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1.
RSC Adv ; 14(11): 7720-7727, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38449823

RESUMO

Chemical warfare agents (CWAs) pose a persistent threat to human safety, and bis(2-chloroethyl) sulfide, or sulfur mustard (SM) is one of the most dangerous substances and is able to cause serious harm. Detecting SM gas is vital, but current methods have high-temperature requirements and limited selectivity, mainly because of the lack of CWA receptor development, and this makes them challenging to use. To address this issue, we present a trisaryl phosphoric triamide-based resin receptor that preferentially interacts with a SM simulant 2-chloroethyl ethyl sulfide (2-CEES) through dipole interactions. The receptor was synthesized through a facile process using an amine and a triethyl phosphate and the properties of its coating were enhanced using epoxy chemistry. The receptor's superior triamide structure was evaluated using a quartz crystal microbalance and reactivity was confirmed by observing the variations in reactivity according to the number of phosphoramides. The receptor showed better reactivity to 2-CEES vapor than to the known poly(epichlorohydrin) and showed selectivity to other volatile organic compounds. Moreover, its durability was evident even 30 days post-coating. The applicability of this receptor extends to array sensors, sound acoustic wave sensors, and chemo-resistive and chemo-capacitive sensors, and it promises advances in chemical warfare agent detection.

2.
J Breast Cancer ; 26(5): 479-491, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37704381

RESUMO

PURPOSE: In this study, we investigated the prognostic implications of focal breast edema on preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer. METHODS: Data of 899 patients with breast cancer at a single institution were retrospectively analyzed. The patients were divided into an edema-positive group (EPG) and an edema-negative group (ENG) based on the presence of peritumoral, prepectoral, or subcutaneous edema. Two radiologists evaluated the presence or absence of focal edema and its subtypes on preoperative breast MRI. Clinicopathologic characteristics and survival outcomes were compared between the two groups and among the three subtypes using Pearson's χ² test, Kaplan-Meier estimator, and Cox proportional hazards model. RESULTS: There were 399 (44.4%) and 500 (55.6%) patients in the EPG and ENG, respectively. The EPG showed significantly higher rates of axillary lymph node metastasis (55.6% vs. 19.2%, p < 0.001) and lymphovascular invasion (LVI) (57.9% vs. 12.6%, p < 0.001) than the ENG. Patients in the EPG showed significantly worse overall survival (OS) rate (log-rank p < 0.001; hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56-9.11) and recurrence-free survival rate (log-rank p < 0.001; HR, 3.00; 95% CI, 1.94-4.63) than those in the ENG. After adjusting for other variables, focal breast edema remained a significant factor affecting the OS rate, regardless of the edema type. Specifically, the presence of subcutaneous edema emerged as the strongest predictor for OS with the highest HR (p < 0.001; HR, 9.10; 95% CI, 3.05-27.15). CONCLUSION: Focal breast edema on preoperative breast MRI implies a higher possibility of LVI and axillary lymph node metastasis, which can lead to a poor prognosis. A detailed description of focal breast edema, especially subcutaneous edema, on preoperative breast MRI may provide prognostic predictions. More intensive surveillance is required for patients with breast cancer and focal preoperative breast edema.

