Optimization of heteronuclear ultrafast 2D NMR for the study of complex mixtures hyperpolarized by dynamic nuclear polarization.

Hyperpolarized 13C NMR at natural abundance, based on dissolution dynamic nuclear polarization (d-DNP), provides rich, sensitive and repeatable 13C NMR fingerprints of complex mixtures. However, the sensitivity enhancement is associated with challenges such as peak overlap and the difficulty to assign hyperpolarized 13C signals. Ultrafast (UF) 2D NMR spectroscopy makes it possible to record heteronuclear 2D maps of d-DNP hyperpolarized samples. Heteronuclear UF 2D NMR can provide correlation peaks that link quaternary carbons and protons through long-range scalar couplings. Here, we report the analytical assessment of an optimized UF long-range HETCOR pulse sequence, applied to the detection of metabolic mixtures at natural abundance and hyperpolarized by d-DNP, based on repeatability and sensitivity considerations. We show that metabolite-dependent limits of quantification in the range of 1-50 mM (in the sample before dissolution) can be achieved, with a repeatability close to 10% and a very good linearity. We provide a detailed comparison of such analytical performance in two different dissolution solvents, D2O and MeOD. The reported pulse sequence appears as an useful analytical tool to facilitate the assignment and integration of metabolite signals in hyperpolarized complex mixtures.

Hyperpolarized 1H and 13C NMR Spectroscopy in a Single Experiment for Metabolomics.

The application of NMR spectroscopy to complex mixture analysis and, in particular, to metabolomics is limited by the low sensitivity of NMR. We recently showed that dissolution dynamic nuclear polarization (d-DNP) could enhance the sensitivity of 13C NMR for complex metabolite mixtures, leading to the detection of highly sensitive 13C NMR fingerprints of complex samples such as plant extracts or urine. While such experiments provide heteronuclear spectra, which are complementary to conventional NMR, hyperpolarized 1H NMR spectra would also be highly useful, with improved limits of detection and compatibility with the existing metabolomics workflow and databases. In this technical note, we introduce an approach capable of recording both 1H and 13C hyperpolarized spectra of metabolite mixtures in a single experiment and on the same hyperpolarized sample. We investigate the analytical performance of this method in terms of sensitivity and repeatability, and then we show that it can be efficiently applied to a plant extract. Significant sensitivity enhancements in 1H NMR are reported with a repeatability suitable for metabolomics studies without compromising on the performance of hyperpolarized 13C NMR. This approach provides a way to perform both 1H and 13C hyperpolarized NMR metabolomics with unprecedented sensitivity and throughput.

Solution-State 2D NMR Spectroscopy of Mixtures HyperpolarizedUsing Optically Polarized Crystals.

The HYPNOESYS method (Hyperpolarized NOE System), which relies on the dissolution of optically polarized crystals, has recently emerged as a promising approach to enhance the sensitivity of NMR spectroscopy in the solution state. However, HYPNOESYS is a single-shot method that is not generally compatible with multidimensional NMR. Here we show that 2D NMR spectra can be obtained from HYPNOESYS-polarized samples, using single-scan acquisition methods. The approach is illustrated with a mixture of terpene molecules and a benchtop NMR spectrometer, paving the way to a sensitive, information-rich and affordable analytical method.

Provider-patient experiences and HIV care utilization among people living with HIV who inject drugs in St. Petersburg, Russia.

Providers' disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients' reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes.We conducted a cross-sectional analysis of the associations between disrespect/abuse from health providers as a barrier to care and the following HIV care outcomes: (i) anti-retroviral treatment (ART) uptake ever, (ii) past 6-month visit to HIV provider, and (iii) CD4 count. Participants (N = 221) were people living with HIV who injected drugs and were not on ART at enrollment.Two in five participants (42%) reported a history disrespect/abuse from a healthcare provider that they cited as a barrier to care. Those reporting this concern had lower odds of ever use of ART (adjusted odds ratio 0.46 [95% CI 0.22, 0.95]); we found no significant associations for the other HIV outcomes. We additionally found higher representation of women among those reporting prevalence of disrespect/abuse from provider as a barrier to care compared to those not reporting this barrier (58.1% versus 27.3%).Almost half of this sample of PWH who inject drugs report disrespect/abuse from a provider as a barrier to healthcare, and this is associated with lower odds of receipt of ART but not with other HIV outcomes studied. There is need for improved focus on quality of respectful and dignified care from providers for PWH who inject drugs, and such focus may improve ART uptake in Russia.

