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Ascl1 and OTP tumor expressions are associated with Disease-Free Survival in Lung Atypical Carcinoids.

According to World Health Organization guidelines, Atypical Carcinoids (ACs) are well-differentiated lung neuroendocrine tumors with 2-10 mitoses2 mm Three hundred-seventy lung carcinoids were collected and centrally reviewed by two expert pathologists. Morphology and immunohistochemical markers (Ki-67, TTF-1, CD44, OTP, SSTR2A, Ascl1, p53 and Rb1) were studied and correlated with disease free survival (DFS) and overall survival (OS). Fifty-eight of 370 tumors were defined as AC. Survival analysis showed that patients with Ascl1ACs and those with OTP-ACs had a significantly worse DFS than patients with Ascl1-ACs and OTPACs, respectively. Combining Ascl1 and OTP expressions, groups were formed reflecting the aggressiveness of disease (p0.0005). Ki-67 ≥10% patients had a significantly worse DFS than patients with Ki-67<10%. At multivariable analysis Ascl1 (present vs absent, HR3.42, 95%CI 1.35-8.65, p0.009) and OTP (present vs absent, HR0.26, 95%CI 0.10-0.68, p0.006) were independently associated with DFS. The prognosis of patients with Ki-67 ≥10% tended to be worse compared to that with Ki-67<10%. On the contrary, OTP (present vs absent, HR0.28, 95%CI 0.09-0.89, p0.03), tumor stage (III-IV vs I-II, HR4.25, 95%CI 1.42-12.73, p0.01) and increasing age (10-year increase, HR1.67, 95%CI 1.04-2.68, p0.03) were independently associated with OS. This retrospective analysis of lung ACs showed that Ascl1 and OTP could be the main prognostic drivers of post-operative recurrence.

Clinical significance of the preoperative prognostic nutritional index on agecomorbidity burdens in patients with resectable non-small cell lung cancer.

Objective nutritional scoring systems using preoperative blood samples have shown the potential to predict the postoperative outcomes of patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether the prognostic impact depends on age and comorbid burdens. We conducted this study to validate the impact of preoperative nutritional status, stratified with age and comorbidity. We reviewed the preoperative prognostic nutritional index (PNI) and postoperative outcomes of 713 consecutive patients with completely resected NSCLC. We identified the optimal cutoff values of the PNI as 46. Significantly higher postoperative complication rates and worse survival rates were observed in the low PNI (≤ 46) group, regardless of agecomorbidity burdens. Multivariate analysis showed that a low PNI (≤ 46) was an independent prognostic factor for poor overall survival (hazard ratio 2.5). A matched-pair analysis gave consistent results, showing that a low PNI (≤ 46) was an independent prognostic factor for poor overall survival (OS hazard ratio 1.8) and recurrence-free survival (RFS hazard ratio 1.6). Nutritional status, indexed by the PNI, is a strong prognostic factor for the postoperative outcomes of patients undergoing curative resection for NSCL, regardless of agecomorbidity burdens.

Workers in Australian prebake aluminium smelters update on risk of mortality and cancer incidence in the Healthwise cohort.

To investigate mortality and the rates of incident cancer among a cohort of aluminium industry workers. Among 4507 male employees who worked in either of two Australian prebake smelters for at least 3 months, data linkage was undertaken with the Australian National Death Index and Australian Cancer Database. Standardised Mortality Ratios (SMRs) and Standardised Incidence Rates (SIRs) were estimated for the whole cohort and for production maintenance and office workers. SMRs and SIRs were calculated by time since first employment. Among production workers, there was an excess risk of mortality from mesothelioma (SMR 2.8, 95% CI 1.3 to 5.2), lung (SMR 1.4, 95% CI 1.0 to 1.8), prostate (SMR 1.9, 95% CI 1.3 to 2.7) and liver cancer (SMR 2.0, 95% CI 1.1 to 3.4) and the SIR was also increased for overall respiratory cancers, specifically lung cancers. An excess risk of death from stomach cancer (SMR 2.9, 95% CI 1.2 to 6.1) and Alzheimers disease (SMR 3.4, 95% CI 1.1 to 7.9) was seen among maintenance workers. The overall risk of death was similar to that of the Australian general population, as was mortality from cancers overall and non-malignant respiratory disease. No excess risk of death from bladder cancer or non-malignant respiratory disease was found. Excess lung cancer mortality and incidence may be explained by smoking and excess mortality from mesothelioma may be explained by asbestos exposure. An excess risk of mortality from liver and prostate cancer has been shown in production workers and requires further investigation.

Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis a phase 3, randomised, double-blind, placebo-controlled study.

Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug. Patients were randomised (21) to tofacitinib 5 mg twice daily (N136) or placebo (N68) switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included ACR205070 response change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout. The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2% placebo, 5.9% p<0.0001). M3 ACR20ACR70PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)serious AEs (M0-3) 68.4%0%, tofacitinib 5 mg twice daily 75.0%4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported. In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated safety outcomes were consistent with the established safety profile in PsA and other indications. NCT03486457.

Examination of the effectiveness of local therapy for oligo-recurrence of EGFR-mutated NSCLC.

The effectiveness of local therapy has been reported in patients with oligo-recurrence of non-small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR-mutated NSCLC. There is currently no consensus on treatment for oligo-recurrence of EGFR-mutated NSCLC. From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo-recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR-mutated oligo-recurrence. We retrospectively examined and compared the effects of EGFR-TKIs with those of radical local therapy in patients with oligo-recurrent EGFR-mutated NSCLC. The five-year post-recurrence survival (PRS) rates of patients with EGFR-mutated oligo-recurrence who received radical local therapy (n 23) and those who did not (n 11) were 59.4 and 45.5%, respectively (p 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo-recurrence (p 0.551). Radical local therapy did not affect PRS in patients with oligo-recurrent EGFR-mutated NSCLC. Even in cases of oligo-recurrence, the administration of local therapy in patients with EGFR-mutated NSCLC might be carefully considered.

Integral mediastinal staging in patients with NON-SMALL cell lung cancer and risk factors for occult N2 disease.

In patients with non-small cell lung cancer (NSCLC), the presence of abnormal hiliar lymph nodes (clinical N1 cN1), central tumor location andor tumor size (diameter >3 cm) increases the risk of occult mediastinal metastasis (OMM). This study investigates prospectively the diagnostic value of an integral mediastinal staging (IMS) strategy that combines EndoBronchial Ultrasound-TransBronchial Needle Aspiration (EBUS-TBNA) and Video-Assisted Mediastinoscopy (VAM) in patients with NSCLC at risk of OMM. Patients with NSCLC and radiologically normal mediastinum assessed non-invasively by positron emission tomography and computed tomography of the chest (PET-CT), and OMM risk factors (cN1, central tumor andor >3 cm) underwent EBUS-TBNA followed by VAM if the former was negative. Those with negative IMS underwent resection surgery of the tumor. EBUS-TBNA identified OMM in 2 out of the 49 patients evaluated (4%) and VAM in 1 of the 47 patients with negative EBUS (2%). Two patients with a negative IMS had OMM at surgery. Overall, the prevalence of OMM was 10%. EBUS-TBNA has a sensitivity of 40%, a negative predictive value (NPV) of 93.6%, and negative likelihood ratio of 0.60 (95%CI0.30-1.16). The risk of not diagnosing OMM after EBUS was 6% and after IMS was 4.4%. Integral mediastinal staging in patients with NSCLC and clinical risk factors for OMM, does not seem to provide added diagnostic value to that of EBUS-TBNA, except perhaps in patients with cN1 disease who deserve further research.

The impact of Body Mass Index (BMI) and residence in Food Priority Areas (FPAs) on patterns-of-care and cancer outcomes in patients with stage III non-small cell lung cancer.

Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at higher risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs impact patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (LA-NSCLC). We aim to analyze the impact of residing in a FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. This is a retrospective study of 573 LA-NSCLC patients consecutively treated from January 2000-January 2020. Chi-square and Mann-Whitney U-tests were done to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR). Cox regression with forward model selection was used for multivariate analysis (MVA). Thirty-two percent of patients resided in a FPA (N183) and were more likely to self-identify as black (p<0.0001), single (p<0.001), <60yo (p0.001) and uninsured (p< 0.0001), with a lower median income (p<0.001). Patients in FPAs also had lower mean pre-chemoradiation (pCRT) albumin (p0.002), lower pCRT body mass index (BMI) (p 0.026) and were less likely to receive trimodality therapy (p<0.001) when compared to non-FPA patients. There was no difference in OS or FFR between the two cohorts. However, in patients with a normal BMI either pCRT (Median OS 18.4m vs 25.0m, p0.005) or after CRT (15.1m vs. 28.1m, p0.002), residing in a FPA resulted in an OS detriment. We demonstrated a clear socioeconomic divide in our stage III NSCLC patient population, where residing in FPAs was associated with less aggressive therapy and an OS detriment for patients with a normal weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

Serinethreonine-protein kinase STK24 induces tumorigenesis by regulating the STAT3VEGFA signaling pathway.

Lung cancer is the most common cause of cancer-related death. Although anti-angiogenesis therapy has been effective in the treatment of non-small cell lung cancer (NSCLC), drug-resistance is a common challenge. Therefore, there is a need to develop new therapeutic strategies for NSCLC. Serinethreonine-protein kinase 24 (STK24), also known as MST3, belongs to the germinal center kinase III (GCKIII) subfamily, and the biological function of STK24 in NSCLC tumorigenesis and tumor angiogenesis is still unclear. In this study, we demonstrated that STK24 was overexpressed in lung cancer tissues compared with normal lung tissues, and lung cancer patients with higher STK24 expression levels had shorter overall survival time. In addition, our in vitro assays using A549 and H226 cell lines revealed that the STK24 expression level of cancer cells was positively correlated with cancer cells proliferation, migration, invasion, and tumor angiogenesis ability in vivo assays also demonstrated that silencing of STK24 dramatically inhibited tumor progress and tumor angiogenesis. To investigate a mechanism, we revealed that STK24 positively regulated the STAT3VEGFA signaling pathway by inhibiting poly-ubiquitin-proteasomal-mediated degradation of STAT3. Furthermore, we performed in vivo assays in BALBc nude mice and in vitro assays to show that STK24-regulated tumor angiogenesis depends on STAT3. These findings deepened our understanding of tumor angiogenesis, and the STK24STAT3VEGFA signaling pathway might be a novel therapeutic target for NSCLC treatment.

Safety and Feasibility of a Novel Externally Cooled Bronchoscopic Radiofrequency Ablation Catheter for Ablation of Peripheral Lung Tumours A First-In-Human Dose Escalation Study.

Radiofrequency ablation (RFA) is an established modality for percutaneous ablation of non-small cell lung cancer (NSCLC) in medically inoperable patients but is underutilized clinically due to side effects. We have developed a novel, completely endobronchial RFA catheter with an externally cooled electrode. The objective of this study was to establish the safety and feasibility of bronchoscopic RFA using a novel, externally cooled catheter for ablation of peripheral NSCLC. Patients with stage I biopsy-confirmed NSCLC underwent bronchoscopic RFA of tumour 7 days prior to lobectomy. The RFA catheter was delivered bronchoscopically to peripheral NSCLC lesions, guided by radial endobronchial ultrasound, with positioning confirmed using intra-procedural cone beam CT. Pre-operative CT chest and histologic examination of resected specimens were used to establish distributionuniformity of ablation and efficacy of tumour ablation. RFA in the first patient was complicated by dispersal of heated saline due to cough, resulting in ICU admission. The patient recovered fully and underwent uncomplicated lobectomy. Subsequently, the protocol was altered to mandate neuromuscular blockade with a pre-determined dose escalation, with algorithm-restricted energy (kJ) and irrigated saline volume (mL) constraints. A further 10 patients consented and seven underwent successful bronchoscopic RFA of peripheral NSCLC. No significant adverse events were noted. Ablation zone included tumour in all cases (proportion of tumour ablated ranged 8-72%), with uniform necrosis of tissue within ablation zones observed at higher energy levels. Ablation zone diameter correlated with RFA energy delivered (R2 0.553), with maximum long axis diameter of ablation zone 3.1 cm (22.9 kJ). Bronchoscopic RFA using an externally cooled catheter is feasible, appears safe, and achieves uniform ablation within the treatment zone. Uncontrolled escape of heated saline poses a major safety risk but can be prevented procedurally through neuromuscular blockade and by limiting irrigation.

A review on electronic nose for diagnosis and monitoring treatment response in lung cancer.

Lung cancer is one of the common malignancies with high mortality rate and a poor prognosis. Most lung cancer cases are diagnosed at an advanced stage either due to limited resources of infrastructure, trained human resources, or delay in clinical suspicion. Low-dose computed tomography (LDCT) has emerged as a screening tool for early lung cancer detection but may not be a feasible option for most developing countries. Electronic nose (eNOSE) is a unique non-invasive device that has been developed for lung cancer diagnosis and monitoring response by exhaled breath analysis of volatile organic compounds (VOCs). The breath-print have been shown to differ not only among lung cancer and other respiratory diseases, but also between various types of lung cancer. Hence, we postulate that the breath-print analysis by electronic nose could be a potential biomarker for the early detection of lung cancer along with monitoring treatment response in a resource-limited setting. In this review, we have consolidated the current published literature suggesting the use of an electronic nose in the diagnosis and monitoring treatment response of lung cancer.

Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer Updated Results From the Phase III Randomized ADAURA Trial.

The phase III ADAURA (ClinicalTrials.gov identifier NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio HR, 0.20 99.12% CI, 0.14 to 0.30 Overall, 682 patients with stage IB-IIIA (American Joint Committee on CancerUnion for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletionL858R) NSCLC were randomly assigned 11 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points. At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo) the DFS HR was 0.23 (95% CI, 0.18 to 0.30) 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34) 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had localregional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis. These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

Long Noncoding RNA IPW Is a Novel Diagnostic and Predictive Biomarker in Lung Adenocarcinoma.

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data.

