Periprosthetic joint infection (PJI) remains one of the most serious. Advances in metal-artefact-reduction sequences (MARS) now allow for improved diagnostic quality imaging in the periprosthetic region. Early studies suggest the diagnostic efficacy of MARS, including subfeatures, yet no formal synthesis of available data exists. A systematic review and meta-analysis were conducted following PRISMA-DTA and PRISMA 2020 guidelines. Eligible studies include diagnostic accuracy studies reporting MARS-MRI compared with established reference standards, such as Musculoskeletal Infection Society (MSIS) or International Consensus Meeting (ICM) criteria, or intraoperative microbiology and histology. Adults (≥18 years) with hip, knee, or shoulder arthroplasty undergoing MRI for suspected infection or aseptic loosening were included. Comprehensive searches were conducted in PubMed, Embase, Scopus, and Web of Science, from 2005 onwards, without language restriction. A total of 11 studies were included in this meta-analysis evaluating MARS-MRI for diagnosing periprosthetic joint infection (PJI). Pooled performance demonstrated high diagnostic accuracy with sensitivity 0.88 (95% CI 0.72-0.95), specificity 0.95 (95% CI 0.80-0.99), and AUC 0.94. Subgroup analysis showed soft tissue changes had the best diagnostic performance (sensitivity 0.82, specificity 0.91), followed by synovitis and effusion, whilst bone changes were less accurate. Overall, MARS-MRI demonstrates excellent utility in diagnosing PJI. MARS-MRI demonstrates high diagnostic accuracy for periprosthetic joint infection (sensitivity 0.88, specificity 0.95, AUC 0.94), particularly with soft tissue changes. It aids antimicrobial stewardship by reducing unnecessary interventions. Further large, multi-centre prospective studies are needed to strengthen evidence and validate clinical utility.

A practical method for the synthesis of N-heterocycles from readily available amines and alkyl halides in HFIP has been developed. HFIP enables sequential alkylation and cyclization in a one-pot process under acidic conditions. A range of indoline and pyrrolidine derivatives were obtained in moderate to good yields with tolerance toward various functional groups and nitrogen substitution patterns. The synthetic utility of this approach was demonstrated through gram-scale reactions, further transformations of pyrrolidines, and a concise formal synthesis of cephalotaxine.

A unified approach has been developed to construct the characteristic 4a,9a-heterocycle-fused tetrahydrocarbazole skeleton present in various monoterpene indole alkaloids. This method hinges on a unique chiral bisphosphine BIBOP-catalyzed asymmetric Staudinger/aza-Wittig reaction followed by imine cyclization. Compared to conventional mono- and bisphosphines, BIBOP exhibits more robust performance across diverse reaction settings. Mechanistic studies revealed that BIBOP(O), the mono-oxidized derivative of BIBOP, could also promote the asymmetric transformation with excellent enantioselectivity. Leveraging the developed method, we have accomplished a concise total synthesis of (-)-minfiensine and a formal synthesis of (+)-aspidophylline A. This work not only establishes a versatile platform for the synthesis of diverse monoterpene indole alkaloids but also offers a new class of organophosphine catalysts applicable to asymmetric Staudinger/aza-Wittig reaction as well as related transformations.

Densely functionalized 6/5/6 polycycles are prevalent in bioactive natural products, yet their efficient assembly remains a persistent synthetic challenge. Here, we report a palladium-catalyzed autotandem cascade that merges Suzuki-Miyaura coupling with an underexplored oxidative cyclometalation to effect C═C-conserving geminal heterocoupling, thereby enabling rapid construction of fused 6/5/6 scaffolds from readily prepared bicyclic precursors and alkenyl boronates. The transformation proceeds under operationally simple conditions, tolerates broad substrate variation, and is scalable to decagram quantities. Its synthetic utility is demonstrated in a formal synthesis of gracilamine and the total syntheses of GA18 methyl ester and xiamycin E, where the geminal heterocoupling forges the fused tricyclic core and provides advanced intermediates for subsequent target-oriented elaboration. Mechanistic studies support an autotandem pathway involving initial cross-coupling followed by oxidative cyclometalation. Collectively, these studies establish a useful method for the modular construction of fused 6/5/6 polycycles.

