Tropical forests are approaching critical temperature thresholds.

The critical temperature beyond which photosynthetic machinery in tropical trees begins to fail averages approximately 46.7 °C (Tcrit)1. However, it remains unclear whether leaf temperatures experienced by tropical vegetation approach this threshold or soon will under climate change. Here we found that pantropical canopy temperatures independently triangulated from individual leaf thermocouples, pyrgeometers and remote sensing (ECOSTRESS) have midday peak temperatures of approximately 34 °C during dry periods, with a long high-temperature tail that can exceed 40 °C. Leaf thermocouple data from multiple sites across the tropics suggest that even within pixels of moderate temperatures, upper canopy leaves exceed Tcrit 0.01% of the time. Furthermore, upper canopy leaf warming experiments (+2, 3 and 4 °C in Brazil, Puerto Rico and Australia, respectively) increased leaf temperatures non-linearly, with peak leaf temperatures exceeding Tcrit 1.3% of the time (11% for more than 43.5 °C, and 0.3% for more than 49.9 °C). Using an empirical model incorporating these dynamics (validated with warming experiment data), we found that tropical forests can withstand up to a 3.9 ± 0.5 °C increase in air temperatures before a potential tipping point in metabolic function, but remaining uncertainty in the plasticity and range of Tcrit in tropical trees and the effect of leaf death on tree death could drastically change this prediction. The 4.0 °C estimate is within the 'worst-case scenario' (representative concentration pathway (RCP) 8.5) of climate change predictions2 for tropical forests and therefore it is still within our power to decide (for example, by not taking the RCP 6.0 or 8.5 route) the fate of these critical realms of carbon, water and biodiversity3,4.

Enantioselective Sulfonimidamide Acylation via a Cinchona Alkaloid-Catalyzed Desymmetrization: Scope, Data Science, and Mechanistic Investigation.

Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products are formed in excellent yield and enantioselectivity with no observed bis-acylation. A data-science-driven approach to substrate scope evaluation was coupled to high throughput experimentation (HTE) to facilitate statistical modeling in order to inform mechanistic studies. Reaction kinetics, catalyst structural studies, and density functional theory (DFT) transition state analysis elucidated the turnover-limiting step to be the collapse of the tetrahedral intermediate and provided key insights into the catalyst-substrate structure-activity relationships responsible for the origin of the enantioselectivity. This study offers a reliable method for accessing enantioenriched sulfonimidamides to propel their application as pharmacophores and serves as an example of the mechanistic insight that can be gleaned from integrating data science and traditional physical organic techniques.

Fe/Thiol Cooperative Hydrogen Atom Transfer Olefin Hydrogenation: Mechanistic Insights That Inform Enantioselective Catalysis.

Asymmetric hydrogenation of activated olefins using transition metal catalysis is a powerful tool for the synthesis of complex molecules, but traditional metal catalysts have difficulty with enantioselective reduction of electron-neutral, electron-rich, and minimally functionalized olefins. Hydrogenation based on radical, metal-catalyzed hydrogen atom transfer (mHAT) mechanisms offers an outstanding opportunity to overcome these difficulties, enabling the mild reduction of these challenging olefins with selectivity that is complementary to traditional hydrogenations with H2. Further, mHAT presents an opportunity for asymmetric induction through cooperative hydrogen atom transfer (cHAT) using chiral thiols. Here, we report insights from a mechanistic study of an iron-catalyzed achiral cHAT reaction and leverage these insights to deliver stereocontrol from chiral thiols. Kinetic analysis and variation of silane structure point to the transfer of hydride from silane to iron as the likely rate-limiting step. The data indicate that the selectivity-determining step is quenching of the alkyl radical by thiol, which becomes a more potent H atom donor when coordinated to iron(II). The resulting iron(III)-thiolate complex is in equilibrium with other iron species, including FeII(acac)2, which is shown to be the predominant off-cycle species. The enantiodetermining nature of the thiol trapping step enables enantioselective net hydrogenation of olefins through cHAT using a commercially available glucose-derived thiol catalyst with up to 80:20 enantiomeric ratio. To the best of our knowledge, this is the first demonstration of asymmetric hydrogenation via iron-catalyzed mHAT. These findings advance our understanding of cooperative radical catalysis and act as a proof of principle for the development of enantioselective iron-catalyzed mHAT reactions.

Scaffold-Oriented Asymmetric Catalysis: Conformational Modulation of Transition State Multivalency during a Catalyst-Controlled Assembly of a Pharmaceutically Relevant Atropisomer.