Single-cell RNA sequencing combined with genome-scale metabolic models (GEMs) has the potential to unravel the differences in metabolism across both cell types and cell states but requires new computational methods. Here, we present a method for generating cell-type-specific genome-scale models from clusters of single-cell RNA-Seq profiles. Specifically, we developed a method to estimate the minimum number of cells required to pool to obtain stable models, a bootstrapping strategy for estimating statistical inference, and a faster version of the task-driven integrative network inference for tissues algorithm for generating context-specific GEMs. In addition, we evaluated the effect of different RNA-Seq normalization methods on model topology and differences in models generated from single-cell and bulk RNA-Seq data. We applied our methods on data from mouse cortex neurons and cells from the tumor microenvironment of lung cancer and in both cases found that almost every cell subtype had a unique metabolic profile. In addition, our approach was able to detect cancer-associated metabolic differences between cancer cells and healthy cells, showcasing its utility. We also contextualized models from 202 single-cell clusters across 19 human organs using data from Human Protein Atlas and made these available in the web portal Metabolic Atlas, thereby providing a valuable resource to the scientific community. With the ever-increasing availability of single-cell RNA-Seq datasets and continuously improved GEMs, their combination holds promise to become an important approach in the study of human metabolism.

Outcome of COVID-19 in hospitalised immunocompromised patients An analysis of the WHO ISARIC CCP-UK prospective cohort study.

Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic. We included patients > 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n 6,499) of immunocompromised and 21% (n 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI 1.39, 1.50, p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI 0.7, 0.85, p < 0.001) or ventilation (adjusted OR 0.65, 95% CI 0.56, 0.76, p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI 1.87, 2.15, p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent. Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group. ISRCTN 66726260.

Quantitation by Liquid Chromatography-Nanoelectrospray Ionization-High-Resolution Tandem Mass Spectrometry of Multiple DNA Adducts Related to Cigarette Smoking in Oral Cells in the Shanghai Cohort Study.

We developed a liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry (LC-NSI-HRMSMS) method for simultaneous quantitative analysis of 5 oral cell DNA adducts associated with cigarette smoking (8

LINC01082 Inhibits Non-Small Cell Lung Cancer by Targeting the miR-543TNRC6A Axis.

Non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases and have poor clinical outcomes. Increasing number of lncRNAs are reported to be implicated in the carcinogenesis of NSCLC. Previous lncRNA-seq results showed that LINC01082 was under-expressed in several cancer types. In the current study, we focused on the role of LINC01082 in NSCLC development. An online bioinformatics tool was utilized to assess the expression profile of LINC01082, miR-543, and TNRC6A in NSCLC samples. RT-qPCR analysis was performed for evaluating LINC01082, TNRC6A and miR-543 expression in cells (NSCLC cells vs. normal lung cells). Impact of LINC01082 upregulation on cell proliferation in vitro was investigated by MTT and EdU experiments. Transwell assay was applied to analyze the migration and invasion of NSCLC cells. The cell apoptosis after plasmid transfection was detected by flow cytometry. The interactions among LINC01082, miR-543 and TNRC6A were measured by RNA pulldown and luciferase reporter assays. We showed that LINC01082 levels were downregulated in NSCLC samples and NSCLC cells. Overexpression of LINC01082 inhibited NSCLC cell proliferation, migration and invasion and strengthened cell apoptosis. LINC01082 directly bound to miR-543, and miR-543 targeted TNRC6A. TNRC6A was downregulated and miR-543 was overexpressed in NSCLC cells. miR-543 inhibition suppressed malignant cellular behaviors. TNRC6A knockdown reversed the effects of LINC01082 on the malignant character of NSCLC cells. In conclusion, LINC01082 exerts an antioncogenic role in NSCLC via interaction with miR-543 to regulate TNRC6A expression.

PneuNet deep learning for COVID-19 pneumonia diagnosis on chest X-ray image analysis using Vision Transformer.

A long-standing challenge in pneumonia diagnosis is recognizing the pathological lung texture, especially the ground-glass appearance pathological texture. One main difficulty lies in precisely extracting and recognizing the pathological features. The patients, especially those with mild symptoms, show very little difference in lung texture, neither conventional computer vision methods nor convolutional neural networks perform well on pneumonia diagnosis based on chest X-ray (CXR) images. In the meanwhile, the Coronavirus Disease 2019 (COVID-19) pandemic continues wreaking havoc around the world, where quick and accurate diagnosis backed by CXR images is in high demand. Rather than simply recognizing the patterns, extracting feature maps from the original CXR image is what we need in the classification process. Thus, we propose a Vision Transformer (VIT)-based model called PneuNet to make an accurate diagnosis backed by channel-based attention through X-ray images of the lung, where multi-head attention is applied on channel patches rather than feature patches. The techniques presented in this paper are oriented toward the medical application of deep neural networks and VIT. Extensive experiment results show that our method can reach 94.96% accuracy in the three-categories classification problem on the test set, which outperforms previous deep learning models.

Automatic segmentation and radiomic texture analysis for osteoporosis screening using chest low-dose computed tomography.

This study developed a diagnostic tool combining machine learning (ML) segmentation and radiomic texture analysis (RTA) for bone density screening using chest low-dose computed tomography (LDCT). A total of 197 patients who underwent LDCT followed by dual-energy X-ray absorptiometry were analyzed. First, an autosegmentation model was trained using LDCT to delineate the thoracic vertebral body (VB). Second, a two-level classifier was developed using radiomic features extracted from VBs for the hierarchical pairwise classification of each patients bone status. All the patients were initially classified as either normal or abnormal, and all patients with abnormal bone density were then subdivided into an osteopenia group and an osteoporosis group. The performance of the classifier was evaluated through fivefold cross-validation. The model for automated VB segmentation achieved a Sorenson-Dice coefficient of 0.87 ± 0.01. Furthermore, the area under the receiver operating characteristic curve scores for the two-level classifier were 0.96 ± 0.01 for detecting abnormal bone density (accuracy 0.91 ± 0.02 sensitivity 0.93 ± 0.03 specificity 0.89 ± 0.03) and 0.98 ± 0.01 for distinguishing osteoporosis (accuracy 0.94 ± 0.02 sensitivity 0.95 ± 0.03 specificity 0.93 ± 0.03). The testing prediction accuracy levels for the first- and second-level classifiers were 0.92 ± 0.04 and 0.94 ± 0.05, respectively. The overall testing prediction accuracy of our method was 0.90 ± 0.05. The combination of ML segmentation and RTA for automated bone density prediction based on LDCT scans is a feasible approach that could be valuable for osteoporosis screening during lung cancer screening. • This study developed an automatic diagnostic tool combining machine learning-based segmentation and radiomic texture analysis for bone density screening using chest low-dose computed tomography. • The developed method enables opportunistic screening without quantitative computed tomography or a dedicated phantom. • The developed method could be integrated into the current clinical workflow and used as an adjunct for opportunistic screening or for patients who are ineligible for screening with dual-energy X-ray absorptiometry.

Non-small cell lung cancer disparities in stage at presentation and treatment for Asian American, Native Hawaiian, and Pacific Islander women.

Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) represent the fastest-growing group in the United States. While described in aggregate, great variations exist within the community. We aimed to determine whether there were differences in stage at presentation and treatment status among AANHPI women with non-small cell lung cancer (NSCLC). Between 2004 and 2016, we identified 522 361 female patients with newly diagnosed NSCLC from the National Cancer Database. Multivariable logistic regression models were used to define adjusted odds ratios (aORs) of presenting with stage IV disease and not receiving treatment. AANHPI women were more likely to present with stage IV disease compared to White (54.32% vs. 40.28%, p < 0.001). Aside from Hawaiian, Pakistani, and Hmong women, all other ethnic groups had greater odds of presenting with stage IV disease than White women. AANHPI women <65 years were more likely to present with stage IV disease (p 0.030). Only Vietnamese women showed a significant difference (aOR 1.30 1.06-1.58, p 0.010) for likelihood of receiving treatment compared to White. Differences in stage at presentation and treatment status in women with NSCLC were observed among AANHPI ethnic groups when populations were disaggregated.

SWEET a single-sample network inference method for deciphering individual features in disease.

Recently, extracting inherent biological system information (e.g. cellular networks) from genome-wide expression profiles for developing personalized diagnostic and therapeutic strategies has become increasingly important. However, accurately constructing single-sample networks (SINs) to capture individual characteristics and heterogeneity in disease remains challenging. Here, we propose a sample-specific-weighted correlation network (SWEET) method to model SINs by integrating the genome-wide sample-to-sample correlation (i.e. sample weights) with the differential network between perturbed and aggregate networks. For a group of samples, the genome-wide sample weights can be assessed without prior knowledge of intrinsic subpopulations to address the network edge number bias caused by sample size differences. Compared with the state-of-the-art SIN inference methods, the SWEET SINs in 16 cancers more likely fit the scale-free property, display higher overlap with the human interactomes and perform better in identifying three types of cancer-related genes. Moreover, integrating SWEET SINs with a network proximity measure facilitates characterizing individual features and therapy in diseases, such as somatic mutation, mut-driver and essential genes. Biological experiments further validated two candidate repurposable drugs, albendazole for head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAD) and encorafenib for HNSCC. By applying SWEET, we also identified two possible LUAD subtypes that exhibit distinct clinical features and molecular mechanisms. Overall, the SWEET method complements current SIN inference and analysis methods and presents a view of biological systems at the network level to offer numerous clues for further investigation and clinical translation in network medicine and precision medicine.

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are attenuated by Hyaluronan.

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants, COVID-19 has led to 651,918,402 confirmed cases, and 6,656,601 deaths worldwide (as of December 27, 2022 httpscovid19.who.int). Despite advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in the proteome of alveolar type II (ATII)-like Rat L2 cells that lack ACE2 receptors. Systems biology analysis revealed that the S1 induced proteomics changes were associated with three significant network hubs E2F1, CREB1 RelA, and ROCK2 RhoA. We also found that pre-treatment of L2 cells with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects on the proteome. Western blotting analysis and cell cycle measurements confirmed the S1-upregulation of E2F1 and ROCK2RhoA in L2 cells and the protective effects of HMW-HA. Taken as a whole, our studies revealed profound and novel biological changes that contribute to our current understanding of both S1 and Hyaluronan biology. This data shows that the S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury (236 words).

Hyperoxia impairs intraflagellar transport and causes dysregulated metabolism with resultant decreased cilia length.

Supplemental oxygen is a lifesaving measure in infants born premature to facilitate oxygenation that may lead to alveolar simplification and loss of proximal airway epithelial cilia. Little is known about the mechanism of hyperoxic ciliary dysfunction in the proximal respiratory tract. We hypothesized that hyperoxia causes intraflagellar transport (IFT) dysfunction with resultant decreased cilia length. Differentiated basal human airway epithelial cells (HAEC) were exposed to hyperoxia or air for up to 48 h. Neonatal mice (<12 h old) were exposed to hyperoxia for 72 h and recovered in air until postnatal day (PND) 60. Cilia length was measured from scanning electron microscopy images using a MATLAB derived program. Proteomics and metabolomics were carried out in cells after hyperoxia. There was a significant time-dependent reduction in cilia length after hyperoxia in HAEC. Proteomic analysis showed decreased abundance of multiple proteins related to IFT including dynein motor proteins after hyperoxia. In neonatal mice exposed to hyperoxia, there was a significant decrease in acetylated α tubulin at PND10 with recovery to normal levels at PND60. In HAEC, abundance of multiple proteins associated with complex I of the electron transport chain were decreased by hyperoxia. Additionally, in HAEC, hyperoxia increased levels of malate, fumarate, and citrate, and reduced the ATPADP ratio at 24 h with a subsequent increase at 36 h. Exposure to hyperoxia reduces cilia length, which is associated with aberrant IFT protein expression and dysregulated metabolism. This delineates potential aberrant IFT protein expression upon hyperoxic exposure on the respiratory epithelium.

Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants.

The SPOT-MAS assay Screening for the Presence Of Tumor by Methylation And Size detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

The DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness.

Hepatocellular carcinoma (HCC) is the most prevalent malignant liver neoplasm. Despite the advances in diagnosis and treatment, the prognosis of HCC patients remains poor. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the glycosylated secretory protein Dickkopf-1 (DKK1), and the DKK1-CKAP4 axis is activated in pancreatic, lung, and esophageal cancer cells. DKK1 and CKAP4 expression have been examined in HCC in independent studies that yielded contradictory results. In this study, the relationship between the DKK1-CKAP4 axis and HCC was comprehensively examined. In 412 HCC cases, patients whose tumors were positive for both DKK1 and CKAP4 had a poor prognosis compared to those who were positive for only one of these markers or negative for both. Deletion of either DKK1 or CKAP4 inhibited HCC cell growth. In contrast to wild-type DKK1, DKK1 lacking the CKAP4 binding region did not rescue the phenotypes caused by DKK1 depletion, suggesting that binding of DKK1 to CKAP4 is required for HCC cell proliferation. Anti-CKAP4 antibody inhibited HCC growth, and its antitumor effect was clearly enhanced when combined with lenvatinib, a multi-kinase inhibitor. These results indicate that simultaneous expression of DKK1 and CKAP4 is involved in the aggressiveness of HCC, and that the combination of anti-CKAP4 antibody and other therapeutics including lenvatinib may represent a promising strategy for treating advanced HCC.

GNB1 promotes hepatocellular carcinoma progression by targeting BAG2 to activate P38MAPK signaling.

G-proteins are intracellular partners of G-protein-coupled receptors. As a member of the G-protein family, GNB1 has been shown to play a pro-cancer role in lung cancer and breast cancer. However, the biological function and detailed mechanisms of GNB1 in hepatocellular carcinoma progression are unclear. In this study, we investigated the effects of GNB1 and its possible mechanism of action in hepatocellular carcinoma (HCC). The clinical significance of GNB1 was evaluated in a large cohort of HCC patients, showing that GNB1 was overexpressed in HCC compared to adjacent normal liver tissues, and increased GNB1 expression was associated with poor prognosis. We also demonstrated that GNB1 enhances cell proliferation, colony formation, and cell migration and invasion in vitro and promotes the epithelial-to-mesenchymal transition process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of GNB1 in tumorigenicity in nude mice. Activation of P38 signaling was found in the GNB1 overexpressed HCC cells. Further intervention of P38 confirmed it as an important signaling pathway for the oncogenic role of GNB1 in HCC. Moreover, co-immunoprecipitation followed by liquid chromatograph-mass spectrometry identified that GNB1 exerted oncogenic functions via the interaction of BAG2 and activated P38 signaling pathway. Together, our results reveal that GNB1 plays a pivotal oncogenic role in HCC by promoting the P38 pathway via cooperating with BAG2. GNB1 may serve as a prognostic biomarker for patients with HCC.

Cerebral tumor embolism from thyroid cancer treated by mechanical thrombectomy illustrative case.