The synthesis of multisubstituted furans, those incorporating further functionalizable groups, remains a significant challenge in organic synthesis. These difficulties largely arise from reliance on prefunctionalized substrates, multistep sequences, harsh conditions, and costly catalytic systems. Herein, we report a rapid, efficient, and operationally simple cascade [3 + 2]-annulation that addresses these limitations while delivering step and atom economy. The method exploits readily available and inexpensive active methylene compounds (β-ketoesters, β-diketones, and related derivatives) as C-C-O 1,3-bis-nucleophiles, in combination with 3-oxetanone as a C-C 1,2-bis-electrophile, under catalysis by sustainable and low-cost Fe-salts. This protocol enables the construction of diverse multisubstituted and fused furan architectures, bearing alkyl, cycloalkyl, alkynyl, aryl, and heteroaryl substituents, as well as functional groups derived from nitriles, sulfones, phosphonates, and amides. The synthetic utility of the approach is further demonstrated by the total synthesis of biologically active methylenomycin furans (MMFs) and methylfuroic acid, and formal syntheses of evodone, tubipofuran, menthofuran, maturone, isomaturone, and rabdoketones. Moreover, the method proves highly effective for late-stage diversification, as illustrated by the functionalization of bioactive natural products, including β-ionone, tonalide, progesterone, and pregnenolone. Collectively, this strategy provides a practical, versatile, and sustainable platform for the streamlined synthesis and diversification of multisubstituted furans.

This network meta-analysis of randomized controlled trials (RCTs) aimed to investigate which hypnotics are associated with the most favorable sleep architecture and respiratory outcomes in adults with obstructive sleep apnea. Primary outcomes included total sleep time (TST) and apnea-hypopnea index (AHI) during TST. Other outcomes were rapid eye movement (REM) sleep time, latency to persistent sleep (LPS), wake after sleep onset (WASO), sleep efficiency (SE), AHI during non-REM or REM sleep, mean peripheral oxygen saturation (SpO2) during TST, mean SpO2 nadir during TST, arousal index (AI), all-cause discontinuation, adverse event-related discontinuation, and incidence of individual adverse events. Effect sizes with 95% confidence intervals were calculated. This systematic review included 32 RCTs (n = 1871, average age = 51.60 years, 62.52% male, mean AHI = 23.60). Our network meta-analysis evaluated brotizolam, daridorexant, eszopiclone, flurazepam, lemborexant, nitrazepam, ramelteon, temazepam, triazolam, zaleplon, zolpidem, zopiclone, and placebo. Compared with placebo, lemborexant increased TST, REM sleep time, and SE and decreased LPS and WASO, whereas both daridorexant and zolpidem increased TST and SE and decreased WASO. These three medications demonstrated respiratory safety and discontinuation profiles similar to those of placebo. Eszopiclone increased TST and SE and decreased LPS, WASO, AHI during TST, and AI, but its effects on LPS, WASO, AHI during TST, and AI disappeared in the sensitivity analysis, excluding continuous positive airway pressure titration studies. Our network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice.

Herein, we report a concise formal synthesis of an epimer of the alkaloid parvistemonine A, starting from the inexpensive and readily available D-glucono-δ-lactone as the sole chiral pool source. The synthesis features a one-pot lactone formation and the direct functionalization of commercially available pyrrole, enabling the convergence of two simple building blocks through a cross-metathesis reaction. This key transformation is followed by a stereoselective intramolecular Michael-type cyclization under acidic conditions, forging a seven-membered ring and establishing the desired framework. Notably, the synthesis proceeds without the use of protecting groups and delivers the tricyclic Stemona backbone in only seven steps, with the cis-fused 5/7/5 framework confirmed by single-crystal X-ray crystallography.