Hyperpolarized 13 C†NMR Spectroscopy of Urine Samples at Natural Abundance by Quantitative Dissolution Dynamic Nuclear Polarization.

Hyperpolarized nuclear magnetic resonance (NMR) offers an ensemble of methods that remarkably address the sensitivity issues of conventional NMR. Dissolution Dynamic Nuclear Polarization (d-DNP) provides a unique and general way to detect 13 C NMR signals with a sensitivity enhanced by several orders of magnitude. The expanding application scope of d-DNP now encompasses the analysis of complex mixtures at natural 13 C abundance. However, the application of d-DNP in this area has been limited to metabolite extracts. Here, we report the first d-DNP-enhanced 13 C NMR analysis of a biofluid -urine- at natural abundance, offering unprecedented resolution and sensitivity for this challenging type of sample. We also show that accurate quantitative information on multiple targeted metabolites can be retrieved through a standard addition procedure.

The association between quality of contraceptive counseling and selection of contraceptive method post-counseling among women in Ethiopia.

OBJECTIVES: To better understand the relationship between high-quality contraceptive counseling and met family planning needs, we examined the association between quality of counseling and selection of a method postvisit among women requesting contraception in Ethiopia. STUDY DESIGN: We used post-counseling survey data from women receiving care in public health centers and nongovernmental clinics in three regions in Ethiopia. Among women whose reason for visit was requesting a contraceptive method, we examined the association between scores on the validated quality of contraceptive counseling (QCC) scale and subscales and selection of a method post-counseling (primary analysis) and type of method selected (secondary analysis). We conducted mixed-effects multivariable logistic regression for the primary analysis and multinomial regression for the secondary analysis. RESULTS: There was a nonsignificant increase in odds of selecting contraception with increasing total QCC scale scores (adjusted odds ratio [aOR] 2.35, 0.43-12.95). However, among women experiencing no disrespect and abuse, there was increasing odds of selecting contraception (aOR 3.46, 95% CI 1.09-10.99) and likelihood of selecting injectable contraception (adjusted relative risk ratio 4.27, 95% CI 1.34-13.60) compared to women experiencing disrespect and abuse. Additionally, 168 (32.1%) of women felt pressured by their provider to use a certain method of which>50% selected long-acting reversible contraception. CONCLUSIONS: Increasing QCC is associated with selecting contraception among women requesting contraception. Additionally, probing for negative experiences can reveal feelings of disrespect and abuse that could lead women to avoid selecting contraception or feeling pressured to use methods heavily promoted by providers. IMPLICATIONS: Our study assesses contraceptive counseling quality using a validated tool with items on provider pressure and other forms of disrespect and abuse; findings highlight the importance of respectful treatment in meeting women's needs and the potential influence of disrespect on decision to select contraception and type of method selected.

Early vs Interval Postpartum Intrauterine Device Placement: A Randomized Clinical Trial.