A new class of superbasic, bifunctional peptidyl guanidine catalysts is presented, which enables the organocatalytic, atroposelective synthesis of axially chiral quinazolinediones. Computational modeling unveiled the conformational modulation of the catalyst by a novel phenyl urea N-cap, that preorganizes the structure into the active, folded state. A previously unanticipated noncovalent interaction involving a difluoroacetamide acting as a hybrid mono- or bidentate hydrogen bond donor emerged as a decisive control element inducing atroposelectivity. These discoveries spurred from a scaffold-oriented project inspired from a fascinating investigational BTK inhibitor featuring two stable chiral axes and relies on a mechanistic framework that was foreign to the extant lexicon of asymmetric catalysis.

Hypoxemia in School-age Children Undergoing One-lung Ventilation: A Retrospective Cohort Study from the Multicenter Perioperative Outcomes Group.

BACKGROUND: Risk factors for hypoxemia in school-age children undergoing one-lung ventilation remain poorly understood. The hypothesis was that certain modifiable and nonmodifiable factors may be associated with increased risk of hypoxemia in school-age children undergoing one-lung ventilation and thoracic surgery. METHODS: The Multicenter Perioperative Outcomes Group database was queried for children 4 to 17 yr of age undergoing one-lung ventilation. Patients undergoing vascular or cardiac procedures were excluded. The original cohort was divided into two cohorts: 4 to 9 and 10 to 17 yr of age inclusive. All records were reviewed electronically for the primary outcome of hypoxemia during one-lung ventilation, which was defined as an oxygen saturation measured by pulse oximetry (Spo2) less than 90% for 3 min or longer continuously, while severe hypoxemia was defined as Spo2 less than 90% for 5 min or longer. Potential modifiable and nonmodifiable risk factors associated with these outcomes were evaluated using separate multivariable least absolute shrinkage and selection operator regression analyses for each cohort. The covariates evaluated included age, extremes of weight, American Society of Anesthesiologists Physical Status of III or higher, duration of one-lung ventilation, preoperative Spo2 less than 98%, approach to one-lung ventilation, right operative side, video-assisted thoracoscopic surgery, lower tidal volume ventilation (defined as tidal volume of 6 ml/kg or less and positive end-expiratory pressure of 4 cm H2O or greater for more than 80% of the duration of one-lung ventilation), and procedure type. RESULTS: The prevalence of hypoxemia in the 4- to 9-yr-old cohort and the 10- to 17-yr-old cohort was 24 of 228 (10.5% [95% CI, 6.5 to 14.5%]) and 76 of 1,012 (7.5% [95% CI, 5.9 to 9.1%]), respectively. The prevalence of severe hypoxemia in both cohorts was 14 of 228 (6.1% [95% CI, 3.0 to 9.3%]) and 47 of 1,012 (4.6% [95% CI, 3.3 to 5.8%]). Initial Spo2 less than 98% was associated with hypoxemia in the 4- to 9-yr-old cohort (odds ratio, 4.20 [95% CI, 1.61 to 6.29]). Initial Spo2 less than 98% (odds ratio, 2.76 [95% CI, 1.69 to 4.48]), extremes of weight (odds ratio, 2.18 [95% CI, 1.29 to 3.61]), and right-sided cases (odds ratio, 2.33 [95% CI, 1.41 to 3.92]) were associated with an increased risk of hypoxemia in the older cohort. Increasing age (1-yr increment; odds ratio, 0.88 [95% CI, 0.80 to 0.97]) was associated with a decreased risk of hypoxemia. CONCLUSIONS: An initial room air oxygen saturation of less than 98% was associated with an increased risk of hypoxemia in all children 4 to 17 yr of age. Extremes of weight, right-sided cases, and decreasing age were associated with an increased risk of hypoxemia in children 10 to 17 yr of age.

Shoulder terminal sensory articular nerve radiofrequency ablation for non-surgical refractory shoulder pain due to rotator cuff pathology and osteoarthritis: A technical note.

BACKGROUND: Given the high prevalence of chronic shoulder pain and encouraging early results of terminal sensory articular branch (TSAB) radiofrequency ablation to treat shoulder pain, research is warranted to refine the procedural technique based on updated neuroanatomical knowledge with the goal of further improving patient outcomes. OBJECTIVE: We describe an updated radiofrequency ablation protocol that accounts for varied locations of the TSABs of suprascapular, axillary, subscapular and lateral pectoral nerves within individual patients. DESIGN: Technical note. METHODS: Cadaveric studies delineating the sensory innervation of the shoulder joint were reviewed, and a more comprehensive radiofrequency ablation (RFA) protocol is proposed relative to historical descriptions. CONCLUSIONS: Based on neuroanatomical dissections of the shoulder joint, the proposed RFA protocol will provide a safe means of more complete sensory denervation and potentially improve clinical outcomes compared to historical descriptions, which must be confirmed in prospective studies.

