bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Cell Infiltration and Relevant Gene Signatures in the Tumor Microenvironment that Significantly Associates With the Prognosis of Patients With Breast Cancer
Authors: Xu Qiang , Yan Xinghe , Han Zhezhu , Jin Xiuying , Jin Yongmin , Sun Honghua , Liang Junhua , Zhang Songnan
Published: February 2022

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in women. Recent studies have investigated the prognostic value of the tumor microenvironment (TME)-related genes in breast cancer. The purpose of this research is to identify the immune-associated prognostic signature for breast cancer evaluate the probability of their prognostic value and compare the current staging system. In this study, we comprehensively evaluated the infiltration patterns of TME in 1,077 breast cancer patients downloaded from TCGA by applying the ssGSEA method to the transcriptome of these patients. Thus, generated two groups of immune cell infiltration. Based on two groups of low infiltration and high infiltration immune cell groups, 983 common differentially expressed genes were found using the limma algorithm. In addition, studying potential mechanisms, the GSEA method was used to indicate some pathways with remarkable enrichment in two clusters of immune cell infiltration. Finally, the seven immune-associated hub genes with survival as prognostic signatures were identified by using univariate Cox, survival, and LASSO analyses and constructed a TME score. The prognostic value of the TME score was self-validated in the TCGA cohort and further validated in an external independent set from METABRIC and GEO database by time-dependent survival receiver operation. Univariate and multivariate analyses of clinicopathological characteristics indicated that the TME score was an independent prognostic factor. In conclusion, the proposed TME score model should be considered as a prognostic factor, similar to the current TNM stage, and the seven immune-related genes can be a valuable potential biomarker for breast cancer.
Steroid Sulfation in Neurodegenerative Diseases
Authors: Vitku Jana , Hill Martin , Kolatorova Lucie , Kubala Havrdova Eva , Kancheva Radmila
Published: February 2022

Steroid sulfation and desulfation participates in the regulation of steroid bioactivity, metabolism and transport. The authors focused on sulfation and desulfation balance in three neurodegenerative diseases: Alzheimer´s disease (AD), Parkinson´s disease (PD), and multiple sclerosis (MS). Circulating steroid conjugates dominate their unconjugated counterparts, but unconjugated steroids outweigh their conjugated counterparts in the brain. Apart from the neurosteroid synthesis in the central nervous system (CNS), most brain steroids cross the blood-brain barrier (BBB) from the periphery and then may be further metabolized. Therefore, steroid levels in the periphery partly reflect the situation in the brain. The CNS steroids subsequently influence the neuronal excitability and have neuroprotective, neuroexcitatory, antidepressant and memory enhancing effects. They also exert anti-inflammatory and immunoprotective actions. Like the unconjugated steroids, the sulfated ones modulate various ligand-gated ion channels. Conjugation by sulfotransferases increases steroid water solubility and facilitates steroid transport. Steroid sulfates, having greater half-lives than their unconjugated counterparts, also serve as a steroid stock pool. Sulfotransferases are ubiquitous enzymes providing massive steroid sulfation in adrenal zona reticularis and zona fasciculata.. Steroid sulfatase hydrolyzing the steroid conjugates is exceedingly expressed in placenta but is ubiquitous in low amounts including brain capillaries of BBB which can rapidly hydrolyze the steroid sulfates coming across the BBB from the periphery. Lower dehydroepiandrosterone sulfate (DHEAS) plasma levels and reduced sulfotransferase activity are considered as risk factors in AD patients. The shifted balance towards unconjugated steroids can participate in the pathophysiology of PD and anti-inflammatory effects of DHEAS may counteract the MS.
Efficient All-Optical Helicity Dependent Switching of Spins in a Pt/Co/Pt Film by a Dual-Pulse Excitation
Authors: Yamada Kihiro T. , Kimel Alexey V. , Prabhakara Kiran Horabail , Ruta Sergiu , Li Tian , Ando Fuyuki , Semin Sergey , Ono Teruo , Kirilyuk Andrei , Rasing Theo
Published: February 2022