Importance: The early postpartum period, 2 to 4 weeks after birth, may be a convenient time for intrauterine device (IUD) placement; the placement could then coincide with early postpartum or well-baby visits. Objective: To determine expulsion rates for IUDs placed early postpartum compared with those placed at the standard interval 6-week visit. Design, Setting, and Participants: In this randomized noninferiority trial, people who had a vaginal or cesarean birth were randomly assigned to undergo early (14-28 days) or interval (42-56 days) postpartum IUD placement. Clinicians blinded to participant study group used transvaginal ultrasonography to confirm IUD presence and position at the 6-month postpartum follow-up. The study assessed 642 postpartum people from 4 US medical centers, enrolled a consecutive sample of 404 participants from March 2018 to July 2021, and followed up each participant for 6 months postpartum. Interventions: Early postpartum IUD placement, at 2 to 4 weeks postpartum, vs standard interval placement 6 to 8 weeks postpartum. Main Outcomes and Measures: The primary outcome was complete IUD expulsion by 6 months postpartum; the prespecified noninferiority margin was 6%. Secondary outcomes were partial IUD expulsion, IUD removal, pelvic infection, patient satisfaction, uterine perforation, pregnancy, and IUD use at 6 months postpartum. IUD malposition was an exploratory outcome. Results: Among 404 enrolled participants, 203 participants were randomly assigned to undergo early IUD placement and 201 to undergo interval IUD placement (mean [SD] age, 29.9 [5.4] years; 46 [11.4%] were Black, 228 [56.4%] were White, and 175 [43.3%] were Hispanic). By 6 months postpartum, 53 participants (13%) never had an IUD placed and 57 (14%) were lost to follow-up. Among the 294 participants (73%) who received an IUD and completed 6-month follow-up, complete expulsion rates were 3 of 149 (2.0% [95% CI, 0.4%-5.8%]) in the early placement group and 0 of 145 (0% [95% CI, 0.0%-2.5%]) in the interval placement group (between-group difference, 2.0 [95% CI, -0.5 to 5.7] percentage points). Partial expulsion occurred in 14 (9.4% [95% CI, 5.2%-15.3%]) participants in the early placement group and 11 (7.6% [95% CI, 3.9%-13.2%]) participants in the interval placement group (between-group difference, 1.8 [95% CI, -4.8 to 8.6] percentage points). IUD use at 6 months was similar between the groups: 141 (69.5% [95% CI, 62.6%-75.7%]) participants in the early group vs 139 (67.2% [95% CI, 60.2%-73.6%]) in the interval group. Conclusions and Relevance: Early IUD placement at 2 to 4 weeks postpartum compared with 6 to 8 weeks postpartum was noninferior for complete expulsion, but not partial expulsion. Understanding the risk of expulsion at these time points may help patients and clinicians make informed choices about the timing of IUD placement. Trial Registration: ClinicalTrials.gov Identifier: NCT03462758.

The associations of everyday and major discrimination exposure with violence and poor mental health outcomes during the COVID-19 pandemic.

Research on discrimination and risks for violence and mental health issues under the pandemic is notably absent. We examined the relative effects of perceived everyday discrimination (e.g., poorer service, disrespectful treatment in a typical week) and major experiences of race-based discrimination (e.g., racial/ethnic discrimination in housing or employment at any point in the lifetime) on experiences of violence and the PHQ-4 assessment of symptoms of depression and anxiety under the pandemic. We analyzed state-representative cross-sectional survey data from California adults (N = 2114) collected in March 2021. We conducted multivariate regression models adjusting for age, race/ethnicity, gender, sexual identity, income, and disability. One in four Californians (26.1%) experienced everyday discrimination in public spaces, due most often to race/ethnicity and gender. We found that everyday discrimination was significantly associated with past year physical violence (single form Adjusted Odds Ratio [AOR] 5.0, 95% CI 2.5-10.3; multiple forms AOR 2.6, 95% CI 1.1-5.8), past year sexual violence (multiple forms AOR 2.5, 95% CI 1.4-4.4), and mental health symptoms (e.g., severe symptoms, multiple forms AOR 3.3, 95% CI 1.6-6.7). Major experiences of race-based discrimination (reported by 10.0% of Californians) were associated with past year sexual violence (AOR 2.0, 95% CI 1.1-3.8) and severe mental health symptoms (AOR 2.7, 95% CI 1.2-6.2). Non-race-based major discrimination (reported by 23.9% of Californians) was also associated with violence and mental health outcomes Everyday discrimination, more than major experiences of discrimination, was associated with higher risk for violence and poor mental health outcomes during the pandemic. Non-race-based forms of major discrimination independently were also associated with these negative outcomes. Findings indicate that efforts to reduce and ultimately eliminate discrimination should be a focus of public health and COVID-19 rebuilding efforts.

Factors affecting delayed and non-receipt of healthcare during the COVID-19 pandemic for women in rural Maharashtra, India: Evidence from a cross-sectional study.