3.
J Anim Sci Technol ; 65(3): 638-651, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37332289

RESUMO

The objective of this study was to quantitatively estimate the level of grazing area damage in outdoor free-range pig production using a Unmanned Aerial Vehicles (UAV) with an RGB image sensor. Ten corn field images were captured by a UAV over approximately two weeks, during which gestating sows were allowed to graze freely on the corn field measuring 100 × 50 m2. The images were corrected to a bird's-eye view, and then divided into 32 segments and sequentially inputted into the YOLOv4 detector to detect the corn images according to their condition. The 43 raw training images selected randomly out of 320 segmented images were flipped to create 86 images, and then these images were further augmented by rotating them in 5-degree increments to create a total of 6,192 images. The increased 6,192 images are further augmented by applying three random color transformations to each image, resulting in 24,768 datasets. The occupancy rate of corn in the field was estimated efficiently using You Only Look Once (YOLO). As of the first day of observation (day 2), it was evident that almost all the corn had disappeared by the ninth day. When grazing 20 sows in a 50 × 100 m2 cornfield (250 m2/sow), it appears that the animals should be rotated to other grazing areas to protect the cover crop after at least five days. In agricultural technology, most of the research using machine and deep learning is related to the detection of fruits and pests, and research on other application fields is needed. In addition, large-scale image data collected by experts in the field are required as training data to apply deep learning. If the data required for deep learning is insufficient, a large number of data augmentation is required.

4.
Chemistry ; 29(52): e202301787, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37370249

RESUMO

Chiral allylic amines are valuable building blocks for biologically important compounds and natural products. In this study, we present the use of cooperative cation-binding catalysis as an efficient method for synthesizing chiral allylic amines. By utilizing a chiral oligoEG and potassium fluoride as a cation-binding catalyst and base, respectively, a wide range of biologically relevant chiral 2-nitroallylic amines are obtained with excellent enantioselectivities (up to >99 % ee) through the organocatalytic asymmetric aza-Henry-like reaction of ß-monosubstituted and ß,ß-disubstituted nitroalkenes with α-amidosulfones as imine precursors. Extensive experimental studies are presented to illustrate plausible mechanisms. Preliminary use of a chiral 2-nitroallylic amine as a Michael acceptor demonstrated its potential application for diversity-oriented synthesis of bioactive compounds.

5.
Cancer Res Treat ; 55(4): 1250-1260, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37232070

RESUMO

PURPOSE: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. MATERIALS AND METHODS: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. RESULTS: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. CONCLUSION: Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.


Assuntos
Neoplasias Gástricas , Idoso , Humanos , Capecitabina , Neoplasias Gástricas/patologia , Oxaliplatina/efeitos adversos , Cisplatino , Recidiva Local de Neoplasia/tratamento farmacológico , Fluoruracila/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Chaperonas Moleculares/uso terapêutico , Proteínas Supressoras de Tumor
6.
Ann Hematol ; 102(6): 1467-1476, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37099081

RESUMO

Although the current standard of care for diffuse large B-cell lymphoma (DLBCL) is six cycles of rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone combination chemotherapy (R-CHOP), a larger than expected number of patients cannot complete planned six cycles for various reasons in the real world. We aimed to evaluate the prognosis of patients with DLBCL after incomplete treatment by analyzing the chemotherapy response and survival according to the cause of discontinuation and the number of cycles. We analyzed a retrospective cohort of patients diagnosed with DLBCL who underwent incomplete cycles of R-CHOP at Seoul National University Hospital and Boramae Medical Center from January 2010 to April 2019. A total of 1183 patients were diagnosed with DLBCL, of which 260 (22%) did not complete six cycles of R-CHOP. The most common cause of discontinuation of chemotherapy was life-threatening infection, and the most common pathogen was Pneumocystis jirovecii. Overall survival (OS) and progression-free survival (PFS) were significantly better in patients who achieved complete response (CR) or partial response (PR) at the first response evaluation. Patients underwent three or more cycles of chemotherapy had a longer OS than those who did not. In patients with limited-stage disease, consolidative radiotherapy showed a significant improvement in OS and PFS. Advanced stage, high comorbidity score, and poor primary response to chemotherapy were poor prognostic factors in patients with unplanned treatment shortening. This study provides real-world outcomes for patients who could not complete the planned six cycles of R-CHOP.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Rituximab , Vincristina , Estudos Retrospectivos , Anticorpos Monoclonais Murinos , Intervalo Livre de Doença , Linfoma Difuso de Grandes Células B/patologia , Ciclofosfamida , Prednisona , Doxorrubicina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Org Lett ; 25(15): 2713-2717, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37052359

RESUMO

Here we describe a biomimetic catalytic retro-aldol reaction of racemic α-substituted ß-hydroxy ketones utilizing a chiral oligoEG cation-binding catalyst as a type-II aldolase mimic. Our investigation of various aldol substrates has demonstrated that our biomimetic retro-aldol protocol enables rapid access to highly enantiomerically enriched aldols with a selectivity factor (s) of up to 70. Additionally, we have demonstrated the synthetic strategy's feasibility for accessing diverse and valuable axially chiral aldehydes.

