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1.
Cell Biosci ; 14(1): 46, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584258

RESUMO

BACKGROUND: The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. RESULTS: We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000 pg/ml. Kaplan-Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. CONCLUSIONS: Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD.

2.
Clin Kidney J ; 17(4): sfae054, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572500

RESUMO

Acute interstitial nephritis (AIN) is a significant contributor to acute kidney injury and can be attributed to a variety of factors, including but not limited to allergens or drugs, infections, autoimmune or systemic diseases, and idiopathic forms of the disease. In some cases, AIN requires a therapeutic action according to a single specific etiology by handling the offending agent and applying an immunosuppressant. Although AIN can be diagnosed through renal biopsy, it is not able to pinpoint the precise cause when multiple causes are suspected to be present simultaneously. Such situations arise when a patient suffering from infection develops AIN during antibiotic therapy, the exact causative factor of which becomes a challenge for the clinicians to determine. This is attributed to the different approaches employed in different etiologies, wherein clinicians are required to maintain the current antibiotic therapy or augment the dose in cases of infection as AIN etiology, without resorting to immunosuppressant therapy as the primary objective is infection killing. In contrast, antibiotics as an etiology for AIN require an alternative drug from the antibiotics group, along with an immunosuppressant. In the interim, delaying the identification of the precise cause may result in interstitial fibrosis and chronic kidney disease. This narrative review highlights certain findings that can be typical of infection-associated ATIN compared with antibiotic-associated ATIN based on clinical history and physical examination, clinical presentation of different antibiotic drug classes, histopathological features, classical and novel biomarkers, serum and urine cytokines and chemokines, cellular biomarkers, and genetic biomarkers. Although these findings cannot provide conclusive and clear recommendations that can be useful in the clinical practice, they can entice researchers to conduct original research on these features to discover clear recommendations.

3.
JAMA Psychiatry ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568605

RESUMO

Importance: Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes. Objective: To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data. Design, Setting, and Participants: This cohort study assessed data from the Taiwan national health insurance database across entire population (N = 26 554 001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n = 34 467). A 1:4 comparison group (n = 137 868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship. Main Outcomes and Measures: Modified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality. Results: This study included 172 335 participants (88 330 male and 84 005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings. Conclusions and Relevance: To our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.

4.
J Hazard Mater ; 470: 134182, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583202

RESUMO

Establishing an economic and sustained Fenton oxidation system to enhance sludge dewaterability and carbamazepine (CBZ) removal rate is a crucial path to simultaneously achieve sludge reduction and harmless. Leveraging the principles akin to "tea making", we harnessed tea waste to continually release tea polyphenols (TP), thus effectively maintaining high level of oxidation efficiency through the sustained Fenton reaction. The results illustrated that the incorporation of tea waste yielded more favorable outcomes in terms of water content reduction and CBZ removal compared to direct TP addition within the Fe(III)/hydrogen peroxide (H2O2) system. Concomitantly, this process mainly generated hydroxyl radical (•OH) via three oxidation pathways, effectively altering the properties of extracellular polymeric substances (EPS) and promoting the degradation of CBZ from the sludge mixture. The interval addition of Fe(III) and H2O2 heightened extracellular oxidation efficacy, promoting the desorption and removal of CBZ. The degradation of EPS prompted the transformation of bound water to free water, while the formation of larger channels drove the discharge of water. This work achieved the concept of treating waste with waste through using tea waste to treat sludge, meanwhile, can provide ideas for subsequent sludge harmless disposal.

5.
bioRxiv ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38586003

RESUMO

The protein kinase C (PKC) family of serine/threonine kinases, which consist of three distinctly regulated subfamilies, have long been established as critical for a variety of cellular functions. However, how PKC enzymes are regulated at different subcellular locations, particularly at emerging signaling hubs such as the ER, lysosome, and Par signaling complexes, is unclear. Here, we present a sensitive Excitation Ratiometric (ExRai) C Kinase Activity Reporter (ExRai-CKAR2) that enables the detection of minute changes in subcellular PKC activity. Using ExRai-CKAR2 in conjunction with an enhanced diacylglycerol (DAG) biosensor capable of detecting intracellular DAG dynamics, we uncover the differential regulation of PKC isoforms at distinct subcellular locations. We find that G-protein coupled receptor (GPCR) stimulation triggers sustained PKC activity at the ER and lysosomes, primarily mediated by Ca 2+ sensitive conventional PKC (cPKC) and novel PKC (nPKC), respectively, with nPKC showing high basal activity due to elevated basal DAG levels on lysosome membranes. The high sensitivity of ExRai-CKAR2, targeted to either the cytosol or Par-complexes, further enabled us to detect previously inaccessible endogenous atypical PKC (aPKC) activity in 3D organoids. Taken together, ExRai-CKAR2 is a powerful tool for interrogating PKC regulation in response to physiological stimuli.

