bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological characteristics and risk factors of lung adenocarcinoma: A retrospective observational study from North China
Authors: Li Daojuan , Shi Jin , Dong Xiaoping , Liang Di , Jin Jing , He Yutong
Published: August 2022

Background

The main aim of the study was to determine the risk factors of lung adenocarcinoma and to analyze the variations in the incidence of lung adenocarcinoma according to time, sex, and smoking status in North China.

Methods

Patients with lung cancer in local household registries diagnosed and treated for the first time in the investigating hospital were enrolled from 11 cities in North China between 2010 and 2017. Baseline characteristics and tumor-related information were extracted from the patients’ hospital medical record, clinical course records, and clinical examination. Some of the variables, such as smoking, alcohol consumption, medical history, and family history of cancer, were obtained from interviews with the enrolled patients. The statistical method used were the chi-square test and multi-factor logistic regression analysis. The time trend was statistically analyzed using Joinpoint regression models, and p values were calculated.

Results

A total of 23,674 lung cancer cases were enrolled. People in severely polluted cities were at higher risk for lung adenocarcinoma (p < 0.001). Most patients with lung adenocarcinoma had no history of lung-related diseases (p = 0.001). Anatomically, lung adenocarcinoma was more likely to occur in the right lung (p < 0.001). Non-manual labor workers were more likely to develop from lung adenocarcinoma than manual workers (p = 0.015). Notably, non-smokers were more likely to develop lung adenocarcinoma than smokers (p < 0.001). The proportion of lung adenocarcinoma increased significantly in Hebei Province (p < 0.001). Among non-smokers, the proportion of lung adenocarcinoma showed a higher rise than in smokers (p < 0.001).

Conclusions

Lung adenocarcinoma is the most common histological type of lung cancer in North China (Hebei Province), and the proportion of lung adenocarcinoma is increasing, especially among non-smokers. Lung adenocarcinoma is more common in women, severely polluted cities, individuals with no history of lung-related diseases, in the right lung, and in non-smokers. These can serve as a great guide in determining the accuracy of lung adenocarcinoma high-risk groups and lung cancer risk assessment models.
A nomogram to predict survival probability of gastric cancer patients undergoing radical surgery and adjuvant chemotherapy
Authors: Ma Ling , Chen Guosheng , Wang Deqiang , Zhang Kai , Zhao Fengjiao , Tang Jie , Zhao Jianyi , Røe Oluf  Dimitri , He Shaohua , Liao Dongcheng , Gu Yanhong , Tao Min , Shu Yongqian , Li Wei , Chen Xiaofeng
Published: August 2022

Gastric cancer (GC) is the third-leading cause of cancer mortality worldwide. The aim of this study was to develop a nomogram that estimates 1-year, 3-year, and 5-year survival probability of GC patients after D2 gastrectomy combined with adjuvant chemotherapy. The results showed that median age is 58 (range: 18-85) years in the training cohort and 59 (range: 32-85) years in the validation cohort. On multivariate analysis, four factors were found to be significantly associated with worse overall survival (OS): late TNM stage, positive resection margin, preoperative carcinoembryonic antigen (CEA) level, and single chemotherapy regimens compared with multiple chemotherapy regimens. All of these findings were validated in the validation cohort. Furthermore, the four factors were included in the final nomogram for the prediction of 1-year, 3-year, and 5-year survival probability, with accurate calibration and reasonable discrimination (C-index = 0.676 for training cohort, and C-index = 0.664 for validation cohort). The AUC values analyzed by the ROC analysis demonstrated a good predictive accuracy of the nomogram for OS (1-year, 3-year, and 5-year OS were 94.43%, 77.42%, and 73.03% in the training cohort, respectively; 96.95%, 81.54%, and 73.41% in the validation cohort, respectively). In conclusion, the proposed nomogram may be used to objectively and accurately predict survival probability of GC patients in a multi-institutional clinical setting.
Polo-like kinase-1, Aurora kinase A and WEE1 kinase are promising druggable targets in CML cells displaying BCR::ABL1-independent resistance to tyrosine kinase inhibitors
Authors: Mancini Manuela , De Santis Sara , Monaldi Cecilia , Castagnetti Fausto , Lonetti Annalisa , Bruno Samantha , Dan Elisa , Sinigaglia Barbara , Rosti Gianantonio , Cavo Michele , Gugliotta Gabriele , Soverini Simona
Published: August 2022

In chronic myeloid leukemia (CML), Aurora kinase A and Polo like kinase 1 (PLK1), two serine-threonine kinases involved in the maintenance of genomic stability by preserving a functional G2/M checkpoint, have been implicated in BCR::ABL1-independent resistance to the tyrosine kinase inhibitor (TKI) imatinib mesylate and in leukemic stem cell (LSC) persistence. It can be speculated that the observed deregulated activity of Aurora A and Plk1 enhances DNA damage, promoting the occurrence of additional genomic alterations contributing to TKI resistance and ultimately driving progression from chronic phase to blast crisis (BC). In this study, we propose a new therapeutic strategy based on the combination of Aurora kinase A or PLK1 inhibition with danusertib or volasertib, respectively, and WEE1 inhibition with AZD1775. Danusertib and volasertib used as single drugs induced apoptosis and G2/M-phase arrest, associated with accumulation of phospho-WEE1. Subsequent addition of the WEE1 inhibitor AZD1775 in combination significantly enhanced the induction of apoptotic cell death in TKI-sensitive and -resistant cell lines as compared to both danusertib and volasertib alone and to the simultaneous combination. This schedule indeed induced a significant increase of the DNA double-strand break marker γH2AX, forcing the cells through successive replication cycles ultimately resulting in apoptosis. Finally, combination of danusertib or volasertib+AZD1775 significantly reduced the clonogenic potential of CD34+ CML progenitors from BC patients. Our results may have implications for the development of innovative therapeutic approaches aimed to improve the outcomes of patients with multi-TKI-resistant or BC CML.
Tumor-specific T cell-mediated upregulation of PD-L1 in myelodysplastic syndrome cells does not affect T-cell killing
Authors: Ferrari Valentina , Tarke Alison , Fields Hannah , Tanaka Tiffany N. , Searles Stephen , Zanetti Maurizio
Published: August 2022

