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1.
Chem Sci ; 15(30): 12058-12066, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39092097

RESUMO

Synthetic photochemistry has undergone significant development, largely owing to the development of visible-light-absorbing photocatalysts (PCs). PCs have significantly improved the efficiency and precision of cycloaddition reactions, primarily through energy or electron transfer pathways. Recent research has identified photocatalysis that does not follow energy- or electron-transfer formalisms, indicating the existence of other, undiscovered photoactivation pathways. This study unveils an alternative route: a charge-neutral photocatalytic process called charge-recombinative triplet sensitization (CRTS), a mechanism with limited precedents in synthetic chemistry. Our investigations revealed CRTS occurrence in DeMayo-type [2 + 2] cycloaddition reactions catalyzed by indole-fused organoPCs. Our mechanistic investigations, including steady-state and transient spectroscopic analyses, electrochemical investigations, and quantum chemical calculations, suggest a mechanism involving substrate activation through photoinduced electron transfer, followed by charge recombination, leading to substrate triplet state formation. Our findings provide valuable insights into the underlying photocatalytic reaction mechanisms and pave the way for the systematic design and realization of innovative photochemical processes.

2.
Nat Commun ; 15(1): 6586, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097596

RESUMO

Photocatalysis provides a versatile approach to redox activation of various organic substrates for synthetic applications. To broaden the scope of photoredox catalysis, developing catalysts with strong oxidizing or reducing power in the excited state is imperative. Catalysts that feature highly cathodic oxidation potentials and long lifetimes in their excited states are particularly in demand. In this research, we demonstrate the catalytic utility of two-coordinate Au(I) complex photocatalysts that exhibit an exclusive ligand-to-ligand charge-transfer (LLCT) transition in C-C cross-coupling reactions between N-heterocycles and (hetero)aryl halides, including redox-resistant (hetero)aryl chlorides. Our photocatalysis system can steer reactions under visible-light irradiation at a catalyst loading as low as 0.1 mol% and exhibits a broad substrate scope with high chemo- and regioselectivity. Our mechanistic investigations provide direct spectroscopic evidence for each step in the catalysis cycle and demonstrate that the LLCT-active Au(I) complex catalysts offer several benefits, including strong visible-light absorption, a 210 ns-long excited-state lifetime without short-lived components, and a 91% yield in the production of free-radical intermediates. Given the wide structural versatility of the proposed catalysts, we envision that our research will provide useful insights into the future utilization of the LLCT-active Au(I) complex for organic transformations.

3.
Nat Immunol ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060650

RESUMO

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1Q333P variant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, spontaneous germinal centers and expansion of age-associated B cells, plasma cells and follicular and extrafollicular helper T cells. B cell phenotypes were cell-autonomous and rescued by ablation of Toll-like receptor 7 (TLR7) or MyD88. The variant increased interferon-ß without altering nuclear factor kappa-light-chain-enhancer of activated B cells signaling, and impaired MyD88 and IRAK1 recruitment to autophagosomes. Additionally, the Q333P variant impaired TNIP1 localization to damaged mitochondria and mitophagosome formation. Damaged mitochondria were abundant in the salivary epithelial cells of Tnip1Q346P mice. These findings suggest that TNIP1-mediated autoimmunity may be a consequence of increased TLR7 signaling due to impaired recruitment of downstream signaling molecules and damaged mitochondria to autophagosomes and may thus respond to TLR7-targeted therapeutics.

