Emergency Patient Triage Improvement through a Retrieval-Augmented Generation Enhanced Large-Scale Language Model.

OBJECTIVES: Emergency medical triage is crucial for prioritizing patient care in emergency situations, yet its effectiveness can vary significantly based on the experience and training of the personnel involved. This study aims to evaluate the efficacy of integrating Retrieval Augmented Generation (RAG) with Large Language Models (LLMs), specifically OpenAI's GPT models, to standardize triage procedures and reduce variability in emergency care. METHODS: We created 100 simulated triage scenarios based on modified cases from the Japanese National Examination for Emergency Medical Technicians. These scenarios were processed by the RAG-enhanced LLMs, and the models were given patient vital signs, symptoms, and observations from emergency medical services (EMS) teams as inputs. The primary outcome was the accuracy of triage classifications, which was used to compare the performance of the RAG-enhanced LLMs with that of emergency medical technicians and emergency physicians. Secondary outcomes included the rates of under-triage and over-triage. RESULTS: The Generative Pre-trained Transformer 3.5 (GPT-3.5) with RAG model achieved a correct triage rate of 70%, significantly outperforming Emergency Medical Technicians (EMTs) with 35% and 38% correct rates, and emergency physicians with 50% and 47% correct rates (p < 0.05). Additionally, this model demonstrated a substantial reduction in under-triage rates to 8%, compared with 33% for GPT-3.5 without RAG, and 39% for GPT-4 without RAG. CONCLUSIONS: The integration of RAG with LLMs shows promise in improving the accuracy and consistency of medical assessments in emergency settings. Further validation in diverse medical settings with broader datasets is necessary to confirm the effectiveness and adaptability of these technologies in live environments.

Enantioselective Construction of Tetrahydroindole Skeletons by Rh-Catalyzed [2+2+2] Cycloaddition of Homopropargyl Enamides with Alkynes.

We have developed the Rh-catalyzed enantioselective [2+2+2] cycloaddition of homopropargyl enamides (tosylamide-tethered 1,6-enynes) with alkynes to construct tetrahydroindole skeletons found in natural alkaloids and pharmaceuticals. This cycloaddition proceeds at room temperature in high yields and regio- and enantioselectivity with a broad substrate scope. The preparative scale reaction followed by substituent conversion on the nitrogen atom and the diastereoselective [4+2] cycloaddition with singlet O2 affords hexahydroindole-diols bearing three stereogenic centers and variable substituents on the nitrogen. Mechanistic studies have revealed that the substituents of the enynes change the ratio of intramolecular and intermolecular rhodacycle formation when using terminal alkynes, varying the ee values of the cycloadducts.

Vibration-mediated long-wavelength photolysis of electronegative bonds beyond S0-S1 and S0-T1 transitions.

Photolysis is an attractive method in organic synthesis to produce free radicals through direct bond cleavage. However, in this method, specific irradiation wavelengths of light have been considered indispensable for excitation through S0-Sn or S0-Tn transitions. Here we report the photoinduced homolysis of electronegative interelement bonds using light at wavelengths much longer than theoretically and spectroscopically predicted for the S0-Sn or S0-Tn transitions. This long-wavelength photolysis proceeds in N-Cl, N-F, and O-Cl bonds at room temperature under blue, green, and red LED irradiation, initiating diverse radical reactions. Through experimental, spectroscopic, and computational studies, we propose that this "hidden" absorption is accessible via electronic excitations from naturally occurring vibrationally excited ground states to unbonded excited states and is due to the electron-pair repulsion between electronegative atoms.

Conversion of T2-Weighted Magnetic Resonance Images of Cervical Spine Trauma to Short T1 Inversion Recovery (STIR) Images by Generative Adversarial Network.