Medication non-adherence affects 40%-50% of chronic disease patients globally, causing preventable morbidity and substantial healthcare costs. Traditional adherence monitoring approaches are retrospective and reactive, limiting timely intervention. Artificial intelligence and machine learning offer novel approaches for prospective adherence risk prediction, enabling anticipatory, resource-efficient interventions. This narrative review synthesizes current evidence on AI-based non-adherence prediction across chronic diseases including HIV, tuberculosis, diabetes, hypertension, and mental health disorders. Machine learning models integrating heterogeneous data sources electronic health records, pharmacy refill patterns, sociodemographic variables, and healthcare utilization achieve discrimination metrics (AUC 0.70-0.95) superior to traditional risk stratification. These AUC values are reported descriptively to reflect model discrimination within individual studies and should not be interpreted as results of formal comparison or quantitative synthesis across diseases or modeling approaches. However, significant barriers constrain clinical translation: limited external validation, algorithmic bias affecting marginalized populations, inadequate interpretability, data privacy concerns, and substantial implementation challenges in resource-limited health systems. Future research priorities include rigorous multicenter external validation, model development in low- and middle-income countries, advancement of interpretable architectures, and prospective randomized trials evaluating clinical outcomes. Responsible AI deployment requires participatory governance, health equity prioritization, and maintenance of clinician oversight throughout implementation. This review critically evaluates AI potential while emphasizing prerequisites for equitable, ethical, and clinically meaningful adherence prediction in global health contexts.

The [3.3.3]propellane scaffold, present in various natural products, is a three-dimensional structure of interest in synthetic chemistry. Traditionally, these compounds are synthesized through a ring-by-ring strategy that is tedious (long steps of synthesis) and challenging (building two adjacent bridgehead quaternary centers of the target motifs is a formidable task). Herein, we report a nickel-catalyzed one-step, three-ring propellanation reaction that constructs the [3.3.3] propellane core from linear yne-vinylcyclobutanones. This method employs Ni(COD)2 and P(Ad)3 as the catalytic system and exhibits a broad substrate scope. The utility of this reaction has been further demonstrated through the formal synthesis of modhephene, a natural product featuring a [3.3.3] propellane skeleton. This propellanation reaction can be envisioned as biscarbene insertion of alkyne into the C-C bond in cyclobutanone and the C-H of the vinyl group in the substrates, but it actually takes place through oxidative cyclometalation of the alkyne and carbonyl group, Cope rearrangement, β-hydrogen elimination, trienolate cyclization, and reductive elimination, supported by DFT calculations and a deuterium labeling experiment. The detailed ligand exchange reaction (reaction initiation process) from Ni(COD)2 to the Ni complex coordinated by the phosphine ligand and substrate, has also been studied computationally. How the tether group in the substrates affects the propellanation reaction and the side rearrangement reaction of vinylcyclobutanones to cyclohexenones has been analyzed, finding that electron-withdrawing tethers such as NTs and O favor the propellanation reaction, while the electron-neutral tether such as CH2 and NBn tether, which is less electron-withdrawing compared to NTs, reduce this preference.

In this study, we present an efficient organocatalytic one-pot strategy for the synthesis of 2-gem-dialkyl/aryl chromenes using a bifunctional 2-aminopyridine catalyst. The reaction employs inexpensive phenols and β,β-disubstituted enals and proceeds through an aza-Friedel-Crafts/oxa-6π electrocyclization cascade sequence. This operationally simple and scalable method exhibits a broad substrate scope and enables concise gram-scale syntheses of bioactive chromenes, including precocene I, confluentin, and α-daurichromenic acid, along with the formal synthesis of rhododaurichromanic acid A and (+) α-tocopherol. Detailed hybrid QM/MM MD and physicochemical studies provide mechanistic insight into the catalytic pathway.

Introduction: Depression represents a major public health challenge, affecting individuals worldwide and remaining a prevalent condition that significantly reduces quality of life. Despite the availability of various therapeutic options, including pharmacological interventions, these treatments are often insufficiently effective. Consequently, the search for safe and effective strategies to alleviate depressive symptoms remains a priority. Numerous studies have examined the potential role of omega-3 fatty acids in both the prevention and treatment of depression. In this context, the involvement of inflammatory processes and stress-related pathophysiological mechanisms appears to be particularly relevant. Therefore, research continues to investigate the potential relationship between omega-3 fatty acid supplementation and clinical improvement in patients with depression. Aim of Study: The purpose of this review is to explore potential novel therapeutic strategies that may benefit patients with depression. Material and methods: This narrative review synthesizes contemporary evidence regarding the role of omega-3 fatty acids in the prevention and treatment of depressive disorders. A targeted literature search was conducted using PubMed and Google Scholar. The search was focused primarily on studies published within the five-ten years. Search terms included combinations of “omega-3 fatty acids,” “eicosapentaenoic acid,” “docosahexaenoic acid,” “major depressive disorder,” “treatment-resistant depression". Randomized controlled trials, clinical trials, meta-analyses, systematic reviews, and high-quality narrative reviews were prioritized. Consistent with the narrative nature of this review, no formal systematic screening protocol, risk-of-bias assessment, or quantitative synthesis was performed. Results and Conclusions: After examining the effects of omega-3 fatty acids in patients across different age groups, both as monotherapy and in combination with other agents, including postpartum women, studies have not produced conclusive evidence directly supporting their beneficial impact on depression.