The effectiveness of intradiscal corticosteroid injection for the treatment of chronic discovertebral low back pain: a systematic review.

OBJECTIVE: Determine the effectiveness of intradiscal corticosteroid injection (IDCI) for the treatment of discovertebral low back pain. DESIGN: Systematic review. POPULATION: Adults with chronic low back pain attributed to disc or vertebral end plate pain, as evidenced by positive provocation discography or Modic 1 or 2 changes on magnetic resonance imaging. INTERVENTION: Fluoroscopically guided or computed tomography-guided IDCI. COMPARISON: Sham/placebo procedure including intradiscal saline, anesthetic, discography alone, or other active treatment. OUTCOMES: Reduction in chronic low back pain reported on a visual analog scale or numeric rating scale and reduction in disability reported by a validated scale such as the Oswestry Disability Index. METHODS: Four reviewers independently assessed articles published before January 31, 2023, in Medline, Embase, CENTRAL, and CINAHL. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The risk of bias in randomized trials was evaluated with the Cochrane Risk of Bias tool (version 2). RESULTS: Of the 7806 unique records screened, 6 randomized controlled trials featuring 603 total participants ultimately met the inclusion criteria. In multiple randomized controlled trials, IDCI was found to reduce pain and disability for 1-6 months in those with Modic 1 and 2 changes but not in those selected by provocation discography. CONCLUSION: According to GRADE, there is low-quality evidence that IDCI reduces pain and disability for up to 6 months in individuals with chronic discovertebral low back pain as evidenced by Modic 1 and 2 changes but not in individuals selected by provocation discography. STUDY REGISTRATION: PROSPERO (CRD42021287421).

Chirality-matched catalyst-controlled macrocyclization reactions.

Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue to attract great interest due to their important applications in physical, pharmacological, and environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over intermolecular reactions in the ring-closing step is often a key challenge. Furthermore, syntheses of macrocycles with stereogenic elements confer an additional challenge, while access to such macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts can have in promoting efficient macrocyclization reactions. We show that the chirality of the catalyst is essential for promoting favorable, matched transition-state relationships that favor macrocyclization of substrates with preexisting stereogenic elements; curiously, the chirality of the catalyst is essential for successful reactions, even though no new static (i.e., not "dynamic") stereogenic elements are created. Control experiments involving either achiral variants of the catalyst or the enantiomeric form of the catalyst fail to deliver the macrocycles in significant quantity in head-to-head comparisons. The generality of the phenomenon, demonstrated here with a number of substrates, stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles, presumably through related, catalyst-defined peripheral interactions with their acyclic substrates.

Overcoming NMR line broadening of nitrogen containing compounds: A simple solution.

This study presents a straightforward solution to the challenge of elucidating the structures of nitrogen containing compounds undergoing isomerization. When spectral line broadening occurs related to isomerization, be it prototropic tautomerism or bond rotations, this poses a significant obstacle to structural elucidation. By adding acids, we demonstrate a simple approach to overcome this issue and effectively sharpen NMR signals for acid stable prototropic tautomers as well as the conformational isomers containing a morpholine or piperazine ring.

Aspartyl ß-Turn-Based Dirhodium(II) Metallopeptides for Benzylic C(sp3)-H Amination: Enantioselectivity and X-ray Structural Analysis.

Amination of C(sp3)-H bonds is a powerful tool to introduce nitrogen into complex organic frameworks in a direct manner. Despite significant advances in catalyst design, full site- and enantiocontrol in complex molecular regimes remain elusive using established catalyst systems. To address these challenges, we herein describe a new class of peptide-based dirhodium(II) complexes derived from aspartic acid-containing ß-turn-forming tetramers. This highly modular system can serve as a platform for the rapid generation of new chiral dirhodium(II) catalyst libraries, as illustrated by the facile synthesis of a series of 38 catalysts. Critically, we present the first crystal structure of a dirhodium(II) tetra-aspartate complex, which unveils retention of the ß-turn conformation of the peptidyl ligand; a well-defined hydrogen-bonding network is evident, along with a near-C4 symmetry that renders the rhodium centers inequivalent. The utility of this catalyst platform is illustrated by the enantioselective amination of benzylic C(sp3)-H bonds, in which state-of-the-art levels of enantioselectivity up to 95.5:4.5 er are obtained, even for substrates that present challenges with previously reported catalyst systems. Additionally, we found these complexes to be competent catalysts for the intermolecular amination of N-alkylamides via insertion into the C(sp3)-H bond α to the amide nitrogen, yielding differentially protected 1,1-diamines. Of note, this type of insertion was also observed to occur on the amide functionalities of the catalyst itself in the absence of the substrate but did not appear to be detrimental to reaction outcomes when the substrate was present.

