intent of screening for employment prenatally could provide greater opportunity to collect and interpret contextual factors that influence how both providers and patients respond to social risk., (© 2022 Wiley Periodicals LLC.)

During yeast stationary phase, a single spherical vacuole (lysosome) is created by the fusion of several small ones. Moreover, the vacuolar membrane is reconstructed into two distinct microdomains. Little is known, however, about how cells maintain vacuolar shape or regulate their microdomains. Here, we show that Fat1p, a fatty acyl coenzyme A (acyl-CoA) synthetase and fatty acid transporter, and not the synthetases Faa1p and Faa4p, is essential for vacuolar shape preservation, the development of vacuolar microdomains, and cell survival in stationary phase of the yeast Saccharomyces cerevisiae. Furthermore, Fat1p negatively regulates general autophagy in both log- and stationary-phase cells. In contrast, Fat1p promotes lipophagy, as the absence of FAT1 limits the entry of lipid droplets into the vacuole and reduces the degradation of liquid droplet (LD) surface proteins. Notably, supplementing with unsaturated fatty acids or overexpressing the desaturase Ole1p can reverse all aberrant phenotypes caused by FAT1 deficiency. We propose that Fat1p regulates stationary phase vacuolar morphology, microdomain differentiation, general autophagy, and lipophagy by controlling the degree of fatty acid saturation in membrane lipids. IMPORTANCE The ability to sense environmental changes and adjust the levels of cellular metabolism is critical for cell viability. Autophagy is a recycling process that makes the most of already-existing energy resources, and the vacuole/lysosome is the ultimate autophagic processing site in cells. Lipophagy is an autophagic process to select degrading lipid droplets. In yeast cells in stationary phase, vacuoles fuse and remodel their membranes to create a single spherical vacuole with two distinct membrane microdomains, which are required for yeast lipophagy. In this study, we discovered that Fat1p was capable of rapidly responding to changes in nutritional status and preserving cell survival by regulating membrane lipid saturation to maintain proper vacuolar morphology and the level of lipophagy in the yeast S. cerevisiae. Our findings shed light on how cells maintain vacuolar structure and promote the differentiation of vacuole surface microdomains for stationary-phase lipophagy.

Competing Interests: JMG has received financial support from Fulbright-García Robles, Fulbright Uruguay, Washington Center for Equitable Growth, Robert Wood Johnson Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (award K12HD043488), all outside of the submitted work. JMG was a volunteer board member of the Pro-Choice Oregon Foundation until September, 2022. LDP has received funding from Fogarty International Center, Women in Science Portland, and Total Worker Health of the National Institute for Occupational Safety and Health, all outside of the submitted work.