ChatGPT4 Outperforms Endoscopists for Determination of Postcolonoscopy Rescreening and Surveillance Recommendations.

BACKGROUND & AIMS: Large language models including Chat Generative Pretrained Transformers version 4 (ChatGPT4) improve access to artificial intelligence, but their impact on the clinical practice of gastroenterology is undefined. This study compared the accuracy, concordance, and reliability of ChatGPT4 colonoscopy recommendations for colorectal cancer rescreening and surveillance with contemporary guidelines and real-world gastroenterology practice. METHODS: History of present illness, colonoscopy data, and pathology reports from patients undergoing procedures at 2 large academic centers were entered into ChatGPT4 and it was queried for the next recommended colonoscopy follow-up interval. Using the McNemar test and inter-rater reliability, we compared the recommendations made by ChatGPT4 with the actual surveillance interval provided in the endoscopist's procedure report (gastroenterology practice) and the appropriate US Multisociety Task Force (USMSTF) guidance. The latter was generated for each case by an expert panel using the clinical information and guideline documents as reference. RESULTS: Text input of de-identified data into ChatGPT4 from 505 consecutive patients undergoing colonoscopy between January 1 and April 30, 2023, elicited a successful follow-up recommendation in 99.2% of the queries. ChatGPT4 recommendations were in closer agreement with the USMSTF Panel (85.7%) than gastroenterology practice recommendations with the USMSTF Panel (75.4%) (P < .001). Of the 14.3% discordant recommendations between ChatGPT4 and the USMSTF Panel, recommendations were for later screening in 26 (5.1%) and for earlier screening in 44 (8.7%) cases. The inter-rater reliability was good for ChatGPT4 vs USMSTF Panel (Fleiss κ, 0.786; 95% CI, 0.734-0.838; P < .001). CONCLUSIONS: Initial real-world results suggest that ChatGPT4 can define routine colonoscopy screening intervals accurately based on verbatim input of clinical data. Large language models have potential for clinical applications, but further training is needed for broad use.

Formal High-Order Cycloadditions of Donor-Acceptor Cyclopropanes with Cycloheptatrienes.

Design of various cycloaddition / annulation processes is one of the most intriguing challenges during all time in the development of the donor-acceptor (D-A) cyclopropanes chemistry. In this work, a new missing class of formal high-order [6+n]-cycloaddition and annulation processes of D-A cyclopropanes with cycloheptatriene systems has been designed and reported, to fill a significant gap in the chemistry of D-A cyclopropanes. The reactivity of methylated cycloheptatrienes from Me1 to Me5 as well as unsubstituted cycloheptatriene was study in detail under GaCl3 activation conditions, which makes it possible to efficiently generate gallium 1,2-zwitterionic complexes or 1,3-zwitterionic intermediates from starting D-A cyclopropanes, when other Lewis acids are ineffective and non-selective. New important examples of formal [6+2]-, [6+3]-, [6+4]-, [6+1]-, and [4+2]- cycloaddition and annulation reactions with cycloheptatrienes along with more complex processes were discovered. Cycloheptatriene itself also can successfully act as a hydride anion donor which allows ionic hydrogenation of D-A cyclopropanes to be performed under mild conditions. As a result, a number of efficient and highly diastereoselective protocols for the synthesis of seven-membered-based carbocycles has been developed.

The role of the local environment on the structural heterogeneity of carotenoid ß-ionone rings.

Our analysis of the X-ray crystal structure of canthaxanthin (CAN) showed that its ketolated ß-ionone rings can adopt two energetically equal, but structurally distinct puckers. Quantum chemistry calculations revealed that the potential energy surface of the ß-ionone ring rotation over the plane of the conjugated π-system in carotenoids depends on the pucker state of the ß-ring. Considering different pucker states and ß-ionone ring rotation, we found six separate local minima on the potential energy surface defining the geometry of the keto-ß-ionone ring-two cis and one trans orientation for each of two pucker states. We observed a small difference in energy and no difference in relative orientation for the cis-minima, but a pronounced difference for the position of trans-minimum in alternative pucker configurations. An energetic advantage of ß-ionone ring rotation from a specific pucker type can reach up to 8 kJ/mol ([Formula: see text]). In addition, we performed the simulation of linear absorption of CAN in hexane and in a unit cell of the CAN crystal. The electronic energies of [Formula: see text] transition were estimated both for the CAN monomer and in the CAN crystal. The difference between them reached [Formula: see text], which roughly corresponds to the energy gap between A and B pucker states predicted by theoretical estimations. Finally, we have discussed the importance of such effects for biological systems whose local environment determines conformational mobility, and optical/functional characteristics of carotenoid.