The PD-1:PD-L1 axis is a binary interaction that delivers inhibitory signals to T cells, impeding both immune surveillance and response to immunotherapy. Here we analyzed a phenomenon whereby tumor-specific T cells induce PD-L1 upregulation in autologous MDS cells in short-term culture, through a mechanism that is cell-contact-independent and partially IFNγ-dependent. After investigating a panel of small-molecule inhibitors, we determined that PD-L1 upregulation was attributed to the PKR-like ER kinase (PERK) branch of the unfolded protein response. Interestingly, we found that the cytotoxic capacity of tumor-specific T cells was not impaired by the expression of PD-L1 on MDS target cells. These results highlight a little appreciated aspect of PD-1:PD-L1 regulation in hematologic cancers and indicate that this phenomenon, while likely to hinder autochthonous immune surveillance, may not be an obstacle to immunotherapies such as personalized adoptive T-cell therapy.
Iron accumulation typifies renal cell carcinoma tumorigenesis but abates with pathological progression, sarcomatoid dedifferentiation, and metastasis
Authors: Greene Christopher J. , Attwood Kristopher , Sharma Nitika J. , Balderman Benjamin , Deng Rongia , Muhitch Jason B. , Smith Gary J. , Gross Kenneth W. , Xu Bo , Kauffman Eric C.
Published: August 2022

Iron is a potent catalyst of oxidative stress and cellular proliferation implicated in renal cell carcinoma (RCC) tumorigenesis, yet it also drives ferroptosis that suppresses cancer progression and represents a novel therapeutic target for advanced RCC. The von Hippel Lindau (VHL)/hypoxia-inducible factor-α (HIF-α) axis is a major regulator of cellular iron, and its inactivation underlying most clear cell (cc) RCC tumors introduces both iron dependency and ferroptosis susceptibility. Despite the central role for iron in VHL/HIF-α signaling and ferroptosis, RCC iron levels and their dynamics during RCC initiation/progression are poorly defined. Here, we conducted a large-scale investigation into the incidence and prognostic significance of total tissue iron in ccRCC and non-ccRCC patient primary tumor cancer cells, tumor microenvironment (TME), metastases and non-neoplastic kidneys. Prussian Blue staining was performed to detect non-heme iron accumulation in over 1600 needle-core sections across multiple tissue microarrays. We found that RCC had significantly higher iron staining scores compared with other solid cancers and, on average, >40 times higher than adjacent renal epithelium. RCC cell iron levels correlated positively with TME iron levels and inversely with RCC levels of the main iron uptake protein, transferrin receptor 1 (TfR1/TFRC/CD71). Intriguingly, RCC iron levels, including in the TME, decreased significantly with pathologic (size/stage/grade) progression, sarcomatoid dedifferentiation, and metastasis, particularly among patients with ccRCC, despite increasing TfR1 levels, consistent with an increasingly iron-deficient tumor state. Opposite to tumor iron changes, adjacent renal epithelial iron increased significantly with RCC/ccRCC progression, sarcomatoid dedifferentiation, and metastasis. Lower tumor iron and higher renal epithelial iron each predicted significantly shorter ccRCC patient metastasis-free survival. In conclusion, iron accumulation typifies RCC tumors but declines toward a relative iron-deficient tumor state during progression to metastasis, despite precisely opposite dynamics in adjacent renal epithelium. These findings raise questions regarding the historically presumed selective advantage for high iron during all phases of cancer evolution, suggesting instead distinct tissue-specific roles during RCC carcinogenesis and early tumorigenesis versus later progression. Future study is warranted to determine how the relative iron deficiency of advanced RCC contributes to ferroptosis resistance and/or introduces a heightened susceptibility to iron deprivation that might be therapeutically exploitable.
Case report and literature review: thyroid carcinoma showing intrathyroid thymic carcinoma
Authors: Yuan Ye , Ke Changshu , Zhang Guopeng , Zhang Jun , Li Qianxia
Published: August 2022

Background

Intrathyroid thymic carcinoma (ITTC) is a rare malignancy of the thyroid gland with histological and immunophenotypic resemblance to thymic carcinoma. Surgery combined with adjuvant radiotherapy improves the survival of patients with ITTC. However, for patients with extensive metastases, there is currently no effective treatment. Chemotherapy is an option but has not demonstrated improved patient survival.

Methods and results

A female patient presented with metastases to the pleura, lung, and bone 16 years after surgery for ITTC. As radiotherapy and chemotherapy failed to control the recurrent disease, lenvatinib treatment was initiated. After 3 months, positron emission tomography/computed tomography showed a substantial reduction of all metastatic lesions and decreased tumor metabolism. The patient continues to receive lenvatinib and remains well and symptom-free.