Background: Pathways to low healthcare utilisation under the COVID-19 pandemic are not well understood. This study aims to understand women's concerns about the health system's priorities and their increased burden of domestic responsibilities during COVID-19 as predictors of delayed or non-receipt of needed care for themselves or their children. Methods: We surveyed married women in rural Maharashtra, India (N = 1021) on their health and economic concerns between Feb 1 and March 26, 2021. This study period was when India emerged from the first wave of the pandemic, which had severely impacted the health systems, and before the second-even more devastating wave had started. We captured if women were concerned about access to non-COVID health services due to healthcare being directed solely to COVID-19) (exposure 1) and whether their domestic responsibilities increased during the pandemic (exposure 2). Our outcomes included women's reports on whether they delayed healthcare seeking (secondary outcome and mediator) and whether they received healthcare for themselves or their children when needed (primary outcome). We conducted adjusted regression models on our predictor variables with each outcome and assessed the mediation effects of delayed healthcare seeking for each of the exposure variables. Findings: We found that women who were concerned that healthcare was directed solely towards COVID-19 were more likely not to receive healthcare when needed (Adjusted Risk Ratio [ARR] = 1.49, 95% CI = 1.14, 1.95). We also found that women whose domestic care burden increased under the pandemic were more likely to delay healthcare seeking (ARR = 1.84, 95% CI = 1.05, 3.21). Delayed healthcare seeking mediated the associations between each of our exposure variables with our outcome variable, non-receipt of needed healthcare. Interpretation: Our findings suggested that women's perceptions of healthcare systems and their domestic labour burdens affected healthcare seeking during the pandemic in India, even before the second wave of COVID-19 incapacitated the health system. Support for women and health systems is needed to ensure healthcare uptake during crises. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA (grant numbers: R01HD084453- 01A1 and RO1HD61115); Department of Biotechnology, Government of India (grant #BT/IN/US/01/BD/2010); the EMERGE project (Bill and Melinda Gates Foundation Grants: OPP1163682 and INV018007; PI Anita Raj), and Bill and Melinda Gates Foundation Grant number INV-002967.

Using machine learning to understand determinants of IUD use in India: Analyses of the National Family Health Surveys (NFHS-4).

Intra-uterine devices (IUDs) are a safe and effective method to delay or space pregnancies and are available for free or at low cost in the Indian public health system; yet, IUD uptake in India remains low. Limited quantitative research using national data has explored factors that may affect IUD use. Machine Learning (ML) techniques allow us to explore determinants of low prevalence behaviors in survey research, such as IUD use. We applied ML to explore the determinants of IUD use in India among married women in the 4th National Family Health Survey (NFHS-4; N = 499,627), which collects data on demographic and health indicators among women of childbearing age. We conducted ML logistic regression (lasso and ridge) and neural network approaches to assess significant determinants and used iterative thematic analysis (ITA) to offer insight into related variable constructs generated from a series of regularized models. We found that couples' shared family planning (FP) goals were the strongest determinants of IUD use, followed by receipt of FP services and desire for no more children, higher wealth and education, and receipt of maternal and child health services. Findings highlight the importance of male engagement and family planning services for IUD uptake and the need for more targeted efforts to support awareness of IUD as an option for spacing, especially for those of lower SES and with lower access to care.

Ultrafast 2D NMR for the analysis of complex mixtures.

2D NMR is extensively used in many different fields, and its potential for the study of complex biochemical or chemical mixtures has been widely demonstrated. 2D NMR gives the ability to resolve peaks that overlap in 1D spectra, while providing both structural and quantitative information. However, complex mixtures are often analysed in situations where the data acquisition time is a crucial limitation, due to an ongoing chemical reaction or a moving sample from a hyphenated technique, or to the high-throughput requirement associated with large sample collections. Among the great diversity of available fast 2D methods, ultrafast (or single-scan) 2D NMR is probably the most general and versatile approach for complex mixture analysis. Indeed, ultrafast NMR has undergone an impressive number of methodological developments that have helped turn it into an efficient analytical tool, and numerous applications to the analysis of mixtures have been reported. This review first summarizes the main concepts, features and practical limitations of ultrafast 2D NMR, as well as the methodological developments that improved its analytical potential. Then, a detailed description of the main applications of ultrafast 2D NMR to mixture analysis is given. The two major application fields of ultrafast 2D NMR are first covered, i.e., reaction/process monitoring and metabolomics. Then, the potential of ultrafast 2D NMR for the analysis of hyperpolarized mixtures is described, as well as recent developments in oriented media. This review focuses on high-resolution liquid-state 2D experiments (including benchtop NMR) that include at least one spectroscopic dimension (i.e., 2D spectroscopy and DOSY) but does not cover in depth applications without spectral resolution and/or in inhomogeneous fields.

