bluuebunny/crossref_metadata_2025 huggingface dataset:
Vagus nerve stimulation for refractory posttraumatic epilepsy: Efficacy and predictors of seizure outcome
Authors: Guo Mengyi , Wang Jing , Tang Chongyang , Deng Jiahui , Zhang Jing , Xiong Zhonghua , Liu Siqi , Guan Yuguang , Zhou Jian , Zhai Feng , Luan Guoming , Li Tianfu
Published: July 2022

Background

Traumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy.

Methods

We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy.

Results

In total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145–20.632) of VNS efficacy.

Conclusion

The results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy.
EEG biomarkers for the diagnosis and treatment of infantile spasms
Authors: Romero Milà Blanca , Remakanthakurup Sindhu Kavyakantha , Mytinger John R. , Shrey Daniel W. , Lopour Beth A.
Published: July 2022

Early diagnosis and treatment are critical for young children with infantile spasms (IS), as this maximizes the possibility of the best possible child-specific outcome. However, there are major barriers to achieving this, including high rates of misdiagnosis or failure to recognize the seizures, medication failure, and relapse. There are currently no validated tools to aid clinicians in assessing objective diagnostic criteria, predicting or measuring medication response, or predicting the likelihood of relapse. However, the pivotal role of EEG in the clinical management of IS has prompted many recent studies of potential EEG biomarkers of the disease. These include both visual EEG biomarkers based on human visual interpretation of the EEG and computational EEG biomarkers in which computers calculate quantitative features of the EEG. Here, we review the literature on both types of biomarkers, organized based on the application (diagnosis, treatment response, prediction, etc.). Visual biomarkers include the assessment of hypsarrhythmia, epileptiform discharges, fast oscillations, and the Burden of AmplitudeS and Epileptiform Discharges (BASED) score. Computational markers include EEG amplitude and power spectrum, entropy, functional connectivity, high frequency oscillations (HFOs), long-range temporal correlations, and phase-amplitude coupling. We also introduce each of the computational measures and provide representative examples. Finally, we highlight remaining gaps in the literature, describe practical guidelines for future biomarker discovery and validation studies, and discuss remaining roadblocks to clinical implementation, with the goal of facilitating future work in this critical area.
Electrical stimulation mapping in the medial prefrontal cortex induced auditory hallucinations of episodic memory: A case report
Authors: Long Qiting , Li Wenjie , Zhang Wei , Han Biao , Chen Qi , Shen Lu , Liu Xingzhou
Published: July 2022

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the prefrontal cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex (MPFC) is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network (DMN). However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography (SEEG) recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power (HGP) induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations.
Visceral adiposity-related dietary patterns and the risk of cardiovascular disease in Iranian adults: A population-based cohort study
Authors: Moslehi Nazanin , Rahimi Sakak Fatemeh , Mahdavi Maryam , Mirmiran Parvin , Azizi Fereidoun
Published: July 2022

Background

Visceral obesity is a significant predictor of cardiovascular disease (CVD). Diet may associate with CVD risk through its effects on visceral adiposity. This study aimed to find dietary patterns (DPs) related to indicators of visceral adiposity and to determine whether the DPs were associated with CVD risk.

Methods

This prospective study included 2,496 participants of the Tehran Lipid and Glucose Study (TLGS) without CVD, who were followed from the third study examination (2005–2008; baseline) to March 2018. DPs at baseline were determined using reduced rank regression (RRR) and partial least squares regression (PLS). The response variables were age and BMI-adjusted waist circumference (WC) and age-adjusted visceral adiposity index (VAI).

Results

Two and three DPs were retained with RRR and PLS, respectively. The first patterns of each method were mainly characterized by adjusted-WC (RRR: 10.8%, PLS: 8.6%); none of them were associated with CVD risk. The second pattern of RRR and the third pattern of PLS were mainly explained by adjusted-VAI (RRR: 3.3, PLS: 2.1%). After adjusting for CVD risk factors, the hazard ratios [95% confidence intervals (CI)] for CVD in the second and third tertiles of the RRR-pattern 2 were 1.76 (1.15, 2.69) and 1.55 (1.00, 2.43) vs. the first tertile (p-trend: 0.058). This pattern had high positive loadings for non-leafy vegetables, pickled vegetables, fried vegetables, and bread and high negative loadings for eggs, cakes, butter, jam-honey, red meat, poultry, fish, juice, non-fermented dairy, and fruits. Per one SD increase in PLS-pattern 3 score, the risk of CVD was 19% higher (95%CI = 3–38%). This positive association was also observed across tertiles of the pattern (p-trend: 0.032). This pattern was characterized by high intakes of leafy vegetables, non-leafy vegetables, organ meat, soft drinks, olive oil, pickled vegetables, fried vegetables, and bread and low intakes of biscuits, cakes, butter, eggs, and non-fermented dairy.