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. A mixed experimental/computational analysis of steric parameters and substrate conformations identifies the importance of remote conformational effects as a key to achieving high enantioselectivity in this desymmetrization reaction.

Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes.

We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation of 23 protected ß-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry of the product is set through selective hydrogen atom transfer from the chiral thiol catalyst to a prochiral C-centered radical. Structure-selectivity relationships derived from structural variation of both the peptide catalyst and olefin substrate provide key insights into the development of an optimal catalyst. Experimental and computational mechanistic studies indicate that hydrogen-bonding, π-π stacking, and London dispersion interactions are contributing factors for substrate recognition and enantioinduction. These findings further the development of radical-based asymmetric catalysis and contribute to the understanding of the noncovalent interactions relevant to such transformations.

Data Science-Enabled Palladium-Catalyzed Enantioselective Aryl-Carbonylation of Sulfonimidamides.

New methods for the general asymmetric synthesis of sulfonimidamides are of great interest due to their applications in medicinal chemistry, agrochemical discovery, and academic research. We report a palladium-catalyzed cross-coupling method for the enantioselective aryl-carbonylation of sulfonimidamides. Using data science techniques, a virtual library of calculated bisphosphine ligand descriptors was used to guide reaction optimization by effectively sampling the catalyst chemical space. The optimized conditions identified using this approach provided the desired product in excellent yield and enantioselectivity. As the next step, a data science-driven strategy was also used to explore a diverse set of aryl and heteroaryl iodides, providing key information about the scope and limitations of the method. Furthermore, we tested a range of racemic sulfonimidamides for compatibility of this coupling partner. The developed method offers a general and efficient strategy for accessing enantioenriched sulfonimidamides, which should facilitate their application in industrial and academic settings.

On the Ability of the N-O Bond to Support a Stable Stereogenic Axis: Peptide-Catalyzed Atroposelective N-Oxidation.

During studies of atroposelective, peptide-catalyzed N-oxidations of pyridines, we observed lower-than-expected barriers to atropisomerization for these stereodynamic processes under the reaction conditions. Mechanistic studies indicate a hydrogen bond-assisted racemization mechanism intrinsic to both the starting materials and products. We also identified a protonation-dependent barrier to rotation that operates for the starting materials alone. Nonetheless, several substrates were amenable to atroposelective N-oxidations via kinetic resolution, yielding krel values of up to 12.6 and the isolation of one N-oxide with >99:1 er after recrystallization.

Catalytic Asymmetric Synthesis of Atropisomeric N-Aryl 1,2,4-Triazoles.

The atroposelective synthesis of N-aryl 1,2,4-triazoles was developed. A cyclodehydration reaction was rendered asymmetric with the use of a chiral phosphoric acid catalyst to afford atropisomeric N-aryl 1,2,4-triazoles in up to 91:9 er. Recrystallization of the isolated heterocycle further enriched the atropisomeric ratio of several analogs to 99:1 er or greater. A divergent and substrate-dependent reaction pathway yielding a different heterocyclic product is also disclosed.

Chemical neurolysis of the genicular nerves for chronic refractory knee pain: an observational cohort study.

OBJECTIVE: Evaluate outcomes of genicular nerve chemical neurolysis (GChN) in a real-world population with chronic knee pain. DESIGN: Restrospective, observational cohort study. SETTING: Tertiary academic medical center. SUBJECTS: Consecutive patients who had undergone GChN ≥3 months prior. METHODS: Standardized surveys were collected by telephone and included the numerical rating scale, opioid analgesic use, and Patient Global Impression of Change. Age, sex, body mass index, duration of pain, history of arthroplasty, lack of effect from previous radiofrequency ablation, percentage relief from a prognostic block, and volume of phenol used at each injection site were extracted from charts. Descriptive statistics were calculated, and logistic regression analyses were performed to identify factors influencing treatment outcome. RESULTS: At the time of follow-up after GChN (mean ± SD: 9.9 ± 6.1 months), 43.5% (95% CI = 33.5-54.1) of participants reported ≥50% sustained pain reduction. On the Patient Global Impression of Change assessment, 45.9% (95% CI = 35.5-56.7) of participants reported themselves to be "very much improved" or "much improved." Of 40 participants taking opioids at baseline, 11 (27.5%; 95% CI = 14.6-43.9) ceased use. Of participants with a native knee treated, 46.3% reported ≥50% pain reduction, whereas of participants with an arthroplasty in the treated knee, 33.3% reported this threshold of pain reduction (P = .326). Logistic regression analyses did not reveal associations between treatment success and any of the factors that we evaluated. CONCLUSIONS: GChN could provide a robust and durable treatment effect in a subset of individuals with chronic knee pain with complicating factors traditionally associated with poor treatment outcomes, such as those with pain refractory to radiofrequency ablation or those who have undergone arthroplasty.