Blood Transfusion is Associated With Adverse Outcomes in Pediatric Solid Tumor Oncology Patients Following Tumor Resection.

BACKGROUND: Packed red blood cell (PRBC) transfusion is a lifesaving intervention that also has proinflammatory and immunosuppressive effects. Adults with a malignancy who receive PRBC transfusion have increased rates of infection, tumor recurrence, and decreased survival. The effect of PRBC transfusion among children with solid tumors is unknown. METHODS: We performed a retrospective review of all children who underwent operative resection of a solid tumor malignancy. Data collected included demographic information, location of operation, nadir hemoglobin, and any PRBC transfusion within 30 days of tumor resection. RESULTS: Three hundred sixty children underwent tumor resection at our institution between 2002 and 2013; 194 (54%) received a perioperative blood transfusion. After adjusting for stage at diagnosis, tumor location, preoperative chemotherapy and nadir hemoglobin, blood transfusion was associated with a higher rate of postoperative infectious complications, shorter disease-free interval, and a higher rate of tumor recurrence. Each additional transfused unit increased the risk of postoperative infection (odds ratio 3.83; 95% confidence interval 1.21, 14.22, P =0.031). CONCLUSIONS: Among children with solid tumor malignancies, PRBC transfusion within 30 days of operation is associated with higher rates of postoperative infection. If transfusion becomes necessary, single unit increments should be transfused. LEVEL OF EVIDENCE: Level III.

PheLiGe: an interactive database of billions of human genotype-phenotype associations.

Genome-wide association studies have provided a vast array of publicly available SNP × phenotype association results. However, they are often in disparate repositories and formats, making downstream analyses difficult and time consuming. PheLiGe (https://phelige.com) is a database that provides easy access to such results via a web interface. The underlying database currently stores >75 billion genotype-phenotype associations from 7347 genome-wide and 1.2 million region-wide (e.g. cis-eQTL) association scans. The web interface allows for investigation of regional genotype-phenotype associations across many phenotypes, giving insights into the biological function affected by the variant in question. Furthermore, PheLiGe can compare regional patterns of association between different traits. This analysis can ascertain whether a co-association is due to pleiotropy or linkage. Moreover, comparison of association patterns for a complex trait of interest and gene expression and protein levels can implicate causal genes.

Comparison of Pediatric Trauma Scoring Tools That Incorporate Neurological Status for Trauma Team Activation.

BACKGROUND: Two novel pediatric trauma scoring tools, SIPAB+ (defined as elevated SIPA with Glasgow Coma Scale ≤8) and rSIG (reverse Shock Index multiplied by Glasgow Coma Scale and defined as abnormal using cutoffs for early outcomes), which combine neurological status with Pediatric Age-Adjusted Shock Index (SIPA), have been shown to predict early trauma outcomes better than SIPA alone. We sought to determine if one more accurately identifies children in need of trauma team activation. METHODS: Patients 1 to 18 years old from the 2014-2018 Pediatric Trauma Quality Improvement Program database were included. Sensitivity and specificity for SIPAB+ and rSIG were calculated for components of pediatric trauma team activation, based on criteria standard definitions. RESULTS: There were 11,426 patients (1.9%) classified as SIPAB+ and 235,672 (39.0%) as having an abnormal rSIG. SIPAB+ was consistently more specific, with specificities exceeding 98%, but its sensitivity was poor (<30%) for all outcomes. In comparison, rSIG was a more sensitive tool, with sensitivities exceeding 60%, and specificity values exceeded 60% for all outcomes. CONCLUSIONS: Trauma systems must determine their priorities to decide how best to incorporate SIPAB+ and rSIG into practice, although rSIG may be preferred as it balances both sensitivity and specificity. LEVEL OF EVIDENCE: Level III.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific T Cells and Antibodies in Coronavirus Disease 2019 (COVID-19) Protection: A Prospective Study.