INTRODUCTION: The short T1 inversion recovery (STIR) sequence is advantageous for visualizing ligamentous injuries, but the STIR sequence may be missing in some cases. The purpose of this study was to generate synthetic STIR images from MRI T2-weighted images (T2WI) of patients with cervical spine trauma using a generative adversarial network (GAN).  Methods: A total of 969 pairs of T2WI and STIR images were extracted from 79 patients with cervical spine trauma. The synthetic model was trained 100 times, and the performance of the model was evaluated with five-fold cross-validation.  Results: As for quantitative validation, the structural similarity score was 0.519±0.1 and the peak signal-to-noise ratio score was 19.37±1.9 dB. As for qualitative validation, the incorporation of synthetic STIR images generated by a GAN alongside T2WI substantially enhances sensitivity in the detection of interspinous ligament injuries, outperforming assessments reliant solely on T2WI. CONCLUSION: The GAN model can generate synthetic STIRs from T2 images of cervical spine trauma using image-to-image conversion techniques. The use of a combination of synthetic STIR images generated by a GAN and T2WI improves sensitivity in detecting interspinous ligament injuries compared to assessments that use only T2WI.

Dearomative Construction of 2D/3D Frameworks from Quinolines via Nucleophilic Addition/Borate-Mediated Photocycloaddition.

Dearomative construction of multiply-fused 2D/3D frameworks, composed of aromatic two-dimensional (2D) rings and saturated three-dimensional (3D) rings, from readily available quinolines has greatly contributed to drug discovery. However, dearomative cycloadditions of quinolines in the presence of photocatalysts usually afford 5,6,7,8-tetrahydroquinoline (THQ)-based polycycles, and dearomative access to 1,2,3,4-THQ-based structures remains limited. Herein, we present a chemo-, regio-, diastereo-, and enantioselective dearomative transformation of quinolines into 1,2,3,4-THQ-based 6-6-4-membered rings without any catalyst, through a combination of nucleophilic addition and borate-mediated [2+2] photocycloaddition. Detailed mechanistic studies revealed that the photoexcited borate complex, generated from quinoline, organolithium, and HB(pin), accelerates the cycloaddition and suppresses the rearomatization that usually occurs in conventional photocycloaddition. Based on our mechanistic analysis, we also developed further photoinduced cycloadditions affording other types of 2D/3D frameworks from isoquinoline and phenanthrene.

Radiation Exposure During Lumbar Interbody Fusion Surgery Can Be Reduced by Using a Three-Dimensional Patient-Specific Template Guide.

BACKGROUND: The use of posterior lumber interbody fusion (PLIF) using cortical bone trajectory (CBT) with a patient-specific 3D template guide is increasingly widespread. To our knowledge, no studies have extensively evaluated the reduction of radiation exposure when using patient-specific drill template guides. The purpose of this study is to compare the intra-operative radiation dose and surgeon's exposure to radiation in CBT-PLIF when using a patient-specific drill guide with that in traditional minimally invasive (MIS)-PLIF. METHODS: In this observational study, we retrospectively compared data from five patients who were treated with single-level CBT-PLIF using a patient-specific drill guide (G group) and five patients who were treated with single-level traditional MIS-PLIF (M group). We compared the surgical time, surgeon's exposure to radiation, and intra-operative radiation time and dose between the two groups of patients. RESULTS: The mean age of the patients was 67.0 years in the M group and 74.2 years in the G group. The average surgical time was 242.8 min in the M group and 189.6 min in the G group (p = 0.020). The surgeon's exposure to radiation was 373.7 µSv in the M group and 81.75 µSv in the G group at chest level outside the protector (p = 0.00092); 42.0 µSv (M group) and 3.6 µSv (G group) at chest level inside the protector (p = 0.0000062); and 4.33 µSv (M group) and 1.20 µSv (G group) at the buttocks of the surgeon (p = 0.0013). Radiation time was 269.8 s (M group) and 56.6 s (G group) (p = 0.0097), and radiation dose was 153.7 mGy (M group) and 30.42 mGy (G group) (p = 0.00057). CONCLUSION: The patient-specific drill template guide is an invaluable tool that facilitates the safe insertion of CBT screws with a low radiation dose from the outset.

A Novel Evaluation for Vertebral Artery Course Using 3D Magnetic Resonance Imaging with Computed Tomography -like Bone Contrast and Magnetic Resonance Angiography: A Proof of Concept Study.

