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.

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.

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.

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.

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.

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.

Rhodium-Catalyzed Intermolecular Cycloaromatization Route to Cycloparaphenylenes that Exhibit Aggregation-Induced Emission.

A high-yielding new route to substituted cycloparaphenylenes has been developed via reductive aromatization of a diyne bearing two cyclohexadiene units giving a cyclophenylene-ethynylene (CPE) followed by the cationic rhodium(I)/dppe complex-catalyzed intermolecular [2+2+2] cycloaddition (cycloaromatization) of the CPE with monoynes. The thus-obtained products, substituted [8]cycloparaphenylene-triphenylenes ([8]CPPTs), exhibited definite aggregation-induced emission (AIE). This molecule is noteworthy as a novel AIE-active cycloarylene that does not have well-known AIE luminogens, such as tetraphenylethene and 1,2,4,5-tetraphenylbenzene skeletons. The single-crystal X-ray diffraction analyses of the AIE-active [8]CPPTs revealed their highly ordered packing structures in which the rotation of the triphenylene moieties is restricted.

Oxidative [4 + 2] annulation of 1-naphthols with alkynes accelerated by an electron-deficient rhodium(III) catalysts.

The 1,3-diethoxycarbonyl-2,4,5-trimethylcyclopentadienyl (CpE) rhodium(III) complex displayed high efficacy in the catalytic oxidative annulation of 1-naphthols with internal alkynes under mild conditions. DFT calculations revealed that lower activation energies for the concerted metalation-deprotonation and the reductive elimination steps are the key to improved reactivity.

Enantioselective Synthesis of Axially Chiral Styrene-Carboxylic Esters by Rhodium-Catalyzed Chelation-Controlled [2+2+2] Cycloaddition.

Axially chiral styrene-carboxylic esters were synthesized in high yields with excellent enantioselectivity by the cationic rhodium(I)/H8 -BINAP complex-catalyzed chelation-controlled [2+2+2] cycloaddition reactions of 1,6- and 1,7-diynes with 1,3-enyne-carboxylic esters. The diastereo- and enantioselective synthesis of C2 symmetric axially chiral cis and trans-stilbene-dicarboxylic esters was also achieved by the double [2+2+2] cycloaddition reactions of two molecules of the 1,6-diyne with 2,3-dialkynylmaleate and 2,3-dialkynylfumarate, respectively. In these reactions, the 1,3-enyne-carboxylic esters coordinating to rhodium with a five-membered chelate were more reactive than those coordinating to rhodium with a six-membered chelate, although both chelation modes realized excellent enantioselectivity. The enantioselection mechanism of the cationic rhodium(I)-catalyzed chelation-controlled [2+2+2] cycloaddition was elucidated by DFT calculations.

Native Amide-Directed C(sp3 )-H Amidation Enabled by Electron-Deficient RhIII Catalyst and Electron-Deficient 2-Pyridone Ligand.

Trivalent group-9 metal catalysts with a cyclopentadienyl-type ligand (CpMIII ; M=Co, Rh, Ir, Cp=cyclopentadienyl) have been widely used for directed C-H functionalizations, albeit that their application to challenging C(sp3 )-H functionalizations suffers from the limitations of the available directing groups. In this report, we describe directed C(sp3 )-H amidation reactions of simple amide substrates with a variety of substituents. The combination of an electron-deficient CpE Rh catalyst (CpE =1,3-bis(ethoxycarbonyl)-substituted Cp) and an electron-deficient 2-pyridone ligand is essential for high reactivity.

Synthesis of Cyclophenacene- and Chiral-Type Cyclophenylene-Naphthylene Belts.