The article outlines the conceptual foundations of a unified system-synergetic theory of information, which represents a significant step forward compared to classical approaches. This theory is the result of a formal synthesis of two leading Russian scientific schools: the synergetic theory of information, which describes information through the prism of dynamic self-organization processes, and the systems theory of information, which defines information through the structural-hierarchical and emergent properties of systems. Unlike classical theory, which views information as a measure of diversity within a set of unrelated elements, the proposed approach introduces the concept of a «system», where interconnections between elements play a pivotal role. This allows for the quantitative measurement of such previously purely qualitative concepts as complexity and emergence. The central result of the theory is the formulation of the universal information variational principle. This principle postulates that the development of any open system — from physical and biological to economic and social — occurs in such a way as to maximize the rate of information increment. It is proposed that this principle be viewed as one of the key regularities of evolution, determining the direction of system development toward increasing complexity and order. The theory offers specific metrics for measuring systemicity and complexity, such as the coefficient of emergence, which indicates how many times the information capacity of a system exceeds the information capacity of a simple set of its elements. In conclusion, this work offers an approach to overcoming a number of limitations inherent in classical information theory and formulates a fruitful program for future research. It opens new horizons for understanding and modeling complex systems by offering a unified explanatory mechanism for a wide range of phenomena. Practical applications of the theory include the development of new methods for big data analysis, the creation of more adaptive and self-learning artificial intelligence systems, and the forecasting of market and social network development. Thus, the proposed theory lays the foundations for the creation of a unified science of complexity, uniting the efforts of scientists from various fields.

The stereoselective conjugate addition of β,β-disubstituted enesulfinamides to α-substituted nitroolefins, followed by transposition of sulfinylamino group, provides an efficient asymmetric synthetic route to 1,4-diketone derivatives. The resulting γ-imino ketone products feature an acyclic quaternary stereocenter bearing two sterically and electronically similar substituents (e.g., methyl and ethyl groups), which are challenging to construct by the conventional synthetic protocols involving C-C bond formation. The synthetic application of the described protocol was demonstrated by the asymmetric formal synthesis of the natural product hamigeran B.

The biosynthetically related daphnane, tigliane, andrhamnofolanediterpenes are a fascinating collection of natural products endowedwith distinct polycyclic architectures and immense therapeutic potential.Containing a common 5,7,6-fused tricyclic core with varied oxidation,these molecules have served as popular and challenging synthetic targetsfor over four decades. Despite much work, however, many complex membersremain inaccessible by synthesis. Inspired by this, we developed aconvergent coupling strategy employing two modular fragments as agateway into this class of diterpenoids. This article details theevolution of such a strategy initially resulting in the total synthesisof the flagship daphnane diterpene orthoester (DDO), resiniferatoxin(RTX). A key trans-fused hydroazulene building blockwas designed and synthesized via a 7-exo-trig Heckcyclization and then coupled with an aldehyde bearing preprogrammedoxidation state for RTX via a diastereoselective aldol reaction. Afterextensive investigations involving many different substrates, a subsequentkey SmI2-mediated 6-exo-trig radical cyclization/1,5-hydrogenatom transfer (HAT) cascade was realized, which enabled rapid accessto the 5,7,6-fused tricyclic core and, ultimately, a total synthesisof (±)-resiniferatoxin in as few as 14 steps. Here we also detailenantioselective syntheses of key building blocks relevant to thesenatural products. Finally, we demonstrate that a modified aldehydefragment can be incorporated into this strategy to intercept a keytricyclic ketone thus achieving formal syntheses of rhamnofolane andtigliane diterpenes, such as crotophorbolone, phorbol, and prostratin.We believe this general strategy could prove useful in accessing variousditerpenes of even higher complexity from the plant families Euphorbiaceae and Thymelaeaceae.