6.
Cancer Lett ; : 216839, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38570084

RESUMO

Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.

7.
Int J Paediatr Dent ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570933

RESUMO

BACKGROUND: Children with dental caries are treated with stainless steel metal crowns (SSC), but the aesthetics and precision still need to be improved. Currently, both 3D-printed resin crowns (PRC) and computer-aided design/computer-aided manufacture (CAD/CAM) resin crowns (CRC) meet the clinical requirements for crown applications in terms of strength, production time, cost, and aesthetics. AIM: This study replaced SSC with customized resin crowns by 3D printing and CAD/CAM. DESIGN: In this study, PRC, CRC, and SSC were used for incisor and molar restorations, and 60 crowns were made with 10 for each group. The fabrication efficiency, surface characteristics, marginal fit, and stability of the two different crowns were evaluated. RESULTS: PRC and CRC show superior color and surface characteristics, though production times are longer (5.3-12.4 times and 3.3-9.1 times, respectively) than for SSC (p < .05). They, however, can be completed within 80 min. Edge gaps for PRC and CRC are significantly lower (13.0-19.2 times and 13.0-13.7 times) than for SSC (p < .05). All materials exhibit good stability. CONCLUSION: The 3D-PRCs and CAD/CAM resin crowns may replace SSCs as a potential choice for clinical child caries.

8.
Opt Express ; 32(7): 11419-11428, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570990

RESUMO

A 10 W super-wideband ultra-low-intensity-noise single-frequency fiber laser (SFFL) at 1 µm is experimentally demonstrated, based on dual gain saturation effects from semiconductors and optical fibers, together with an analog-digital hybrid optoelectronic feedback loop. Three intensity-noise-inhibited units synergistically work, which actualizes a connection of effective bandwidth and enhancement of noise-suppressing amplitude. With the cascade action of the semiconductor optical amplifier and optical fiber amplifier, the laser power is remarkably boosted. Eventually, an SFFL with an output power of 10.8 W and a relative intensity noise (RIN) below -150 dB/Hz at the frequency range over 1 Hz is realized. More meaningfully, within the total frequency range of 10 Hz to 10 GHz exceeding 29 octaves, the RIN is controlled to below -160 dB/Hz, approaching the shot-noise limit (SNL) level. To the best of our knowledge, this is the lowest RIN result of SFFL within such an extensive frequency range, and this is the highest output power of the near-SNL super-wideband SFFL. Furthermore, a linewidth of less than 0.8 kHz, a long-term stable polarization extinction ratio of 20 dB, and an optical signal-to-noise ratio of over 60 dB are obtained simultaneously. This start-of-the-art SFFL has provided a systematic solution for high-power and low-noise light sources, which is competitive for sophisticated applications, such as free-space laser communication, space-based gravitational wave detection, and super-long-distance space coherent velocity measurement and ranging.

9.
Ren Fail ; 46(1): 2330621, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38561250

RESUMO

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.


Assuntos
Injúria Renal Aguda , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Meios de Contraste/efeitos adversos , Fatores de Risco , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica
10.
Orphanet J Rare Dis ; 19(1): 144, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575988

RESUMO

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient's cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. RESULTS: The GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density. CONCLUSIONS: Elevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis.


Assuntos
Doença de Gaucher , Osteoporose , Humanos , Densidade Óssea/genética , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Inflamassomos , Osteoporose/genética , Osteoporose/tratamento farmacológico
11.
Sci Rep ; 14(1): 8151, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589538

RESUMO

This study demonstrates a novel use of the U-Net convolutional neural network (CNN) for modeling pixel-based electrostatic potential distributions in GaN metal-insulator-semiconductor high-electron mobility transistors (MIS-HEMTs) with various gate and source field plate designs and drain voltages. The pixel-based images of the potential distribution are successfully modeled from the developed U-Net CNN with an error of less than 1% error relative to a TCAD simulated reference of a 500-V electrostatic potential distribution in the AlGaN/GaN interface. Furthermore, the modeling time of potential distributions by U-Net takes about 80 ms. Therefore, the U-Net CNN is a promising approach to efficiently model the pixel-based distributions characteristics in GaN power devices.