Conclusion

For patients with ITTC who have progressive, life-threatening metastases, lenvatinib represents a valuable salvage therapy that may offer a sustained reduction in tumor burden and maintenance of quality of life.
Polymeric immunoglobulin receptor suppresses colorectal cancer through the AKT-FOXO3/4 axis by downregulating LAMB3 expression
Authors: Zhang Ding , Huang Hao , Zheng Ting , Zhang Lei , Cui Binbin , Liu Yanlong , Tan Shiheng , Zhao Liyuan , Tian Tian , Gao Lijing , Fu Qingzhen , Cheng Zesong , Zhao Yashuang
Published: August 2022

Colorectal cancer (CRC) remains one of the most common malignancies worldwide and its mechanism is unclear. Polymeric immunoglobulin receptor (PIGR) which plays an important role in mucosal immunity is widely expressed in the mucosal epithelium and is dysregulated in different tumors. However, the role and underlying mechanisms of PIGR in CRC remain unclear. Here, we demonstrated that PIGR was hypermethylated and downregulated in our cohort (N = 272), and these features were associated with reduced overall survival in patients (HRmethylation1.61, 95% CI [1.11-2.33]). These findings were validated by external TCGA and GEO data. Moreover, PIGR overexpression inhibits CRC cell malignant phenotypesin vitroand impedes CRC cells growth in male BALB/c nude mice. Mechanistically, PIGR physically associates with RE1 silencing transcription factor (REST) and blocks the transcription of laminin subunit beta 3 (LAMB3). Subsequently, the AKT-FOXO3/4 axis was suppressed by downregulated LAMB3. In the drug sensitive assay, PIGR-overexpressing cells were more sensitive to cisplatin and gemcitabine. Together, PIGR may serve as a powerful prognostic biomarker and putative tumor suppressor by suppressing the AKT-FOXO3/4 axis by downregulating LAMB3 in CRC. Our study may offer a novel therapeutic strategy for treating CRC patients who highly express PIGR with cisplatin and gemcitabine.
Diagnostic accuracy of Raman spectroscopy in oral squamous cell carcinoma
Authors: Han Ruiying , Lin Nan , Huang Juan , Ma Xuelei
Published: August 2022

Background

Raman spectroscopy (RS) has shown great potential in the diagnosis of oral squamous cell carcinoma (OSCC). Although many single-central original studies have been carried out, it is difficult to use RS in real clinical settings based on the current limited evidence. Herein, we conducted this meta-analysis of diagnostic studies to evaluate the overall performance of RS in OSCC diagnosis.

Methods

We systematically searched databases including Medline, Embase, and Web of Science for studies from January 2000 to March 2022. Data of true positives, true negatives, false positives, and false negatives were extracted from the included studies to calculate the pooled sensitivity, specificity, accuracy, positive and negative likelihood ratios (LRs), and diagnostic odds ratio (DOR) with 95% confidence intervals, then we plotted the summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) to evaluate the overall performance of RS. Quality assessments and publication bias were evaluated by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist in Review Manager 5.3. The statistical parameters were calculated with StataSE version 12 and MetaDiSc 1.4.

Results

In total, 13 studies were included in our meta-analysis. The pooled diagnostic sensitivity and specificity of RS in OSCC were 0.89 (95% CI, 0.85–0.92) and 0.84 (95% CI, 0.78–0.89). The AUC of SROC curve was 0.93 (95% CI, 0.91–0.95).

Conclusions

RS is a non-invasive diagnostic technology with high specificity and sensitivity for detecting OSCC and has the potential to be applied clinically.
Visual analysis of global research output of lymphedema based on bibliometrics
Authors: Zhang Yun-dong , Zhang Xue , Wang Xin-yu , Han Dong-mei , Du Jian-shi
Published: August 2022

Background

Globally, several generations of doctors in the field of lymphedema have created numerous publications. To date, no bibliometric analysis has been performed specifically on these publications. For the further promotion of research on lymphedema and to align with the international research frontiers, it is essential to understand the current state of Lymphedema research output.

Objective

This study aims to statistically and visually analyze the characteristics of publications output, distribution of contributions and development process of lymphedema, enriching the knowledge base of Lymphedema, and then seek potential research topics and collaborators.

Methods

Based on the Web of Science core collection database, we firstly analyzed the quantity and quality of publications in the field of lymphedema, secondly profiled the publishing groups in terms of country, institution, author’s publication and cooperation network, and finally sorted out and summarized the hot topics of research.

Results

A total of 8569 papers were retrieved from 1900-2021. The top4 journals with the most publications were LYMPHOLOGY, LYMPHATIC RESEARCH AND BIOLOGY, PLASTIC AND RECONSTRUCTIVE SURGERY and ANNALS OF SURGICAL ONCOLOGY. The top 4 countries with the most publications were USA, Japan, UK, and China. The United States dominates the total number of publications and the international cooperation network. The most productive research institution is Harvard University, and the research institution with the most collaborating institutions is Memorial Sloan Kettering Cancer Center. Mortimer, Peter S contributes the most research in this field. The research achievements of Japanese scholars in this field are of great significance. The top 5 ranked keywords are “Breast Cancer”, “Health-Related Quality Of Life”, “Lymphscintigraphy”, “Lymphovenous Anastomosis”, and “Lymphangiogenesis”.