Conclusion

For each of the RRR and PLS approaches, a visceral-related DP that was positively linked to CVD was identified. These two patterns had a modest correlation. The pattern generated by PLS explained more variations in food groups and offered stronger evidence of association with CVD than the RRR-derived pattern.
Valerian essential oil for treating insomnia via the serotonergic synapse pathway
Authors: Wang Wenfei , Wang Yichun , Guo Qiuting , Li Huiting , Wang Zhaoqiang , Li Jia , Li Taotao , Tang Tiantian , Wang Yujiao , Jia Yanzhuo , Wang Yao , Zou Junbo , Shi Yajun , Guo Dongyan , Yang Ming , Zhang Xiaofei , Sun Jing
Published: July 2022

Valerian volatile oil can be used in the treatment of insomnia; however, the active components and mechanisms of action are currently unclear. Therefore, we used transcriptome sequencing and weight coefficient network pharmacology to predict the effective components and mechanism of action of valerian volatile oil in an insomnia model induced by intraperitoneal injection of para-Chlorophenylalanine (PCPA) in SD rats. Valerian essential oil was given orally for treatment and the contents of 5-hydroxytryptamine receptor 1 A (5-HT1AR), γ-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA), western blot, Polymerase Chain Reaction (PCR), and immunohistochemistry. The results showed that after treatment with valerian essential oil, insomnia rats showed significantly prolonged sleep duration and alleviated insomnia-induced tension and anxiety. Regarding the mechanism of action, we believe that caryophyllene in valerian essential oil upregulates the 5-HT1AR receptor to improve the activity or affinity of the central transmitter 5-HT, increase the release of 5-HT, couple 5-HT with a G protein coupled receptor, convert adenosine triphosphate (ATP) into cAMP (catalyzed by ADCY5), and then directly regulate the downstream pathway. Following pathway activation, we propose that the core gene protein kinase PKA activates the serotonergic synapse signal pathway to increase the expression of 5-HT and GABA, thus improving insomnia symptoms and alleviating anxiety. This study provides a theoretical basis for the application of valerian volatile oil in health food.
Taste peptides derived from Stropharia rugosoannulata fermentation mycelium and molecular docking to the taste receptor T1R1/T1R3
Authors: Li Wen , Chen Wanchao , Wu Di , Zhang Zhong , Yang Yan
Published: July 2022

This study identified the peptides in the fermentation mycelia of Stropharia rugosoannulata. The molecular weight of the peptides was below 3,000 Da. Heptapeptides to decapeptides were the main peptides in the fermentation mycelia of S. rugosoannulata. More than 50% of the peptides had salty and umami taste characteristics, and the long-chain peptides (decapeptides to 24 peptides) also played an essential role in the pleasant taste characteristics of mycelium. In the salty and umami peptide of S. rugosoannulata, the distribution of non-polar hydrophobic amino acids and polar-uncharged amino acids accounted for a relatively high proportion, and the proportion of polar-uncharged amino acids further increased, with the extension of the peptide chain. P, F, I, l, V, G, S, T, and D were the amino acids with a high proportion in the peptides. The taste peptides can bind to more than 60% of the active amino acid residues in the cavity-binding domain of the T1R1/T1R3 receptors. Hydrogen bond interaction was the primary mode of interaction between the peptides and the receptor. The first and second amino acid residues (such as S, V, E, K, G, and A) at the C-terminal and N-terminal of the peptides were easy to bind to T1R1/T1R3 receptors. Asp108, Asn150, Asp147, Glu301, Asp219, Asp243, Glu70, Asp218 in T1R1, and Glu45, Glu148, Glu301, Glu48, and Ala46 in TIR3 were the key active amino acid sites of taste peptides binding to T1R1/T1R3 receptors.
Differential responses to 223Ra and Alpha-particles exposure in prostate cancer driven by mitotic catastrophe
Authors: Guerra Liberal Francisco D. C. , Moreira Hugo , Redmond Kelly M. , O’Sullivan Joe M. , Alshehri Ali H. D. , Wright Timothy C. , Dunne Victoria L. , Campfield Caoimhghin , Biggart Sandra , McMahon Stephen J. , Prise Kevin M.
Published: July 2022

Introduction

Radium-223 (223Ra) has been shown to have an overall survival benefit in metastatic castration-resistant prostate cancer (mCRPC) involving bone. Despite its increased clinical usage, relatively little is known regarding the mechanism of action of 223Ra at the cellular level.

Methods

We evaluated the effects of 223Ra irradiation in a panel of cell lines and then compared them with standard X-ray and external alpha-particle irradiation, with a particular focus on cell survival and DNA damage repair kinetics.

Results

223Ra exposures had very high, cell-type-dependent RBE50% ranging from 7 to 15. This was significantly greater than external alpha irradiations (RBE50% from 1.4 to 2.1). These differences were shown to be partially related to the volume of 223Ra solution added, independent of the alpha-particle dose rate, suggesting a radiation-independent mechanism of effect. Both external alpha particles and 223Ra exposure were associated with delayed DNA repair, with similar kinetics. Additionally, the greater treatment efficacy of 223Ra was associated with increased levels of residual DNA damage and cell death by mitotic catastrophe.