We report the synthesis of a [20]cyclophenacene-type cyclophenylene-naphthylene (CPN) belt and the enantioselective synthesis of chiral-type CPN belts (up to >99 % ee) by the cationic rhodium(I)-catalyzed intramolecular [2+2+2] cycloaddition of naphthalene-embedded cyclic polyynes. The synthesis of a depth-expanded CPN belt was also attempted, but the final intramolecular [2+2+2] cycloaddition was unsuccessful. Theoretical calculations clarified that the reactivity depends on the stability of the transition state in the initial oxidative cycloaddition step which is subject to molecular strain. The cylindrical structures of these CPN belts were confirmed by X-ray crystallographic analyses. As a result of π-extension through the introduction of naphthalenes in the chiral-type CPN belts, the anisotropy dissymmetry factors of electronic circular dichroism and circularly polarized luminescence are amplified compared with the corresponding zigzag-type chiral cyclophenylene belts.

Photo-Induced ortho-C-H Borylation of Arenes through In Situ Generation of Rhodium(II) Ate Complexes.

Photoinduced in situ "oxidation" of half-sandwich metal complexes to "high-valent" cationic metal complexes has been used to accelerate catalytic reactions. Here, we report the unprecedented photoinduced in situ "reduction" of half-sandwich metal [Rh(III)] complexes to "low-valent" anionic metal [Rh(II)] ate complexes, which facilitate ligand exchange with electron-deficient elements (diboron). This strategy was realized by using a functionalized cyclopentadienyl (CpA3) Rh(III) catalyst we developed, which enabled the basic group-directed room temperature ortho-C-H borylation of arenes.

Illuminating Stannylation.

We have developed photoboosted stannylation reactions of terminal alkynes (linear-selective hydrostannylation) and fluoroarenes (defluorostannylation), in which the stannyl anion is photoexcited to an excited triplet (T1) stannyl diradical species. This unprecedented T1-stannyl diradical species shows completely different reactivity and selectivity from those of stannyl anions and stannyl radicals. This methodology is operationally simple, has broad functional group tolerance, and proceeds in high yield without the need for any catalyst.

Rhodium-Catalyzed Enantioselective Synthesis, Structures, and Properties of Single and Double Azahelicene-Like Molecules.

The enantioselective synthesis of aza[6] and [7]helicene-like molecules have been achieved by the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed intramolecular [2+2+2] cycloaddition of cyanodiynes. This protocol was successfully applied to the diastereo- and enantioselective synthesis of an S-shaped double aza[6]helicene-like molecule with a high ee value of 89 %. Although no epimerization and racemization were observed in the double carbo[6]helicene-like molecule at 80 °C, epimerization and racemization of the double aza[6]helicene-like molecule proceeded at 80 °C. This double aza[6]helicene-like molecule showed good fluorescent quantum yields and chiroptical responses under both neutral and acidic conditions.

Effect of electromyography-triggered peripheral magnetic stimulation on voluntary swallow in healthy humans.

BACKGROUND: Electrical stimulation therapy is effective for patients with dysphagia. However, because of the pain, strong stimulation cannot be applied. Although magnetic stimulation induces less pain, there are no reports on magnetic stimulation being synchronised with a swallowing reflex. OBJECTIVE: This study aimed to determine whether it is possible to induce magnetic stimulation during a voluntary swallowing using electromyography (EMG)-triggered peripheral magnetic stimulation and to evaluate its effect on healthy individuals. METHODS: A total of 20 healthy adults in seated position were instructed to swallow saliva and 10 ml of barium under videofluoroscopy. For concomitant use of magnetic stimulation, a magnetic stimulus for suprahyoid muscles at 30 Hz frequency was applied for 2 s when the EMG level in the sternohyoid muscle exceeded the threshold. During the voluntary swallowing, the movement of the hyoid bone and opening width of the upper oesophageal sphincter (UES) were measured. Furthermore, pressure topography was evaluated in 6 subjects using high-resolution manometry. RESULTS: The magnetic stimulation significantly extended the movement time of the hyoid bone (p < 0.001). During liquid deglutition, significant increases were observed in the anterior maximum movement distance of the hyoid bone (p < 0.05), opening width of the UES (p < 0.001) and anterior movement distance of the hyoid bone at the maximum UES opening (p < 0.01). In the pressure topography, the maximum pressure immediately after UES closure significantly decreased with magnetic stimulation (p < 0.05). CONCLUSION: EMG-triggered peripheral magnetic stimulation made it possible to apply magnetic stimulation during a voluntary swallowing.