Conclusion

More and more scholars are devoted to the research of cancer-related Lymphedema. It is foreseeable that breast cancer-related lymphedema and lymphangiogenesis will remain a focus of future research. Advances in Lymphatic vessel imaging and the development of lymphatic microsurgery will further play a role in the clinical workup of lymphedema. Meanwhile, This study can help researchers identify potential collaborators and partner institutions and contribute to further research.
Beneficial effects of preoperative superselective embolization on carotid body tumor surgery: A 13-year single-center experience
Authors: Li Nan , Wan Yuan , Chen Wei , Yang Jianyong , Chang Guangqi , Huang Yonghui
Published: August 2022

Purpose

This study presented our 13-year experience managing patients with CBTs (carotid body tumors) and was aimed to investigate the impact of pre-TAE (preoperative transarterial embolization) on CBT surgical resection.

Methods

This retrospective study reviewed 169 surgically excised CBTs between May 2007 and October 2020. According to whether to carry out the pre-TAE, the patients were classified into the embolization (EG) (n = 130) and non-embolization groups (NEG) (n = 39). Tumor classification was based on Shamblin criteria and tumor size. The demographic data, clinical features, and intraoperative and postoperative information about the patients were retrieved and analyzed.

Results

The average tumor size was (43.49 vs. 35.44 mm, p = 0.04) for EG and NEG. The mean surgical time (195.48 vs. 205.64 mins, p = 0.62) and intraoperative BL (blood loss) (215.15 vs. 251.41 cc, p = 0.59) were less, but the incidence of revascularization required (29% vs. 33%, p = 0.62) and total complications (26% vs. 36%, p = 0.32) were lower in EG compared to NEG. Similarly, according to the subgroup analysis, no significant differences were detected in the surgical time, BL, adverse events (AEs), and the revascularization in EG when compared to NEG for type I (n = 5 vs. 7), II (n = 105 vs. 27), and III (n = 20 vs. 5), respectively except for the surgical duration in type III (p < 0.05). However, a significantly lower incidence of AEs (230.25 vs. 350 cc, p = 0.038) and a decline in BL (28.57% vs. 48.15%, p = 0.049) in EG were observed compared to those in NEG patients for large CBTs (≥ 30 mm as the cutoff point). No surgery-related mortality was observed during the follow-up.

Conclusions

CBTs can be surgically resected safely and effectively with a need for pre-TAE, which significantly decreases the overall BL and AEs for large lesions (≥ 30 mm).
The potential effects and mechanisms of breast inflammatory lesions on the occurrence and development of breast cancer
Authors: Chang Zhaoxia , Zhang Ying , Fan Jue , Zhang Lixing , Liu Suling , Liu Guangyu , Tu Juchuanli
Published: August 2022

Breast cancer as the most common cancer in women has become the leading cause of cancer death for women. Although many inflammatory factors increase the risk of breast cancer, there are very few studies on the mechanisms by which inflammation affects the initiation and progression of breast cancer. Here, we profiled and compared the transcriptome of normal tissues, inflammatory breast tissues, benign breast tumors, and malignant breast tumors. To find key regulatory factors, a protein interaction network between characteristic modules in inflammatory lesions and ER-negative (ER−) breast cancer was constructed and inflammation-cancer interface genes were identified. We found that the transcriptional profile of inflammatory breast tissues was similar with ER− malignant tumors, featured with low ER expression levels and similar immune signaling pathway activation. Through comprehensive protein network analysis, we identified the interface genes and chemokine signaling pathway that have the potential to promote inflammatory cancer transformation. These interface genes could be used as a risk factor to provide a certain basis for the clinical early detection and treatment of breast cancer. This is the first study to explore the association between breast inflammatory lesions and breast cancer at the transcriptome level. Our inflammation data and research results provide a basis for future inflammation-cancer transformation analysis.
Case Report: A rare case of small bowel obstruction secondary to plasma cell myeloma
Authors: Bonometti Arturo , Aronico Nicola , Santacroce Giovanni , Fraticelli Sara , Lucioni Marco , Cartia Claudio Salvatore , Vanoli Alessandro , Latorre Mario Andrea , Arcaini Luca , Paulli Marco , Di Sabatino Antonio
Published: August 2022

Gastrointestinal (GI) involvement of plasma cell neoplasms is extremely rare. Herein, we describe the case of a 74-year-old Caucasian woman who came to our attention with abdominal pain, food vomiting, and weight loss of 10 kg over 1 year. A computed tomography scan of the abdomen revealed circumferential thickening of terminal ileum, for which the patient underwent an urgent 20-cm-long ileal resection. Histopathological and immunophenotypic analysis revealed a plasma cell neoplasm of the ileum. Subsequent investigations found a serum monoclonal immunoglobulin A component, an osteolytic lesion of the left jaw, and a clonal bone marrow plasma cell infiltrate carrying 1q21 amplification. Given the final diagnosis of plasma cell myeloma (PCM), the patient underwent a VMD (bortezomib, melphalan, and dexamethasone) chemotherapy regimen, achieving a complete remission after a 12-month treatment. For disease relapse, two further chemotherapy regimens were later attempted. At the last follow-up 4 years after the diagnosis, the patient is still alive. This case draws attention to the extramedullary presentation of plasma cell neoplasms, even if rare, as a prompt diagnosis seems to result in a better prognosis. In addition, it highlights the relevance of a multidisciplinary approach, involving gastroenterologists, hematologists, and pathologists, to the diagnosis and management of these neoplasms.
Different multiparametric MRI-based radiomics models for differentiating stage IA endometrial cancer from benign endometrial lesions: A multicenter study
Authors: Bi Qiu , Wang Yaoxin , Deng Yuchen , Liu Yang , Pan Yuanrui , Song Yang , Wu Yunzhu , Wu Kunhua
Published: August 2022

Purpose

The aim of this study was to evaluate the value of different multiparametric MRI-based radiomics models in differentiating stage IA endometrial cancer (EC) from benign endometrial lesions.