Gender differences in work attendance among health care workers in Northern Nigeria during the COVID-19 pandemic.

Background: The COVID-19 pandemic has resulted in the overwork of health care workers (HCWs) and greater household burdens for women. This study examines gender differences in HCWs' work attendance under COVID-19 and household burdens as a potential mediator of the gender difference in Northern Nigeria. Methods: From April to May 2021, we conducted a cross-sectional survey on work and household burdens with a convenience sample of male and female HCWs (N=334) across 16 facilities in the Gombe, Katsina, and Zamfara states in Northern Nigeria. We used a series of multilevel modified Poisson regression models to examine the associations between gender and HCW work attendance. We also tested the mediation effect of household burdens on this observed association. Findings: Only 2·10% of HCWs reported <5 days of work in a typical week; 35·33% worked 6-7 days a week (i.e., HCW overwork). Males were more likely than females to report HCW overwork (46·33% vs. 22·93%), and females were more likely than males to report an increase in household burden (59·24% vs. 40·68%). Adjusted regression models found that men were more likely than women to report HCW overwork (ARR: 1·76, 95% CI: 1·17-2·66). Increased household burdens mediated 9 percent of the total effect between gender and HCW work attendance. Interpretation: The COVID-19 pandemic in Northern Nigeria made female HCWs contend with the dual burdens of formal and informal care work. This contributes to lower attendance among female HCWs and overwork for their male counterparts. Funding: Bill and Melinda Gates Foundation Grant Numbers: OPP1163682 & INV018007.

Impulsivity and linkage to HIV Care among People living with HIV in St. Petersburg, Russia.

This study evaluated the association between impulsivity and linkage to HIV care among Russians living with HIV recruited from an inpatient narcology hospital. Linking Infectious and Narcology Care (LINC) study participants who completed the Barratt Impulsiveness Scale (BIS) were included in these analyses. The primary independent variable was impulsivity score which was categorized as high impulsivity (BIS score > 71) vs. low impulsivity (BIS score < = 71). The primary outcome, linkage to care post recruitment, was defined as one or more HIV medical care visits at 12-month follow-up. Multiple logistic regression models were used to evaluate the association between high impulsivity and linkage to HIV care controlling for potential confounders. Participants (N = 227) were adults with a mean age of 34 years (SD = 5), and the majority were male (74%). We did not detect a significant association between impulsivity and linkage to HIV care after adjusting for respondents' age, gender, CD4 cell count, and depression score. We also found that substance use and hazardous drinking did not appear to confound the relationship. Although our study was unable to detect an association between impulsivity and linkage to HIV care, it may provide direction for future research exploring the associations between impulsivity and HIV care.

Pd(II)-Catalyzed Transient Directing Group-Assisted Regioselective Diverse C4-H Functionalizations of Indoles.

The development of a rational strategy for achieving site-selective C4-H halogenation of indoles is an appealing yet challenging task. Herein, we disclose a Pd(II)-catalyzed transient directing group (TDG)-assisted methodology for realizing C4 chlorination/bromination of indoles employing glycine as the TDG and NFSI as a bystanding oxidant. The use of inexpensive and commercially available CuX2 as the halide source is the key highlight of this protocol. Furthermore, the TDG methodology was also extended to accessing C4 acetoxylated indoles employing acetic acid as the acetate source and 1-fluoro-2,4,6-trimethylpyridinium triflate as the oxidant.

Help seeking behavior by women experiencing intimate partner violence in india: A machine learning approach to identifying risk factors.