Objective: To evaluate the performance of photon-counting detector CT (PCD-CT) angiography for the detection and quantification of vascular stenosis. Methods: Web of Science, PubMed, and Cochrane databases were searched from January 1980 to December 2025 to identify studies assessing PCD-CT angiography for the detection and quantification of vascular stenosis, using invasive angiography as the reference standard. The risk of bias of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Diagnostic performance metrics, including sensitivity and specificity and quantification values, were extracted from the included studies and a formal narrative synthesis was performed. The meta-analysis included studies reporting true-positive, false-positive, true-negative, and false-negative data. A meta-analysis was conducted only when a minimum of two eligible studies assessed diagnostic performance within the given vascular territory. Statistical analyses were performed using R software (v4.5.0), applying a random-effects model for the meta-analysis. Results: Of 415 identified studies, 20 were included in the systematic review, comprising a total of 9165 participants, with the majority (17/20, 85%) focusing on coronary artery stenosis. In the meta-analysis of three studies, ultra-high-resolution (UHR) PCD-CT demonstrated excellent diagnostic performance for detecting coronary stenosis for patients with ≥50%, having a pooled sensitivity of 96.1% (95% confidence level (CI): 89.3-99.6), specificity of 87.5% (95% CI: 78.2-93.3), positive predictive value (PPV) of 91.9% (95% CI: 70.3-98.2), and negative predictive value (NPV) of 94.8% (95% CI: 86.0-98.6). Compared with conventional energy-integrating detector CT (EID-CT), PCD-CT consistently showed superior diagnostic performance, particularly in the specificity and PPV. In terms of stenosis quantification, PCD-CT showed closer agreement with reference standards than EID-CT, leading to the reclassification of coronary stenosis severity in up to 49% of patients. Evidence for non-coronary vascular territories, including intracranial and peripheral arteries remains limited but suggests promising diagnostic performance. For lower-limb arterial stenosis, the reported sensitivity was 77.4-91%, and specificity was 72.1-91%. For intracranial in-stent stenosis, PCD-CT demonstrated a sensitivity of 100% and a specificity of 89%. Conclusions: PCD-CT angiography provides high diagnostic performance and improved stenosis quantification for coronary artery stenosis. UHR PCD-CT has excellent diagnostic performance for detecting coronary stenosis and consistently outperforms conventional EID-CT, especially in the specificity and positive predictive value.

ABSTRACT Most forensic psychiatric patients are diagnosed with schizophrenia or schizoaffective disorder. Psychotherapy is recognized as an important part of treatment for this patient population, yet no clinical guidelines exist. This mixed-method systematic review aimed to evaluate the scope, quality, and findings of psychotherapy research involving this population. Following the Joanna Briggs Institute methodology, thirteen studies were included after critical appraisal. A convergent-segregated synthesis approach was used due to heterogeneity in study designs and outcomes. Only two studies provided sufficient qualitative data for formal synthesis, while the remaining studies were narratively summarized. Meta-analysis was not feasible due to methodological heterogeneity and small sample sizes. Most studies examined cognitive-behavioral or skills-based interventions, suggesting potential improvements in social functioning, psychiatric symptoms, and reductions in violence. However, these findings were largely derived from small, non-controlled studies. A smaller number of studies have explored music and art therapies, suggesting potential benefits for negative symptoms and self-narrative, though the evidence remains limited. High-quality research, including patient perspectives, women, and the phenomena of the working alliance, is critical to develop the evidence base for forensic psychiatric patients who are diagnosed with schizophrenia or schizoaffective disorder.