Methods

The data of patients with endometrial lesions from two centers were collected. The radiomics features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, and late contrast-enhanced T1-weighted imaging (LCE-T1WI). After data dimension reduction and feature selection, nine machine learning algorithms were conducted to determine which was the optimal radiomics model for differential diagnosis. The univariate analyses and logistic regression (LR) were performed to reduce valueless clinical parameters and to develop the clinical model. A nomogram using the radscores combined with clinical parameters was developed. Two integrated models were obtained respectively by the ensemble strategy and stacking algorithm based on the clinical model and optimal radiomics model. The area under the curve (AUC), clinical decisive curve (CDC), net reclassification index (NRI), and integrated discrimination index (IDI) were used to evaluate the performance and clinical benefits of the models.

Results

A total of 371 patients were incorporated. The LR model was the optimal radiomics model with the highest average AUC (0.854) and accuracy (0.802) in the internal and external validation groups (AUC = 0.910 and 0.798, respectively), and outperformed the clinical model (AUC = 0.739 and 0.592, respectively) or the radiologist (AUC = 0.768 and 0.628, respectively). The nomogram (AUC = 0.917 and 0.802, respectively) achieved better discrimination performance than the optimal radiomics model in two validation groups. The stacking model (AUC = 0.915) and ensemble model (AUC = 0.918) had a similar performance compared with the nomogram in the internal validation group, whereas the AUCs of the stacking model (AUC = 0.792) and ensemble model (AUC = 0.794) were lower than those of the nomogram and radiomics model in the external validation group. According to the CDC, NRI, and IDI, the optimal radiomics model, nomogram, stacking model, and ensemble model achieved good net benefits.

Conclusions

Multiparametric MRI-based radiomics models can non-invasively differentiate stage IA EC from benign endometrial lesions, and LR is the best machine learning algorithm. The nomogram presents excellent and stable diagnostic efficiency.
Influences on cognitive outcomes in adult patients with gliomas: A systematic review
Authors: Kirkman Matthew A. , Hunn Benjamin H. M. , Thomas Michael S. C. , Tolmie Andrew K.
Published: August 2022

People with brain tumors, including those previously treated, are commonly affected by a range of neurocognitive impairments involving executive function, memory, attention, and social/emotional functioning. Several factors are postulated to underlie this relationship, but evidence relating to many of these factors is conflicting and does not fully explain the variation in cognitive outcomes seen in the literature and in clinical practice. To address this, we performed a systematic literature review to identify and describe the range of factors that can influence cognitive outcomes in adult patients with gliomas. A literature search was performed of Ovid MEDLINE, PsychINFO, and PsycTESTS from commencement until September 2021. Of 9,998 articles identified through the search strategy, and an additional 39 articles identified through other sources, 142 were included in our review. The results confirmed that multiple factors influence cognitive outcomes in patients with gliomas. The effects of tumor characteristics (including location) and treatments administered are some of the most studied variables but the evidence for these is conflicting, which may be the result of methodological and study population differences. Tumor location and laterality overall appear to influence cognitive outcomes, and detection of such an effect is contingent upon administration of appropriate cognitive tests. Surgery appears to have an overall initial deleterious effect on cognition with a recovery in most cases over several months. A large body of evidence supports the adverse effects of radiotherapy on cognition, but the role of chemotherapy is less clear. To contrast, baseline cognitive status appears to be a consistent factor that influences cognitive outcomes, with worse baseline cognition at diagnosis/pre-treatment correlated with worse long-term outcomes. Similarly, much evidence indicates that anti-epileptic drugs have a negative effect on cognition and genetics also appear to have a role. Evidence regarding the effect of age on cognitive outcomes in glioma patients is conflicting, and there is insufficient evidence for gender and fatigue. Cognitive reserve, brain reserve, socioeconomic status, and several other variables discussed in this review, and their influence on cognition and recovery, have not been well-studied in the context of gliomas and are areas for focus in future research.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42017072976
Application of deep learning in the real-time diagnosis of gastric lesion based on magnifying optical enhancement videos
Authors: Ma Mingjun , Li Zhen , Yu Tao , Liu Guanqun , Ji Rui , Li Guangchao , Guo Zhuang , Wang Limei , Qi Qingqing , Yang Xiaoxiao , Qu Junyan , Wang Xiao , Zuo Xiuli , Ren Hongliang , Li Yanqing
Published: August 2022

Background and aim

Magnifying image-enhanced endoscopy was demonstrated to have higher diagnostic accuracy than white-light endoscopy. However, differentiating early gastric cancers (EGCs) from benign lesions is difficult for beginners. We aimed to determine whether the computer-aided model for the diagnosis of gastric lesions can be applied to videos rather than still images.