Development in mechanical thrombectomy is progressing dramatically. Tumor embolism has been rarely reported on the basis of pathological study of the retrieved thrombus. Herein, the authors report a case of cerebral tumor embolism from advanced thyroid cancer, which was successfully treated with mechanical thrombectomy. A 57-year-old man was diagnosed with thyroid cancer with multiple lung metastases and chemotherapy was planned. He experienced left hemiparesis and was bought to the emergency section of the authors hospital. Magnetic resonance angiography revealed right internal carotid artery occlusion and endovascular treatment was performed. Using a combination of aspiration catheter and stent retriever, white jelly-like embolus was retrieved. The pathological study demonstrated thyroid cancer embolism. Pulmonary vein invasion following lung metastasis of thyroid cancer was most presumably the cause of the tumor embolism. Lung metastasis invading the pulmonary vein may be a cause of tumor embolism. Mechanical thrombectomy using a combination of stent retriever and aspiration catheter is effective in removing the tumor embolus and the pathological examination of the embolus is essential.

Lung cancer registries in Denmark, Finland, Norway and Sweden a comparison and proposal for harmonization.

Lung cancer is the leading cause of cancer-related death in all Nordic countries which, though similar in demographics and healthcare systems, have noticeable differences in lung cancer survival. Historically, Denmark and Finland have had higher lung cancer incidences and lower survival than Norway and Sweden. All four countries have national cancer registries. Data in these registries are often compared, but their full potential as a source of learning across the Nordic countries is impeded by differences between the registries. In this paper, we describe and compare the Nordic registries on lung cancer-specific data and discuss how a more harmonized registration practice could increase their usefulness as a source for mutual learning and quality improvements. We describe and compare the characteristics of data on lung cancer cases from registries in Denmark, Finland, Norway and Sweden. Moreover, we compare the results from the latest annual reports and specify how data may be acquired from the registries for research. Denmark has a separate clinical lung cancer registry with more detailed data than the other Nordic countries. Finland and Norway report lung cancer survival as relative survival, whereas Denmark and Sweden report overall survival. The Danish Lung Cancer Registry and the Swedish Cancer Registry do not receive data from the Cause of Death registries in contrast to the Finnish Cancer Registry and the Cancer Registry of Norway. The lung cancer registries in Denmark, Finland, Norway and Sweden have high level of completeness. However, several important differences between the registries may bias comparative analyses.

Single-cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity.

Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) is an important factor in the integrated stress response (ISR) in mammals and may play a crucial role in tumorigenesis. In our studies, we found an inhibitor of PPP1R15A, Sephin1, plays a protumorigenic role in mouse tumor models. By analyzing the single-cell transcriptome data of the mouse tumor models, we found that in C57BL6 mice, Sephin1 treatment could lead to higher levels of ISR activity and lower levels of antitumor immune activities. Specifically, Sephin1 treatment caused reductions in antitumor immune cell types and lower expression levels of cytotoxicity-related genes. In addition, T cell receptor (TCR) repertoire analysis demonstrated that the clonal expansion of tumor-specific T cells was inhibited by Sephin1. A special TCR macrophage subtype in tumor was identified to be significantly depleted upon Sephin1 treatment, implying its key antitumor role. These results suggest that PPP1R15A has the potential to be an effective target for tumor therapy.

Normally happening substances like flavonoids are regarded as active candidates for the treatment and prevention of cancer The purpose of this study was to see how Iraqi Plant powder was extracted by reflex apparatus, then thin-layer chromatography (TLC) was used to determine total flavonoids. Cytotoxicity assay (MTT) was used to determine the cytotoxic activity of the prepared plant against human breast cancer (MCF-7), cells human cervix cancer (HELA), human colon cancer (Caco-2) and human lung fibroblast normal cell line (WISH). The flavonoids Rutin, Quercetin, Kaempferol, and luteolin were detected using the Thin Layer Chromatography (TLC) technique. In contrast to the negative control, the extract inhibited cell growth to a highest of 82.158% for MCF-7 and 61.360% for Caco-2 at the concentration (100 µgml), and (54.880%) for Hela cell line at the concentration (100 µgml). In addition, the concentration (6.25 µgml) of total flavonoid extract produced a decrease in the growth of the normal WISH cell line to reach (1.094%).

Evaluation of lncRNA FOXD2-AS1 Expression as a Diagnostic Biomarker in Colorectal Cancer.

Colorectal cancer (CRC) is still considered one of the prevalent cancers worldwide. Investigation of potential biomarkers for early detection of CRC is essential for the effective management of patients using therapeutic strategies. Considering that, this study was aimed to examine the changes in lncRNA FOXD2-AS1 expression through colorectal tumorigenesis. Fifty CRC tumor tissues and fifty adjacent normal tissue samples were prepared and involved in the current study. Total RNA was extracted from the samples and then reverse transcribed to complementary DNA. Next, the expression levels of lncRNA FOXD2-AS1 were evaluated using real-time PCR in CRC samples compared to normal ones. Also, receiver operating characteristic curve analysis was used to evaluate the diagnostic value of FOXD2-AS1 for CRC. The obtained results showed that the expression level of FOXD2-AS1 gene was significantly (p<0.0001) up-regulated in tumor tissues compared to normal marginal tissues. Also, a significant correlation was observed between higher the expression of FOXD2-AS1and the differentiation of tumor cells. Furthermore, ROC curve analysis estimated an AUC value of 0.59 for FOXD2-AS1, suggesting its potential as a diagnostic target. Taken together, the current study implied that tissue-specific upregulation of lncRNA FOXD2-AS1 might be appropriate diagnostic biomarkers for CRC. Nonetheless, more studies are needed to validate these results and further illustrate FOXD2-AS1 function through colorectal tumorigenesis.

Alectinib-Induced Severe Hemolytic Anemia in a Patient with ALK-Positive Non-Small Cell Lung Cancer A Case Report.

Alectinib is a selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor as standard therapy for ALK-rearranged non-small cell lung cancer (NSCLC). Hemolytic anemia is considered as a rare but significant adverse event with alectinib. Here, we report a case of a 73-year-old female with lung adenocarcinoma, harbouring an ALK fusion gene, who received alectinib as second-line therapy and developed gradually progressive grade 4 (6.4 gdL) drug-induced hemolytic anemia (DIHA) after complete response. We discontinued alectinib and performed a blood transfusion for the severe anemia. The anemia improved with no recurrence of lung adenocarcinoma over 10 months. Regular hematologic monitoring and the possibility of DIHA should be considered in case of progressive hemolytic anemia during alectinib treatment.

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC.

We present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC. Patients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mgm A total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% 95% confidence interval 21.0%-50.9%), and the median duration of response was 7.1 months (95% confidence interval 4.2-12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event. The combination of avelumab cetuximab and chemotherapy showed antitumor activity and tolerable safety however, the ORR was not improved compared with those reported for current standards of care (NCT03717155).

Two Cases of Subsequent Hepatocellular Carcinoma in Immune Checkpoint Inhibitor-Responsive NSCLC A Case Report.

As novel therapeutic regimens continue to lead to increased survival of patients with lung cancer, it is imperative to remain mindful of the accompanying increase in the incidence of new primary malignancies. Although the most common secondary malignancies in patients with lung cancer have historically included colon, rectal, esophageal, and thyroid cancers, we report here two rare cases of new primary hepatocellular carcinomas in patients receiving immune checkpoint inhibitor therapy for NSCLC. In both cases, the diagnosis of hepatocellular carcinoma, rather than assuming a hepatic metastasis, was crucial for determining the appropriate approach for treatment. These cases thus underscore the importance of appropriate diagnostics to ensure that the proper therapeutics are chosen and present important considerations for the lung cancer community going forward.

Ultrafast Gene Fusion Assessment for Nonsquamous NSCLC.

Gene fusion testing of A total of 195 NS-NSCLC cases (113 known gene fusions and 82 wild-type tumors) were included retrospectively. To validate the detection of a The accuracy was 92.3% and 93.1% for Idylla and Genexus, respectively. Both systems improved the sensitivity for detection by including a 5-3 imbalance analysis. Although detection of UFGFA using NGS and reverse-transcriptase polymerase chain reaction approaches had an equal level of detection of gene fusion but with some technique-specific limitations. Nevertheless, UFGFA detection in routine clinical care is feasible with both systems allowing faster initiation of therapy and a broad degree of screening.

A worldwide pandemic infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a deadly disease called COVID-19. Interaction of the virus and the Angiotensin converting-enzyme 2 (ACE2) receptor leads to an inflammatory-induced tissue damage. This is a narrative review in which using PubMed, Scopus, ISI, Cochrane, ScienceDirect, Google scholar, and Arxiv preprint databases, the molecular mechanisms of therapeutic and protective effects of TvL and its active compounds have been discussed regarding the molecular pathogenesis in COVID-19. Thyme could suppress TNF-alpha, IL-6, and other inflammatory cytokines. It also enhances the anti-inflammatory cytokines like TGF-beta and IL-10. Thyme extract acts also as an inhibitor of cytokines IL-1-beta and IL-8, at both mRNA and protein levels. Thymol may also control the progression of neuro-inflammation toward neurological disease by reducing some factors. Thyme and its active ingredients, especially Thymol and Carvacrol, have also positive effects on the renin-angiotensin system (RAS) and intestinal microbiota. Accordingly, TvL and its bioactive components may prevent COVID-19 complications and has a potential protective role against the deleterious consequences of the disease.

Hub Genes and Immune Cell Infiltration in Hypoxia-Induced Pulmonary Hypertension Bioinformatics Analysis and In Vivo Validation.

Hypoxia-induced pulmonary hypertension (HPH) represents a severe pulmonary disorder with high morbidity and mortality, which necessitates identifying the critical molecular mechanisms underlying HPH pathogenesis. The mRNA expression microarray GSE15197 (containing 8 pulmonary tissues from HPH and 13 normal controls) was downloaded from Gene Expression Omnibus (GEO). Gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were executed by RStudio software. The Protein-Protein Interaction (PPI) network was visualized and established using Cytoscape, and the cytoHubba app from Cytoscape was used to pick out the hub modules. The infiltration of immune cells in HPH was analyzed using the CIBERSORTx. To confirm the potential hub genes, real-time quantitative reverse transcription PCR (qRT-PCR) was conducted using lung tissues of rat HPH models and controls. A total of 852 upregulated and 547 downregulated genes were identified. The top terms in biological processes were apoptosis, proliferation, and regulation of the MAPK cascade, including ERK12. Cytoplasm, cytosol, and membrane were enriched in cellular component groups. Molecular functions mainly focus on protein binding, protein serinethreonine kinase activity and identical protein binding. KEGG analysis identified pathways in cancer, regulation of actin cytoskeleton and rap1 signaling pathway. There was significantly different immune cell infiltration between HPH and normal control samples. High proportions of the memory subsets of B cells and CD4 cells, Macrophages M2 subtype, and resting Dendritic cells were found in HPH samples, while high proportions of naive CD4 cells and resting mast cells were found in normal control samples. The qRTPCR results showed that among the ten identified hub modules, FBXL3, FBXL13 and XCL1 mRNA levels were upregulated, while NEDD4L, NPFFR2 and EDN3 were downregulated in HPH rats compared with control rats. Our study revealed the key genes and the involvement of immune cell infiltration in HPH, thus providing new insight into the pathogenesis of HPH and potential treatment targets for patients with HPH.

Deep learning based on enhanced MRI T1 imaging to differentiate small-cell and non-small-cell primary lung cancers in patients with brain metastases.

To differentiate the primary small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) for patients with brain metastases (BMs) based on a deep learning (DL) model using contrast-enhanced magnetic resonance imaging (MRI) T1 weighted (T1CE) images. Out of 711 patients with BMs of lung cancer origin (SCLC 232, NSCLC 479), the MRI datasets of 192 patients (lesions widths and heights > 30 pixels) with BMs from lung cancer (73 SCLC and 119 NSCLC) confirmed pathologically were enrolled, retrospectively. A typical convolutional neural network ResNet18 was applied for the automatic classification of BMs lesions from lung cancer based on T1CE images, with training and testing groups randomized per patient to eliminate learning bias. A 5-fold cross-validation was performed to evaluate the classification of the model. The receiver operating characteristic (ROC) curve, accuracy, precision, recall and f1 score were calculated. For a 5-fold cross-validation test, the DL model achieved AUCs of 0.8019 and 0.8024 for SCLC and NSCLC patients with BMs, respectively, and a mean overall accuracy of 0.7515±0.04. The DL model performed well in differentiating the primary SCLC and NSCLC with BMs. The proposed DL model is feasible and effective in differentiating the pathological subtypes of SCLC and NSCLC causing BMs, which may be used as a new tool for oncologists to diagnose noninvasively BMs and guide therapy based on the imaging structure of tumors.

A novel nomogram to predict lymph node metastasis in cT1 non-small-cell lung cancer based on PETCT and peripheral blood cell parameters.

Accurately evaluating the lymph node status preoperatively is critical in determining the appropriate treatment plan for non-small-cell lung cancer (NSCLC) patients. This study aimed to construct a novel nomogram to predict the probability of lymph node metastasis in clinical T1 stage patients based on non-invasive and easily accessible indicators. From October 2019 to June 2022, the data of 84 consecutive cT1 NSCLC patients who had undergone PETCT examination within 30 days before surgery were retrospectively collected. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of lymph node metastasis. A nomogram based on these predictors was constructed. The area under the receiver operating characteristic (ROC) curve and the calibration curve was used for assessment. Besides, the model was confirmed by bootstrap resampling. Four predictors (tumor SUVmax value, lymph node SUVmax value, consolidation tumor ratio and platelet to lymphocyte ratio) were identified and entered into the nomogram. The model indicated certain discrimination, with an area under ROC curve of 0.921(95%CI 0.866-0.977). The calibration curve showed good concordance between the predicted and actual possibility of lymph node metastasis. This nomogram was practical and effective in predicting lymph node metastasis for patients with cT1 NSCLC. It could provide treatment recommendations to clinicians.

Patient-derived cell-based pharmacogenomic assessment to unveil underlying resistance mechanisms and novel therapeutics for advanced lung cancer.