8.
Org Lett ; 25(7): 1056-1060, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36762981

RESUMO

Sulfur(VI) fluoride exchange (SuFEx) is recognized as another emerging tool for click chemistry. The preparation of the functionalized alkyl sulfonyl fluorides as key SuFEx hubs via C(sp3)-C(sp3) bond formation is exceptionally challenging. We report herein a new efficient method for accessing alkyl sulfonyl fluorides incorporating γ-geminal dithioester via phosphazene catalysis. The aqueous, neutral organosuperbase catalytic system amplifies the reactivity by taking advantage of the hydrophobic amplification. SuFEx-active products are applied to the click connection of bioactive molecules. Density functional theory studies show that the selective outcome of the product is guided by an ion-pair organosuperbase catalyst assembly that is potentially stabilized by a hydrogen-bonding interaction between the catalyst and the DTM in the C(sp3)-C(sp3) bond-forming transition structure.

9.
J Surg Oncol ; 127(4): 587-597, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36367404

RESUMO

BACKGROUND: Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8+ and forkhead box P3 (FOXP3)+ lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers. METHODS: Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers. RESULTS: Immune cell PD-L1-positivity, tumor size < 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1(-) and leptin(-) subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1+ and leptin+ subgroups. CONCLUSIONS: The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1(-) or tumor leptin(-) subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1+ or leptin+ subgroups.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Colangiocarcinoma , Infecções por Vírus Epstein-Barr , Humanos , Prognóstico , Antígeno B7-H1/metabolismo , Linfócitos do Interstício Tumoral , Leptina/metabolismo , Herpesvirus Humano 4 , Neoplasias do Sistema Biliar/cirurgia , Neoplasias do Sistema Biliar/patologia , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Fatores de Transcrição Forkhead , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos
10.
Skeletal Radiol ; 52(4): 733-742, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36305913

RESUMO

OBJECTIVE: To investigate the difference in time-to-fusion between two sets of interbody fusion criteria (absence of peri-graft radiolucency vs. trabecular bone bridging), and to determine the effect of osteoporosis on time-to-fusion. MATERIALS AND METHODS: This retrospective study enrolled 79 patients treated for degenerative disease with one-level transforaminal lumbar interbody fusion from February 2012 to December 2018, and who had both pre- and post-operative CTs. Patients were divided into osteoporosis, osteopenia, and normal groups based on L1 vertebral body attenuation values in pre-operative CT with cutoff of 90 Hounsfield units (HU) and 120 HU. The osteoporosis, osteopenia, and normal groups included 36 patients (mean age: 69.9 years; 8 men and 28 women), 18 patients (mean age: 62.6 years; 7 men and 11 women), and 25 patients (mean age: 56.6 years; 15 men and 10 women), respectively. Fusion was assessed annually on post-operative CT images using absence of peri-graft radiolucency and trabecular bone bridging criteria. Time-to-fusion was estimated using the Kaplan-Meier method, and differences between the groups were examined using the log-rank test. Cox proportional hazards regression was performed. RESULTS: Time-to-fusion took significantly longer in the osteoporosis group in both fusion criteria (0.5 years in normal vs. 2 years in osteopenia vs. 3 years in osteoporosis for absence of peri-graft radiolucency; p = 0.003, and 3 years vs. 4 years vs. 5 years for trabecular bone bridging; p = 0.001). Only osteoporosis grouping was independent risk factor for slow trabecular bone fusion (hazard ratio:0.339; p = 0.003). CONCLUSION: The median time to fusion was significantly longer when using trabecular bone bridging criteria than absence of peri-graft radiolucency criteria.