OBJECTIVE: Vertebral artery (VA) injury poses a significant risk in cervical spine surgery, necessitating accurate preoperative assessment. This study aims to introduce and validate a novel approach that combines the Fast field echo that resembles a computed tomography using restricted echo spacing (FRACTURE) sequence with Time of Flight (TOF) Magnetic Resonance Angiography (MRA) for comprehensive evaluation of VA courses in the cervical spine. MATERIALS AND METHODS: A total of eight healthy volunteers and two patients participated in this study. The FRACTURE sequence provided high-resolution bone images of the cervical spine, while TOF MRA offered non-invasive vascular imaging. Fusion images were created by merging FRACTURE and MRA modalities to simultaneously visualize cervical spine structures and VA courses. Board-certified orthopedic spine surgeons independently evaluated images to assess the visibility of anatomical characteristics of the VA course by Likert-scale. RESULTS: The FRACTURE-MRA fusion images effectively depicted the extraosseous course of the VA at the craniovertebral junction, the intraosseous course of the VA at the craniovertebral junction, the VA entrance level to the transverse foramen, and the side-to-side asymmetry of bilateral VAs. Additionally, clinical cases demonstrated the utility of the proposed technique in identifying anomalies and guiding surgical interventions. CONCLUSIONS: The integration of the FRACTURE sequence and TOF MRA presents a promising methodology for the precise evaluation of VA courses in the cervical spine. This approach improves preoperative planning for cervical spine surgery with detailed anatomy and is a valuable alternative to conventional methods without contrast agents.

Visible-Light-Induced trans-Hydroboration of Diaryl Alkynes Utilizing Excited State of Borate Complexes.

We have developed visible-light-induced trans-hydroboration of diaryl alkynes via direct photoexcitation of in-situ-generated diboron complexes, affording previously elusive (E)-1,2-diaryl-vinylboronates with high stereoselectivity. Experimental, spectroscopic, and theoretical mechanistic studies revealed that the triplet-state borate complex facilitates B-B bond cleavage and the desired C-B bond formation. This methodology does not require any catalyst and is operationally simple. The highly borylated 1,2-diaryl alkenes [1-(2-borylphenyl)vinyl)boronates] are shown to be useful as building blocks.

Machine Learning Web Application for Predicting Functional Outcomes in Patients With Traumatic Spinal Cord Injury Following Inpatient Rehabilitation.

Accurately predicting functional outcomes in patients with spinal cord injury (SCI) helps clinicians set realistic functional recovery goals and improve the home environment after discharge. The present study aimed to develop and validate machine learning (ML) models to predict functional outcomes in patients with SCI and deploy the models within a web application. The study included data from the Japan Association of Rehabilitation Database from January 1, 1991, to December 31, 2015. Patients with SCI who were admitted to an SCI center or transferred to a participating post-acute rehabilitation hospital after receiving acute treatment were enrolled in this database. The primary outcome was functional ambulation at discharge from the rehabilitation hospital. The secondary outcome was the total motor Functional Independence Measure (FIM) score at discharge. We used binary classification models to predict whether functional ambulation was achieved, as well as regression models to predict total motor FIM scores at discharge. In the training dataset (70% random sample) using demographic characteristics and neurological and functional status as predictors, we built prediction performance matrices of multiple ML models and selected the best one for each outcome. We validated each model's predictive performance in the test dataset (the remaining 30%). Among the 4181 patients, 3827 were included in the prediction model for the total motor FIM score. The mean (standard deviation [SD]) age was 50.4 (18.7) years, and 3211 (83.9%) patients were male. There were 3122 patients included in the prediction model for functional ambulation. The CatBoost Classifier and regressor models showed the best performances in the training dataset. On the test dataset, the CatBoost Classifier had an area under the receiver operating characteristic curve of 0.8572 and an accuracy of 0.7769 for predicting functional ambulation. Likewise, the CatBoost Regressor performed well, with an R2 of 0.7859, a mean absolute error of 9.2957, and a root mean square error of 13.4846 for predicting the total motor FIM score. The final models were deployed in a web application to provide functional predictions. The application can be found at http://3.138.174.54:8501. In conclusion, our prediction models developed using ML successfully predicted functional outcomes in patients with SCI and were deployed in an open-access web application.