Considerations for Lumbar Medial Branch Nerve Radiofrequency at Spinal Motion Segments Adjacent to a Fusion Construct.

Instrumented lumbar spinal fusion is common and results in biomechanical changes at adjacent spinal segments that increase facet load bearing. This can cause facet-mediated pain at levels adjacent to the surgical construct. Medial branch nerve radiofrequency ablation (RFA) exists as a treatment for some cases. It is important to acknowledge that the approach and instrumentation used during some specific lumbar fusion approaches will disrupt the medial branch nerve(s). Thus, the proceduralist must consider the fusion approach when determining which medial branch nerves are necessary to anesthetize for diagnosis and then to potentially target with RFA. This article discusses the relevant technical considerations for preparing for RFA to denervate lumbosacral facet joints adjacent to fusion constructs.

Mental health of help-seeking outpatients pre and post COVID-19: A real-world data, multicentre study.

OBJECTIVE: A great deal of research addresses the mental health implications of the COVID-19 pandemic for the general population. Little is known about the implications for mental health of help-seeking outpatients and for the effectiveness of mental health services. The present study investigated the mental health and treatment response of help-seeking outpatients before and during the COVID-19 pandemic. METHOD: Routine outcome monitoring data from 3706 clients in the United States and Northern Europe was analysed using multilevel modelling with global subjective well-being as the dependent variable. RESULTS: As opposed to before the pandemic, during the pandemic, well-being scores were significantly higher at intake and improvement throughout treatment was significantly smaller in the US sample, while both were comparable in the EU sample. CONCLUSION: Although there is also evidence of less effective treatments since the pandemic, no conclusive picture emerges that portrays the impact of the pandemic on mental health as uniform. More research is needed to elucidate the impact of the pandemic on the help-seeking population.

Sharing FAIR monitoring program data improves discoverability and reuse.

Data resulting from environmental monitoring programs are valuable assets for natural resource managers, decision-makers, and researchers. These data are often collected to inform specific reporting needs or decisions with a specific timeframe. While program-oriented data and related publications are effective for meeting program goals, sharing well-documented data and metadata allows users to research aspects outside initial program intentions. As part of an effort to integrate data from four long-term large-scale US aquatic monitoring programs, we evaluated the original datasets against the FAIR (Findable, Accessible, Interoperable, Reusable) data principles and offer recommendations and lessons learned. Differences in data governance across these programs resulted in considerable effort to access and reuse the original datasets. Requirements, guidance, and resources available to support data publishing and documentation are inconsistent across agencies and monitoring programs, resulting in various data formats and storage locations that are not easily found, accessed, or reused. Making monitoring data FAIR will reduce barriers to data discovery and reuse. Programs are continuously striving to improve data management, data products, and metadata; however, provision of related tools, consistent guidelines and standards, and more resources to do this work is needed. Given the value of these data and the significant effort required to access and reuse them, actions and steps intended on improving data documentation and accessibility are described.

Asymmetric Photochemical [2 + 2]-Cycloaddition of Acyclic Vinylpyridines through Ternary Complex Formation and an Uncontrolled Sensitization Mechanism.

Stereochemical control of photochemical reactions that occur via triplet energy transfer remains a challenge. Suppressing off-catalyst stereorandom reactivity is difficult for highly reactive open-shell intermediates. Strategies for suppressing racemate-producing, off-catalyst pathways have long focused on formation of ground state, substrate-catalyst chiral complexes that are primed for triplet energy transfer via a photocatalyst in contrast to their off-catalyst counterparts. Herein, we describe a strategy where both a chiral catalyst-associated vinylpyridine and a nonassociated, free vinylpyridine substrate can be sensitized by an Ir(III) photocatalyst, yet high levels of diastereo- and enantioselectivity in a [2 + 2] photocycloaddition are achieved through a preferred, highly organized transition state. This mechanistic paradigm is distinct from, yet complementary to current approaches for achieving high levels of stereocontrol in photochemical transformations.