Development and validation of a random survival forest model for predicting long-term survival of early-stage young breast cancer patients based on the SEER database and an external validation cohort.

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

Safety and oncological outcome of early intraoperative intravesicle mitomycin C vs. deferred instillation in patients receiving robot-assisted radical nephroureterectomy.

Introduction: Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. Methods: This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. Results: A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. Conclusion: IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion.

INTRODUCTION: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. METHODS: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. RESULTS: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. CONCLUSIONS: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding.

BACKGROUND: Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. RESULTS: This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. CONCLUSIONS: ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.

New α-Glucosidase Inhibitors from the Whole Plant of Hypericum beanii Based on Ligand Fishing and Molecular Networking Analysis.

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.

Recent progress in neonatal hyperoxic lung injury.

With the progress in neonatal intensive care, there has been an increase in the survival rates of premature infants. However, this has also led to an increased incidence of neonatal hyperoxia lung injury and bronchopulmonary dysplasia (BPD), whose pathogenesis is believed to be influenced by various prenatal and postnatal factors, although the exact mechanisms remain unclear. Recent studies suggest that multiple mechanisms might be involved in neonatal hyperoxic lung injury and BPD, with sex also possibly playing an important role, and numerous drugs have been proposed and shown promise for improving the treatment outcomes of hyperoxic lung injury. Therefore, this paper aims to analyze and summarize sex differences in neonatal hyperoxic lung injury, potential pathogenesis and treatment progress to provide new ideas for basic and clinical research in this field.

L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

Application of Computed Tomography Angiography in Preoperative Diagnosis of Coarctation of Aorta and Evaluation of Aortic Dilatation in Infants.

OBJECTIVE: To evaluate the occurrence of aortic dilatation and its associated predictors with coarctation of the aorta (CoA) in infants using multi-slice computed tomography (MSCT). METHODS: The clinical data of 47 infantile patients with CoA diagnosed by MSCT and 28 infantile patients with simple ventricular septal defect were analyzed retrospectively. Aortic diameters were measured at six different levels, and aortic sizes were compared by z score. The coarctation site-diaphragm ratio was used to describe the degree of narrowing. Relevant clinical data were collated and analyzed. RESULTS: The dilation rate and z score of the ascending aorta in the severe CoA group were significantly higher than those in the mild CoA group (11 [52.38%] vs. 21 [80.77%], P=0.038 and 2.00 ± 0.48 vs. 2.36 ± 0.43, P=0.010). Pearson's correlation analysis found that the z score of the ascending aorta was negatively correlated with the coarctation site-diaphragm ratio value (r=-0.410, P=0.004). A logistic retrospective analysis found that an increased degree of coarctation was an independent predictor of aortic dilatation (adjusted odds ratio 0.002; 95% confidence interval 0.00-0.819; P=0.043). The z score of the ascending aorta in the severe CoA group was significantly higher than that in the ventricular septal defect group (P<0.05). CONCLUSION: Most infants with CoA can also have significant dilatation of the ascending aorta, and the degree of this dilatation is related to the degree of coarctation. Assessment of aortic diameter and related malformations by MSCT can predict the risk of aortic dilatation in infants with CoA.

Sustained oxidation of Tea-Fe(III)/H2O2 simultaneously achieves sludge reduction and carbamazepine removal: The crucial role of EPS regulation.

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.

Ultrafine Pt Nanoparticles on Defective Tungsten Oxide for Photocatalytic Ethylene Synthesis.

The selective conversion of ethane (C2H6) to ethylene (C2H4) under mild conditions is highly wanted, yet very challenging. Herein, it is demonstrated that a Pt/WO3-x catalyst, constructed by supporting ultrafine Pt nanoparticles on the surface of oxygen-deficient tungsten oxide (WO3-x) nanoplates, is efficient and reusable for photocatalytic C2H6 dehydrogenation to produce C2H4 with high selectivity. Specifically, under pure light irradiation, the optimized Pt/WO3-x photocatalyst exhibits C2H4 and H2 yield rates of 291.8 and 373.4 µmol g-1 h-1, respectively, coupled with a small formation of CO (85.2 µmol g-1 h-1) and CH4 (19.0 µmol g-1 h-1), corresponding to a high C2H4 selectivity of 84.9%. Experimental and theoretical studies reveal that the vacancy-rich WO3-x catalyst enables broad optical harvesting to generate charge carriers by light for working the redox reactions. Meanwhile, the Pt cocatalyst reinforces adsorption of C2H6, desorption of key reaction species, and separation and migration of light-induced charges to promote the dehydrogenation reaction with high productivity and selectivity. In situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory calculation expose the key intermediates formed on the Pt/WO3-x catalyst during the reaction, which permits the construction of the possible C2H6 dehydrogenation mechanism.

Augmented ERO1α upon mTORC1 activation induces ferroptosis resistance and tumor progression via upregulation of SLC7A11.

BACKGROUND: The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. METHODS: Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT-PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. RESULTS: ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. CONCLUSIONS: The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors.

Restoration of Range of Motion in the Cervical Spine through Single-Segment Artificial Disc Replacement Using the Baguera®C Prosthesis.

Background: Anterior cervical discectomy and fusion (ACDF) is a standard procedure for degenerative diseases of the cervical spine, providing nerve decompression and spinal stabilization. However, it limits cervical spine motility, restricts fused segment activity, and may lead to adjacent degeneration. Cervical disc arthroplasty (CDA) is an accepted alternative that preserves the structure and flexibility of the cervical spine. This study aimed to explore the dynamic changes in the range of motion (ROM) of the cervical spine after CDA using a viscoelastic artificial disc, as well as the factors affecting mobility restoration. Methods: A retrospective analysis was conducted on 132 patients who underwent single-level anterior cervical discectomy and CDA from January 2015 to June 2022. Result: Analysis of data from 132 patients revealed a significant improvement in clinical outcomes. The mean ROM of C2-C7 and functional spinal unit (FSU) segments significantly increased from 2 to 36 months post-operatively. Cervical spine flexibility was preserved and enhanced after prosthesis implantation. However, it took six months for the cervical spine motility to stabilize. In addition, sex and age were found to impact motility restoration, with female and younger patients exhibiting larger ROMs post-surgery. Additionally, CDA at the C5-C6 level resulted in the greatest increase in ROM, potentially improving overall kinematic ability. Conclusions: Single-segment artificial disc arthroplasty effectively restores the ROM in degenerative cervical spine conditions.

Development and evaluation of a deep learning-based model for simultaneous detection and localization of rib and clavicle fractures in trauma patients' chest radiographs.

Purpose: To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm. Materials and methods: We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps. Results: The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures. Conclusion: The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization.

Light-gated Integrator for Highlighting Kinase Activity in Living Cells.

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.

A nationwide case-referent study on elevated risks of adenocarcinoma lung cancer by long-term PM2.5 exposure in Taiwan since 1997.

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.

The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review.

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.

Evaluation of the clinical application of personalized 3D printing and CAD/CAM resin crowns to replace stainless steel crowns in paediatric dentistry.

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.