Assuntos
Osteoporose , Fusão Vertebral , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Densidade Óssea , Osso Esponjoso , Estudos Retrospectivos , Osteoporose/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia
11.
J Anim Sci Technol ; 65(6): 1254-1269, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38616875

RESUMO

This study aims to predict the change in corn share according to the grazing of 20 gestational sows in a mature corn field by taking images with a camera-equipped unmanned air vehicle (UAV). Deep learning based on convolutional neural networks (CNNs) has been verified for its performance in various areas. It has also demonstrated high recognition accuracy and detection time in agricultural applications such as pest and disease diagnosis and prediction. A large amount of data is required to train CNNs effectively. Still, since UAVs capture only a limited number of images, we propose a data augmentation method that can effectively increase data. And most occupancy prediction predicts occupancy by designing a CNN-based object detector for an image and counting the number of recognized objects or calculating the number of pixels occupied by an object. These methods require complex occupancy rate calculations; the accuracy depends on whether the object features of interest are visible in the image. However, in this study, CNN is not approached as a corn object detection and classification problem but as a function approximation and regression problem so that the occupancy rate of corn objects in an image can be represented as the CNN output. The proposed method effectively estimates occupancy for a limited number of cornfield photos, shows excellent prediction accuracy, and confirms the potential and scalability of deep learning.

12.
PLoS One ; 17(10): e0276497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36269747

RESUMO

Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients.


Assuntos
Cetuximab , Neoplasias Colorretais , Exantema , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Cetuximab/efeitos adversos , Quimiocina CXCL10 , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Selectina E , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/metabolismo , Exantema/etiologia , Exantema/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Interleucina-10 , Interleucina-13 , Interleucina-17 , Interleucina-1alfa , Interleucina-1beta , Interleucina-4 , Interleucina-6 , Interleucina-8 , Selectina-P , Fator de Necrose Tumoral alfa/uso terapêutico
14.
ChemSusChem ; 15(18): e202201000, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35799476

RESUMO

Herein, a water-accelerated, N-heterocyclic carbene (NHC)-catalyzed aza-Michael addition reaction was reported to access ß-aminosulfonyl fluorides, which are key hubs of the sulfur(VI) fluoride exchange (SuFEx) reaction. As a crucial reaction medium, water considerably enhanced the reaction rate with excellent chemo- and site-selectivity (up to >99 : 1) compared to conventional solvents. In addition, the late-stage ligation of bioactive molecules with the aliphatic ß-amino SuFEx hub was demonstrated. Mechanistic studies on experimental, analytical, and computational approaches support noncovalent activation over NHC catalysis "on-water".


Assuntos
Fluoretos , Água , Catálise , Metano/análogos & derivados , Solventes , Enxofre
15.
Breast Cancer ; 29(5): 889-898, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35616777

RESUMO

PURPOSE: The 21-gene recurrence score (RS) assay is currently used for predicting chemotherapeutic benefits for hormone receptor-positive (HR +) early-stage breast cancer patients without consideration regarding racial differences in that predictive value. This study aimed at demonstrating racial differences in the predictive values of the 21-gene RS assay. METHODS: The study cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) database. Breast cancer-specific mortality (BCSM) was compared between patients who received chemotherapy (the "CTx group") and those who did not (the "no CTx group") to estimate the predictive value of the assay. This comparison was repeated for each racial group. RESULTS: Among 88,498 T1 - 2N0 HR + breast cancer patients who had results of 21-gene RS, 13,123 patients had RS > 25, which included 10,697 Whites, 1282 Blacks, and 1,144 Asian Americans/Pacific Islanders (AAPIs). Chemotherapy was administered to 8364 patients (63.4%). The adjusted hazard ratio for BCSM in the CTx group (vs. no CTx group) was 0.734 (95% confidence interval [CI] 0.588-0.917) in Whites, 0.748 (95% CI 0.428-1.307) in Blacks, and 1.343 (95% CI 0.558-3.233) in AAPIs. No subgroup within patients with RS > 25 among non-White women showed a significant predictive value of the 21-gene RS assay, except for Black women with grade 3 tumors. CONCLUSION: The predictive value of the 21-gene RS assay for assessing chemotherapy benefit was validated in White women based on the SEER database, although the predictive value was not warranted in non-White women.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Modelos de Riscos Proporcionais , Fatores Raciais , Programa de SEER
16.
ChemSusChem ; 15(15): e202200634, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35638148