A pharmacogenomic platform using patient-derived cells (PDCs) was established to identify the underlying resistance mechanisms and tailored treatment for patients with advanced or refractory lung cancer. Drug sensitivity screening and multi-omics datasets were acquired from lung cancer PDCs (n 102). Integrative analysis was performed to explore drug candidates according to genetic variants, gene expression, and clinical profiles. PDCs had genomic characteristics resembled with those of solid lung cancer tissues. PDC molecular subtyping classified patients into four groups (1) inflammatory, (2) epithelial-to-mesenchymal transition (EMT)-like, (3) stemness, and (4) epithelial growth factor receptor (EGFR)-dominant. EGFR mutations of the EMT-like subtype were associated with a reduced response to EGFR-tyrosine kinase inhibitor therapy. Moreover, although RB1TP53 mutations were significantly enriched in small-cell lung cancer (SCLC) PDCs, they were also present in non-SCLC PDCs. In contrast to its effect in the cell lines, alpelisib (a PI3K-AKT inhibitor) significantly inhibited both RB1TP53 expression and SCLC cell growth in our PDC model. Furthermore, cell cycle inhibitors could effectively target SCLC cells. Finally, the upregulation of transforming growth factor-β expression and the YAPTAZ pathway was observed in osimertinib-resistant PDCs, predisposing them to the EMT-like subtype. Our platform selected XAV939 (a WNT-TNKS-β-catenin inhibitor) for the treatment of osimertinib-resistant PDCs. Using an in vitro model, we further demonstrated that acquisition of osimertinib resistance enhances invasive characteristics and EMT, upregulates the YAPTAZ-AXL axis, and increases the sensitivity of cancer cells to XAV939. Our PDC models recapitulated the molecular characteristics of lung cancer, and pharmacogenomics analysis provided plausible therapeutic candidates.

The prognostic value of the advanced lung cancer inflammation index in patients with gastrointestinal malignancy.

Systemic inflammation is crucial for the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is considered to be a better indicator of systemic inflammation than current biomarkers. However, the prognostic value of the ALI in gastrointestinal neoplasms remains unclear. We performed the first meta-analysis to explore the association between ALI and gastrointestinal oncologic outcomes to help physicians better evaluate the prognosis of those patients. Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by December 29, 2022. Clinical outcomes were overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). A total of 18 articles with 6898 patients were included in this meta-analysis. The pooled results demonstrated that a low ALI was correlated with poor OS (HR 1.914, 95% CI 1.514-2.419, P < 0.001), DFS (HR 1.631, 95% CI 1.197-2.224, P 0.002), and PFS (HR 1.679, 95% CI 1.073-2.628, P 0.023) of patients with gastrointestinal cancers. Subgroup analysis revealed that a low ALI was associated with shorter OS (HR 2.279, 95% CI 1.769-2.935, P < 0.001) and DFS (HR 1.631, 95% CI 1.197-2.224, P 0.002), and PFS (HR 1.911, 95% CI 1.517-2.408, P 0.002) of patients with colorectal cancer. However, the ALI was not related to CSS in the patients with gastrointestinal malignancy (HR 1.121, 95% CI 0.694-1.812, P 0.640). Sensitivity analysis supported the stability and dependability of the above results. The pre-treatment ALI was a useful predictor of prognosis in patients with gastrointestinal cancers.

Serum cross-linked N-telopeptide of type I collagen as a potential diagnostic marker for bone metastasis in lung cancer An updated meta-analysis.

To investigate the clinical value of serum type I collagen cross-linked amino terminal peptide (NTx) for the diagnosis of bone metastasis in lung cancer patients by evidence-based medicine. Diagnostic studies relevant to NTx as a serum marker for the diagnosis of bone metastasis in lung cancer patients included in the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and VIP database from the establishment of the databases to November 2022 were retrieved. Meta-analysis was conducted with Stata 16.0 software to calculate the combined sensitivity (SEN), specificity (SPN), positive likelihood ratio (LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and its 95% confidence interval (CI). The total subject working characteristic curve (summary receiver operating characteristic (SROC) curve) was drawn, and the area under the curve was calculated to evaluate its diagnostic value. A total of 1742 patients with lung cancer were included in 14 articles. Meta-analysis showed heterogeneity among the studies. The results of random-effect model analysis demonstrated that the combined SEN, SPN, LR, -LR, and DOR were 0.76 (95% CI 0.66-0.83), 0.80 (95% CI 0.74-0.85), 3.80 (95% CI 2.90-4.80), 0.30 (95% CI 0.22-0.42), and 12 (95% CI 8-19), respectively, and the area under SROC was 0.85. Serum NTx has a high clinical value in the diagnosis of bone metastasis in lung cancer patients and can be used as an effective complementary means for imaging diagnosis of bone metastasis in lung cancer patients.

Incidence trends and spatial distributions of lung adenocarcinoma and squamous cell carcinoma in Taiwan.

Lung cancer is the second most common cancer in Taiwan. After Taiwan implemented the Tobacco Hazards Prevention Act in 1997, smoking rates declined. However, the incidence rates of lung cancer for both sexes are still increasing, possibly due to risk factors other than smoking. We used age-period-cohort analysis to examine the secular trends of lung cancer incidence rates by histological type in Taiwan. A stabilized kriging method was employed to map these lung cancer incidence rates. Lung adenocarcinoma incidence rates increased, but lung squamous cell carcinoma incidence rates decreased, for both the sexes in recent birth cohorts, particularly in women. In Taiwan, the hotspots of lung adenocarcinoma incidence rates were in the northern, northeastern, and western coastal areas the incidence rates increased rapidly in the western and southern coastal regions and southern mountainous regions. The high incidence rates of lung squamous cell carcinoma in men were in the southwestern and northeastern coastal areas. The incidence rates rapidly increased in the central and southern coastal and mountainous regions. For both sexes in Taiwan, lung squamous cell carcinoma incidence rates declined from 1997 to 2017, but lung adenocarcinoma increased. The increased incidence rates of lung adenocarcinoma may be related to indoor and outdoor air pollution. Some areas in Taiwan have increasing lung cancer incidence rates, including the northwestern and southern coasts and mountains, and warrant particular attention.

Schwann cell-derived exosomes containing MFG-E8 modify macrophagemicroglial polarization for attenuating inflammation via the SOCS3STAT3 pathway after spinal cord injury.

Macrophagemicroglia polarization acts as an important part in regulating inflammatory responses in spinal cord injury (SCI). However, the regulation of inflammation of Schwann cell-derived exosomes (SCDEs) for SCI repair is still unclear. Therefore, we intend to find out the effect of SCDEs on regulating the inflammation related to macrophage polarization during the recovery of SCI. Firstly, the thesis demonstrated that SCDEs could attenuate the LPS- inflammation in BMDMs by suppressing M1 polarization and stimulating M2 polarization. Similarly, SCDEs improved functional recovery of female Wistar rats of the SCI contusion model according to BBB (Basso, Beattie, and Bresnahan) score, electrophysiological assay, and the gait analysis system of CatWalk XT. Moreover, MFG-E8 was verified as the main component of SCDEs to improve the inflammatory response by proteomic sequencing and lentiviral transfection. Improvement of the inflammatory microenvironment also inhibited neuronal apoptosis. The knockout of MFG-E8 in SCs can reverse the anti-inflammatory effects of SCDEs treatment. The SOCS3STAT3 signaling pathway was identified to participate in upregulating M2 polarization induced by MFG-E8. In conclusion, our findings will enrich the mechanism of SCDEs in repairing SCI and provide potential applications and new insights for the clinical translation of SCDEs treatment for SCI.

An Unsupervised Learning-Based Regional Deformable Model for Automated Multi-Organ Contour Propagation.

The aim of this study is to evaluate a regional deformable model based on a deep unsupervised learning model for automatic contour propagation in breast cone-beam computed tomography-guided adaptive radiation therapy. A deep unsupervised learning model was introduced to map breasts tumor bed, clinical target volume, heart, left lung, right lung, and spinal cord from planning computed tomography to cone-beam CT. To improve the traditional image registration methods performance, we used a regional deformable framework based on the narrow-band mapping, which can mitigate the effect of the image artifacts on the cone-beam CT. We retrospectively selected 373 anonymized cone-beam CT volumes from 111 patients with breast cancer. The cone-beam CTs are divided into three sets. 311 20 42 cone-beam CT images were used for training, validating, and testing. The manual contour was used as reference for the testing set. We compared the results between the reference and the model prediction for evaluating the performance. The mean Dice between manual reference segmentations and the model predicted segmentations for breast tumor bed, clinical target volume, heart, left lung, right lung, and spinal cord were 0.78 ± 0.09, 0.90 ± 0.03, 0.88 ± 0.04, 0.94 ± 0.03, 0.95 ± 0.02, and 0.77 ± 0.07, respectively. The results demonstrated a good agreement between the reference and the proposed contours. The proposed deep learning-based regional deformable model technique can automatically propagate contours for breast cancer adaptive radiotherapy. Deep learning in contour propagation was promising, but further investigation was warranted.

Development and Validation of CT-Based Radiomics Signature for Overall Survival Prediction in Multi-organ Cancer.

The malignant tumors in nature share some common morphological characteristics. Radiomics is not only images but also data we think that a probability exists in a set of radiomics signatures extracted from CT scan images of one cancer tumor in one specific organ also be utilized for overall survival prediction in different types of cancers in different organs. The retrospective study enrolled four data sets of cancer patients in three different organs (420, 157, 137, and 191 patients for lung 1 training, lung 2 testing, and two external validation set kidney and head and neck, respectively). In the training set, radiomics features were obtained from CT scan images, and essential features were chosen by LASSO algorithm. Univariable and multivariable analyses were then conducted to find a radiomics signature via Cox proportional hazard regression. The Kaplan-Meier curve was performed based on the risk score. The integrated time-dependent area under the ROC curve (iAUC) was calculated for each predictive model. In the training set, Kaplan-Meier curve classified patients as high or low-risk groups (p-value < 0.001 log-rank test). The risk score of radiomics signature was locked and independently evaluated in the testing set, and two external validation sets showed significant differences (p-value < 0.05 log-rank test). A combined model (radiomics clinical) showed improved iAUC in lung 1, lung 2, head and neck, and kidney data set are 0.621 (95% CI 0.588, 0.654), 0.736 (95% CI 0.654, 0.819), 0.732 (95% CI 0.655, 0.809), and 0.834 (95% CI 0.722, 0.946), respectively. We believe that CT-based radiomics signatures for predicting overall survival in various cancer sites may exist.

Aquaporins in Tumor.

Recent researches have demonstrated that aquaporins (AQPs), including water-selective channels, aquaglyceroporins and superaquaporins, are generally expressed in various tumors, such as lung, colorectal, liver, brain, breast tumors, etc. Therefore, it is imperative to study the accurate relationship between AQPs and tumor, which may provide innovative approaches to treat and prevent tumor development. In this chapter, we mainly reviewed the expression and pathophysiological function of AQPs in tumor, and summarize recent work on AQPs in tumor. Although, the underlying mechanism of AQP in tumor is not very clear, growing evidences suggest that cell migration, adhesion, angiogenesis, and division contribute to tumor development, in which AQPs might be involved. Therefore, it is still necessary to conduct further studies to determine the specific roles of AQPs in the tumor.

Quantitative Comparison of Gold Nanoparticle Delivery

There are still some gaps in existing knowledge in the field of cancer nanotheranostics,

Use of genome-wide testing in oncology French expert opinion based on the Delphi methodology.

In oncology, genome-wide testing is a major element in facilitating the implementation of precision medicine. However, current recommendations do not always specify the indication and utility of these tests according to the type of cancer. A national consensus approach based on a modified Delphi methodology was set up to provide expert opinion on the use of genome-wide testing in clinical practice in France. Four groups of experts - 4 each representing the following topics of interest - were defined non-small cell lung cancer (NSCLC), breast cancer, melanoma, and cancer of unknown primary (CUP). In each group, assertions were formulated by a lead expert (8, 5, 7 and 6, respectively) and rated by five panellists involved in the management of these cancers, on a scale from 1 (strongly disagree) to 9 (strongly agree). Consensus was reached when 75% of the scores were above 7. In case of disagreement, the panellists were asked to justify their rate. In total, 24 statements reached consensus after two to four rounds of rating, depending on the group. While the experts advocated the routine use of genome-wide testing in the diagnostic management of NSCLC and CUP, they did not recommend the systematisation of these tests for breast cancer and melanoma. Nevertheless, access to innovation in France could soon remove certain barriers and allow greater standardisation of broad molecular screening in oncology.

The gut microbiome, short chain fatty acids, and related metabolites in cystic fibrosis patients with and without colonic adenomas.

Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas. Colonic aspirates were obtained from adults with and without CF undergoing colon cancer screening or surveillance colonoscopy. Microbiome characterization was performed by 16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was performed by LC-MS. 42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced alpha diversity and decreased relative abundance of many SCFA-producing taxa. There were no significant differences in SCFA levels in CF patients, although there were reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients with adenomas, but not controls with adenomas, had significantly increased relative abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration and the presence of adenomas. CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.

Unresectable stage III non-small cell lung cancer Insights from a Portuguese expert panel.

The management of unresectable stage III non-small cell lung cancer (NSCLC) is clinically challenging and there is no current consensus on optimal strategies. Herein, a panel of Portuguese experts aims to present practical recommendations for the global management of unresectable stage III NSCLC patients. A group of Portuguese lung cancer experts debated aspects related to the diagnosis, staging and treatment of unresectable stage III NSCLC in light of current evidence. Recent breakthroughs in immunotherapy as part of a standard therapeutic approach were also discussed. This review exposes the major conclusions obtained. Practical recommendations for the management of unresectable stage III NSCLC were proposed, aiming to improve the pathways of diagnosis and treatment in the Portuguese healthcare system. Clinical heterogeneity of patients with stage III NSCLC hinders the development of single standardised algorithm where all fit. A timely diagnosis and a proper staging contribute to the best management of each patient, optimizing treatment tolerance and effectiveness. The expert panel considered chemoradiotherapy as the preferable approach when surgery is not possible. Management of adverse events and immunotherapy as a consolidation therapy are also essential steps for a successful strategy.

Targeting regulated cell death with plant natural compounds for cancer therapy A revisited review of apoptosis, autophagy-dependent cell death, and necroptosis.