BACKGROUND: During the ongoing coronavirus disease 2019 (COVID-19) pandemic, many individuals were infected with and have cleared the virus, developing virus-specific antibodies and effector/memory T cells. An important unanswered question is what levels of T-cell and antibody responses are sufficient to protect from the infection. METHODS: In 5340 Moscow residents, we evaluated anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M (IgM)/immunoglobulin G (IgG) titers and frequencies of the T cells specific to the membrane, nucleocapsid, and spike proteins of SARS-CoV-2, using interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay. Additionally, we evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFN-γ and interleukin 2 followed by flow cytometry. We analyzed the COVID-19 rates as a function of the assessed antibody and T-cell responses, using the Kaplan-Meier estimator method, for up to 300 days postinclusion. RESULTS: We showed that T-cell and antibody responses are closely interconnected and are commonly induced concurrently. Magnitudes of both responses inversely correlated with infection probability. Individuals positive for both responses demonstrated the highest levels of protectivity against the SARS-CoV-2 infection. A comparable level of protection was found in individuals with antibody response only, whereas the T-cell response by itself granted only intermediate protection. CONCLUSIONS: We found that the contribution of the virus-specific antibodies to protection against SARS-CoV-2 infection is more pronounced than that of the T cells. The data on the virus-specific IgG titers may be instructive for making decisions in personalized healthcare and public anti-COVID-19 policies. Clinical Trials Registration. NCT04898140.

Fundamentals of Curvilinear Ferromagnetism: Statics and Dynamics of Geometrically Curved Wires and Narrow Ribbons.

Low-dimensional magnetic architectures including wires and thin films are key enablers of prospective ultrafast and energy efficient memory, logic, and sensor devices relying on spin-orbitronic and magnonic concepts. Curvilinear magnetism emerged as a novel approach in material science, which allows tailoring of the fundamental anisotropic and chiral responses relying on the geometrical curvature of magnetic architectures. Much attention is dedicated to magnetic wires of Möbius, helical, or DNA-like double helical shapes, which act as prototypical objects for the exploration of the fundamentals of curvilinear magnetism. Although there is a bulk number of original publications covering fabrication, characterization, and theory of magnetic wires, there is no comprehensive review of the theoretical framework of how to describe these architectures. Here, theoretical activities on the topic of curvilinear magnetic wires and narrow nanoribbons are summarized, providing a systematic review of the emergent interactions and novel physical effects caused by the curvature. Prospective research directions of curvilinear spintronics and spin-orbitronics are discussed, the fundamental framework for curvilinear magnonics are outlined, and mechanically flexible curvilinear architectures for soft robotics are introduced.

Discreet Values of Shock Index Pediatric Age-Adjusted (SIPA) to Predict Intervention in Children With Blunt Organ Injuries.

INTRODUCTION: Elevated shock index pediatric age-adjusted (SIPA) has been shown to be associated with the need for both blood transfusion and intervention in pediatric patients with blunt liver and spleen injuries (BLSI). SIPA has traditionally been used as a binary value, which can be classified as elevated or normal, and this study aimed to assess if discreet values above SIPA cutoffs are associated with an increased probability of blood transfusion and failure of nonoperative management (NOM) in bluntly injured children. MATERIALS AND METHODS: Children aged 1-18 y with any BLSI admitted to a Level-1 pediatric trauma center between 2009 and 2020 were analyzed. Blood transfusion was defined as any transfusion within 24 h of arrival, and failure of NOM was defined as any abdominal operation or angioembolization procedure for hemorrhage control. The probabilities of receiving a blood transfusion or failure of NOM were calculated at different increments of 0.1. RESULTS: There were 493 patients included in the analysis. The odds of requiring blood transfusion increased by 1.67 (95% CI 1.49, 1.90) for each 0.1 unit increase of SIPA (P < 0.001). A similar trend was seen initially for the probability of failure of nonoperative management, but beyond a threshold, increasing values were not associated with failure of NOM. On subanalysis excluding patients with a head injury, increased 0.1 increments were associated with increased odds for both interventions. CONCLUSIONS: Discreet values above age-related SIPA cutoffs are correlated with higher probabilities of blood transfusion in pediatric patients with BLSI and failure of NOM in those without head injury. The use of discreet values may provide clinicians with more granular information about which patients require increased resources upon presentation.