Conclusions

These results suggest that 223Ra exposure may be associated with greater biological effects than would be expected by direct comparison with a similar dose of external alpha particles, highlighting important challenges for future therapeutic optimization.
In 18F-positron emission tomography/computed tomography-guided precision radiotherapy for centrally located non-small cell lung cancer, tumor related atelectasis is a prognostic factor of survival
Authors: Wang Nan , Qiao Yun , Song Yingqiu , Wang Zheng , Li Xia , Liu Chengsen , Wang Ye , Wu Yu , He Rong , Wang Chenyu , Ren Yangwu , Li Guang , Wang Tianlu
Published: July 2022

Purpose

Tumor related atelectasis(TRA) is an essential factor affecting survival that can cause chest pain, cough, hemoptysis, chest tightness, dyspnea, and even death. In the current study, we explored the possible impact of TRA on survival in cancer patients and the guiding significance of 18F-positron emission tomography/computed(PET/CT) in radiotherapy for patients with atelectasis tumors.

Methods

In this retrospective study, we analyzed the treatment model and survival of patients with centrally located non-small cell lung cancer(NSCLC) treated with radiotherapy at two medical centers between May 2005 and August 2019. We identified 152 eligible patients and used propensity score matching (1:1) to process the data to reduce confounding factors, data bias, and mal-distribution.

Results

We used propensity scores created well-matched groups of 57 patients overall with or without TRA. The one-year survival rate of all patients was 71.9%, and the two-year survival rate was 33.3%. Compared to the atelectasis group, the overall survival (OS) of patients in the non-atelectasis group was significantly prolonged (25 months vs. 17 months, p = 0.004), as well as in the atelectasis recovery group (28 months vs. 14 months, p = 0.008). In multivariate analysis, non-atelectasis was closely correlated with favorable OS (HR, 1.804 (−2.840); 95% CI, 1.145–2.840; p = 0.011).

Conclusion

PET/CT can accurately stage NSCLC and better guide the treatment of NSCLC complicated with atelectasis. Tumor-associated atelectasis in patients with centrally located NSCLC can lead to is a poor prognostic marker.
Deep learning auto-segmentation of cervical skeletal muscle for sarcopenia analysis in patients with head and neck cancer
Authors: Naser Mohamed A. , Wahid Kareem A. , Grossberg Aaron J. , Olson Brennan , Jain Rishab , El-Habashy Dina , Dede Cem , Salama Vivian , Abobakr Moamen , Mohamed Abdallah S. R. , He Renjie , Jaskari Joel , Sahlsten Jaakko , Kaski Kimmo , Fuller Clifton D.
Published: July 2022

Background/Purpose

Sarcopenia is a prognostic factor in patients with head and neck cancer (HNC). Sarcopenia can be determined using the skeletal muscle index (SMI) calculated from cervical neck skeletal muscle (SM) segmentations. However, SM segmentation requires manual input, which is time-consuming and variable. Therefore, we developed a fully-automated approach to segment cervical vertebra SM.

Materials/Methods

390 HNC patients with contrast-enhanced CT scans were utilized (300-training, 90-testing). Ground-truth single-slice SM segmentations at the C3 vertebra were manually generated. A multi-stage deep learning pipeline was developed, where a 3D ResUNet auto-segmented the C3 section (33 mm window), the middle slice of the section was auto-selected, and a 2D ResUNet auto-segmented the auto-selected slice. Both the 3D and 2D approaches trained five sub-models (5-fold cross-validation) and combined sub-model predictions on the test set using majority vote ensembling. Model performance was primarily determined using the Dice similarity coefficient (DSC). Predicted SMI was calculated using the auto-segmented SM cross-sectional area. Finally, using established SMI cutoffs, we performed a Kaplan-Meier analysis to determine associations with overall survival.

Results

Mean test set DSC of the 3D and 2D models were 0.96 and 0.95, respectively. Predicted SMI had high correlation to the ground-truth SMI in males and females (r>0.96). Predicted SMI stratified patients for overall survival in males (log-rank p = 0.01) but not females (log-rank p = 0.07), consistent with ground-truth SMI.

Conclusion

We developed a high-performance, multi-stage, fully-automated approach to segment cervical vertebra SM. Our study is an essential step towards fully-automated sarcopenia-related decision-making in patients with HNC.
Case report and literature review: Hemophagocytic lymphohistiocytosis in a pregnant woman with systemic lupus erythematosus with Syntaxin 11 gene defect
Authors: Ren Wei , Yang Siyuan , Liu Haiying , Pan Zhenglun , Li Zhao , Qiao Peng , Ma Hui
Published: July 2022