Tadalafil is sufficiently effective for severe chronic prostatitis/chronic pelvic pain syndrome in patients with benign prostatic hyperplasia.

OBJECTIVES: To investigate the efficacy of tadalafil for patients with benign prostatic hyperplasia and chronic prostatitis/chronic pelvic pain syndrome. METHODS: Tadalafil 5 mg was given each morning for 12 weeks to patients diagnosed as having either moderate or severe lower urinary tract symptoms. Voiding symptoms were compared between patients with a high (≥4; high group) and low (<4; low group) pain subscore of the National Institutes of Health Chronic Prostatitis Symptom Index before and after tadalafil administration. The correlation between changes in the Chronic Prostatitis Symptom Index and the International Prostate Symptom Score during treatment was also investigated. RESULTS: At baseline, the pain subscore of the Chronic Prostatitis Symptom Index was high (≥4) in 24 of 74 (32.4%) patients. The International Prostate Symptom Score in the group with a high pain subscore was significantly higher than that in the group with a low pain subscore. International Prostate Symptom Score, National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscore were all significantly improved after treatment. The change in the Chronic Prostatitis Symptom Index total score correlated positively with the change in the International Prostate Symptom Score. The decrease in the International Prostate Symptom Score was significantly greater in the group with high versus low pain subscore. CONCLUSIONS: Tadalafil is sufficiently effective in the treatment of patients with benign prostatic hyperplasia and severe chronic prostatitis/chronic pelvic pain syndrome.

Repetitive Peripheral Magnetic Stimulation for Strengthening of the Suprahyoid Muscles: A Randomized Controlled Trial.

OBJECTIVE: Head lift exercise is a widely known form of training in the rehabilitation of patients with dysphagia. This study aimed to compare muscular strength reinforcement training of the suprahyoid muscles using repetitive peripheral magnetic stimulation (rPMS) with head lift exercises in a randomized controlled trial. MATERIALS AND METHODS: Twenty-four healthy adults were randomly assigned to either the magnetic stimulation group (M group) or the head lift exercise group (H group). Both groups underwent training five days a week for two weeks. The primary outcome was the cervical flexor strength, and secondary outcomes were jaw-opening force, tongue pressure, muscle fatigue of the hyoid and laryngeal muscles, displacement of the hyoid bone and opening width of the upper esophageal sphincter (UES) while swallowing 10 mL of liquid, training performance rate, and pain. RESULTS: No dropouts were reported during the two-week intervention period. Cervical flexor strength significantly increased solely in the M group. Tongue pressure significantly improved in both groups. There were no significant differences in the jaw-opening force, median frequency rate of the anterior belly of the digastric muscle, sternohyoid muscle, sternocleidomastoid muscle, anterior and superior hyoid bone displacement, and UES opening width in both groups. CONCLUSIONS: Two-week rPMS of the suprahyoid muscles increased the strength of these muscles compared with the head lift exercise during the same period.

Silaboration of [1.1.1]Propellane: A Storable Feedstock for Bicyclo[1.1.1]pentane Derivatives.

The silaboration of [1.1.1]propellane enables direct introduction of B and Si functional groups onto the bicyclo[1.1.1]pentane (BCP) scaffold in high yield under mild, additive-free conditions. The silaborated BCP can be obtained on a gram-scale in a single step without the need for column-chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C-B/C-Si bonds on the BCP scaffold, including development of a modified Suzuki-Miyaura cross-coupling reaction at the highly sterically hindered bridgehead sp3 carbon center of the BCP skeleton using a combination of highly activated BCP boronic esters, copper(I) oxide, and a PdCl2 (dppf) catalyst system.