RESUMO

ß-Sulfido sulfonyl fluoride and its derivatives have been gaining attention recently in the fields of medicinal chemistry and material science. The conventional method for the synthesis of functionalized alkyl sulfonyl fluorides requires several chemical transformations. Therefore, a direct establishment of such chemical structures remains challenging, and an efficient catalytic approach is highly desired. Herein a significant "on-water" hydrophobic amplification was achieved, enabling a high-turnover catalytic thia-Michael addition to produce unprecedented ß-arylated-ß-sulfido sulfonyl fluorides. Amounts as low as 100 ppm (0.01 mol %) of the phosphazene superbase were sufficient to successfully catalyze the reaction with excellent chemo-/site-selectivity and with optimal functional group tolerance. Several ß-arylated ethene sulfonyl fluorides were converted into thia-Michael adducts up to >99 % yields. The mild conditions, high turnover, neutral pH, and scalability of the sustainable catalytic process benefit the preparation of potential pharmaceuticals (e. g., polyisoprenylated methylated protein methyl esterase inhibitors) and organic materials (e. g., electrolyte additives).


Assuntos
Fluoretos , Água , Catálise , Fluoretos/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Água/química
17.
Nat Commun ; 13(1): 2702, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577799

RESUMO

A tetrasubstituted carbon atom connected by three sp3 or sp2-carbons with single nitrogen, i.e., the α-tertiary amine (ATA) functional group, is an essential structure of diverse naturally occurring alkaloids and pharmaceuticals. The synthetic approach toward ATA structures is intricate, therefore, a straightforward catalytic method has remained a substantial challenge. Here we show an efficient water-accelerated organocatalytic method to directly access ATA incorporating homoallylic amine structures by exploiting readily accessible general ketones as useful starting material. The synergistic action of a hydrophobic Brønsted acid in combination with a squaramide hydrogen-bonding donor under aqueous condition enabled the facile formation of the desired moiety. The developed exceptionally mild but powerful system facilitated a broad substrate scope, and enabled efficient multi-gram scalability.


Assuntos
Aminas , Água , Aminas/química , Carbono/química , Catálise , Estrutura Molecular , Estereoisomerismo
18.
Ann Hematol ; 101(7): 1499-1508, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35482090

RESUMO

Sweet syndrome is a neutrophilic dermatosis occasionally associated with malignancies. Due to its rarity, the clinical features of Sweet syndrome are still unclear. Thus, we aimed to analyze clinical features, treatment, and outcomes of these patients according to associated disease. We conducted a retrospective, longitudinal cohort study from January 2000 to August 2020. We reviewed the medical records of 52 patients with Sweet syndrome. The median age of patients was 57.5 years old (range, 17-84), and 48.1% were female. Of the 52 patients analyzed, 27 patients (51.9%) had malignancy-associated Sweet syndrome. Sweet syndrome was diagnosed concurrently with (N = 8), before (N = 5), and after (N = 14) the diagnosis of malignancy. The idiopathic Sweet syndrome was most common in the non-malignancy group (56.0%). Myelodysplastic syndrome was the most common malignancy associated with Sweet syndrome (47.6%). Leukopenia (p = 0.005), anemia (p < 0.001), and thrombocytopenia (p = 0.008) were significantly associated with malignancy. The majority of patients showed rapid improvement of symptoms after steroid administration. The symptoms of some patients with malignancy did not improve with steroid alone; however, their symptoms often improved when steroids were combined with a treatment for the associated malignancy. Relapse and aggravation of Sweet syndrome were common in the malignancy group. Sweet syndrome showed a broad spectrum of clinical features related to various diseases. Sweet syndrome often occurred as a paraneoplastic feature. Therefore, active systemic evaluation is needed in the first diagnosis of Sweet syndrome without clear etiology.