T-Cell Receptor Repertoire as a Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) are effective in treating renal cell carcinoma (RCC) but can also cause immune-related adverse events (irAEs). The relationship between irAEs and the T-cell receptor (TCR) repertoire in RCC patients treated with ICIs remains unclear. We analyzed the relationship between the severity and diversity of irAEs and the TCR repertoire in RCC patients who received dual checkpoint inhibitors (ipilimumab + nivolumab). The TCRß (TRB) repertoires were characterized in peripheral blood samples from six patients with RCC before the initiation of ICI therapy. The diversity and clonality of the TCR repertoire were compared between patients with grade 2 and grade 3 irAEs. The median proportion of top 10 unique reads in the TCR repertoire was significantly higher in grade 3 compared with grade 2 irAEs in RCC patients receiving immune checkpoint inhibitors (grade 2: 0.196%; grade 3: 0.346%; p = 0.0038). We provide insight into the relationship between TCR repertoire and irAEs in RCC patients treated with ICIs. TCR repertoire clonality may be associated with the development of irAEs in RCC patients.

Posterior Decompression and Fixation for Thoracic Spine Ossification: A 10-Year Follow-Up Study.

Ossification of the posterior longitudinal ligament of the thoracic spine (T-OPLL) causes symptoms including leg and back pain, and motor and sensory deficits. This study retrospectively reviewed 32 patients who initially underwent posterior decompression with instrumented fusion (PDF) for T-OPLL between 2001 and 2012, with 20 qualifying for the final analysis after applying exclusion criteria. Exclusions included unknown preoperative neurological findings, follow-up less than 10 years, or prior spinal surgeries at other levels. Outcomes were assessed using the Japanese Orthopedic Association (JOA) score, recovery rate, and kyphotic angle. The average preoperative JOA score of 3.6 improved to 7.4 at 1 year post-surgery and remained at 7.4 at 10 years, with a recovery rate of 52%. The kyphotic angle at T4-12 increased from 26 degrees preoperatively to 29 degrees postoperatively and to 37 degrees at 10 years. At the fused levels, the angle remained at 26 degrees immediately post-operation and increased to 32 degrees at 10 years. Forty percent of patients required additional surgery, primarily for conditions related to cervical OPLL, such as myelopathy, or lumbar OPLL, such as radiculopathy, or cauda equina syndrome. In conclusion, PDF effectively reduces T-OPLL symptoms over the long term, but the high rate of additional surgeries calls for careful patient follow-up.

Differences in Risk Factors for Decreased Cervical Lordosis after Multiple-Segment Laminoplasty for Cervical Spondylotic Myelopathy and Ossification of the Posterior Longitudinal Ligament: A Pilot Study.

STUDY DESIGN: Retrospective study. PURPOSE: To compare the radiographic risk factors for decreased cervical lordosis (CL) after laminoplasty, focusing on the difference between cervical spondylotic myelopathy (CSM) and cervical ossification of the posterior longitudinal ligament (C-OPLL). OVERVIEW OF LITERATURE: A few reports compared the risk factors for decreased CL between CSM and C-OPLL although these two pathologies have their characteristics. METHODS: This study included 50 patients with CSM and 39 with C-OPLL who underwent multi-segment laminoplasty. Decreased CL was defined as the difference between preoperative and 2-year postoperative neutral C2-7 Cobb angles. Radiographic parameters included preoperative neutral C2-7 Cobb angles, C2-7 sagittal vertical axis (SVA), T1 slope (T1S), dynamic extension reserve (DER), and range of motion. The radiographic risk factors were investigated for decreased CL in CSM and C-OPLL. Additionally, the Japanese Orthopedic Association (JOA) score was assessed preoperatively and 2 years postoperatively. RESULTS: C2-7 SVA (p =0.018) and DER (p =0.002) were significantly correlated with decreased CL in CSM, while C2-7 Cobb angle (p =0.012) and C2-7 SVA (p =0.028) were correlated with decreased CL in C-OPLL. Multiple linear regression analysis revealed that greater C2-7 SVA (B =0.22, p =0.026) and small DER (B =-0.53, p =0.002) were significantly associated with decreased CL in CSM. By contrast, greater C2-7 SVA (B =0.36, p =0.031) was significantly associated with decreased CL in C-OPLL. The JOA score significantly improved in both CSM and C-OPLL (p <0.001). CONCLUSIONS: C2-7 SVA was associated with a postoperative decreased CL in both CSM and C-OPLL, but DER was only associated with decreased CL in CSM. Risk factors for decreased CL slightly differed depending on the etiology of the condition.