Hemophagocytic lymphohistiocytosis is an extremely rare occurrence during pregnancy. Early recognition of its signs and symptoms is critical for early intervention, and delays in diagnosis may be life-threatening. A 23-year-old nulliparous woman presented with a persistent fever as high as 39°C with bilateral edema of the lower limbs at 24 weeks of gestation. Typical laboratory findings included pancytopenia, high triglycerides, ferritin, transaminases, bilirubin, and hypoproteinemia. Active systemic lupus erythematosus was diagnosed using an autoimmune work-up and a Systemic Lupus Erythematosus Disease Activity Index 2000 score of 17 points. Her bone marrow aspirate revealed prominent hemophagocytosis; hence, HLH was confirmed. Genetic tests showed mutations in Syntaxin 11 mutations. Considering the potential impact of drugs on the fetus, the patient and her family members chose to terminate the pregnancy through medical induction of labor. Afterwards, her condition improved with immunosuppressive therapy.
A real-world study of anlotinib as third-line or above therapy in patients with her-2 negative metastatic breast cancer
Authors: Shao Yingbo , Luo Zhifen , Yu Yang , He Yaning , Liu Chaojun , Chen Qi , Zhu Fangyuan , Nie Bing , Liu Hui
Published: July 2022

Background

Antiangiogenic agents provides an optional treatment strategy for patients with metastatic breast cancer. The present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with HER-2 negative metastatic breast cancer.

Methods

Patients with HER-2 negative metastatic breast cancer who have failed from prior therapy and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2018 to December 2020 were retrospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety.

Results

47 patients with HER-2 negative metastatic breast cancer received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 10 patients achieved PR, 25 patients had SD and 12 patients had PD. The overall ORR and DCR were 21.3% and 74.5%, respectively. Subgroup analysis suggested that there were no statistically significant differences in ORR and DCR with respect to HR status (positive vs. negative), treatment programs (monotherapy vs. combination) and treatment type in combination group (chemotherapy vs. immunotherapy). The patients who did not received previously anti-angiogenesis therapy had superior DCR (84.8% vs. 50.0%, P=0.012). Median PFS and OS were 5.0 months (95% CI=4.3-5.7) and 21.0 (95% CI=14.9-27.1) months, respectively. The PFS (6.5m vs. 3.5m, P=0.042)and OS (28.2m vs. 12.6m, P=0.040) were better in HR positive patients than HR negative patients. And simultaneously, patients who received anlotinib combination therapy obtained better PFS (5.5m vs. 3.0m, P=0.045). The incidence of Grade 3-4 adverse events(AEs) was 31.9%.

Conclusions

Anlotinib monotherapy or combination therapy provide a viable third-line or above therapeutic strategy in patients with HER-2 negative metastatic breast cancer, a median PFS of 5.0 months was obtained with well tolerated toxicity.
The correlation between multimodal radiomics and pathology about thermal ablation lesion of rabbit lung VX2 tumor
Authors: Chen Jin , Yan Yuan , Lin QingFeng , Chen Jian , Chen Jie , Lin ZhengYu
Published: July 2022

Objective

To explore the correlation of CT-MRI pathology with lung tumor ablation lesions by comparing CT, MRI, and pathological performance of rabbit lung VX2 tumor after thermal ablation.

Methods

Thermal ablation including microwave ablation (MWA) and radiofrequency ablation (RFA) was carried out in 12 experimental rabbits with lung VX2 tumors under CT guidance. CT and MRI performance was observed immediately after ablation, and then the rabbits were killed and pathologically examined. The maximum diameter of tumors on CT before ablation, the central hypointense area on T2-weighted image (T2WI) after ablation, and the central hyperintense area on T1-weighted image (T1WI) after ablation and pathological necrosis were measured. Simultaneously, the maximum diameter of ground-glass opacity (GGO) around the lesion on CT after ablation, the surrounding hyperintense area on T2WI after ablation, the surrounding isointense area on T1WI after ablation, and the pathological ablation area were measured, and then the results were compared and analyzed.

Results

Ablation zones showed GGO surrounding the original lesion on CT, with a central hypointense and peripheral hyperintense zone on T2WI as well as a central hyperintense and peripheral isointense zone on T1WI. There was statistical significance in the comparison of the maximum diameter of the tumor before ablation with a central hyperintense zone on T1WI after ablation and pathological necrosis. There was also statistical significance in the comparison of the maximum diameter of GGO around the lesion on CT with the surrounding hyperintense zone on T2WI and isointense on T1WI after ablation and pathological ablation zone. There was only one residual tumor abutting the vessel in the RFA group.

Conclusions

MRI manifestations of thermal ablation of VX2 tumors in rabbit lungs have certain characteristics with a strong pathological association. CT combined with MRI multimodal radiomics is expected to provide an effective new method for clinical evaluation of the immediate efficacy of thermal ablation of lung tumors.
Prediction of prognosis and pathologic grade in follicular lymphoma using 18F-FDG PET/CT
Authors: Li Hongyan , Wang Min , Zhang Yajing , Hu Fan , Wang Kun , Wang Chenyang , Gao Zairong
Published: July 2022

Purpose

We investigated the utility of a new baseline PET parameter expressing lesion dissemination and metabolic parameters for predicting progression-free survival (PFS) and pathologic grade in follicular lymphoma (FL).