All-optical helicity dependent switching (AO-HDS), deterministic control of magnetization by circularly polarized laser pulses, allows to efficiently manipulate spins without the need of a magnetic field. However, AO-HDS in ferromagnetic metals so far requires many laser pulses for fully switching their magnetic states. Using a combination of a short, 90-fs linearly polarized pulse and a subsequent longer, 3-ps circularly polarized pulse, we demonstrate that the number of pulses for full magnetization reversal can be reduced to four pulse pairs in a single stack of Pt/Co/Pt. The obtained results suggest that the dual-pulse approach is a potential route towards realizing efficient AO-HDS in ferromagnetic metals.
Fabric Classification Using a Finger-Shaped Tactile Sensor via Robotic Sliding
Authors: Wang Si-ao , Albini Alessandro , Maiolino Perla , Mastrogiovanni Fulvio , Cannata Giorgio
Published: February 2022

Tactile sensing endows the robots to perceive certain physical properties of the object in contact. Robots with tactile perception can classify textures by touching. Interestingly, textures of fine micro-geometry beyond the nominal resolution of the tactile sensors can also be identified through exploratory robotic movements like sliding. To study the problem of fine texture classification, we design a robotic sliding experiment using a finger-shaped multi-channel capacitive tactile sensor. A feature extraction process is presented to encode the acquired tactile signals (in the form of time series) into a low dimensional (≤7D) feature vector. The feature vector captures the frequency signature of a fabric texture such that fabrics can be classified directly. The experiment includes multiple combinations of sliding parameters, i.e., speed and pressure, to investigate the correlation between sliding parameters and the generated feature space. Results show that changing the contact pressure can greatly affect the significance of the extracted feature vectors. Instead, variation of sliding speed shows no apparent effects. In summary, this paper presents a study of texture classification on fabrics by training a simple k-NN classifier, using only one modality and one type of exploratory motion (sliding). The classification accuracy can reach up to 96%. The analysis of the feature space also implies a potential parametric representation of textures for tactile perception, which could be used for the adaption of motion to reach better classification performance.
Association Between Turning Mobility and Cognitive Function in Chronic Poststroke
Authors: Kuan Yi-Chun , Lin Li-Fong , Wang Chien-Yung , Hu Chia-Chen , Liang Pei-Jung , Lee Shu-Chun
Published: February 2022

Turning difficulties are common in patients with stroke. The detrimental effects of dual tasks on turning indicate a correlation between turning and cognition. Cognitive impairment is prevalent after stroke, and stroke patients with mild cognitive impairment had a poorer turning performance than did stroke patients with intact cognitive abilities. Therefore, we investigated the association between turning mobility and cognitive function in patients with chronic poststroke. Ninety patients with chronic stroke (>6 months post-stroke) were recruited. Angular velocity was assessed using wearable sensors during 180° walking turns and 360° turning on the spot from both sides. Global cognition and distinct cognitive domains were assessed using the Mini-Mental State Examination. In patients with stroke, turning mobility was significantly associated with global cognitive function and distinct cognitive domains, such as visuospatial ability and language. The balance function and lower limbs strength were mediators of the association between cognition and turning. The association highlights the complexity of the turning movement and dynamic motor and cognitive coordination necessary to safely complete a turn. However, our findings should be regarded as preliminary, and a thorough neuropsychological assessment to provide a valid description of distinct cognitive domains is required.
Deep Brain Stimulation for Refractory Temporal Lobe Epilepsy. Current Status and Future Trends
Authors: Velasco Francisco , Saucedo-Alvarado Pablo E. , Vazquez-Barron Daruny , Trejo David , Velasco Ana Luisa
Published: February 2022

A comparative analysis of the targets for deep brain stimulation (DBS) to treat refractory temporal lobe epilepsy and the rationale for its use is presented, with an emphasis on the latency to obtain the significant antiepileptic effect and the long-term seizure control. The analysis includes consideration of surgical techniques currently used to optimize antiseizure effects and decrease surgical risks. Seizure control is similar for programed DBS and DBS responsive to abnormal cortical or subcortical electroencephalogram (EEG) activity. There is no difference in the long-term seizure control between programmed and responsive and intermittent or continuous DBS. However, intermittent programed DBS may have a significant antiseizure effect starting in the first month when applied to a non-sclerotic tissue such as the parahippocampal cortex. DBS induces no neuropsychological deterioration.
Treatment of Third Branch Trigeminal Neuralgia With a Balloon Inflated in the Foramen Ovale
Authors: Lu Zhangfan , Wang Jiadong , Cao Yang , Sun Chenglong , Du Quan , Shen Yongfeng , Yu Wenhua , Du Yuanfeng
Published: February 2022

Objective

To investigate the efficacy of modified percutaneous balloon compression for simple third branch pain and its postoperative complications.