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity.

Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the combined contribution of ACE*Ya5ACE, CDH4*Yb8NBC516, COL13A1*Ya5ac1986, HECW1*Ya5NBC182, LAMA2*Ya5-MLS19, PLAT*TPA25, PKHD1L1*Yb8AC702, SEMA6A*Yb8NBC597, STK38L*Ya5ac2145 and TEAD1*Ya5ac2013 Alu elements to longevity. The study group included 2054 unrelated individuals aged from 18 to 113 years who are ethnic Tatars from Russia. We analyzed the dynamics of the allele and genotype frequencies of the studied Alu polymorphic loci in the age groups of young (18-44 years old), middle-aged (45-59 years old), elderly (60-74 years old), old seniors (75-89 years old) and long-livers (90-113 years old). Most significant changes in allele and genotype frequencies were observed between the long-livers and other groups. The search for polygenic predictors of longevity was performed using the APSampler program. Attaining longevity was associated with the combinations LAMA2*ID + CDH4*D (OR = 2.23, PBonf = 1.90 × 10-2) and CDH4*DD + LAMA2*ID + HECW1*D (OR = 4.58, PBonf = 9.00 × 10-3) among persons aged between 18 and 89 years, LAMA2*ID + CDH4*D + SEMA6A*I for individuals below 75 years of age (OR = 3.13, PBonf = 2.00 × 10-2), LAMA2*ID + HECW1*I for elderly people aged 60 and older (OR = 3.13, PBonf = 2.00 × 10-2) and CDH4*DD + LAMA2*D + HECW1*D (OR = 4.21, PBonf = 2.60 × 10-2) and CDH4*DD + LAMA2*D + ACE*I (OR = 3.68, PBonf = 1.90 × 10-2) among old seniors (75-89 years old). The key elements of combinations associated with longevity were the deletion alleles of CDH4 and LAMA2 genes. Our results point to the significance for human longevity of the Alu polymorphic loci in CDH4, LAMA2, HECW1, SEMA6A and ACE genes, involved in the integration systems.

Nematic shells: new insights in topology- and curvature-induced effects.

Within the framework of continuum theory, we draw a parallel between ferromagnetic materials and nematic liquid crystals confined on curved surfaces, which are both characterized by local interaction and anchoring potentials. We show that the extrinsic curvature of the shell combined with the out-of-plane component of the director field gives rise to chirality effects. This interplay produces an effective energy term reminiscent of the chiral term in cholesteric liquid crystals, with the curvature tensor acting as a sort of anisotropic helicity. We discuss also how the different nature of the order parameter, a vector in ferromagnets and a tensor in nematics, yields different textures on surfaces with the same topology as the sphere. In particular, we show that the extrinsic curvature governs the ground state configuration on a nematic spherical shell, favouring two antipodal disclinations of charge +1 on small particles and four +1/2 disclinations of charge located at the vertices of a square inscribed in a great circle on larger particles.

Coupling of Styrylmalonates with Furan and Benzofuran Carbaldehydes: Synthesis and Chemistry of Substituted (4-Oxocyclopent-2-enyl)malonates.

On the basis of the reaction of ß-styrylmalonates with furfural derivatives in the presence of GaCl3 that occurs with opening of the furan ring, an efficient diastereoselective method for the synthesis of trisubstituted cyclopentenones containing a 1,4-diketone moiety was developed. The regularities of the reaction were studied, and a number of chemical reactions of the resulting substrates were carried out. A mechanism for the formation of substituted (4-oxo-2-arylcyclopent-2-enyl)malonates was suggested.

Reactions of Styrylmalonates with Aromatic Aldehydes: Detailed Synthetic and Mechanistic Studies.