Methods

The baseline 18F-FDG PET/CT images of 126 patients with grade 1–3A FL were retrospectively analyzed. A novel PET/CT parameter characterizing lesion dissemination, the distance between two lesions that were furthest apart (Dmax), was calculated. The total metabolic tumor volume and total lesion glycolysis (TLG) were computed by using 41% of the maximum standardized uptake value (SUVmax) thresholding method.

Results

The 5-year PFS rate was 51.9% for all patients. In the multivariate analysis, high Dmax [P = 0.046; hazard ratio (HR) = 2.877], high TLG (P = 0.004; HR = 3.612), and elevated serum lactate dehydrogenase (P = 0.041; HR = 2.287) were independent predictors of PFS. A scoring system for prognostic stratification was established based on these three adverse factors, and the patients were classified into three risk categories: low risk (zero to one factor, n = 75), intermediate risk (two adverse factors, n = 29), and high risk (three adverse factors, n = 22). Patients in the high-risk group had a shorter 3-year PFS (21.7%) than those in the low- and intermediate-risk groups (90.6 and 44.6%, respectively) (P < 0.001). The C-index of our scoring system for PFS (0.785) was superior to the predictive capability of the Follicular Lymphoma International Prognostic Index (FLIPI), FLIPI2, and PRIMA-Prognostic Index (C-index: 0.628–0.701). The receiver operating characteristic curves and decision curve analysis demonstrated that the scoring system had better differentiation and clinical utility than these existing indices. In addition, the median SUVmax was significantly higher in grade 3A (36 cases) than in grades 1 and 2 FL (90 cases) (median: 13.63 vs. 11.45, P = 0.013), but a substantial overlap existed (range: 2.25–39.62 vs. 3.17–39.80).

Conclusion

TLG and Dmax represent two complementary aspects of the disease, capturing the tumor burden and lesion dissemination. TLG and Dmax are promising metrics for identifying patients at a high risk of progression or relapse. Additionally, SUVmax seems to have some value for distinguishing grade 3A from low-grade FL but cannot substitute for biopsy.
Identification of molecular subtypes, risk signature, and immune landscape mediated by necroptosis-related genes in non-small cell lung cancer
Authors: Zhu Jiaqi , Wang Jinjie , Wang Tianyi , Zhou Hao , Xu Mingming , Zha Jiliang , Feng Chen , Shen Zihao , Jiang Yun , Chen Jianle
Published: July 2022

Background

Non-small cell lung cancer (NSCLC) is a highly heterogeneous malignancy with an extremely high mortality rate. Necroptosis is a programmed cell death mode mediated by three major mediators, RIPK1, RIPK3, and MLKL, and has been shown to play a role in various cancers. To date, the effect of necroptosis on NSCLC remains unclear.

Methods

In The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we downloaded transcriptomes of lung adenocarcinoma (LUAD) patients and their corresponding clinicopathological parameters. We performed multi-omics analysis using consensus clustering based on the expression levels of 40 necroptosis-related genes. We constructed prognostic risk models and used the receiver operating characteristic (ROC) curves, nomograms, and survival analysis to evaluate prognostic models.

Results

With the use of consensus clustering analysis, two distinct subtypes of necroptosis were identified based on different mRNA expression levels, and cluster B was found to have a better survival advantage. Correlation results showed that necroptosis was significantly linked with clinical features, overall survival (OS) rate, and immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis confirmed that these differential genes were valuable in various cellular and biological functions and were significantly enriched in various pathways such as the P53 signaling pathway and cell cycle. We further identified three genomic subtypes and found that gene cluster B patients had better prognostic value. Multivariate Cox analysis identified the 14 best prognostic genes for constructing prognostic risk models. The high-risk group was found to have a poor prognosis. The construction of nomograms and ROC curves showed stable validity in prognostic prediction. There were also significant differences in tumor immune microenvironment, tumor mutational burden (TMB), and drug sensitivity between the two risk groups. The results demonstrate that the 14 genes constructed in this prognostic risk model were used as tumor prognostic biomarkers to guide immunotherapy and chemotherapy. Finally, we used qRT-PCR to validate the genes involved in the signature.

Conclusion

This study promotes our new understanding of necroptosis in the tumor microenvironment of NSCLC, mines prognostic biomarkers, and provides a potential value for guiding immunotherapy and chemotherapy.
Synchronous Microwave Ablation Combined With Cisplatin Intratumoral Chemotherapy for Large Non-Small Cell Lung Cancer
Authors: Huang Guanghui , Li Wenhong , Meng Min , Ni Yang , Han Xiaoying , Wang Jiao , Zou Zhigeng , Zhang Tiehong , Dai Jianjian , Wei Zhigang , Yang Xia , Ye Xin
Published: July 2022

Background

Microwave ablation (MWA) and intratumoral chemotherapy (ITC) are useful for treating tumors in animal models; however, their clinical use in patients with large non−small cell lung cancer (NSCLC) remains unknown. This retrospective study aimed to evaluate preliminary outcomes of MWA + ITC for large NSCLC.