Methods

Clinical data and surgical records of 132 patients with third branch pain treated with percutaneous balloon compression from March 2015 to May 2019 were retrospectively analyzed, of which 81 cases were in the modified group and 51 cases were in the classic group. The modified technique was to compress again at the foramen ovale to enhance the compression in V3 after compression of the Gasserian ganglion.

Results

In the modified group, the overall therapeutic efficiency was 96.3%, with 77 patients (95.1%) having immediate postoperative pain relief and one patient (1.2%) having occasional pain without the need for medication. In the classic group, immediate postoperative pain relief was seen in 43 cases (84.3%), and two patients (3.9%) had occasional pain with no need for medication. The rate of complete pain relief was significantly higher in the modified group than in the classic group (P < 0.05). Postoperative follow-up ranged from 14 to 48 months. The pain-free rates were 77.8 and 54.9% in the modified and classic groups, respectively. The incidence of facial numbness in the region of the first branch was significantly lower than in the classic group (P < 0.001).

Conclusion

The modified procedure has significant advantages over the classic procedure in improving surgical efficacy, reducing postoperative recurrence rate, and decreasing postoperative numbness in the region, and can be used to treat simple trigeminal neuralgia in the third branch.
Blunted Post-COVID-19 Humoral Immunity in Patients With CNS Demyelinating Disorders on Anti-CD20 Treatments
Authors: Money Kelli M. , Baber Ursela , Saart Emma , Samaan Soleil , Sloane Jacob A.
Published: February 2022

With unclear characteristics of post-infection and post-vaccination immunity, the multiple sclerosis community lacks evidence to guide patients on their continued coronavirus disease 2019 (COVID-19) infection risk. As disease modifying treatments all modulate the immune system, we expect their use to alter acquired immunity to COVID-19, but the specific impact of individual treatments is unclear. To address this, we analyzed the patient and COVID-19 specific characteristics associated with post-infection humoral immunity in 58 patients with central nervous system (CNS) demyelinating disorders in the Boston metropolitan area. Univariate analysis of variance was performed using Mann Whitney U test for continuous variables, and Chi Square or Fisher Exact test for nominal variables. Univariate and stepwise multivariate nominal logistic regression identified clinical characteristics associated with COVID-19 specific nucleocapsid IgG antibody formation post-infection. Our cohort demonstrated a 42% post-infection seropositive rate with a significantly higher rate observed with shorter duration between infection and antibody collection and use of natalizumab over no/other treatment. Use of anti-CD20 treatments compared to no/other treatment was associated with a significantly lower rate of seropositivity. However, only shorter duration between infection and antibody collection as well as use of no/other treatment compared to anti-CD20 treatment were found to be independently associated with increased likelihood of post-infection seropositivity. Additionally, we demonstrate durability of antibody response up to 9 months in a small subset of patients. Thus, our data supports that patients with CNS demyelinating disorders regardless of DMT are able to form a measurable antibody response after COVID-19 infection, and that patients on anti-CD20 treatments form less robust immunity after COVID-19 infection.
Learning Words While Listening to Syllables: Electrophysiological Correlates of Statistical Learning in Children and Adults
Authors: Soares Ana Paula , Gutiérrez-Domínguez Francisco-Javier , Lages Alexandrina , Oliveira Helena M. , Vasconcelos Margarida , Jiménez Luis
Published: February 2022