Methods

A total of 719 magnifying optical enhancement images of EGCs, 1,490 optical enhancement images of the benign gastric lesions, and 1,514 images of background mucosa were retrospectively collected to train and develop a computer-aided diagnostic model. Subsequently, 101 video segments and 671 independent images were used for validation, and error frames were labeled to retrain the model. Finally, a total of 117 unaltered full-length videos were utilized to test the model and compared with those diagnostic results made by independent endoscopists.

Results

Except for atrophy combined with intestinal metaplasia (IM) and low-grade neoplasia, the diagnostic accuracy was 0.90 (85/94). The sensitivity, specificity, PLR, NLR, and overall accuracy of the model to distinguish EGC from non-cancerous lesions were 0.91 (48/53), 0.78 (50/64), 4.14, 0.12, and 0.84 (98/117), respectively. No significant difference was observed in the overall diagnostic accuracy between the computer-aided model and experts. A good level of kappa values was found between the model and experts, which meant that the kappa value was 0.63.

Conclusions

The performance of the computer-aided model for the diagnosis of EGC is comparable to that of experts. Magnifying the optical enhancement model alone may not be able to deal with all lesions in the stomach, especially when near the focus on severe atrophy with IM. These results warrant further validation in prospective studies with more patients. A ClinicalTrials.gov registration was obtained (identifier number: NCT04563416).

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT04563416.
Efficacy and safety profile of COVID-19 mRNA vaccine in patients with hematological malignancies: Systematic review and meta-analysis
Authors: Rinaldi Ikhwan , Pratama Samuel , Wiyono Lowilius , Tandaju Jeremy Rafael , Wardhana Indy Larasati , Winston Kevin
Published: August 2022

Patient populations, including those with hematological malignancies, have different responses to COVID-19 vaccines. This study aimed to quantitatively analyze the efficacy and safety of COVID-19 mRNA vaccines in patients with hematological malignancies. Studies reporting on the efficacy and safety of COVID-19 mRNA vaccines in cohorts with hematological malignancies compared to healthy controls were systematically searched in four databases. Meta-analysis and subgroup analyses were performed to generate quantitative synthesis. Fifteen studies with 2,055 cohorts with hematological malignancies and 1,105 healthy subjects as control were included. After two doses of COVID-19 vaccination, only 60% of cohorts with hematological malignancies were seroconverted compared to healthy controls (RR 0.60; 95%CI 0.50–0.71). A single dose of the vaccine resulted in a significantly lower seroconversion rate (RR 0.30; 95%CI 0.16–0.54). Non-Hodgkin lymphoma cohorts had the lowest rate of seroconversion (RR 0.5; 95%CI 0.35–0.71) and those who received active treatments had lower immunological responses (RR 0.59; 95%CI 0.46–0.75). Antibody titers were lower in cohorts with hematological malignancies without any differences in adverse effects in both groups. In conclusion, cohorts with hematological malignancies showed a lower seroconversion rate and antibody titers after receiving COVID-19 mRNA vaccines. The type of malignancy and the status of treatment had a significant impact on the response to vaccination. The vaccines were shown to be safe for both patients with hematological malignancies and healthy controls. Booster doses and stricter health protocols might be beneficial for patient populations.
Assessing the robustness of radiomics/deep learning approach in the identification of efficacy of anti–PD-1 treatment in advanced or metastatic non-small cell lung carcinoma patients
Authors: Ren Qianqian , Xiong Fu , Zhu Peng , Chang Xiaona , Wang Guobin , He Nan , Jin Qianna
Published: August 2022

Administration of anti–PD-1 is now a standard therapy in advanced non-small cell lung carcinoma (NSCLC) patients. The clinical application of biomarkers reflecting tumor immune microenvironment is hurdled by the invasiveness of obtaining tissues despite its importance in immunotherapy. This study aimed to develop a robust and non-invasive radiomics/deep learning machine biomarker for predicting the response to immunotherapy in NSCLC patients. Radiomics/deep learning features were exacted from computed tomography (CT) images of NSCLC patients treated with Nivolumab or Pembrolizumab. The robustness of radiomics/deep learning features was assessed against various perturbations, then robust features were selected based on the Intraclass Correlation Coefficient (ICC). Radiomics/deep learning machine-learning classifiers were constructed by combining seven feature exactors, 13 feature selection methods, and 12 classifiers. The optimal model was selected using the mean area under the curve (AUC) and relative standard deviation (RSD). The consistency of image features against various perturbations was high (the range of median ICC: 0.78–0.97), but the consistency was poor in test–retest testing (the range of median ICC: 0.42–0.67). The optimal model, InceptionV3_RELF_Nearest Neighbors classifiers, had the highest prediction efficacy (AUC: 0.96 and RSD: 0.50) for anti–PD-1/PD-L1 treatment. Accuracy (ACC), sensitivity, specificity, precision, and F1 score were 95.24%, 95.00%, 95.50%, 91.67%, and 95.30%, respectively. For successful model robustification, tailoring perturbations for robustness testing to the target dataset is key. Robust radiomics/deep learning features, when paired with machine-learning methodologies, will work on the exactness and the repeatability of anticipating immunotherapy adequacy.
Clinical and molecular evaluation of patients with ovarian cancer in the context of drug resistance to chemotherapy
Authors: Opławski Marcin , Średnicka Agata , Niewiadomska Ewa , Boroń Dariusz , Januszyk Piotr , Grabarek Beniamin Oskar
Published: August 2022