Regulated cell death (RCD) refers to programmed cell death regulated by various protein molecules, such as apoptosis, autophagy-dependent cell death, and necroptosis. Accumulating evidence has recently revealed that RCD subroutines have several links to many types of human cancer therefore, targeting RCD with pharmacological small-molecule compounds would be a promising therapeutic strategy. Moreover, plant natural compounds, small-molecule compounds synthesized from plant sources, and their derivatives have been widely reported to regulate different RCD subroutines to improve potential cancer therapy. Thus, in this review, we focus on updating the intricate mechanisms of apoptosis, autophagy-dependent cell death, and necroptosis in cancer. Moreover, we further discuss several representative plant natural compounds and their derivatives that regulate the above-mentioned three subroutines of RCD, and their potential as candidate small-molecule drugs for the future cancer treatment.

Did you forget your cell sex An update on the inclusion of sex as a variable in

I dont know the question, but sex is definitely the answer, was a Woody Allen quote cited by Fuller and Insel in an Editorial Comment in 2013 on the importance of cell sex in submissions to AJP-Cell Physiology, and in biomedical research in general. The notion that cell sex is important is axiomatic in studies on prostate cancer or placental physiology. Indeed, most researchers are aware that HeLa cells are female cervical derived, and CHO are female hamster ovary cells, yet beyond those well-known examples, it would be fair to assume that the sex of cells derived from kidney, lung, or liver, for example, is given cursory, if any thought. What possible impact could the presence or absence of a Y chromosome have on protein trafficking in a non-reproductive tissue However, this approach to cell, and indeed organismal physiology, seems to be in conflict with accumulating data, that shows that far from being irrelevant, genes expressed off sex chromosomes have an impact on cells as diverse and neurons and renal cells. Moreover, it is also the policy of AJP-Cell Physiology, that the source of all cells utilized should be clearly indicated when submitting an article for publication. In 2013, we wrote a review examining how faithfully such requirements were adhered to in submissions to Cell Physiology. Nearly a decade later, it seems fitting to revisit the topic, and ask if any improvements have been made in the description of cells and cell lines utilized in publications submitted to AJP-Cell Physiology.

DNA methylation analysis identifies novel genetic loci associated with circulating fibrinogen levels in blood.

Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined by inter-individual differences in DNA methylation at CpG sites, and vice versa. We performed an epigenome-wide association study (EWAS) of circulating fibrinogen levels in 18,037 White, Black, American Indian, and Hispanic participants representing 14 studies from the CHARGE consortium. Circulating leukocyte DNA methylation was measured in 12,904 participants using the Illumina 450K array, and in 5,133 participants using the EPIC array. Each study performed an EWAS of fibrinogen using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific meta-analysis, followed by cross-replication of epigenome-wide significant associations. We compared models with and without C-reactive protein (CRP) adjustment to examine the role of inflammation. We identified 208 and 87 significant CpG sites associated with fibrinogen from the 450K (p-value<1.03×10 We identified 83 CpG sites associated with circulating fibrinogen levels. These associations are partially driven by inflammatory pathways shared by both fibrinogen and CRP.

Treatment outcomes of older participants in a randomized trial comparing two schedules of twice-daily thoracic radiotherapy in limited stage small-cell lung cancer.

Half of patients with limited stage small cell lung cancer (LS SCLC) are >70 years, but account for <20% of participants in most trials. Comorbidities, reduced organ- and physical function might lead to more treatment toxicity and population-based studies indicate that fewer older than younger LS SCLC patients receive standard chemoradiotherapy, although there is limited evidence for such a policy. We compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health related quality of life (HRQoL) and treatment outcomes between patients >70 and <70 years in an open label randomized phase II trial comparing twice-daily thoracic radiotherapy (TRT) of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent platinumetoposide chemotherapy. 170 patients who were >18 years and had performance status (PS) 0-2 were randomized. Of these, 53 patients (60 Gy25, 45 Gy28) were >70 years and 117 (60 Gy64, 45 Gy53) were younger. There were no significant differences in baseline characteristics, treatment completion rates, toxicity, or response rates across age groups. HRQoL mean scores was similar during year one, but older patients reported more decline on functional scales than younger patients during year two. OS was significantly shorter for older patients while there was no significant difference in PFS or TTP. Patients >70 years tolerated concurrent twice daily chemoradiotherapy and achieved similar disease control as younger patients, indicating that older patients should receive the same treatment as younger patients.

Robot-assisted Lung Surgery Techniques, Evidence and Data on Anatomical Resections.

Thanks to improved visualisation and instruments with an endowrist function, robot-assisted thoracic surgery has led to technical progress in thoracic surgery. This makes it easier to carry out complex thoracic surgical interventions, e.g. with an intrathoracic suture. As a result, this technology is increasingly being adopted and implemented in therapeutic use. Worldwide, the number of thoracotomies for lung cancer has decreased, while the number of minimally invasive surgical thoracic resections has increased. The aim of this work is to give an up-to-date overview of robotic operations on bronchial carcinoma. Die roboterassistierte Thoraxchirurgie (RATS) hat dank verbesserter Visualisierung und optimierter Instrumente (sog. Endowrist-Funktion) einen enormen technischen Fortschritt in der thoraxchirurgischen Versorgung von Patienten gebracht. Auch die Durchführung komplexer thorakaler oder mediastinaler chirurgischer Eingriffe, bspw. mit einer intrathorakalen Naht, sind nunmehr möglich. Infolgedessen wird diese Technologie zunehmend übernommen und in der therapeutischen Anwendung implementiert. Während die Zahl der konventionellen Thorakotomien bei Lungenkrebs weltweit zurückgeht, ist ein kontinuierlicher Anstieg der minimalinvasiven Resektionen beim Bronchialkarzinom zu beobachten. Ziel dieser Arbeit ist es, einen aktuellen Überblick über roboterassistierte Operationen beim Lungenkarzinom zu geben.

Host Recovery from Respiratory Viral Infection.

Emerging and re-emerging respiratory viral infections pose a tremendous threat to human society, as exemplified by the ongoing COVID-19 pandemic. Upon viral invasion of the respiratory tract, the host initiates coordinated innate and adaptive immune responses to defend against the virus and to promote repair of the damaged tissue. However, dysregulated host immunity can also cause acute morbidity, hamper lung regeneration, andor lead to chronic tissue sequelae. Here, we review our current knowledge of the immune mechanisms regulating antiviral protection, host pathogenesis, inflammation resolution, and lung regeneration following respiratory viral infections, mainly using influenza virus and SARS-CoV-2 infections as examples. We hope that this review sheds light on future research directions to elucidate the cellular and molecular cross talk regulating host recovery and to pave the way to the development of pro-repair therapeutics to augment lung regeneration following viral injury. Expected final online publication date for the

The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients.

Recently, several clinical trials of immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC) have shown limited benefits because of unselected patients. Thus, we aimed to explore whether YES-associated protein 1 (YAP-1) and POU domain class 2 transcription factor 3 (POU2F3) could identify SCLC patients with durable benefits from immunotherapy as potential biomarkers. We performed IHC of YAP-1 and POU2F3, and RNA-seq on tissues of ES- SCLC patients. An open-source plugin based on IHC-profiler was conducted to calculate the expression levels of YAP-1 and POU2F3. Patients with ES-SCLC were retrospectively investigated in the Guangdong Provincial Peoples Hospital from January 2018 to July 2021, and 21 patients whoever received atezolizumab plus etoposidecarboplatin (ECT) regimen also had tissue samples reachable. The median IHC-score of YAP-1 in responders (CRPR patients) was significantly lower than in nonresponders (SDPD patients) at 13.97 (95% CI 8.97-16.30) versus 23.72 (95% CI 8.13-75.40). The IHC-score of YAP-1 and PFS showed a negative correlation by Spearman (r-0.496). However, POU2F3 did not show a correlation with efficacy. Besides, patients with YAP-1 high expression had IL6, MYCN, and MYCT1 upregulated, while analysis of immune cell infiltration only showed that M0 macrophages were significantly higher. The expression of YAP-1 negatively correlated with the efficacy of ECT in ES-SCLC patients while POU2F3 did not reveal the predictive value. However, prospective investigations with a large sample size are needed.

Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveals

Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. When compared with wild-type patients, those with

Competence remodels the pneumococcal cell wall exposing key surface virulence factors that mediate increased host adherence.

Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation, and virulence. Competent bacteria produce so-called fratricins such as CbpD that kill noncompetent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phosphorylcholine residues found on wall and lipoteichoic acids (WTA and LTA) that together with PGN are major constituents of the pneumococcal cell wall. Competent pneumococci are protected against fratricide by producing the immunity protein ComM. How competence and fratricide contribute to virulence is unknown. Here, using a genome-wide CRISPRi-seq screen, we show that genes involved in teichoic acid (TA) biosynthesis are essential during competence. We demonstrate that LytR is the major enzyme mediating the final step in WTA formation, and that, together with ComM, is essential for immunity against CbpD. Importantly, we show that key virulence factors PspA and PspC become more surface-exposed at midcell during competence, in a CbpD-dependent manner. Together, our work supports a model in which activation of competence is crucial for host adherence by increased surface exposure of its various CBPs.

Regular glucosamine use may have different roles in the risk of site-specific cancers findings from a large prospective cohort.

Previous studies indicated that glucosamine supplements may have a general anti-cancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. A total of 450,207 eligible participants (mean age 56.2 years females 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer (HR1.04, 95% CI 1.01-1.06), skin cancer (HR1.11, 95% CI 1.07-1.15) and prostate cancer (HR1.07, 95% CI 1.01-1.13), and with a reduced risk of lung cancer (HR0.88, 95% CI 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age and education for the association of glucosamine use with overall cancer risk (all P-interaction <0.027). These results remained unchanged in the sensitivity analysis. Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer and overall cancer. The roles of glucosamine use potentially differ in the development of different site-specific cancers.

The Outcomes of Surgical and Nonsurgical Treatment in Patients With Spinal Metastases of Lung Cancer Protocol for a Prospective Cohort Study.

Spinal metastases of lung cancer (SMLC) usually have a high degree of malignancy and require multimodality treatment. Patients with SMLC who experience clinical symptoms (eg, local pain, emerging or potential spinal instability, and progressive neurological dysfunction) require surgical treatment. However, there are discrepancies in the comparison of outcomes between surgical treatment and nonsurgical treatment. This paper presents the protocol for a study that aims to compare the clinical outcomes of surgical treatment and nonsurgical treatment for SMLC, explore the prognostic factors of SMLC, and establish a survival prediction model based on these prognostic factors. This is a prospective cohort study, with an anticipated sample size of 240 patients (120 patients in the surgical group and 120 patients in the nonsurgical group). We will collect baseline data, including demographic, clinical, and radiological information, as well as data from patient-reported questionnaires. Patients will be followed up at 3, 6, 12, and 24 months after treatment, and survival status will be assessed every 3 months. The primary outcome is the overall survival period. Prognostic factors associated with overall survival will be analyzed by univariate and multivariate Cox proportional hazards regression. Odds ratios with 95% CIs will be presented. Statistical significance is set at P<.05. This study has been approved by our institutes Medical Science Research Ethics Committee (IRB00006761-M2021085) after a careful audit of the design and content. Patient enrollment began in June 2022 at our hospital. Data collection is expected to be completed by early 2026, and the study results will be published by mid-2027. In this study, we propose to set up a prospective cohort of patients with SMLC to investigate the outcomes between surgical treatment and nonsurgical treatment. We will explore the role of surgical treatment in SMLC and provide guidance to peer surgeons. Chinese Clinical Trial Registry, ChiCTR2100048151 httpwww.chictr.org.cnshowproj.aspxproj129450. DERR1-10.219638273.

Five-year cancer survival by stage at diagnosis in Canada.

Cancer survival estimates provide insights into the effectiveness of early detection and treatment. The stage of cancer at diagnosis is an important determinant of survival, reflecting the extent and spread at the time of disease detection. This work provides stage-specific, five-year survival results not previously available for Canada. Data reflect the population-based Canadian Cancer Registry death-linked analytic file covering the period from 2010 to 2017. The stage at diagnosis was determined by the Collaborative Stage Data Collection System. Five-year net survival (NS) estimates for Canada excluding Quebec were derived using the Pohar Perme estimator for the five most commonly diagnosed cancers. Except for prostate cancer, NS decreased monotonically with increased stage at diagnosis. For example, female breast cancer NS estimates were 100% (stage I), 92% (stage II), 74% (stage III) and 23% (stage IV). Apart from lung cancer, stage I NS exceeded 90% for all cancers studied. The largest sex-specific difference in NS was for lung cancer stage I (female 66% male 56%). Stage-specific NS generally decreased with age, particularly for early-stage lung cancer. Between the 2010-to-2012 and 2015-to-2017 periods, NS improved among stage IV prostate, female breast and lung cancer cases, as well as for stage I and III lung cancer cases however, it did not improve at any stage for colon or rectal cancer cases. The work highlights the importance of detecting cancer early, when treatment is most effective. It demonstrates some progress in stage-specific survival among top cancers in Canada and offers data to inform health policy, including screening, and clinical decisions regarding cancer treatment.

Clinical Indicators of Effects of Yoga Breathing Exercises on Patients With Lung Cancer After Surgical Resection A Randomized Controlled Trial.

Cancer itself and surgery pose a heavy burden on adults with lung cancer. Yoga breathing exercises have been proposed as a form of pulmonary rehabilitation exercises to improve these patients perioperative outcomes. To investigate the impact of yoga breathing exercises based on a problem-solving model on dyspnea, exercise capacity, anxiety, depression, and postoperative indwelling time of thoracic drainage tube and compliance in adults with lung cancer undergoing surgery. One hundred eight lung cancer patients were randomly assigned to receive problem-solving model-based yoga breathing exercises, yoga breathing exercises, or usual care. Outcomes were collected at admission, the day before surgery, and at discharge. Patients in the combined intervention group showed a significantly greater improvement in dyspnea, exercise capacity, and anxiety compared with the control group. Yoga breathing training can significantly improve patients dyspnea and anxiety. Significant difference favoring the combined group was observed in exercise capability and compliance between the 2 intervention groups. However, there was no significant difference in depression or indwelling time of thoracic drainage tube among the 3 groups at any time point. Findings indicate that yoga breathing exercises are effective in alleviating perioperative symptoms of lung resection patients. Compared with yoga breathing exercises, applying additional problem-solving model may achieve a better effect. Yoga breathing exercises can be considered as a promising pulmonary rehabilitation strategy for lung cancer patients with surgery. The problem-solving model could be integrated into yoga breathing exercises in clinical practice to enhance the rehabilitation effect.

Cancer beliefs and diet self-management among cancer survivors with comorbid diabetes.