From an early age, exposure to a spoken language has allowed us to implicitly capture the structure underlying the succession of speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), the ability to pick up patterns in the sensory environment without intention or reinforcement, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language, including the discovery of word boundaries in the continuous acoustic stream. Although extensive evidence has been gathered from artificial languages experiments showing that children and adults are able to track the regularities embedded in the auditory input, as the probability of one syllable to follow another syllable in the speech stream, the developmental trajectory of this ability remains controversial. In this work, we have collected Event-Related Potentials (ERPs) while 5-year-old children and young adults (university students) were exposed to a speech stream made of the repetition of eight three-syllable nonsense words presenting different levels of predictability (high vs. low) to mimic closely what occurs in natural languages and to get new insights into the changes that the mechanisms underlying auditory statistical learning (aSL) might undergo through the development. The participants performed the aSL task first under implicit and, subsequently, under explicit conditions to further analyze if children take advantage of previous knowledge of the to-be-learned regularities to enhance SL, as observed with the adult participants. These findings would also contribute to extend our knowledge of the mechanisms available to assist SL at each developmental stage. Although behavioral signs of learning, even under explicit conditions, were only observed for the adult participants, ERP data showed evidence of online segmentation in the brain in both groups, as indexed by modulations in the N100 and N400 components. A detailed analysis of the neural data suggests, however, that adults and children rely on different mechanisms to assist the extraction of word-like units from the continuous speech stream, hence supporting the view that SL with auditory linguistic materials changes through development.
Translationally Relevant Magnetic Resonance Imaging Markers in a Ferret Model of Closed Head Injury
Authors: Hutchinson Elizabeth B. , Romero-Lozano Anakaren , Johnson Hannah R. , Knutsen Andrew K. , Bosomtwi Asamoah , Korotcov Alexandru , Shunmugavel Anandakumar , King Sarah G. , Schwerin Susan C. , Juliano Sharon L. , Dardzinski Bernard J. , Pierpaoli Carlo
Published: February 2022

Pre-clinical models of traumatic brain injury (TBI) have been the primary experimental tool for understanding the potential mechanisms and cellular alterations that follow brain injury, but the human relevance and translational value of these models are often called into question. Efforts to better recapitulate injury biomechanics and the use of non-rodent species with neuroanatomical similarities to humans may address these concerns and promise to advance experimental studies toward clinical impact. In addition to improving translational aspects of animal models, it is also advantageous to establish pre-clinical outcomes that can be directly compared with the same outcomes in humans. Non-invasive imaging and particularly MRI is promising for this purpose given that MRI is a primary tool for clinical diagnosis and at the same time increasingly available at the pre-clinical level. The objective of this study was to identify which commonly used radiologic markers of TBI outcomes can be found also in a translationally relevant pre-clinical model of TBI. The ferret was selected as a human relevant species for this study with folded cortical geometry and relatively high white matter content and the closed head injury model of engineered rotation and acceleration (CHIMERA) TBI model was selected for biomechanical similarities to human injury. A comprehensive battery of MRI protocols based on common data elements (CDEs) for human TBI was collected longitudinally for the identification of MRI markers and voxelwise analysis of T2, contrast enhancement and diffusion tensor MRI values. The most prominent MRI findings were consistent with focal hemorrhage and edema in the brain stem region following high severity injury as well as vascular and meningeal injury evident by contrast enhancement. While conventional MRI outcomes were not highly conspicuous in less severe cases, quantitative voxelwise analysis indicated diffusivity and anisotropy alterations in the acute and chronic periods after TBI. The main conclusions of this study support the translational relevance of closed head TBI models in intermediate species and identify brain stem and meningeal vulnerability. Additionally, the MRI findings highlight a subset of CDEs with promise to bridge pre-clinical studies with human TBI outcomes.
Omega-3 Fatty Acids Improve Functionality of High-Density Lipoprotein in Individuals With High Cardiovascular Risk: A Randomized, Parallel, Controlled and Double-Blind Clinical Trial
Authors: Cartolano Flávia De Conti , Dias Gabriela Duarte , Miyamoto Sayuri , Damasceno Nágila Raquel Teixeira
Published: February 2022