4.
Healthcare (Basel) ; 12(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38998878

RESUMO

Korean medicine (KM) is used to treat anxiety disorders, but there is limited research on its effects. This study aimed to examine the associations between improved QoL and reduced clinical symptoms and KM in patients with anxiety disorders. The medical records of patients with anxiety who were treated with KM (acupuncture, psychotherapy, Chuna therapy, aromatherapy, or herbal medicine) for at least 4 weeks were retrospectively analyzed. Clinical, QoL, and cost outcomes were measured at baseline and at weeks 4 and 12 (Anxiety: State-Trait Anxiety Inventory [STAI X-1 (state), X-2 (trait)], Beck Anxiety Inventory [BAI]; anger: State-Trait Anger Expression Inventory State [STAXI-S (state), T (trait)], Anger Expression Inventory [AXI-K-I (anger-in), AXI-K-O (anger-out), AXI-K-C (anger-control); depression: Beck Depression Inventory-II [BDI II], QoL: QoL-related instruments Euro Quality of Life 5 Dimensions utility score [EQ-5D], Euro QoL Visual Analog Scale [EQ-VAS]). The total costs for each item were calculated in terms of NHIS-covered costs and patients' out-of-pocket costs from the perspective of the healthcare system. The medical records of 67 patients were evaluated. The KM treatments were found to be associated with decreased anxiety (STAI X-1; STAI X-2; BAI, p < 0.0001), depression (BDI-II, p < 0.0001), and anger (AKI-K-I; AKI-K-O, p < 0.05) and increased QoL (EQ-5D; EQ-VAS, p < 0.0001). An average of USD 1360 was paid for the KM treatments for 4 weeks. The study findings suggested that KM may improve clinical symptoms and QoL outcomes in patients with anxiety disorders.

5.
Clin Mol Hepatol ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034610
6.
J Thorac Dis ; 16(6): 3644-3654, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983158

RESUMO

Background: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure. However, some patients still experience severe pain after VATS. Pain after VATS can disturb deep breathing and coughing, and can increase postoperative pulmonary complications. Therefore, multidisciplinary pain management is emphasized for enhanced recovery after VATS. Nefopam is a centrally-acting, non-opioid, non-steroidal analgesic drug, and its pain reduction effect in many surgeries has been reported. We sought to determine whether administration of nefopam is effective as multimodal analgesia in VATS. Methods: This study enrolled patients aged 19 years or older, and scheduled for elective VATS lobectomy with American Society of Anesthesiologists (ASA) physical class I-III. Forty-six participants were randomly divided into a group receiving nefopam (group N), and a control group (group O) in a 1:1 ratio. The study participants, and the researcher collecting the data were blinded to the group allocation. For the group N, nefopam 20 mg was administered before surgical incision and also at the end of surgery while chest tube was inserted. For the group O, normal saline 100 mL was administered. The primary outcome of this study was the pain score, by verbal numerical rating scale, at rest and upon coughing. Results: Forty-five participants (group N =22, group O =23) were involved in the statistical analysis. Nefopam reduced pain at rest at 0 h [8 (IQR, 5-10) vs. 4 (IQR, 2-7), P=0.01], and at 0-1 h [5 (IQR, 5-8) vs. 3 (IQR, 2-5), P=0.001]. Pain upon coughing decreased with nefopam at 0 h [9 (IQR, 6-10) vs. 6 (IQR, 2-8), P=0.009], 0-1 h [6 (IQR, 5-8) vs. 5 (IQR, 2-6), P=0.001], and at 12-24 h [4 (IQR, 3-7) vs. 3 (IQR, 1-4), P=0.03]. Injection of 20 mg of nefopam before incision and at the end of surgery relieved postoperative pain at 0 h, 1 h at rest and at 0 h, 1 h, 12-24 h with coughing after VATS. Conclusions: Therefore, nefopam can serve as a useful component of multimodal analgesia for pain management after VATS. Trial Registration: ClinicalTrials.gov (NCT05173337).

7.
Clin Chim Acta ; 561: 119847, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38969088

RESUMO

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.


Assuntos
Testes de Função Tireóidea , Humanos , Testes de Função Tireóidea/normas , Tireotropina/sangue , Tireotropina/análise , Tiroxina/sangue , Tiroxina/análise , Masculino , Feminino , Adulto , Tri-Iodotironina/sangue , Tri-Iodotironina/análise , Pessoa de Meia-Idade , Glândula Tireoide/fisiologia
8.
J Breast Cancer ; 27(3): 201-214, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38951111

RESUMO

PURPOSE: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods. METHODS: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established. RESULTS: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%. CONCLUSION: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing.

9.
J Clin Neurol ; 20(4): 431-438, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38951976

RESUMO

BACKGROUND AND PURPOSE: Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. METHODS: There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). RESULTS: The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. CONCLUSIONS: These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.

10.
Antioxidants (Basel) ; 13(7)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39061935

RESUMO

Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the "electron transport chain" and "cell redox homeostasis" pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait-module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in "RNA binding", "mRNA metabolic process", etc., as well as in GO terms, and "spliceosome" and "nucleotide excision repair" pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.