Reactions of styrylmalonates with aromatic aldehydes in the presence of Lewis and Brønsted acids and their regularities have been studied in detail. Approaches to the synthesis of various polysubstituted 5,6-dihydropyran-2-ones, indenes, aryl-containing dienes and trienes, cyclopentadienes, and polycyclic lactones have been developed with chemo-, regio-, stereo-, and diastereoselectivity control. The mechanisms of these reactions were studied in depth using multinuclear NMR experiments, monitoring the reactions in the NMR tube, and 18O isotope labeling.

GaCl3-Mediated Cascade [2 + 4]-Cycloaddition/[4 + 2]-Annulation of Donor-Acceptor Cyclopropanes with Conjugated Dienes: Strategy for the Construction of Benzobicyclo[3.3.1]nonane Skeleton.

Structurally important benzobicyclo[3.3.1]nonane derivatives were synthesized by a gallium trichloride mediated reaction of readily available donor-acceptor cyclopropanes (DACs) with 1,3-dienes as a one-pot cascade ionic [2 + 4]-cycloaddition/Friedel-Crafts-type cyclization process. At the first stage, DACs act as sources of formal gallium 1,2-zwitterionic complexes to give 6-benzylcyclohex-3-ene-1,1-dicarboxylates that are converted under certain conditions in the presence of GaCl3 to give benzobicyclo[3.3.1]nonanes in 30-74% yields. The process is tolerant of varying substituents at different positions of the main framework. Further, potentially useful modifications of benzobicyclo[3.3.1]nonane derivatives are demonstrated. 2-Cyclopropylbutadiene reacts with DAC at higher temperature more deeply with cleavage of three-membered rings in both cyclopropane substrates, and twofold alkylation of the Ph-substituent at ortho- and meta-positions, that leads to a 1,2,7,8,9,10-hexahydro-6H-7,10a-methanocycloocta[cd]indene skeleton. Cyclopropane-1,1-diesters containing a bulky substituent in the ester group react with isoprene in a different way to give bicyclic lactones containing a 2-oxabicyclo[2.2.2]octan-3-one moiety.

Curvilinear One-Dimensional Antiferromagnets.

Antiferromagnets host exotic quasiparticles, support high frequency excitations and are key enablers of the prospective spintronic and spin-orbitronic technologies. Here, we propose a concept of a curvilinear antiferromagnetism where material responses can be tailored by a geometrical curvature without the need to adjust material parameters. We show that an intrinsically achiral one-dimensional (1D) curvilinear antiferromagnet behaves as a chiral helimagnet with geometrically tunable Dzyaloshinskii-Moriya interaction (DMI) and orientation of the Néel vector. The curvature-induced DMI results in the hybridization of spin wave modes and enables a geometrically driven local minimum of the low-frequency branch. This positions curvilinear 1D antiferromagnets as a novel platform for the realization of geometrically tunable chiral antiferromagnets for antiferromagnetic spin-orbitronics and fundamental discoveries in the formation of coherent magnon condensates in the momentum space.

The Relationship between the Spatial Arrangement of Pigments and Exciton Transition Moments in Photosynthetic Light-Harvesting Complexes.

Considering bacteriochlorophyll molecules embedded in the protein matrix of the light-harvesting complexes of purple bacteria (known as LH2 and LH1-RC) as examples of systems of interacting pigment molecules, we investigated the relationship between the spatial arrangement of the pigments and their exciton transition moments. Based on the recently reported crystal structures of LH2 and LH1-RC and the outcomes of previous theoretical studies, as well as adopting the Frenkel exciton Hamiltonian for two-level molecules, we performed visualizations of the LH2 and LH1 exciton transition moments. To make the electron transition moments in the exciton representation invariant with respect to the position of the system in space, a system of pigments must be translated to the center of mass before starting the calculations. As a result, the visualization of the transition moments for LH2 provided the following pattern: two strong transitions were outside of LH2 and the other two were perpendicular and at the center of LH2. The antenna of LH1-RC was characterized as having the same location of the strongest moments in the center of the complex, exactly as in the B850 ring, which actually coincides with the RC. Considering LH2 and LH1 as supermolecules, each of which has excitation energies and corresponding transition moments, we propose that the outer transitions of LH2 can be important for inter-complex energy exchange, while the inner transitions keep the energy in the complex; moreover, in the case of LH1, the inner transitions increased the rate of antenna-to-RC energy transfer.