12.
Materials (Basel) ; 17(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38591506

RESUMO

With the miniaturization and high integration of electronic devices, high-performance thermally conductive composites have received increasing attention. The construction of hierarchical structures is an effective strategy to reduce interfacial thermal resistance and enhance composite thermal conductivity. In this study, by decorating carbon fibers (CF) with needle-like ZnO nanowires, hierarchical hybrid fillers (CF@ZnO) were rationally designed and synthesized using the hydrothermal method, which was further used to construct oriented aligned filler networks via the simple freeze-casting process. Subsequently, epoxy (EP)-based composites were prepared using the vacuum impregnation method. Compared with the pure CF, the CF@ZnO hybrid fillers led to a significant increase in thermal conductivity, which was mainly due to the fact that the ZnO nanowires could act as bridging links between CF to increase more thermally conductive pathways, which in turn reduced interfacial thermal resistance. In addition, the introduction of CF@ZnO fillers was also beneficial in improving the thermal stability of the EP-based composites, which was favorable for practical thermal management applications.

13.
bioRxiv ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38562887

RESUMO

Protein kinases are key signaling nodes that regulate fundamental biological and disease processes. Illuminating kinase signaling from multiple angles can provide deeper insights into disease mechanisms and improve therapeutic targeting. While fluorescent biosensors are powerful tools for visualizing live-cell kinase activity dynamics in real time, new molecular tools are needed that enable recording of transient signaling activities for post hoc analysis and targeted manipulation. Here, we develop a light-gated kinase activity coupled transcriptional integrator (KINACT) that converts dynamic kinase signals into "permanent" fluorescent marks. KINACT enables robust monitoring of kinase activity across scales, accurately recording subcellular PKA activity, highlighting PKA signaling heterogeneity in 3D cultures, and identifying PKA activators and inhibitors in high-throughput screens. We further leverage the ability of KINACT to drive signaling effector expression to allow feedback manipulation of the balance of GαsR201C-induced PKA and ERK activation and dissect the mechanisms of oncogenic G protein signaling.

14.
Clin Exp Med ; 24(1): 66, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564029

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Mieloblastina , Prognóstico , Peroxidase , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Recidiva
15.
Med Biol Eng Comput ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558351

RESUMO

Unplanned readmission after primary total knee arthroplasty (TKA) costs an average of US $39,000 per episode and negatively impacts patient outcomes. Although predictive machine learning (ML) models show promise for risk stratification in specific populations, existing studies do not address model generalizability. This study aimed to establish the generalizability of previous institutionally developed ML models to predict 30-day readmission following primary TKA using a national database. Data from 424,354 patients from the ACS-NSQIP database was used to develop and validate four ML models to predict 30-day readmission risk after primary TKA. Individual model performance was assessed and compared based on discrimination, accuracy, calibration, and clinical utility. Length of stay (> 2.5 days), body mass index (BMI) (> 33.21 kg/m2), and operation time (> 93 min) were important determinants of 30-day readmission. All ML models demonstrated equally good accuracy, calibration, and discriminatory ability (Brier score, ANN = RF = HGB = NEPLR = 0.03; ANN, slope = 0.90, intercept = - 0.11; RF, slope = 0.93, intercept = - 0.12; HGB, slope = 0.90, intercept = - 0.12; NEPLR, slope = 0.77, intercept = 0.01; AUCANN = AUCRF = AUCHGB = AUCNEPLR = 0.78). This study validates the generalizability of four previously developed ML algorithms in predicting readmission risk in patients undergoing TKA and offers surgeons an opportunity to reduce readmissions by optimizing discharge planning, BMI, and surgical efficiency.