BACKGROUND: Despite the low prevalence of help-seeking behavior among victims of intimate partner violence (IPV) in India, quantitative evidence on risk factors, is limited. We use a previously validated exploratory approach, to examine correlates of help-seeking from anyone (e.g. family, friends, police, doctor etc.), as well as help-seeking from any formal sources. METHODS: We used data from a nationally-representative health survey conducted in 2015-16 in India, and included all variables in the dataset (~6000 variables) as independent variables. Two machine learning (ML) models were used- L-1, and L-2 regularized logistic regression models. The results from these models were qualitatively coded by researchers to identify broad themes associated with help-seeking behavior. This process of implementing ML models followed by qualitative coding was repeated until pre-specified criteria were met. RESULTS: Identified themes associated with help-seeking behavior included experience of injury from violence, husband's controlling behavior, husband's consumption of alcohol, and being currently separated from husband. Themes related to women's access to social and economic resources, such as women's employment, and receipt of maternal and reproductive health services were also noted to be related factors. We observed similarity in correlates for seeking help from anyone, vs from formal sources, with a greater focus on women being separated for help-seeking from formal sources. CONCLUSION: Findings highlight the need for community programs to reach out to women trapped in abusive relationships, as well as the importance of women's social and economic connectedness; future work should consider holistic interventions that integrate IPV screening and support services with women's health related services.

Cobalt-catalyzed highly diastereoselective [3 + 2] carboannulation reactions: facile access to substituted indane derivatives.

Efficient oxidative [3 + 2] annulation reaction involving aryl hydrazones and heterobicyclic alkenes has been realized with inexpensive and earth-abundant cobalt salts under aerobic conditions. The reaction proceeds via directing-group-assisted C-H activation and exo-selective migratory insertion, followed by the intramolecular nucleophilic attack of the alkylcobalt(III) species onto the imine with high anti-diastereoselectivity to provide complex indane derivatives. The generation of three contiguous stereogenic centers within the indanyl unit and the avoidance of the use of stoichiometric amounts of metal oxidants make this transformation more valuable and appealing.

Fine optimization of a dissolution dynamic nuclear polarization experimental setting for 13C NMR of metabolic samples.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables 13C NMR-based analysis of metabolites at natural abundance. We have recently demonstrated the successful introduction of d-DNP into a full untargeted metabolomics workflow applied to the study of plant metabolism. Here we describe the systematic optimization of d-DNP experimental settings for experiments at natural 13C abundance and show how the resolution, sensitivity, and ultimately the number of detectable signals improve as a result. We have systematically optimized the parameters involved (in a semi-automated prototype d-DNP system, from sample preparation to signal detection, aiming at providing an optimization guide for potential users of such a system, who may not be experts in instrumental development). The optimization procedure makes it possible to detect previously inaccessible protonated 13C signals of metabolites at natural abundance with at least 4 times improved line shape and a high repeatability compared to a previously reported d-DNP-enhanced untargeted metabolomic study. This extends the application scope of hyperpolarized 13C NMR at natural abundance and paves the way to a more general use of DNP-hyperpolarized NMR in metabolomics studies.

Weakly Supervised Classification of Vital Sign Alerts as Real or Artifact.

A significant proportion of clinical physiologic monitoring alarms are false. This often leads to alarm fatigue in clinical personnel, inevitably compromising patient safety. To combat this issue, researchers have attempted to build Machine Learning (ML) models capable of accurately adjudicating Vital Sign (VS) alerts raised at the bedside of hemodynamically monitored patients as real or artifact. Previous studies have utilized supervised ML techniques that require substantial amounts of hand-labeled data. However, manually harvesting such data can be costly, time-consuming, and mundane, and is a key factor limiting the widespread adoption of ML in healthcare (HC). Instead, we explore the use of multiple, individually imperfect heuristics to automatically assign probabilistic labels to unlabeled training data using weak supervision. Our weakly supervised models perform competitively with traditional supervised techniques and require less involvement from domain experts, demonstrating their use as efficient and practical alternatives to supervised learning in HC applications of ML.

Rh(III)-Catalyzed Stereoselective C-C Bond Cleavage of ACPs with N-Phenoxyacetamides: The Critical Role of the Nucleophilic Directing Group.

Rh(III)-catalyzed redox-neutral chemodivergent coupling of N-phenoxyacetamides and alkylidenecyclopropanes (ACPs) has been documented. The reaction proceeds via C-H activation, regioselective migratory insertion and stereoselective ß-carbon elimination followed by ß-hydride elimination, resulting in o-dienylation of phenols in nonpolar solvents, whereas [3 + 2]-annulation leading to dihydrobenzofurans was realized in polar fluorinated solvents. It was observed that the nucleophilic directing group controls the elimination of ß-carbon and so plays a vital role for achieving high stereoselectivities. The synthetic utility of the dienylation and annulation was demonstrated by carrying out gram scale reactions and further derivatization.