[Regression of cutaneous basal cell and squamous cell carcinoma under pembrolizumab]. / Régression de carcinomes basocellulaire et épidermoïde cutanés sous pembrolizumab.

BACKGROUND: The recommended treatments for advanced squamous cell carcinoma (SCC) (chemotherapy, radiotherapy, anti-EGFR) and advanced basal cell carcinoma (BCC) (vismodegib and sonidegib) have many side effects. Nivolumab (anti-PD1 antibody) may be used as second-line therapy in SCC of the head and neck. We report the case of a patient with advanced SCC and BCC which regressed under pembrolizumab. PATIENTS AND METHODS: A 69-year-old man consulted for a large vertex SCC measuring 15cm in diameter. He also had BCC on the left nostril and sternal Bowen disease. Radiological assessment revealed cervical and parotid lymph node involvement. Treatment with pembrolizumab 2mg/kg every 3 weeks was decided at a Multidisciplinary Concertation Meeting. Tumor regression of the vertex SCC was noted at the third course of treatment, as well as regression of the nasal BCC and the sternal Bowen disease. A complete response was observed after 11 courses of treatment for SCC, 7 courses for BCC, and 10 courses for Bowen disease. CONCLUSION: We report an original case of cure of BCC with anti-PD1 (pembrolizumab) prescribed for locally advanced inoperable SCC. The place of this treatment in the therapeutic arsenal remains to be defined. Clinical trials are in progress concerning use of this treatment in advanced cutaneous SCC and inoperable BCC.

Three-Component GaHal3-Promoted Reactions of Substituted Methylidenemalonates and Donor-Acceptor Cyclopropanes with Propargyl Halides: Cascade Diastereoselective Construction of Five-Membered Lactones.

A new cascade three-component process for high trans,trans-diastereoselective assembly of five-membered (1-halovinyl)lactones has been developed. The process is based on reactions of substituted methylidenemalonates and cyclopropanedicarboxylates with 3-haloprop-1-ynes in the presence of GaHal3 and involves the intermediate in situ generation of 1,2-zwitterionic gallium complexes with [Ga(L)3]3+[GaX4-]3 composition. Chloro, bromo, and iodo derivatives can be obtained successfully. Mechanistic and stereochemical aspects of the process we developed have been studied and considered in detail.

Multiplet of Skyrmion States on a Curvilinear Defect: Reconfigurable Skyrmion Lattices.

Typically, the chiral magnetic Skyrmion is a single-state excitation. Here we propose a system, where multiplet of Skyrmion states appears and one of these states can be the ground one. We show that the presence of a localized curvilinear defect drastically changes the magnetic properties of a thin perpendicularly magnetized ferromagnetic film. For a large enough defect amplitude a discrete set of equilibrium magnetization states appears forming a ladder of energy levels. Each equilibrium state has either a zero or a unit topological charge; i.e., topologically trivial and Skyrmion multiplets generally appear. Transitions between the levels with the same topological charge are allowed and can be utilized to encode and switch a bit of information. There is a wide range of geometrical and material parameters, where the Skyrmion level has the lowest energy. Thus, periodically arranged curvilinear defects can result in a Skyrmion lattice as the ground state.

Cascade Cleavage of Three-Membered Rings in the Reaction of D-A Cyclopropanes with 4,5-Diazaspiro[2.4]hept-4-enes: A Route to Highly Functionalized Pyrazolines.

A new cascade process for reactions of donor-acceptor cyclopropanes (DACs) with spiro[cyclopropanepyrazolines] in the presence of EtAlCl2 or Ga halides is reported. The action of a Lewis acid results in DAC activation and addition of the carbocationic intermediate to the azocyclopropane system of the pyrazoline with opening of the second three-membered ring and addition of a halide anion from the Lewis acid. A specific feature of this process is that one activated cyclopropane ring activates another one, and depending on the component ratio, the process can involve two DAC molecules and one pyrazoline molecule or one DAC molecule and two pyrazoline molecules. The process is tolerant to various functional groups and occurs with a wide range of substrates to give polyfunctionalized structures based on a 2-pyrazoline moiety.