Methods

From November 2015 to April 2020, a total of 44 NSCLC patients with a mean lesion diameter of 6.1 ± 1.5 cm were enrolled and underwent synchronous MWA + ITC procedures. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were progression-free survival (PFS), complications, overall survival (OS), and associated prognostic factors.

Results

The median follow-up time was 19.0 months. At the 1-month CT scan, complete tumor ablation was observed in 47.7% of cases. Median LPFS was 12.1 months; 1-, 2-, and 3-year LPFS rates were 51.2%, 27.9%, and 13.6%, respectively. A shorter LPFS was significantly associated with large lesions (HR 1.23, 95% CI 1.02–1.49; p = 0.032). Median PFS was 8.1 months; 1-, 2-, and 3-year PFS rates were 29.5%, 18.2%, and 9.1%, respectively. LPFS was significantly superior to PFS (p = 0.046). Median OS was 18.8 months. The 1-, 2-, 3-, and 5-year OS rates were 65.9%, 43.2%, 26.4%, and 10.0%, respectively. In univariate comparisons, high performance status (PS) score, smoking, and larger lesions were significantly correlated with poor survival. In multivariate analysis, advanced age, higher PS score, higher stage, larger lesion, and prior systematic treatment were independent prognostic factors for shorter OS. Adverse events were well tolerated and all patients recovered after appropriate intervention.

Conclusions

MWA + ITC is a safe and effective new modality of local treatment for large NSCLC and can significantly prolong LPFS.
Construction and validation of a cuproptosis-related lncRNA signature as a novel and robust prognostic model for colon adenocarcinoma
Authors: Xu Miaorong , Mu Jiayi , Wang Jiaojiao , Zhou Qin , Wang Jianwei
Published: July 2022

Background

Cuproptosis, a newly identified form of programmed cell death, is thought to play a role in tumorigenesis. Long non-coding RNAs (lncRNAs) are reported to be associated with tumor progression and prognosis in colon adenocarcinoma (COAD). However, the role and prognostic value of cuproptosis-related lncRNAs in COAD remains unknown. This study is devoted to constructing and validating a cuproptosis-related lncRNA signature that can predict COAD patient outcomes using bioinformatics methods.

Methods

The COAD mRNA and lncRNA expression profiles and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and 2,567 cuproptosis-related lncRNAs were obtained. A 10 cuproptosis-related-lncRNA prognostic signature was then constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression model and patients were divided into high- and low-risk groups. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and a nomogram were employed to evaluate the predictive power of the signature. The immune characteristics and drug sensitivity were also investigated based on the signature. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to verify the risk model. In vitro experiments were conducted to validate the expression of the ten lncRNAs during cuproptosis.

Results

The high-risk group was associated with shorter overall survival (OS) time in COAD patients (p<0.001). Multivariate Cox regression indicated that a high-risk score was an independent risk factor for poor prognosis (p<0.001). ROC curve analysis was performed to confirm the validity of the signature (area under the curve (AUC) at 3 years: 0.879). Gene Ontology (GO) enrichment analysis revealed that the signature was highly correlated with the immune response in biological processes. The immune function, the score of the immune cells, and the expression of immune checkpoints were significantly different between the two risk groups. Three drugs, LAQ824, FH535, YM155, were found to be more sensitive in the high-risk group. Finally, the expression levels of the ten lncRNAs comprising the signature were tested by qRT-PCR.

Conclusion

A ten-cuproptosis-related lncRNA signature was constructed that provided promising insights into personalized prognosis and drug selection among COAD patients.
A Global Collaboration to Develop and Pilot Test a Mobile Application to Improve Cancer Pain Management in Nepal
Authors: LeBaron Virginia T. , Horton Bethany J. , Adhikari Abish , Chapagain Sandhya , Dhakal Manita , Gongal Rajesh , Kattel Regina , Koirala Ganesh , Kutcher Anna , Hass Ben , Maurer Martha , Munday Daniel , Neupane Bijay , Sharma Krishna , Shilpakar Ramila , Shrestha Amuna , Shrestha Sudip , Thapa Usha , Dillingham Rebecca , Paudel Bishnu D.
Published: July 2022

Introduction

Quality palliative care, which prioritizes comfort and symptom control, can reduce global suffering from non-communicable diseases, such as cancer. To address this need, the Nepalese Association of Palliative Care (NAPCare) created pain management guidelines (PMG) to support healthcare providers in assessing and treating serious pain. The NAPCare PMG are grounded in World Health Organization best practices but adapted for the cultural and resource context of Nepal. Wider adoption of the NAPCare PMG has been limited due to distribution of the guidelines as paper booklets.

Methods

Building on a long-standing partnership between clinicians and researchers in the US and Nepal, the NAPCare PMG mobile application (“app”) was collaboratively designed. Healthcare providers in Nepal were recruited to pilot test the app using patient case studies. Then, participants completed a Qualtrics survey to evaluate the app which included the System Usability Scale (SUS) and selected items from the Mobile App Rating Scale (MARS). Descriptive and summary statistics were calculated and compared across institutions and roles. Regression analyses to explore relationships (α = 0.05) between selected demographic variables and SUS and MARS scores were also conducted.