Enantioselective Synthesis of Axially Chiral Figure-Eight Spirocycloparaphenylenes via Rh-Catalyzed Intermolecular [2 + 2 + 2] Cycloaddition.

We have achieved the enantioselective synthesis of axially chiral figure-eight spiro[9.9]cycloparaphenylene (CPP) tetracarboxylates with up to 75:25 er via the cationic Rh(I)/(R)-H8-BINAP complex-catalyzed chemo-, regio-, and enantioselective intermolecular double [2 + 2 + 2] cycloaddition of an achiral symmetric tetrayne with dialkyl acetylenedicarboxylates followed by reductive aromatization. The spiro[9.9]CPP tetracarboxylates are highly distorted at the phthalate moieties with large dihedral and boat angles and exhibit weak aggregation-induced emission enhancement behavior.

Stereoselective synthesis of [2.2]triphenylenophanes via intramolecular double [2 + 2 + 2] cycloadditions.

Planar chiral [2.2]cyclophanes with two aromatic rings in close proximity have attracted much attention for their applications as chiral materials and catalysts because of their stable chirality and transannular interactions. Although numerous [2.2]cyclophanes have been synthesized to date, only a few polycyclic aromatic hydrocarbon (PAH)-based ones have been reported, and the simultaneous control of two planar chiralities of the two aromatic rings facing each other has not been achieved. Here we report the enantio- and/or diastereoselective synthesis of planar chiral PAH-based [2.2]cyclophanes ([2.2]triphenylenophanes) via the high-yielding base-mediated intermolecular macrocyclization and Rh- or Ni-catalyzed intramolecular double [2 + 2 + 2] cycloadditions. DFT calculations have revealed that the second [2 + 2 + 2] cycloaddition kinetically determines the diastereoselectivity. Single crystal X-ray diffraction analyses have confirmed that the facing triphenylene or [5]helicene skeletons strongly repel each other, resulting in curved structures with bulged centers.

Shape- and Size-Tunable Synthesis of Covalent Organic Cages through Rh-Catalyzed Regioselective [2+2+2] Cycloaddition.

Covalent organic cages have potential applications in molecular inclusion/recognition and porous organic crystals. Bridging arene units with sp3 atoms enables facile construction of rigid isolated internal vacancies, and various prismatic arene cages have been synthesized by kinetically controlled covalent bond formation. However, the synthesis of a tetrahedral one, which requires twice as much bond formation as prismatic ones, has been limited to a thermodynamically controlled dynamic SN Ar reaction, and this reversible covalent bond formation made the resulting cage product chemically unstable. Here we report the Rh-catalyzed high-yielding and highly 1,3,5-selective room temperature [2+2+2] cycloaddition of push-pull alkynes and its application to the synthesis of chemically stable aryl ether cages of various shapes and sizes, including prismatic and tetrahedral forms. These aryl ether cages are highly crystalline and intertwine with each other to form regular packing structures. Some aryl ether cages encapsulated isolated water molecules in their hydrophobic cavity by hydrogen bonding with the multiple ester moieties.

An Electron-Deficient CpE Iridium(III) Catalyst: Synthesis, Characterization, and Application to Ether-Directed C-H Amidation.

The synthesis, characterization, and catalytic performance of an iridium(III) catalyst with an electron-deficient cyclopentadienyl ligand ([CpE IrI2 ]2 ) are reported. The [CpE IrI2 ]2 catalyst was synthesized by complexation of a precursor of the CpE ligand with [Ir(cod)OAc]2 , followed by oxidation, desilylation, and removal of the COD ligand. The electron-deficient [CpE IrI2 ]2 catalyst enabled C-H amidation reactions assisted by a weakly coordinating ether directing group. Experimental mechanistic studies and DFT calculations suggested that the high catalytic performance of [CpE IrI2 ]2 is due to its electron-deficient nature, which accelerates both C-H activation and IrV -nitrenoid formation.

Dearomative triple elementalization of quinolines driven by visible light.