Abstract Primary bone malignancies are a rare musculoskeletal tumor that carries a high mortality and significant patient burden. The most common primary bone malignancies are osteosarcoma, Ewing's sarcoma, and chondrosarcoma, each with its own unique radiological presentation. These tumors are difficult to diagnose due to their relative rarity and their ability to mimic other conditions, such as infection. As a result, diagnosis can be delayed, which worsens prognosis. Radiomics poses a solution to this problem, quantifying previously subjective changes and detecting small nuances on imaging. While small studies populate the literature field, there is no formal synthesis of evidence. This systematic review and meta-analysis aims to bridge this knowledge gap and evaluate the utility of radiomics in primary bone tumors. Parallel searches were conducted in PubMed, Embase, Scopus, and Web of Science for studies assessing the use of radiomics in the diagnosis of primary bone tumors. Papers were screened and extracted by two independent reviewers, with conflicts resolved through consensus. A bivariate random-effects meta-analysis was conducted to achieve pooled estimates of the diagnostic capabilities of radiomics. Searches retrieved 330 eligible papers, 13 of which were included in the meta-analysis. Pooled estimates show a sensitivity of 0.81 (95% confidence interval [CI]: 0.75–0.85), a specificity of 0.86 (95% CI: 0.79–0.90), and a diagnostic odds ratio of 30.63 (95% CI: 16.35–57.40). These results demonstrate the significant potential of radiomics in the diagnosis of primary bone malignancies. While the pooled estimates demonstrate the promise radiomics offers to aid radiological diagnosis of primary bone tumors, there are a few limitations to their integration in clinical workflow. Due to the rarity of primary bone malignancies, studies are often restricted to smaller populations, limiting the transferability and introducing publication bias in pooled analysis. To further strengthen the literature field and the clinical integration of radiomics in primary bone tumors, large multicenter prospective cohort studies should be conducted to best assess the role of radiomics in diagnostic workflows.

In this study, dual photoredox/CpTi(IV) catalysis has been developed for the reductive cyclization of 3a-bromo-hexahydropyrroloindoline or 3-bromo-tetrahydrofuroindole with the appendage nitrile, providing rapid access to a series of 4a,9a-heterocycle-fused tetrahydrocarbazoles in satisfactory yields. Utilizing this methodology, formal synthesis of minfiensine, strictamine, and aspidophylline A was achieved based on a sequential catalytic asymmetric bromocyclization/reductive cyclization with improved synthetic efficiency for demonstrating its broad synthetic potential.

We report a Rh-catalyzed asymmetric hydroformylation of 1,1-disubstituted alkenyl boronic esters that provides direct access to a previously inaccessible class of dual-functional linchpin synthons bearing both an aldehyde and a boronic ester. These two orthogonal and highly programmable functional groups offer exceptional diversification potential, enabling independent or sequential derivatizations through numerous established reaction platforms. Using a Rh/(S,S)-DTBM-YanPhos system, the transformation proceeds with high chemoselectivity, broad substrate scope, and excellent enantioselectivity, thereby addressing long-standing challenges in the synthesis of chiral alkyl boron reagents. Scale-up studies delivered TON of up to 4050, underscoring the robustness and practical utility of the method. The synthetic value of the resulting bifunctional products is further showcased through concise derivatizations and formal syntheses of (S)-Fluoxetine and (R)-Atomoxetine, highlighting their potential as versatile, densely functionalized building blocks for complex molecule construction.

Site- and chemoselective oxidation of polycyclic terpenes remains a central challenge in synthesis. We report a chemoenzymatic platform that operates directly on sclareolide to program C1, C3, and C5 C-H hydroxylation. Directed evolution of the nonheme Fe(II)/α-ketoglutarate oxygenase AndA furnishes STAC variants with complementary C1α/C3α/C5α selectivity and up to 82-fold activity improvements, delivering five privileged oxidized labdane scaffolds on gram to decagram scale. A C5-hydroxylation module streamlines access to (+)-phorbadione via a concise formal synthesis from sclareolide. Orthogonal C1/C3/C5 oxidation, combined with Suárez oxidative cleavage and an amine-catalyzed formal [3 + 3] annulation, converges on a common diol that undergoes late-stage diversification. These sequences enable the first syntheses of arisugacin J, arisugacin D, arisugacin M, terreulactone C, and terreulactone B. This work establishes AndA as an Fe/αKG analogue of P450BM3 for tunable, multisite terpene oxidation and illustrates a general strategy for platform synthesis of densely oxidized meroterpenoids from chiral-pool feedstocks.