Results

Ninety eight healthcare providers (n = 98) pilot tested the NAPCare PMG app. Overall, across institutions and roles, the app received an SUS score of 76.0 (a score > 68 is considered above average) and a MARS score of 4.10 (on a scale of 1 = poor, 5 = excellent). 89.8% (n = 88) “agreed” or “strongly agreed” that the app will help them better manage cancer pain. Age, years of experience, and training in palliative care were significant in predicting SUS scores (p-values, 0.0124, 0.0371, and 0.0189, respectively); institution was significant in predicting MARS scores (p = 0.0030).

Conclusion

The NAPCare PMG mobile app was well-received, and participants rated it highly on both the SUS and MARS. Regression analyses suggest end-user variables important to consider in designing and evaluating mobile apps in lower resourced settings. Our app design and pilot testing process illustrate the benefits of cross global collaborations to build research capacity and generate knowledge within the local context.
Non-myeloablative conditioning is sufficient to achieve complete donor myeloid chimerism following matched sibling donor bone marrow transplant for myeloproliferative leukemia virus oncogene (MPL) mutation-driven congenital amegakaryocytic thrombocytopenia: Case report
Authors: Oved Joseph Hai , Shah Yash B. , Venella Kimberly , Paessler Michele E. , Olson Timothy S.
Published: July 2022

Background

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare platelet production disorder caused mainly by loss of function biallelic mutations in myeloproliferative leukemia virus oncogene (MPL), the gene encoding the thrombopoietin receptor (TPOR). Patients with MPL-mutant CAMT are not only at risk for life-threatening bleeding events, but many affected individuals will also ultimately develop bone marrow aplasia owing to the absence of thrombopoietin/TPOR signaling required for maintenance of hematopoietic stem cells. Curative allogeneic stem cell transplant for patients with CAMT has historically used myeloablative conditioning; however, given the inherent stem cell defect in MPL-mutant CAMT, a less intensive regimen may prove equally effective with reduced morbidity, particularly in patients with evolving aplasia.

Methods

We report the case of a 2-year-old boy with MPL-mutant CAMT and bone marrow hypocellularity who underwent matched sibling donor bone marrow transplant (MSD-BMT) using a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and antithymocyte globulin (ATG).

Results

The patient achieved rapid trilinear engraftment and resolution of thrombocytopenia. While initial myeloid donor chimerism was mixed (88% donor), due to the competitive advantage of donor hematopoietic cells, myeloid chimerism increased to 100% by 4 months post-transplant. Donor chimerism and blood counts remained stable through 1-year post-transplant.

Conclusion

This experience suggests that non-myeloablative conditioning is a suitable approach for patients with MPL-mutant CAMT undergoing MSD-BMT and is associated with reduced risks of conditioning-related toxicity compared to traditional myeloablative regimens.
Cardiac manifestations in a Chinese cohort of fetuses from mothers with anti-Ro and anti-La antibodies
Authors: Wang Xin , Liu Xiao-wei , Han Ling , Li Meng-tao , Zhao Jiu-liang , Sun Lin , Han Jian-cheng , Zeng Xiao-feng , Tian Xin-ping , Zhao Ying , He Yi-hua
Published: July 2022

Objectives

To analyze the clinical characteristics, echocardiographic features, and prognosis of fetuses based on three groups of cardiac manifestations associated with maternal anti-Ro and anti-La antibodies in China. This study included three groups: the isolated-arrhythmia, isolated-endocardial fibroelastosis (EFE), and mixed groups.

Methods

We prospectively evaluated 36 fetuses with cardiac manifestations due to maternal anti-Ro and anti-La antibodies from our center between 2016 and 2020 in China. Clinical and echocardiographic data were collected.

Results

There were 13 patients (36%) in the isolated-arrhythmia group, eight (22%) in the isolated-EFE group, and 15 (42%) in the mixed group. All patients in the isolated-EFE group presented with mild EFE. Severe EFE was identified in four patients (27%) in the mixed group. Atrioventricular block (AVB) was more common in the isolated-arrhythmia group (13, 100%) than in the mixed group (6, 40%; p = 0.001). Moderate-severe mitral regurgitation (p = 0.006), dilated cardiomyopathy (DCM, p = 0.017), and low cardiovascular profile scores (p = 0.013) were more common in the mixed group than in the other two groups. Twenty-one mothers decided to terminate the pregnancy and 15 fetuses were born with regular perinatal treatment. They all survived at 1 year of age. One patient in the isolated-arrhythmia group and two in the mixed group required a pacemaker due to third-degree AVB or atrioventricular junctional rhythm. Five patients in the isolated-EFE group and five in the mixed group had no DCM or heart failure and the location of mild EFE was significantly reduced.