Illness beliefs impact disease self-management however, little is known about the impact of patients beliefs about one illness on the management of another illness. We sought to understand how cancer beliefs impact diet self-management for cancer survivors with diabetes and whether a change in beliefs leads to a change in dietary adherence. Seventy-eight participants with diabetes and recently diagnosed early-stage breast, prostate, lung, or colon cancer were recruited. Participants were surveyed at enrollment and after 12 months about their cancer and diabetes illness beliefs and dietary adherence. Associations between beliefs about cancer and diabetes to diet adherence at baseline and at 12 months were assessed. Change in diet adherence was examined in relation to beliefs about each illness. The mean age was 62 years, and 23 (32%) identified as black non-Hispanic, 22 (31%) as white non-Hispanic, and 14 (19%) as Hispanic. Participants with more threatening beliefs about both cancer and diabetes at baseline had worse adherence to a diabetes diet than those with less threatening beliefs. However, at 12 months, those with more threatening cancer beliefs had better dietary adherence than participants with less threatening beliefs. Diabetes beliefs were not associated with diet adherence at 12 months. While threatening illness beliefs may initially result in worse diet adherence, over time these beliefs may result in increased activation for better self-care and improved diet adherence. Understanding how cancer beliefs impact diet self-management for diabetes may provide coping strategies to improve cancer survivors management of comorbidities.

Cancer-associated fibroblasts in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.

Clinical spectrum of Chinese hospitalized lung cancer patients with concomitant interstitial lung disease before and after the new era of LC treatment.

This study aimed to explore the general characteristics and spectrum of hospitalized Chinese patients suffering from lung cancer with concomitant interstitial lung disease (LC-ILD). Furthermore, we compared their features before and after the period of immunotherapy for lung cancer. A retrospective analysis of the clinical characteristics of hospitalized LC patients with definite pathological diagnoses was performed from 2014 to 2021. ILD was defined after the review of chest CT imaging. There were 13,085 hospitalized LC patients. Among them, 509 patients (3.89%) had 551 cases of ILD. There were variable underlying causes of ILD, including idiopathic interstitial pneumonia (360 patients), LC treatment-associated ILD (134 cases), and connective tissue disease-associated ILD (55 patients). Although most LC-ILD patients were suffering from adenocarcinoma (20440.1%), SCLC patients were prone to concomitant ILD (10.8% of all SCLC cases), followed by SCC (9.6% of all SCC cases). All but 10 LC-ILD patients received anti-LC treatment however, only 39 (10.8%) LC-IIP patients received anti-ILD treatment. There were more LC-ILD patients in the 2018-2021 group than in the 2014-2017 group (5.16% vs. 2.03%, p < 0.001). The underlying causes of ILD were significantly different between the 2018-2021 group and the 2014-2017 group (p < 0.001). After adjusting for the number of hospitalized patients having the same LC pathological pattern, SCLC was determined to be the most likely to be concomitant with ILD, followed by SCC. Most LC-ILD patients were scheduled for anti-LC therapy however, treatments for concomitant IIP were usually ignored. LC treatment-associated ILD should receive more attention than before.

A Proactive Approach to Prevent Hematopoietic Exhaustion During Cancer Chemotherapy in Older Patients Temporary Cell-Cycle Arrest.

Age is associated with the decline of multiple organ systems. In older patients, hematological toxicities associated with chemotherapy are often dose limiting, impairing dose intensity and treatment efficacy. Contrary to the classical path using growth factors to activate tissue regeneration, a novel strategy is emerging to prevent chemotherapy toxicity that involves temporary cell-cycle arrest of normal cells, such as hematopoietic or epithelial precursors. This proactive approach may allow the sparing of the stem cell reserve of these tissues. Two molecules are included in this new category, trilaciclib and ALRN-6924, which induce cell-cycle arrest by two different pathways. Previous approaches, such as the use of myelopoietic growth factors, were reactive and they might even have accelerated the depletion of stem cells by enhancing the commitment of these elements. Trilaciclib causes cell-cycle arrest by CDK 46 inhibition and ALRN-6924 by p53 activation. In a pooled analysis of three randomized phase II studies of patients with small cell lung cancer, trilaciclib prevented neutropenia, thrombocytopenia, and anemia. Similar chemoprotective results were observed with ALRN-6924 in an open-label phase Ib study of patients with p53-mutated small cell lung cancer. Trilaciclib is now approved as a myelopreservation agent in patients with extensive-stage small cell lung cancer. ALRN-6924 is currently in phase Ib clinical development in patients with p53-mutated cancer. In addition to preserving the normal hemopoietic pool, these drugs promise to preserve the stem cell reserve of other normal tissues with high turnover, preventing potentially other dose-limiting toxicities, such as mucositis and diarrhea. An ex vivo study provided early evidence that ALRN-6924 may prevent chemotherapy-induced alopecia. By affording protection from multiple toxicities with a single drug, trilaciclib and ALRN-6924 have the potential to transform the current standards of supportive care for oncology patients and may prevent the depletion of tissue stem cells already compromised with age.

Long-term survival outcomes after lobe-specific nodal dissection in patients with early non-small-cell lung cancer.

We investigated the long-term outcomes of lobe-specific nodal dissection (LSD) and systematic nodal dissection (SND) in patients with non-small-cell lung cancer (NSCLC). Patients with c-stage I and II NSCLC who underwent lobectomy with mediastinal nodal dissection were retrospectively analysed. After propensity score matching, we assessed the overall survival (OS), recurrence-free survival (RFS) and cumulative incidence of death (CID) from primary lung cancer and other diseases. The median follow-up period was 8.4 years. Among 438 propensity score-matched pairs, OS and RFS were similar between the LSD and SND groups hazard ratio (HR), 0.979 95% confidence interval (CI), 0.799-1.199 and HR, 0.912 95% CI, 0.762-1.092, respectively, but the LSD group showed a better prognosis after 5 years postoperatively. CID from primary lung cancer was similar between the 2 groups (HR, 1.239 95% CI, 0.940-1.633). However, the CID from other diseases was lower in the LSD group than in the SND group (HR, 0.702 95% CI, 0.525-0.938). According to c-stage, the LSD group tended towards worse OS and RFS, with higher CID from primary lung cancer than the SND group, in patients with c-stage II. LSD provides acceptable long-term survival for patients with early-stage NSCLC. However, LSD may not be suitable for patients with c-stage II NSCLC due to the higher mortality risk from primary lung cancer.

Extrachromosomal DNA Amplification Contributes to Small Cell Lung Cancer Heterogeneity and is Associated with Worse Outcomes.

Small-cell lung cancer is an aggressive neuroendocrine lung cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of MYC amplification and phenotypic plasticity, characterized by neuroendocrine and non-neuroendocrine cell states is not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA sequencing, and fluorescence in situ hybridization to find extrachromosomal DNA (ecDNA) as a primary source of MYC amplifications and driver fusions in SCLC. ecDNAs bring to proximity enhancer elements and oncogenes, creating SCLC transcription-amplifying units, driving exceptionally high MYC gene dosage. We demonstrate that cell-free nucleosome profiling can non-invasively detect ecDNA amplifications in plasma, facilitating its genome-wide interrogation in SCLC and other cancers. Altogether, our work provides the first comprehensive map of SCLC ecDNA and describe a new mechanism that governs MYC-driven SCLC heterogeneity. ecDNA-enabled transcriptional flexibility may explain the significantly worse survival outcomes of SCLC tumors harboring complex ecDNA amplifications.

LKB1-dependent regulation of TPI1 creates a divergent metabolic liability between human and mouse lung adenocarcinoma.

KRAS is the most frequently mutated oncogene in human lung adenocarcinomas (hLUAD) and activating mutations frequently co-occur with loss-of-function mutations in TP53 or STK11LKB1. However, mutation of all three genes is rarely observed in hLUAD, even though engineered co-mutation is highly aggressive in mouse lung adenocarcinoma (mLUAD). Here we provide a mechanistic explanation for this difference by uncovering an evolutionary divergence in regulation of triosephosphate isomerase (TPI1). In hLUAD, TPI1 activity is regulated via phosphorylation at Ser21 by the Salt Inducible Kinases (SIKs) in an LKB1-dependent manner, modulating flux between completion of glycolysis and production of glycerol lipids. In mice, Ser21 of TPI1 is a Cys residue which can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with KRAS and TP53 mutations, explaining why loss of LKB1 creates a liability in these tumors.

Microsampling in Targeted Mass Spectrometry-Based Protein Analysis of Low-Abundance Proteins.

This paper presents a protocol with detailed descriptions for efficient sample cleanup of low-abundance proteins from dried samples. This is performed using bead-based proteolysis prior to proteotypic peptide affinity-capture and liquid chromatography tandem mass spectrometry (LC-MSMS) determination. The procedure can be applied to both conventional dried samples using paper cards (e.g., dried blood spots DBSs and dried serum spots DSSs), as well as samples collected with newer sampling methods such as volumetric absorptive microsampling (VAMS). In addition to describing this procedure, the preparation of both trypsin beads and antibody-coated beads is presented in a step-by-step manner in this work. The advantages of the presented procedure are time-efficient proteolysis using beads and selective robust cleanup using peptide affinity-capture. The current procedure describes the determination of the low-abundance small-cell lung cancer (SCLC) biomarker, progastrin-releasing peptide (ProGRP), in dried serum (both DSSs and VAMS). Detailed procedures for bead preparation make it easier to implement the workflow in new applications or other laboratories. It is demonstrated that the results may be dependent on the sampling material for the present project, higher signal intensities were seen for samples collected using VAMS compared to DSSs.

RBM15 silencing promotes ferroptosis by regulating the TGF-βSmad2 pathway in lung cancer.

We assessed the function and mechanism of RNA binding motif protein 15 (RBM15) silencing in lung cancer development. The effects of RBM15 knockdown on A549 and H1299 cells were evaluated by MTT, EdU, wound healing, and transwell assay. We then detected the functions of RBM15 silencing on lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe RBM15 was highly expressed in lung cancer cells. RBM15 silencing reduced the viability, inhibited cell proliferation, invasion, and migration, and suppressed tumor growth in the xenograft mouse model. Knockout of RBM15 regulated ferroptosis-related gene expression. LIP, Fe We demonstrated that RBM15 silencing promoted ferroptosis in lung cancer cells by TGF-βSmad2 pathway, thereby inhibiting lung cancer cell growth, which may provide new light for lung cancer treatment.

Association between β-carotene supplementation and risk of cancer a meta-analysis of randomized controlled trials.

β-Carotene, which is derived from most fruits and vegetables, is the most common type of carotenes. Existing studies have demonstrated that β-carotene is associated with some positive health outcomes. However, results about the effects of supplemental β-carotene on cancer are inconsistent. To determine the association between supplemental β-carotene intake and the risk of cancers. Eight databases (PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wangfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) were systematically searched until September 2022. Only reports from randomized controlled trials in which an association between supplemental β-carotene intake and the risk of cancer was found were included in the meta-analysis. A total of 18 eligible studies based on 8 different randomized controlled trials were included in the meta-analysis, with varying sample sizes from 391 to 39 876 participants. There was no significant association between supplemental β-carotene intake and overall cancer incidence rate after synthesizing all the results (risk ratio RR 1.02 95% confidence interval CI, 0.99-1.05). Results from subgroup analysis indicated that intake of supplemental β-carotene significantly increased the risk of lung cancer (RR 1.19 95%CI 1.08-1.32), whereas no significant associations were observed for other site-specific cancers. In addition, smokers and the subgroup of participants with only low-dose β-carotene intake had a risk increment of cancer if they took supplemental β-carotene (RR 1.16 95%CI 1.05-1.29). β-Carotene supplementation has no beneficial or harmful effect on cancer incidence moreover, it might have potentially harmful effects on lung cancer, especially for people who smoke. On the basis of the evidence from this study, supplemental intake of β-carotene is not recommended for preventing cancer, and the establishment of a tolerable upper intake level of β-carotene should be considered.

Immune checkpoint inhibitors as first-line therapy for non-small cell lung cancer A systematic evaluation and meta-analysis.

Recently, immune checkpoint inhibitors (ICIs) present promising application prospects in treating non-small cell lung cancer (NSCLC). This study aimed to investigate optimal treatment strategy by comparing the first-line treatment strategies with ICIs in NSCLC. We retrieved relevant studies on first-line therapy of NSCLC with ICIs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were treatment-related serious adverse events (tr-SAEs) with grade 3 or higher and objective response rate (ORR). We also conducted a Bayesian network meta-analysis. We included 14 studies involving 7,823 patients and compared seven different interventions. In PD-L1 nonselective NSCLC, nivolumabipilimumab had good PFS and ORR, pembrolizumab significantly prolonged OS, and nivolumab had the fewest adverse events (AEs). For PD-L1-positive patients, nivolumab remarkably prolonged OS. For those with negative PD-L1, nivolumabipilimumab also showed an advantage. In addition, nivolumabipilimumab significantly prolonged the PFS in both PD-L1-negative and -positive patients. For patients with PD-L1 tumor proportion score (TPS) within 1-49%, atezolizumabchemotherapy remarkably prolonged PFS and OS. For those with PD-L1 TPS ≥50%, pembrolizumab prolonged OS and atezolizumabchemotherapy significantly prolonged PFS. Nivolumab combined with ipilimumab showed advantages in OS, PFS and ORR in most patients. Nivolumabipilimumab may be the optimal first-line therapy for NSCLC.

Role of Glucosamine and Chondroitin in the Prevention of Cancer A Meta-Analysis.

The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function of glucosamine andor chondroitin intake against cancer risk. We searched the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR), corresponding to the 95% confidence interval (95% CI), was used to assess the association between chondroitin andor glucosamine intake and cancer risk. Thirteen studies met the inclusion criteria, with 1,690,918 participants and 55,045 cancer cases. Overall, chondroitin andor glucosamine intake was associated with a lower risk of colorectal cancer (OR 0.91, 95% CI, 0.87-0.94) and lung cancer (OR 0.84, 95% CI, 0.79-0.89). Subgroup analysis supported the protective effect of different SYSADOAs (chondroitin andor glucosamine) intake. However, the protective effect was not observed in the only chondroitin intake group and in the NSAIDs group. Our meta-analysis found that the intake of glucosamine andor chondroitin decreased the risk of colorectal and lung cancers. Moreover, NSAIDs use may have a synergistic protective effect.

Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice.

Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. These effects are potentially beneficial for ameliorating cancer-related fatigue, which affects the quality of life of patients with cancer. This study aimed to determine the anti-fatigue and antitumor effects of caffeine in tumor-bearing mice. BALBc mice were intravenously injected with C26 colon carcinoma cells and fed with normal or 0.05% caffeine-supplemented diet. Fatigue-like behavior was assessed by running performance using a treadmill test. Lung, blood, liver, muscle, and epididymal adipose tissue samples were collected on day 13 and examined. The antitumor effect of caffeine was assessed using subcutaneous tumor-bearing mice fed with 0.05% caffeine-supplemented diet, and the tumor volume was measured. C26 tumor-bearing mice showed fatigue-like behavior associated with hypoglycemia, depleted liver glycogen and non-esterified fatty acid (NEFA) levels. C26 tumor-bearing mice fed with 0.05% caffeine-supplemented diet showed improved running performance associated with restored NEFA levels. However, exacerbated hypoglycemia and liver glycogen levels after caffeine consumption may be due to tumor-induced catabolic signals, as the tumor volume was not affected. Collectively, caffeine may exert anti-fatigue effects through enhanced lipolysis leading to restored NEFA levels, which can be used as an alternative energy source.

Inhibitory Effect of

As a common malignant tumor, the morbidity and mortality of lung cancer have been rising in recent years. The concept of premetastatic niche may lead to a revolutionary change in antitumor metastasis therapeutic strategies. Traditional Chinese medicine with multitargets and lower poisonous agents may be a potentially effective means to intervene in the premetastatic niche (PMN) to prevent and treat tumor metastasis.

Critical Evaluation of Secondary Cancer Risk After Breast Radiation Therapy with Hybrid Radiotherapy Techniques.

As hybrid radiotherapy technique can effectively balance dose distribution between targets and organs, it is necessary to evaluate the late effects related to radiotherapy. The aim of the study was to calculate and provide individual estimates of the risks for hybrid radiotherapy techniques in breast cancer patients. Whole-breast irradiation was performed in 43 breast cancer patients by using 3D conformal, intensity-modulated and hybrid techniques. The excess absolute risk (EAR), lifetime attributable risk (LAR) and normal tissue complication probability (NTCP) were calculated to estimate risks in organs. The risk variability in contralateral breast was assessed by using the patients anatomic parameters. Compared with IMRT and FinF, hybrid techniques achieved satisfactory dose distribution and comparable or lower estimated risks in organs. The LAR was estimated to be up to 0.549% for contralateral lung with advantages of tangential techniques over H-VMAT. For ipsilateral lung, the LAR was estimated to be up to 9.021%, but lower in H-VMAT and FinF without significant difference. The risk of thyroid was negligible in overall estimation. For contralateral breast, the LAR was estimated to be up to 0.865% with advantages of MH-IMRT and H-VMAT over TF-IMRT. The fraction of individual variability could be explained by using anatomic parameters of minimum breast distance (MBD) and minimum target concave angle (θ The optimal treatment should be performed individually according to anatomic parameters and balances between EAR and NTCP. Individual assessment may assist in achieving optimal balances between targets and organs as well as supporting clinical decision-making processes.

Suitability of transbronchial needle aspiration for genotyping peripheral pulmonary tumors.

Transbronchial needle aspiration (TBNA) is a sampling tool that has demonstrated a higher accuracy in the diagnosis of peripheral pulmonary lesions (PPL) compared to other techniques. However, there are no studies investigating the value of TBNA in defining the genotype of peripheral lung cancer. To evaluate the accuracy of TBNA in defining the molecular characteristics of peripheral lung cancer. Consecutive patients who underwent TBNA for the diagnosis of a PPL at the Pulmonary Unit of the Azienda Ospedali Riuniti of Ancona (Italy) between January 2020 and September 2022 were included in the study. TBNA was performed under fluoroscopic guidance and the additional support of an ultrasound miniprobe, with an ultrathin bronchoscope with a flexible 21G needle. Samples were smeared on glass slides for cytological evaluation and flushed in 10% neutral-buffered formalin for cell-blocks. 154 patients were enrolled55 were diagnosed with adenocarcinoma and 21 with squamous cell carcinoma. TBNA correctly diagnosed 4355 (78.2%) patients with adenocarcinoma and 1721 (81.0%) patients with squamous cell carcinoma, with a sensitivity of 77.5%. Complete genotyping for guiding targeted therapies was obtained in 52 patients (86.6%). TBNA is a valid tool for the diagnosis of PPL, allowing a correct diagnosis and a complete genotyping of the tumors in a considerable proportion of patients.

Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics.

To analyze and identify the core genes related to the expression and prognosis of lung cancer including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by bioinformatics technology, with the aim of providing a reference for clinical treatment. Five sets of gene chips, GSE7670, GSE151102, GSE33532, GSE43458, and GSE19804, were obtained from the Gene Expression Omnibus (GEO) database. After using GEO2R to analyze the differentially expressed genes (DEGs) between lung cancer and normal tissues online, the common DEGs of the five sets of chips were obtained using a Venn online tool and imported into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein-protein interaction (PPI) network was constructed by STRING online software for further study, and the core genes were determined by Cytoscape software and KEGG pathway enrichment analysis. The clustering heat map was drawn by Excel software to verify its accuracy. In addition, we used the University of Alabama at Birmingham Cancer (UALCAN) website to analyze the expression of core genes in P53 mutation status, confirmed the expression of crucial core genes in lung cancer tissues with Gene Expression Profiling Interactive Analysis (GEPIA) and GEPIA2 online software, and evaluated their prognostic value in lung cancer patients with the Kaplan-Meier online plotter tool. CHEK1, CCNB1, CCNB2, and CDK1 were selected. The expression levels of these four genes in lung cancer tissues were significantly higher than those in normal tissues. Their increased expression was negatively correlated with lung cancer patients (including LUAD and LUSC) prognosis and survival rate. CHEK1, CCNB1, CCNB2, and CDK1 are the critical core genes of lung cancer and are highly expressed in lung cancer. They are negatively correlated with the prognosis of lung cancer patients (including LUAD and LUSC) and closely related to the formation and prediction of lung cancer. They are valuable predictors and may be predictive biomarkers of lung cancer.

Cedrol, a Sesquiterpene Isolated from Juniperus chinensis, Inhibits Human Colorectal Tumor Growth associated through Downregulation of Minichromosome Maintenance Proteins.

Cedrol, a sesquiterpene alcohol, isolated from

MET amplifications (METamp) occur in 5% of NSCLC and represent in most case mechanisms of resistance to ALK andor EGFR-targeted therapies. METamp detection can be performed using different techniques, although Fluorescence In-Situ Hybridization (FISH) remains the gold-standard, especially in the context of subclonality. To date current evaluation algorithms of MET amplifications are time consuming. Aim of the study was to identify a faster, equally reliable diagnostic algorithm for the detection of METamp, which is currently classified in negativity and lowintermediatehigh-level amplification. N497 NSCLC cases with available MET-FISH data had been selected. The results based on the first evaluated 20 cells had been re-calculated and compared with the definitive results based on 60 cells. For n464 (93.4%) identical results had been obtained when counting 20 cells instead of 60 cells. Thirty-three cases (5.6%) showed a discrepancy, leading to an incorrect upgrade to a higher diagnostic category (n25) and to an incorrect downgrade (n8). We propose a simplified, yet equally reliable MET FISH-algorithm after accurate screening of the whole tumor slide, twenty tumor cells have to be evaluated and results calculated If the result is negative, or if all criteria of high-level METamp are fulfilled, the case can be signed out as such. All other cases should be considered as equivocal and additional 40 cells have to be counted. Given that, reliable results can be obtained by counting 20 cells only and an equivocal category for cases that need further investigation have been clearly defined.

Case Report Chemotherapy-free treatment with camrelizumab and anlotinib for elderly patients with

Functional Impact of a Cancer-Related Variant in Human Δ

Pyrroline-5-carboxylate reductase (PYCR) is a proline biosynthetic enzyme that catalyzes the NAD(P)H-dependent reduction of Δ

Syntheses, Structural Characterization, and Cytotoxicity Assessment of Novel Mn(II) and Zn(II) Complexes of Aroyl-Hydrazone Schiff Base Ligand.

This work describes the syntheses, structural characterization, and biological profile of Mn(II)- and Zn(II)-based complexes

Predictive models for the risk and prognosis of bone metastasis in patients with newly-diagnosed esophageal cancer A retrospective cohort study.

Esophageal cancer (EC) is a common malignant tumor worldwide, and patients with both EC and bone metastasis (BM) have a poor prognosis. We aimed to determine the risk and prognostic factors for BM in patients with newly diagnosed EC and to conduct two nomograms to predict the probability of BM and overall survival after BM. Data from patients with EC from 2010 to 2015 were reviewed in the Surveillance, Epidemiology, and End Results (SEER) database. We divided participants into training and validation cohorts using univariate and multivariate logistic regression analyses and Cox regression models to explore the risk and prognostic factors of BM, respectively. Moreover, two nomograms were developed for predicting the risk and prognosis of BM in patients with EC. Then we used receiver operating characteristic curves, decision curve analysis, and calibration curves to evaluate the nomogram models. The overall survival of patients with EC and BM was analyzed using the Kaplan-Meier method. A total of 10,730 patients with EC were involved, 735 of whom had BM at the time of diagnosis. Histologic type, sex, age, N stage, primary site, liver, lung, and brain metastases, and tumor differentiation grade were identified as independent BM risk factors. Histological type, chemotherapy, brain, liver, and lung metastases were identified as prognostic risk factors for patients with EC and BM. We developed diagnostic and prognostic nomograms according to the results. Receiver operating characteristic curves, calibration, and Kaplan-Meier curves, and decision curve analysis all indicated that both nomograms had great clinical predictive ability and good clinical application potential. Two novel nomograms were constructed to predict the risk and prognosis of BM in patients with EC. These prediction models can effectively assist clinicians in clinical decision-making based on their good accuracy and reliability.

Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminalHER2-low breast cancer Case report.

Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal BHER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes punctuated, branched and convergent. Punctuated evolution of the trunk was supported by

Surgical management of superior sulcus tumors A twenty-year experience of an oncological high volume referral centre.

Superior sulcus tumour, which affects the lungs apex, is an uncommon subtype of non-small cell lung cancer (NSCLC). The current study examined the clinical characteristics and management of superior sulcus NSCLC patients in a high-volume referral oncological centre over 22 years. Retrospective review of 100 surgeries with curative intent for superior sulcus NSCLC over 22 years (July 1998 - December 2020). The surgical approach was defined according to the lesion site and the anatomy of the thoracic inlet. Survival curves, including non-cancer-related deaths, were drawn using the Kaplan-Meier methods, and the log-rank test was used to evaluate differences in survival across groups of patients. Cox proportional hazards regression was used to assess the association between selected clinical and pathologic characteristics on OS. 54 patients received induction treatments. The surgical approach was anterior thoracotomy in 53 patients, Paulson incision in 30, and a combined in 8. The median postoperative length of stay was 11 days (range 5 - 27 days). Overall 90-day mortality was 6.93%. The median OS was 24.3 months. After a median follow-up of 3 years, 5-year and 10-year OS rates were 33.9% and 26.4%, respectively. A significantly lower 5-year OS was observed in patients with the nodal disease (46.6% in pN0 vs 13.2% in pN p 0.024), without preoperative treatments (41.0% in patients without preoperative treatments versus 17.4% p 0.09) and anteriorly located tumour (anterior vs posterior 17.4% vs 49.1% p 0.032). Cox proportional hazards regression showed better survival in the pT1 stage (HR 4.6 95% CI 1.9 - 11.2 p 0.00076) and in R0 (HR 4.2 95% CI 1.4 - 12.5 p 0.010). Superior sulcus tumours still represent a life-threatening condition that, while curable in a significant proportion of cases, requires complex procedures with high surgical risks and a multimodality treatment setting. An optimal surgical approach should be planned to maximise resection completeness and survival. Other factors affecting survival are related to tumour staging, emphasising the importance of a meticulous preoperative workup and candidate selection to identify those expected to benefit from a survival benefit.

Case report Pharmacokinetics of pembrolizumab in a patient with stage IV non-small cell lung cancer after a single 200 mg administration.

Pembrolizumab is a well-tolerated biologic agent with a potentially stable and durable anti-tumor response. Unfortunately, discontinuation of therapy can occur as a consequence of immune-related adverse effects (irAEs). These irAEs appear independent of dose and exposure. However, such irAEs might also result from pembrolizumabs highly specific mechanism of action and current dosing regimens. However, the currently available pharmacokinetic (PK) and pharmacodynamic (PD) data to reassess dosing strategies are insufficient.To highlight the importance of additional PKPD studies, we present a case describing the complexity of pembrolizumabs PKPD after a single 200 mg pembrolizumab dose in a treatment-naive patient with non-small cell lung cancer (NSCLC). A 72-year-old man with stage IV NSCLC presented hepatotoxic symptoms 19 days after receiving the first 200 mg pembrolizumab dose. Hence, pembrolizumab therapy was paused, and prednisolone therapy was initiated, which successfully inhibited the toxic effect of pembrolizumab. However, repeated flare-ups due to prednisolone tapering suggest that the toxic effect of pembrolizumab outlasts the presence of pembrolizumab in the bloodstream. This further suggests that the T-cell-mediated immune response outlasts the programmed cell death protein 1 (PD-1) receptor occupancy by pembrolizumab, which challenges the need for the current fixed-interval strategies and their stop criteria.Furthermore, a validated ELISA quantified pembrolizumab levels in 15 samples within 123 days after administration. A shift in the pembrolizumab clearance rate was evident ensuing day 77 (0.6 µgmL) after administration. Pembrolizumab levels up to day 77 (9.1-0.6 µgmL) strongly exhibited a linear, first-order clearance (R

High-risk patients with locally advanced non-small cell lung cancer treated with stereotactic body radiation therapy to the peripheral primary combined with conventionally fractionated volumetric arc therapy to the mediastinal lymph nodes.