The present study aimed to evaluate changes in the expression patterns at the gene and protein levels associated with drug resistance. The study group included 48 women who had a histopathologically confirmed diagnosis of stage I-IV ovarian cancer, they were divided into two subgroups (groups A and B). In group A, there were 36 patients in whom surgical treatment was supplemented with first-line chemotherapy according to current standards. Within this patient group, 5 had stage I (14%), 5 had stage II (14%), 25 had stage III (69%), and 1 had stage IV ovarian cancer (3%). Drug resistance was found after the third cycle of chemotherapy in 17 patients (71%) and after the sixth cycle in 7 patients (29%). Group B included 12 women with type I ovarian cancer, including 11 with stage I and 1 patient with stage IV ovarian cancer. The oncological treatment required only surgery. The control group (C) included 50 women in whom the uterus and adnexa were surgically removed for non-oncological reasons. Significantly higher levels of carcinoma antigen 125 CA-125 and human epididymis protein 4 HE4 were observed in group A and in menopausal women. Moreover, drug resistance was associated with significantly higher levels of CA-125 (p < 0.05). The genes UBA2, GLO1, STATH, and TUFT1 were differentiated in test samples from control samples. Moreover, drug resistance was associated with significantly higher expression of GLO1. The results of these assessments indicated the strong link between UBA2 and hsa-miR-133a-3p and hsa-miR-133b; GLO1 and hsa-miR-561-5p; STATH and hsa-miR-137-3p and hsa-miR-580-3p; and TUFT1 and hsa-miR-1233-3p and hsa-miR-2052. Correlation analysis showed a significant correlation between CA-125 and HE4 levels. Moreover, a significant correlation between TUFT1 mRNA and UBA2, GLO1, STATH (negative correlation), and TUFT1 in relation to CA-125 and HE4 (p < 0.05) was noted in all patients. In view of the lack of screening tests for ovarian cancer, the occurrence of the described correlation may be inscribed as an attempt to establish an assay that meets the criteria of a screening test and thus increase the early diagnosis of ovarian cancer.
PD-1 and LAG-3 expression in EBV-associated pediatric Hodgkin lymphoma has influence on survival
Authors: Jimenez Oscar , Mangiaterra Tamara , Colli Sandra , García Lombardi Mercedes , Preciado Maria Victoria , De Matteo Elena , Chabay Paola
Published: August 2022

In pediatric Hodgkin lymphoma (HL), the inability of the cytotoxic microenvironment induced by EBV presence to eliminate tumor cells could reflect the fact that the virus might be able to induce the expression of exhaustion markers to evade an immune response. Therefore, the expression of exhaustion markers in pediatric EBV–associated HL was evaluated. A balance between cytotoxic GrB and Th1 Tbet markers with regulatory Foxp3 was proved in EBV+ cases. In addition, exclusively in EBV-associated cHL, a correlation between PD-1 and LAG-3 expression was observed. Furthermore, those cases also displayed a trend to worse survival when they expressed LAG-3 and inferior event-free survival when both PD-1 and LAG-3 molecules were present. Therefore, even though a cytotoxic and inflammatory environment was supposed to be triggered by EBV presence in pediatric cHL, it seems that the virus may also induce the synergic effect of inhibitory molecules LAG-3 and PD-1 in this series. These observations may reflect the fact that the permissive and exhausted immune microenvironment succeeds to induce lymphomagenesis.
Inhibitory of active dual cancer targeting 5-Fluorouracil nanoparticles on liver cancer in vitro and in vivo
Authors: Cheng Mingrong , Dai Dejian
Published: August 2022

The chitosan (CS) material as the skeleton nano-drug delivery system has the advantages of sustained release, biodegradability, and modifiability, and has broad application prospects. In the previous experiments, biotin (Bio) was grafted onto CS to synthesize biotin-modified chitosan (Bio-CS), and it was confirmed that it has liver cancer targeting properties. Single-targeted nanomaterials are susceptible to pathological and physiological factors, resulting in a state of ineffective binding between ligands and receptors, so there is still room for improvement in the targeting of liver cancer. Based on the high expression of folate (FA) receptors on the surface of liver cancers, FA was grafted onto Bio-CS by chemical synthesis to optimize the synthesis of folic acid-modified biotinylated chitosan (FA-CS-Bio), verified by infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. The release of FA-CS-Bio/fluorouracil (5-FU) had three obvious stages: fast release stage, steady release stage, and slow release stage, with an obvious sustained release effect. Compared with Bio-CS, FA-CS-Bio could promote the inhibition of the proliferation and migration of liver cancer by 5-FU, and the concentration of 5-FU in hepatoma cells was significantly increased dose-dependently. Laser confocal experiments confirmed that FA-CS-Bio caused a significant increase in the fluorescence intensity in liver cancer cells. In terms of animal experiments, FA-CS-Bio increased the concentration of 5-FU in liver cancer tissue by 1.6 times on the basis of Bio-CS and the number of monophotons in liver cancer tissue by in vivo dynamic imaging experiments was significantly stronger than that of Bio-CS, indicating that the targeting ability of FA-CS-Bio was further improved. Compared with Bio-CS, FA-CS-Bio can significantly prolong the survival time of 5-FU in the orthotopic liver cancer transplantation model in mice, and has a relieving effect on liver function damage and bone marrow suppression caused by 5-FU. In conclusion, FA-CS-Bio nanomaterials have been optimized for synthesis. In vivo and in vitro experiments confirmed that FA-CS-Bio can significantly improve the targeting of liver cancer compared with Bio-CS. FA-CS-Bio/5-FU nanoparticles can improve the targeted inhibition of the proliferation and migration of liver cancer cells, prolong the survival period of tumor-bearing mice, and alleviate the toxic and side effects.
Olanzapine-induced lipid disturbances: A potential mechanism through the gut microbiota-brain axis
Authors: Zhu Zhenyu , Gu Yuxiu , Zeng Cuirong , Yang Man , Yu Hao , Chen Hui , Zhang Bikui , Cai Hualin
Published: August 2022