11.
Ann Lab Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953115

RESUMO

Background: Healthcare 4.0. refers to the integration of advanced technologies, such as artificial intelligence (AI) and big data analysis, into the healthcare sector. Recognizing the impact of Healthcare 4.0 technologies in laboratory medicine (LM), we seek to assess the overall awareness and implementation of Healthcare 4.0 among members of the Korean Society for Laboratory Medicine (KSLM). Methods: A web-based survey was conducted using an anonymous questionnaire. The survey comprised 36 questions covering demographic information (seven questions), big data (10 questions), and AI (19 questions). Results: In total, 182 (17.9%) of 1,017 KSLM members participated in the survey. Thirty-two percent of respondents considered AI to be the most important technology in LM in the era of Healthcare 4.0, closely followed by 31% who favored big data. Approximately 80% of respondents were familiar with big data but had not conducted research using it, and 71% were willing to participate in future big data research conducted by the KSLM. Respondents viewed AI as the most valuable tool in molecular genetics within various divisions. More than half of the respondents were open to the notion of using AI as assistance rather than a complete replacement for their roles. Conclusions: This survey highlighted KSLM members' awareness of the potential applications and implications of big data and AI. We emphasize the complexity of AI integration in healthcare, citing technical and ethical challenges leading to diverse opinions on its impact on employment and training. This highlights the need for a holistic approach to adopting new technologies.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38954528

RESUMO

OBJECTIVES: Musclin, recently identified as a myokine, has been recognized for its physiological significance in potentiating the functional properties of natrieutic peptides (NPs) through competitive inhibition of their clearance receptor, natrieutic peptide receptor C (NPR-C). This study, for the first time in the literature, investigated the dynamic response of musclin during and after aerobic exercise in humans, exploring its potential as a myokine and its interaction with NPs and NPR-C in the context of exercise-induced metabolic responses. METHODS: Twenty-one inactive young males participated, and we assessed changes in serum levels of musclin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), epinephrine (Epi), and glycerol as an indicative of lipid mobilization, during and after moderate-intensity aerobic exercise. Furthermore, we evaluated the gene expression of NPR-C in subcutaneous fat biopsies. RESULTS: Serum musclin levels increased significantly during aerobic exercise, followed by a decline during recovery, remaining elevated compared to baseline. Significant correlations were found between musclin responses and lean body mass (LBM), indicating its regulation by skeletal muscle mass and exercise. Exercise-induced changes in musclin positively correlated with those of ANP, potentially preventing ANP degradation. Additionally, a potential interplay between NPR-C expression and musclin dynamics on ANP was suggested. However, musclin's influence on lipid mobilization was not predominant when considering other lipolytic factors during exercise. DISCUSSION: Musclin's classification as a myokine is supported by its response to aerobic exercise and its association with LBM. Additionally, its interactions with NPR-C and NPs suggest its physiological relevance and potential clinical implications.

13.
Korean Circ J ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38956936

RESUMO

BACKGROUND AND OBJECTIVES: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio (HR), 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

14.
Arch Pathol Lab Med ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38960391

RESUMO

CONTEXT.­: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors. OBJECTIVE.­: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs). DESIGN.­: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden. RESULTS.­: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs). CONCLUSIONS.­: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important.

15.
J Cardiovasc Imaging ; 32(1): 13, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39075626

RESUMO

Cardio-oncology is a critical field due to the escalating significance of cardiovascular toxicity as a side effect of anticancer treatments. Cancer therapy-related cardiac dysfunction (CTRCD) is a prevalent condition associated with cardiovascular toxicity, necessitating effective strategies for prediction, monitoring, management, and tracking. This comprehensive review examines the definition and risk stratification of CTRCD, explores monitoring approaches during anticancer therapy, and highlights specific cardiovascular toxicities linked to various cancer treatments. These include anthracyclines, HER2-targeted agents, vascular endothelial growth factor inhibitors, immune checkpoint inhibitors, chimeric antigen receptor T-cell therapies, and tumor-infiltrating lymphocytes therapies. Incorporating the Korean data, this review offers insights into the regional nuances in managing CTRCD. Using systematic follow-up incorporating cardiovascular imaging and biomarkers, a better understanding and management of CTRCD can be achieved, optimizing the cardiovascular health of both cancer patients and survivors.