A very narrow therapeutic window exists when delivering curative chemoradiotherapy for inoperable locally advanced non-small cell lung cancer (NSCLC), particularly when large distances exist between areas of gross disease in the thorax. In the present study, we hypothesize that a novel technique of stereotactic body radiation therapy (SBRT) to the primary tumor in combination with volumetric arc therapy (VMAT) to the mediastinal lymph nodes (MLN) is a suitable approach for high-risk patients with large volume geographically distant locally advanced NSCLC. In this single institutional review, we identified high-risk patients treated between 2014 and 2017 with SBRT to the parenchymal lung primary as well as VMAT to the involved MLN using conventional fractionation. Dosimetrically, comparative plans utilizing VMAT conventionally fractionated delivered to both the primary and MLN were analyzed. Clinically, toxicity (CTCAE version 5.0) and oncologic outcomes were analyzed in detail. A total of 21 patients were identified, 86% (n18) of which received chemotherapy as a portion of their treatment. As treatment phase was between 2014 and 2017, none of the patients received consolidation immunotherapy. Target volume (PTV) dose coverage (99 vs. 87%) and CTV volume (307 vs. 441 ml) were significantly improved with SBRTMLN vs. for VMAT alone (p<0.0001). Moreover, low-dose lung (median V5Gy % 71 vs. 77, p<0.0001), heart (median V5Gy % 41 vs. 49, p<0.0001) and esophagus (median V30Gy % 54 vs. 55, p0.03) dose exposure were all significantly reduced with SBRTMLN. In contrast, there was no difference observed in high-dose exposure of lungs, heart, and spinal cord. Following SBRTMLN treatment, we identified only one case of high-grade pneumonitis. As expected, we observed a higher rate of esophagitis with a total of seven patients experience grade 2 toxicity. Overall, there were no grade 4 toxicities identified. After a median 3 years follow up, disease progression was observed in 70% of patients irradiated using SBRTMLN, but never in the spared bridging tissue between pulmonary SBRT and mediastinal VMAT. For high risk patients, SBRTMLN is dosimetrically feasible and can provide an alternative to dose reductions necessitated by otherwise very large target volumes.

Differential value of diffusion kurtosis imaging and intravoxel incoherent motion in benign and malignant solitary pulmonary lesions.

To investigate the diagnostic value of diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) whole-lesion histogram parameters in differentiating benign and malignant solitary pulmonary lesions (SPLs). Patients with SPLs detected by chest CT examination and with further routine MRI, DKI and IVIM-DWI functional sequence scanning data were recruited. According to the pathological results, SPLs were divided into a benign group and a malignant group. Independent samples t tests (normal distribution) or Mann‒Whitney U tests (nonnormal distribution) were used to compare the differences in DKI (Dk, K), IVIM (D, D, f) and ADC whole-lesion histogram parameters between the benign and malignant SPL groups. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the histogram parameters and determine the optimal threshold. The area under the curve (AUC) of each histogram parameter was compared by the DeLong method. Spearman rank correlation was used to analyze the correlation between histogram parameters and malignant SPLs. Most of the histogram parameters for diffusion-related values (Dk, D, ADC) of malignant SPLs were significantly lower than those of benign SPLs, while most of the histogram parameters for the K value of malignant SPLs were significantly higher than those of benign SPLs. DKI (Dk, K), IVIM (D) and ADC were effective in differentiating benign and malignant SPLs and combined with multiple parameters of the whole-lesion histogram for the D value, had the highest diagnostic efficiency, with an AUC of 0.967, a sensitivity of 90.00% and a specificity of 94.03%. Most of the histogram parameters for the Dk, D and ADC values were negatively correlated with malignant SPLs, while most of the histogram parameters for the K value were positively correlated with malignant SPLs. DKI (Dk, K) and IVIM (D) whole-lesion histogram parameters can noninvasively distinguish benign and malignant SPLs, and the diagnostic performance is better than that of DWI. Moreover, they can provide additional information on SPL microstructure, which has important significance for guiding clinical individualized precision diagnosis and treatment and has potential clinical application value.

Efficacy and safety evaluation of neoadjuvant immunotherapy plus chemotherapy for resectable non-small cell lung cancer in real world.

The combination of immunotherapy and chemotherapy has shown great efficacy in stage IV non-small cell lung cancer (NSCLC) and is now widely used in clinical treatment strategy. This study retrospectively analyzed the efficacy and safety of neoadjuvant immunotherapy plus chemotherapy for resectable NSCLC in real world. We retrospectively analyzed patients with NSCLC who received neoadjuvant immunotherapy plus chemotherapy and underwent complete tumor resection in Zhejiang Cancer Hospital between January 2019 and January 2021. Tumor staging was based on the eighth TNM classification system of the American Joint Committee on Cancer staging criteria. The safety and toxicity (including operative and postoperative complications) and the efficacy including objective response rate (ORR), disease control rate (DCR), tumor major pathological remission (MPR), and pathological complete response (pCR) were evaluated. In total, 368 patients with NSCLC were administered with neoadjuvant immunotherapy. Of them, 211 patients were included in this retrospective study. Most patients had stage II-III disease, with 75 (35.5%) and 88 (41.7%) patients diagnosed with clinical stages IIB and IIIA, respectively. A total of 206 patients (97.6%) received at least two doses of neoadjuvant immunotherapy plus chemotherapy. In addition, 121 patients (57.3%) have achieved MPR, and 80 patients (37.9%) have achieved pCR, with ORR at 69.2% and DCR at 97.7%. Treatment-related adverse events occurred in 46.4% of patients, and the incidence rate of grade 3 or 4 treatment-related adverse events was 13.3% (1398). Moreover, adverse events of any grade of surgical complication occurred in 15.6% of patients. One-year disease-free survival was 80.6% (170211). Neoadjuvant immunotherapy plus chemotherapy has significant efficacy with a high pCR and tolerable adverse effects for patients with resectable stage II-III NSCLC in real world.

Case report Identification of acute promyelocytic leukemia during osimertinib resistance followed by granulocyte colony-stimulating factor and pembrolizumab.

The occurrence of acute promyelocytic leukemia (APL) during the management of lung cancer is rare and life-threatening. It was mainly reported to be secondary to chemoradiotherapy. A few studies reported an increased incidence of therapy-related acute promyelocytic leukemia (t-APL) after gefitinib became available. We reported a patient who developed thrombocytopenia after receiving oral osimertinib in combination with intensity-modulated radiotherapy (IMRT). For half a year, she had an unrecoverable low platelet count, which progressed to concomitant leukopenia and the transient appearance of orthochromatic normoblasts in the peripheral blood test, indicating a dormant myeloid disorder. Due to simultaneous resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), pembrolizumab and granulocyte colony-stimulating factor (G-CSF) were administered, revealing prominent signs of hematological malignancy in a peripheral blood test that was later identified as t-APL. In general, patients undergoing EGFR-TKI combined with local radiotherapy should be concerned about their hematological assessment. If patients exhibit unrecoverable abnormalities in routine blood tests, a secondary nonsolid malignancy other than myelosuppression should be considered, and further lung cancer treatment should be discontinued.

Prediction of portal dosimetry quality assurance results using log files-derived errors and machine learning techniques.

This work aims to use machine learning models to predict gamma passing rate of portal dosimetry quality assurance with log file derived features. This allows daily treatment monitoring for patients and reduce wear and tear on EPID detectors to save cost and prevent downtime. 578 VMAT trajectory log files selected from prostate, lung and spine SBRT were used in this work. Four machine learning models were explored to identify the best performing regression model for predicting gamma passing rate within each sub-site and the entire unstratified data. Predictors used in these models comprised of hand-crafted log file-derived features as well as modulation complexity score. Cross validation was used to evaluate the model performance in terms of R Using gamma passing rate of 1%1mm criteria and entire dataset, LASSO regression has a R Log file-derived features can predict gamma passing rate of portal dosimetry with an average error of less than 2% using the 1%1mm criteria. This model can potentially be applied to predict the patient specific QA results for every treatment fraction.

A signature-based classification of lung adenocarcinoma that stratifies tumor immunity.

Immune-related subgroup classification in immune checkpoint blockade (ICB) therapy is largely inconclusive in lung adenocarcinoma (LUAD). First, the single-sample Gene Set Enrichment Analysis (ssGSEA) and K-means algorithms were used to identify immune-based subtypes for the LUAD cohort based on the immunogenomic profiling of 29 immune signatures from The Cancer Genome Atlas (TCGA) database (n 504). Second, we examined the prognostic and predictive value of immune-based subtypes using bioinformatics analysis. Survival analysis and additional COX proportional hazards regression analysis were conducted for LUAD. Then, the immune score, tumor-infiltrating immune cells (TIICs), and immune checkpoint expression of the three subtypes were analyzed. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) of the differentially expressed genes (DEGs) between three immune-based subtypes were subsequently analyzed for functional enrichment pathways. A total of three immune-based subtypes with distinct immune signatures have been identified for LUAD and designated as cluster 1 (C1), cluster 2 (C2), and cluster 3 (C3). Patients in C3 had higher stromal, immune, and ESTIMATE scores, whereas those in C1 had the opposite. Patients in C1 had an enrichment of macrophages M0 and activation of dendritic cells, whereas tumors in C3 had an enrichment of CD8 LUAD subtypes based on immune signatures may aid in the development of novel treatment strategies for LUAD.

The apolipoprotein B and apolipoprotein A-I Ratio serves as a strong prognostic factor for the overall survival of patients with colorectal cancer.

The lipid metabolism status of patients with colorectal cancer (CRC) has not been understood comprehensively. The present study investigated the characteristics of lipid metabolism parameters in CRC patients with or without metastases and identified the independent prognostic factors of long-term prognosis. The clinicopathological data of 231 CRC patients along with 259 formalin-fixed paraffin-embedded samples with or without liver or lung metastasis were retrieved and stained for apolipoprotein B (apoB) In the multivariable analysis, apoA1, apoB and apolipoprotein B and apolipoprotein A-I (apoBA) ratio, were identified as independent prognostic factors for OS. Moreover, the apoBA ratio showed a significantly negative association with OS time (R-0.187, The apoBA ratio was a reliable independent prognostic factor for predicting the long-term OS of CRC patients. Moreover, the IHC of the primary CRC and metastatic lesions verified the metastatic potential of apoB through a different aspect. Lipid metabolism status for cancer progression reported in the present study possessed potentially prognostic value, but bench-scale studies are needed for their future clinical applications.

Case Report Immune checkpoint inhibitor-related vitiligo-like depigmentation in non-melanoma advanced cancer A report of three cases and a pooled analysis of individual patient data.

Vitiligo-like depigmentation is a common skin adverse event in patients receiving immunotherapy for malignant melanoma, but has been rarely reported in patients with non-melanoma malignancies. To better understand this immune-related adverse event, we reviewed a series of cases of immunotherapy induced vitiligo-like depigmentation in patients with cancers other than malignant melanoma. We report three cases of vitiligo-like depigmentation after immune checkpoint inhibitor treatment in gastric adenocarcinoma, lung adenocarcinoma, and squamous cell carcinoma. The first case was treated with camrelizumab, the second was treated with QL1706 injection and sintilimab, and the third was treated with tislelizumab. Pembrolizumab, nivolumab, and ipilimumab caused the majority of vitiligo-like depigmentation, and all three of our patients experienced similar vitiligo-like depigmentation after taking other immune checkpoint inhibitors. Three patients who presented with vitiligo-like depigmentation after treatment with immune checkpoint inhibitors were selected. The clinical features, including radiological and histological examination, and the treatment process were reviewed. Eighteen previously published cases of vitiligo-like depigmentation were also used to analyze the results. The severity of vitiligo-like depigmentation in these cases was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. Vitiligo-like depigmentation occurred in 13 men (61.90%) and 8 women (38.10%), aged from 46 to 79 years, with an average age of 69.9 years. Of the 21 reviewed cases, vitiligo-like depigmentation was described in lung cancer (1321, 61.90%), clear cell renal cell carcinoma (221, 9.52%), acute myeloid leukemia (121, 4.76%), cholangiocarcinoma (121, 4.76%), urothelial carcinoma (121, 4.76%), oral squamous cell carcinoma (121, 4.76%), esophageal squamous cell carcinoma (121, 4.76%), and gastric adenocarcinoma (121, 4.76%). The severity of vitiligo-like depigmentation after immunotherapy was unrelated to sex, age, cancer type, previous autoimmune diseases, and medication. Vitiligo-like depigmentation is a non-specific skin adverse event in melanoma immunotherapy, but arises as a direct result of treatment with immune checkpoint inhibitors. Vitiligo-like depigmentation has an irregular location, is not limited to direct sunlight cracks, and has also been reported on hair on the head, eyelashes, and eyebrows. People without any skin or autoimmune diseases can also experience vitiligo-like depigmentation after immunotherapy the incidence of which is irrespective of sex, age, cancer type, previous autoimmune diseases, and medication.

Platelet-lymphocyte ratio is a prognostic marker in small cell lung cancer-A systemic review and meta-analysis.

The aim of this study was to evaluate the relationship between platelet-lymphocyte ratio (PLR) and prognosis in small cell lung cancer (SCLC) patients. A comprehensive search was carried out to collect related studies. Two independent investigators extracted the data of hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) or progression-free survival (PFS). A random-effect model was applied to analyze the effect of different PLR levels on OS and PFS in SCLC patients. Moreover, subgroup analysis was conducted to seek out the source of heterogeneity. A total of 26 articles containing 5,592 SCLC patients were included for this meta-analysis. SCLC patients with a high PLR level had a shorter OS compared with patients with a low PLR level, in both univariate (HR 1.56, 95% CI 1.28-1.90, PLR was a good predictor for prognosis of SCLC patients, especially in patients received chemotherapy dominant treatments and predicting OS. httpswww.crd.york.ac.ukPROSPERO, identifier CRD42022383069.

Initial clinical experience with magnetic resonance-guided radiotherapy in pediatric patients Lessons learned from a single institution with proton therapy.

Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children. All patients treated with MRgRT since inception at our institution between 42018 and 42022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments. Between 42018 and 42022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumorcystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments. In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracicabdominalpelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing.

Machine-learning-based prediction of the effectiveness of the delivered dose by exhale-gated radiotherapy for locally advanced lung cancer The additional value of geometric over dosimetric parameters alone.

This study aimed to assess interfraction stability of the delivered dose distribution by exhale-gated volumetric modulated arc therapy (VMAT) or intensity-modulated arc therapy (IMAT) for lung cancer and to determine dominant prognostic dosimetric and geometric factors. Clinical target volume (CTV Altogether, 218 dose fractions (10 patients) were evaluated. There was a significant interpatient heterogeneity between the distributions of the normalized Accumulated dose distributions over the treatment series were robust against interfraction CTV deformations using exhale gating and online image guidance. D