Objective: Long-term use of olanzapine can induce various side effects such as lipid metabolic disorders, but the mechanism remains to be elucidated. The gut microbiota-brain axis plays an important role in lipid metabolism, and may be related to the metabolic side effects of olanzapine. Therefore, we explored the mechanism by which olanzapine-induced lipid disturbances through the gut microbiota-brain axis.

Methods: Sprague Dawley rats were randomly divided into two groups, which underwent subphrenic vagotomy and sham surgery. Then the two groups were further randomly divided into two subgroups, one was administered olanzapine (10 mg/kg/day) by intragastric administration, and the other was administered normal saline by intragastric administration (4 ml/kg/day) for 2 weeks. The final changes in lipid parameters, gut microbes and their metabolites, and orexin-related neuropeptides in the hypothalamus were investigated among the different groups.

Results: Olanzapine induced lipid disturbances as indicated by increased weight gain, elevated ratio of white adipose tissue to brown adipose tissue, as well as increased triglyceride and total cholesterol. Olanzapine also increased the Firmicutes/Bacteroides (F/B) ratio in the gut, which was even aggravated by subphrenic vagotomy. In addition, olanzapine reduced the abundance of short-chain fatty acids (SCFAs) metabolism related microbiome and 5-hydroxytryptamine (5-HT) levels in the rat cecum, and increased the gene and protein expression of the appetite-related neuropeptide Y/agouti-related peptide (NPY/AgRP) in the hypothalamus.

Conclusion: The abnormal lipid metabolism caused by olanzapine may be closely related to the vagus nerve-mediated gut microbiota-brain axis.
Programming physical quantum systems with pulse-level control
Authors: Smith Kaitlin N. , Ravi Gokul Subramanian , Alexander Thomas , Bronn Nicholas T. , Carvalho André R. R. , Cervera-Lierta Alba , Chong Frederic T. , Chow Jerry M. , Cubeddu Michael , Hashim Akel , Jiang Liang , Lanes Olivia , Otten Matthew J. , Schuster David I. , Gokhale Pranav , Earnest Nathan , Galda Alexey
Published: August 2022

Quantum information processing holds great potential for pushing beyond the current frontiers in computing. Specifically, quantum computation promises to accelerate the solving of certain problems, and there are many opportunities for innovation based on proposed applications in chemistry, engineering, finance, and more. To harness the full power of quantum computing, however, we must not only place emphasis on manufacturing better qubits, advancing our algorithms, and developing quantum software. We must also refine device-level quantum control to scale to the fault tolerant quantum regime. On May 17–18, 2021, the Chicago Quantum Exchange (CQE) partnered with IBM Quantum and Super.tech to host the Pulse-level Quantum Control Workshop. At the workshop, representatives from academia, national labs, and industry addressed the importance of fine-tuning quantum processing at the physical layer. This work summarizes the key topics of the Pulse-level Quantum Control Workshop for the quantum community at large.
Salivary Testosterone and Cortisol Levels in Tunisian Elderly Male Patients With Mild Alzheimer’s Disease. Implications of Musical Therapy And/Or Physical Rehabilitation
Authors: Chéour Sarah , Chéour Chouaieb , Kilani Chiraz , Guemri Aymen , Zineddine Dawser , Khélifa Riadh , Supriya Rashmi , Bragazzi Nicola Luigi , Chéour Foued , Baker Julien S. , Gaied-Chortane Sabri
Published: August 2022

Changes in salivary testosterone (T) and cortisol (C) levels were assessed in elderly Tunisian male patients with mild Alzheimer’s disease (AD) subjected to music therapy and/or physical rehabilitation. Male patients with mild AD (N = 26; age = 76.23 ± 4.27 years; weight: 74.76 ± 5.36 kg) were randomly assigned into four groups for three 60-min sessions per week for 4 months; including Group1 or control group (Co) (n = 6); Group2 (n = 6), participated in physical rehabilitation (PR); Group3 (n = 7), subjected to music therapy (MT) and Group4 (n = 7), participated simultaneously in music therapy and physical rehabilitation (MT + PR). Salivary T levels increased (ηp2 = 0.7) and C levels decreased (ηp2 = 0.69), significantly (p < 0.001) in the PR, MT and MT + PR groups compared to the Co group respectively. Also, increases in salivary T levels and decreases in C levels in MT + PR group were greater compared to the other groups. MT increased T levels (p < 0.001) and decreased C levels (p < 0.05) to a greater extent than the PR group respectively. Changes in salivary T levels were positively (r = 0.83; p < 0.001) and C levels were negatively (r = -0.86; p < 0.001) correlated in the PR, MT and MT + PR groups with changes in MMSE in AD patients. This study highlights that combination of MT and PR holds potential to treat AD.