Organoboron and organosilicon compounds are used not only as synthetic building blocks but also as functional materials and pharmaceuticals, and compounds with multiple boryl and silyl groups are beginning to be used for these purposes. Especially in drug discovery, methodology providing easy stereoselective access to aliphatic nitrogen heterocycles bearing multiple boryl or silyl groups from readily available aromatic nitrogen heterocycles would be attractive. However, such transformations remain challenging, and available reactions have been mostly limited to dearomative hydroboration or hydrosilylation reactions. Here, we report the dearomative triple elementalization (carbo-sila-boration) of quinolines via the addition of organolithium followed by photo-boosted silaboration, affording the desired products with complete chemo-, regio-, and stereoselectivity. The reaction proceeds via the formation of silyl radicals instead of silyl anions. We also present preliminary studies to illustrate the potential of silaboration products as synthetic platforms.

Characterization of Serotype CD Mosaic Botulinum Neurotoxin in Comparison with Serotype C and A.

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, cleaves proteins involved in neurotransmitter release, thereby triggering flaccid paralyses, which are responsible for botulism. BoNT is classified into seven serotypes (BoNT/A-G); BoNT/A and BoNT/B are used as medical therapeutics and anti-wrinkle reagents. In this study, we investigated the efficacy of BoNT/CD, a mosaic toxin of BoNT/C and BoNT/D, to assess its potential as a therapeutic alternative for BoNT/A. In a cultured neuron assay, BoNT/CD cleaved syntaxin and SNAP-25 with higher efficacy than BoNT/C and BoNT/A. Intramuscularly administrated BoNT/CD induced dose-dependent muscle paralysis, and the paralysis lasted ~21 days in a mouse digit abduction score assay (BoNT/A-induced paralysis lasted ~30 days). BoNT/C failed to induce local paralysis without systemic toxicity. Multiple alignment analyses of the amino acid sequences of the receptor binding domain (HC) of eight BoNT/CDs and two BoNT/Ds showed sequence clustering in five groups. Comparing BoNT/CD strain 003-9 (BoNT/CD003-9) and strain 6813 (BoNT/CD6813) showed that both BoNT/CDs displayed similar efficacies in cultured neurons, but BoNT/CD003-9 displayed higher efficacy in a mouse model than BoNT/CD6813. These findings suggest that BoNT/CD may be a potential alternative for patients who do not respond to existing BoNT-based therapeutics.

Rhodium-Catalyzed Chemo-, Regio-, Diastereo-, and Enantioselective Intermolecular [2+2+2] Cycloaddition of Three Unsymmetric 2π Components.

We have developed the Rh+ /H8 -binap-catalyzed chemo-, regio-, diastereo-, and enantioselective intermolecular [2+2+2] cycloaddition of three unsymmetric 2π components. Thus, two arylacetylenes react with a cis-enamide to yield a protected chiral cyclohexadienylamine. Moreover, replacing one arylacetylene with a silylacetylene enables the [2+2+2] cycloaddition of three distinct unsymmetric 2π components. These transformations proceed with excellent selectivity (complete regio- and diastereoselectivity and up to >99 % yield and >99 % ee). Mechanistic studies suggest the chemo- and regioselective formation of a rhodacyclopentadiene intermediate from the two terminal alkynes.

Photocatalytic Generations of Secondary and Tertiary Silyl Radicals from Silylboranes Using an Alkoxide Cocatalyst.

Silyl radicals are valuable species to prepare diverse organosilicon compounds. However, unlike stable tertiary silyl radicals, the use of secondary silyl radicals has been problematic in silylation reactions due to their instability. Here, we present photocatalytic in situ generations of both secondary and tertiary silyl radicals by one-electron oxidation of ate complexes, formed from silylboranes and an alkoxide cocatalyst, achieving highly efficient hydrosilylation and deuterosilylation of electron-rich alkenes and dienes as well as electron-deficient alkenes. The theoretical studies show that anionic borate complexes activated with an alkoxide have lower oxidation potentials than neutral borate complexes, allowing the formation of secondary silyl radicals. The calculated reaction pathways reveal that anionic conditions using the conjugate acid-base pair of NaOEt (cocatalyst) and EtOH (solvent) are the key to expanding the scope of silyl radicals and alkenes.