Conclusion

Fetal cardiac manifestations due to maternal anti-Ro and anti-La antibodies can be divided into three groups, i.e., the isolated-arrhythmia, isolated-EFE, and mixed groups. AVB usually occurs in the isolated-arrhythmia group. Severe EFE, moderate-severe mitral regurgitation, and DCM mainly appear in the mixed group. Location of mild EFE significantly reduces after birth and the outcome of fetuses with mild EFE depends on the presence of arrhythmia and its subtypes.
Endophytic and rhizospheric bacteria associated with Paspalum atratum and its potential for plant growth promotion with different phosphate sources
Authors: de Paula Ailton Ferreira , Cruz Felipe de Paula Nogueira , Dinato Naiana Barbosa , de Andrade Paulo Henrique Marques , de Moraes Amanda Carolina Prado , Junior Waldomiro Barioni , Bernardi Alberto Carlos de Campos , Vigna Bianca Baccili Zanotto , Fávero Alessandra Pereira , Lacava Paulo Teixeira
Published: July 2022

The genusPaspalumbelongs to the family Poaceae and has several species that are native to Brazil. ThePaspalumGermplasm Bank (GB) of the Brazilian Agricultural Research Corporation comprises approximately 450 accessions from 50 species. Among these accessions,Paspalum atratum(BGP 308) has economic potential for forage purposes. However, the endophytic and rhizospheric microbial communities within this accession and their ability to promote plant growth remain unknown. The present study aimed to isolate the endophytic and rhizospheric bacteria associated withP. atratumand to assess their potential for plant growth improvement, so-called plant growth-promoting bacteria (PGPB). For thein vitrotests, the ability of nitrogen-fixing bacteria (NFB), phosphate solubilization (PS) and indoleacetic acid (IAA) production were evaluated. A total of 116 endophytic and rhizosphere bacteria were obtained from the isolation. In thein vitrotests, 43 (37.00%) of these isolates showed positive NFB, PS, and IAA results. These isolates were identified by 16S rDNA sequencing. The phosphate solubilization index (PSI) ranged from 2 to 3.61, all 43 strains performed biological nitrogen fixation and the IAA production ranged from 12.85 to 431.41 μg ml−1. Eight of these 43 isolates were evaluatedin vivoin a greenhouse usingP. atratumcaryopsis. The pots were filled with soil prepared with three different phosphate sources and one control without phosphate. After growth, the plants were submitted to morphological, bromatological and chemical determination. Data were analyzed using analysis of variance (ANOVA) and principal component analysis (PCA). In thein vivotest, treatments 105 (Pseudomonassp.) and 458 (Pseudomonassp.) were the most significant for the crystalline phosphate source, 109 (Bacillussp.) for the sedimentary phosphate source and, as for the soluble phosphate source most treatments that received bacterial isolates had higher phosphorus content in the dry matter than the uninoculated soluble phosphate control. The 105FCR (crystalline phosphate + Pseudomonassp.), 109FSE (sedimentary phosphate + Bacillussp.), and 110 FSE (sedimentary phosphate + Enterobactersp.) treatments showed the best results for plant growth promotion. This work made it possible to determine the bacterial community associated withP. atratum(BGP308) and to obtain new potential plant growth-promoting strains.
Untargeted LC–MS/MS-Based Metabolomic Profiling for the Edible and Medicinal Plant Salvia miltiorrhiza Under Different Levels of Cadmium Stress
Authors: Yuan Jun , Liu Rongpeng , Sheng Shasha , Fu Haihui , Wang Xiaoyun
Published: July 2022

Salvia miltiorrhiza, a medicinal and edible plant, has been extensively applied to treat cardiovascular diseases and chronic hepatitis. Cadmium (Cd) affects the quality of S. miltiorrhiza, posing serious threats to human health. To reveal the metabolic mechanisms of S. miltiorrhiza's resistance to Cd stress, metabolite changes in S. miltiorrhiza roots treated with 0 (CK), 25 (T1), 50 (T2) and 100 (T3) mg kg−1 Cd by liquid chromatography coupled to mass spectrometry (LC–MS/MS) were investigated. A total of 305 metabolites were identified, and most of them were amino acids, organic acids and fatty acids, which contributed to the discrimination of CK from the Cd-treated groups. Among them, S. miltiorrhiza mainly upregulated o-tyrosine, chorismate and eudesmic acid in resistance to 25 mg kg−1 Cd; DL-tryptophan, L-aspartic acid, L-proline and chorismite in resistance to 50 mg kg−1 Cd; and L-proline, L-serine, L-histidine, eudesmic acid, and rosmarinic acid in resistance to 100 mg kg−1 Cd. It mainly downregulated unsaturated fatty acids (e.g., oleic acid, linoleic acid) in resistance to 25, 50, and 100 mg kg−1 Cd and upregulated saturated fatty acids (especially stearic acid) in resistance to 100 mg kg−1 Cd. Biosynthesis of unsaturated fatty acids, isoquinoline alkaloid, betalain, aminoacyl-tRNA, and tyrosine metabolism were the significantly enriched metabolic pathways and the most important pathways involved in the Cd resistance of S. miltiorrhiza. These data elucidated the crucial metabolic mechanisms involved in S. miltiorrhiza Cd resistance and the crucial metabolites that could be used to improve resistance to Cd stress in medicinal plant breeding.