16.
Environ Res ; : 118889, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599452

RESUMO

BACKGROUND: The effects of long-term PM2.5 exposures since 1968 on adenocarcinoma lung cancer (AdLC) were not studied before. METHODS: This case-referent study used nationwide cancer registry data since 1997 and air pollution data since 1968 in Taiwan to estimate risks of 30-year PM2.5 exposures on AdLC. Cases were all AdLC, while references were all non-AdLC. Individuals' 30-year PM2.5 exposures were estimated by PM2.5 levels at their residence for 30 years prior their diagnosis dates. We applied multiple logistic regression analyses to estimate PM2.5 exposures on incidence rate ratios (IRRs) between cases and references, adjusting for sex, age, smoking, cancer stage, and EGFR mutation. RESULTS: Elevation in annual ambient PM2.5 concentrations since 1968 were associated with increase in annual age-adjusted AdLC incidence since 1997. AdLC incidences were higher among females, nonsmokers, the elderly aged above 65, cases of stages IIIB to IV, and EGFR mutation. Study subjects' PM2.5 exposures averaged at 33.7±7.4 µg/m3 with 162±130 high PM2.5 pollution days over 30 years. Multiple logistic models showed an increase in 10 µg/m3 of PM2.5 exposures were significantly associated with 1.044 of IRR between all AdLC and all non-AdLC cases during 2011-2020. Our models also showed that females and nonsmokers and adults less than 65 years had higher IRRs than their respective counterparts. Restricted analyses showed similar effects of PM2.5 exposures on IRRs between stage 0-IIIA and IIIB-IV cases and between EGFR+ and EGFR- cases. CONCLUSIONS: Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.

17.
J Prosthodont ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600720

RESUMO

Traditionally, artificial teeth arrangements or the definitive complete dentures are used to establish important prosthodontic parameters such as the occlusal plane orientation, vertical dimension, and the incisal edge position. The relationship of these elements with the underlying bony structures is commonly evaluated using advanced planning protocols such as the dual scan technique. This technique article presents an uncomplicated alternative approach to establish these parameters intraorally using a 3D-printed shell complete denture generated from a 3D scan of the patient's existing complete denture.

19.
Adv Sci (Weinh) ; : e2307852, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477561

RESUMO

First-line treatment of multiple myeloma, a prevalent blood cancer lacking a cure, using anti-CD38 daratumumab antibody and lenalidomide is often inadequate due to relapse and severe side effects. To enhance drug safety and efficacy, an antibody-drug conjugate, TE-1146, comprising six lenalidomide drug molecules site-specifically conjugated to a reconfigured daratumumab to deliver cytotoxic lenalidomide to tumor cells is developed. TE-1146 is prepared using the HighDAR platform, which employs i) a maleimide-containing "multi-arm linker" to conjugate multiple drug molecules creating a drug bundle, and ii) a designed peptide with a Zn2+ -binding cysteine at the C-termini of a reconfigured daratumumab for site-specific drug bundle conjugation. It is shown that TE-1146 remains intact and effectively enters CD38-expressing tumor cells, releasing lenalidomide, leading to enhanced cell-killing effects compared to lenalidomide/daratumumab alone or their combination. This reveals the remarkable potency of lenalidomide once internalized by myeloma cells. TE-1146 precisely delivers lenalidomide to target CD38-overexpressing tumor cells. In contrast, lenalidomide without daratumumab cannot easily enter cells, whereas daratumumab without lenalidomide relies on Fc-dependent effector functions to kill tumor cells.

20.
J Biophotonics ; : e202400026, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453163

RESUMO

Macrophage polarization in neurotoxic (M1) or neuroprotective (M2) phenotypes is known to play a significant role in neuropathic pain, but its behavioral dynamics and underlying mechanism remain largely unknown. Two-photon excitation microscopy (2PEM) is a promising functional imaging tool for investigating the mechanism of cellular behavior, as using near-infrared excitation wavelengths is less subjected to light scattering. However, the higher-order photobleaching effect in 2PEM can seriously hamper its applications to long-term live-cell studies. Here, we demonstrate a GHz femtosecond (fs) 2PEM that enables hours-long live-cell imaging of macrophage behavior with reduced higher-order photobleaching effect-by leveraging the repetition rate of fs pulses according to the fluorescence lifetime of fluorophores. Using this new functional 2PEM platform, we measure the polarization characteristics of macrophages, especially the long-term cellular behavior in efferocytosis, unveiling the dynamic mechanism of neuroprotective macrophage polarization in neuropathic pain. These efforts can create new opportunities for understanding long-term cellular dynamic behavior in neuropathic pain, as well as other neurobiological problems, and thus dissecting the underlying complex pathogenesis.

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