16.
Org Lett ; 26(24): 5192-5195, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38856648

RESUMO

A double deoxygenative C-N coupling protocol has been developed by employing acyloxyamines through N-O bond activation. The C-N bond formation under mild reaction conditions, employing NiCl2 as the catalyst and cataCXiumA as a ligand, results in the production of a diverse array of alkylated secondary or tertiary amines, including heterocyclic amines. This method introduces a novel catalytic strategy that emphasizes the versatility of nickel-catalyzed reactions, extending beyond traditional synthetic boundaries.

17.
Curr Issues Mol Biol ; 46(6): 5655-5667, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38921009

RESUMO

In this in vivo study on hairless mice, we examined the effects of light-emitting diode (LED) treatment applied prior to ultraviolet B (UVB) irradiation. We found that pre-treating with LED improved skin morphological and histopathological conditions compared to those only exposed to UVB irradiation. In our study, histological evaluation of collagen and elastic fibers after LED treatment prior to UVB irradiation showed that this pretreatment significantly enhanced the quality of fibers, which were otherwise poor in density and irregularly arranged due to UV exposure alone. This suggests that LED treatment promotes collagen and elastin production, leading to improved skin properties. Additionally, we observed an increase in Claudin-1 expression and a reduction in nuclear factor-erythroid 2-related factor 2 (Nrf-2) and heme-oxygenase 1 (HO-1) expression within the LED-treated skin tissues, suggesting that LED therapy may modulate key skin barrier proteins and oxidative stress markers. These results demonstrate that pretreatment with LED light can enhance the skin's resistance to UVB-induced damage by modulating gene regulation associated with skin protection. Further investigations are needed to explore the broader biological effects of LED therapy on other tissues such as blood vessels. This study underscores the potential of LED therapy as a non-invasive approach to enhance skin repair and counteract the effects of photoaging caused by UV exposure.

18.
Sci Rep ; 14(1): 14797, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926407

RESUMO

Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Curva ROC
19.
Medicine (Baltimore) ; 103(23): e38452, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847700

RESUMO

Percutaneous epidural adhesiolysis (PEA) is an effective treatment for patients with lumbar radiculopathy unresponsive to single steroid injections. Various approaches and instruments have been developed to access these lesions. This study aimed to evaluate the utility of a retrodiscal approach for epidural adhesiolysis using a WHIP catheter®. This retrospective study was conducted at Bundang Seoul National University Hospital, reviewing cases from January to December 2022. Forty-seven patients diagnosed with lumbar radiculopathy, aged 20 to 80 years, who underwent PEA with the WHIP catheter® were included. Outcomes assessed Numeric Rating Scale (NRS) for pain, Patients' Global Impression of Change (PGIC) scores, and the incidence of procedure-related complications. Follow-up evaluations occurred at 1, 3, and 6 months post-procedure. Among 47 patients, 41 completed the study, showing significant pain reduction at all follow-up points: 1 month (N = 41, 1.32 ±â€…1.68, P < .001), 3 months (N = 31, 1.90 ±â€…2.14, P < .001), and 6 months (N = 30, 2.50 ±â€…2.30, P < .001). PGIC scores indicated that 40% of the patients reported substantial improvement at one-month post-procedure. The complications were minimal, with only one case of intradiscal injection and 2 cases of vascular uptake. The retrodiscal approach PEA using the WHIP catheter® demonstrated significant efficacy in pain reduction with minimal safety concerns for patients with lumbar radiculopathy. These findings suggest that this procedure is a viable option for patients who are unresponsive to conservative treatment. However, the retrospective nature of this study and its small sample size necessitate further prospective controlled studies to confirm our results and establish long-term outcomes.


Assuntos
Catéteres , Radiculopatia , Humanos , Estudos Retrospectivos , Radiculopatia/terapia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Vértebras Lombares , Resultado do Tratamento , Idoso de 80 Anos ou mais , Medição da Dor , Espaço Epidural , Aderências Teciduais/terapia , Aderências Teciduais/cirurgia , Adulto Jovem , Injeções Epidurais/métodos
20.
Neuroepidemiology ; : 1-9, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880093

RESUMO

INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

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