Assuntos
Anemia , Leucopenia , Síndromes Mielodisplásicas , Neoplasias , Síndrome de Sweet , Trombocitopenia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Feminino , Humanos , Leucopenia/etiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Retrospectivos , Síndrome de Sweet/complicações , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamento farmacológico , Trombocitopenia/complicações , Adulto Jovem
19.
ACS Sens ; 7(2): 423-429, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35119283

RESUMO

G-, V-, and A-series nerve agents are extremely toxic organophosphorus chemical warfare agents (CWAs) that incorporate P═O functional groups. Their colorless, tasteless, and odorless nature makes rapid and efficient detection challenging. Here, we report an unprecedented N-triflyl phosphoric triamide (N-TPT) receptor, which is a new class of triple hydrogen bonding donor molecular sensors for CWA recognition via noncovalent host-guest-type interactions. The highly robust trifurcate structures were designed based on density functional theory (DFT) computations and synthesized from N-triflyl phosphorimidoyl trichloride by simple stepwise processes. Quartz crystal microbalance (QCM) analysis allowed robust detection of typical CWA simulants, such as dimethyl methylphosphonate. The concentration-dependent QCM profiles were fitted with the Sips isotherm model, revealing that the thermodynamic parameters of the binding behaviors are roughly correlated with the calculated results. Developed N-TPT receptors show higher binding abilities than previously reported receptors and reasonable selectivity over other volatile compounds.


Assuntos
Substâncias para a Guerra Química , Técnicas de Microbalança de Cristal de Quartzo , Substâncias para a Guerra Química/análise , Técnicas de Microbalança de Cristal de Quartzo/métodos
20.
Medicine (Baltimore) ; 100(44): e27724, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34871268

RESUMO

RATIONALE: An allergic transfusion reaction is a common side effect of transfusions of red blood cells. Using washed red blood cells is the most effective method for preventing such a reaction. However, the availability of other washed transfusion components, including platelets, is limited. PATIENT CONCERNS: A 69-year-old patient with acute myeloid leukemia progressed from myelodysplastic syndrome and was treated with azacitidine. She experienced a minor reaction to platelet transfusion that initially responded to the administration of corticosteroids and antihistamines. However, she worsened even after subsequent preventive treatments and was referred to the emergency department due to anaphylaxis. The patient developed hypotension, chest pain, and dyspnea 10 minutes after the initiation of platelet transfusion. DIAGNOSES: She was diagnosed with platelet-induced anaphylaxis. INTERVENTIONS: In an attempt to prevent anaphylaxis, 150 mg of omalizumab was prescribed 1 week prior to transfusion. However, she experienced anaphylaxis again and was administered intramuscular epinephrine. For the following transfusion, we treated her with a 300 mg dose of omalizumab 24 hours before the transfusion. OUTCOMES: She tolerated well and continued to receive further chemotherapy and platelet transfusion with premedication. LESSONS: This case suggests that omalizumab is a good candidate for the management of severe allergic transfusion reactions.


Assuntos
Anafilaxia , Omalizumab/uso terapêutico , Transfusão de Plaquetas/efeitos adversos , Reação Transfusional/tratamento farmacológico , Idoso , Transfusão de Sangue , Feminino , Humanos
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