Omega-3 (ω-3) fatty acids have been extensively studied for primary and secondary prevention of cardiovascular health, but their ability to modulate HDL functionality remains unclear. The purpose of this study was to investigate the role of ω-3, rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA), on HDL functionality. For that, 147 individuals with high cardiovascular risk were randomized in ω-3 (1 g of fish oil each - 370 mg of EPA and 230 mg of DHA, 3 times per day total EPA+DHA = 1,800 mg) or ω-6 groups (1 g of sunflower oil each - 760 mg of linoleic acid, 3 times per day; total linoleic acid = 2,280 mg). Fasting blood samples were collected at baseline time and after 8 weeks of follow-up and, and the lipid profile and glucose metabolism were evaluated from plasma. From HDL, the fatty acid profile, apolipoproteins (Apo AI, CII and CIII), paraoxonase-1 (PON1), cholesteryl ester transfer protein (CETP), subfractions and antioxidant activity were investigated. Omega-3 improved large HDL (HDL = 28.7%) and reduced small HDL (HDL10 = −10.6%) and the non-esterified fatty acids in HDL (NEFAs-HDL) level (−16.2%). A significant reduction in CETP activity was observed in the ω-3group (Δ ω-6 = 3.60 pmol/ul/h and Δ ω-3 = −1.99 pmol/ul/h; p = 0.044). The antioxidant capacity estimated by Lag time analysis did not change after the ω-3intervention. Changes in PON1 and Apo AI were inversely associated with increased incorporation of EPA (AOR = 0.446; IC = 0.200–0.994) and DHA (AOR = 0.351; IC = 0.150–0.821) in HDL, respectively. Cardioprotective profile obtained by pooled fatty acids analysis was related to a decrease in Apo CIII (r = −0.638; p = 0.002) and CETP (r = −0.341; p = 0.012) and an increase in Apo CII (r = 0.448; p = 0.042) and PON1 (r = 0.388; p = 0.003). In conclusion, omega-3 was effective in the reduction of cardiovascular risk associated with HDL functionality by size improvement and changes in its lipid, antioxidant and enzyme composition.
Multi-Omic Analysis in a Metabolic Syndrome Porcine Model Implicates Arachidonic Acid Metabolism Disorder as a Risk Factor for Atherosclerosis
Authors: Xu Song-Song , Zhang Xiu-Ling , Liu Sha-Sha , Feng Shu-Tang , Xiang Guang-Ming , Xu Chang-Jiang , Fan Zi-Yao , Xu Kui , Wang Nan , Wang Yue , Che Jing-Jing , Liu Zhi-Guo , Mu Yu-Lian , Li Kui
Published: February 2022

Background

The diet-induced gut microbiota dysbiosis has been suggested as a major risk factor for atherothrombosis, however, the detailed mechanism linking these conditions is yet to be fully understood.

Methods

We established a long-term excessive-energy diet-induced metabolic syndrome (MetS) inbred Wuzhishan minipig model, which is characterized by its genetic stability, small size, and human-like physiology. The metabolic parameters, atherosclerotic lesions, gut microbiome, and host transcriptome were analyzed. Metabolomics profiling revealed a linkage between gut microbiota and atherothrombosis.

Results

We showed that white atheromatous plaque was clearly visible on abdominal aorta in the MetS model. Furthermore, using metagenome and metatranscriptome sequencing, we discovered that the long-term excessive energy intake altered the local intestinal microbiota composition and transcriptional profile, which was most dramatically illustrated by the reduced abundance of SCFAs-producing bacteria including Bacteroides, Lachnospiraceae, and Ruminococcaceae in the MetS model. Liver and abdominal aorta transcriptomes in the MetS model indicate that the diet-induced gut microbiota dysbiosis activated host chronic inflammatory responses and significantly upregulated the expression of genes related to arachidonic acid-dependent signaling pathways. Notably, metabolomics profiling further revealed an intimate linkage between arachidonic acid metabolism and atherothrombosis in the host-gut microbial metabolism axis.

Conclusions

These findings provide new insights into the relationship between atherothrombosis and regulation of gut microbiota via host metabolomes and will be of potential value for the treatment of cardiovascular diseases in MetS.
Prevalence and Prognostic Significance of Malnutrition in Hypertensive Patients in a Community Setting
Authors: Yang Zhi-wen , Wei Xue-biao , Fu Bing-qi , Chen Ji-yan , Yu Dan-qing
Published: February 2022

Background

Malnutrition is a significantly poor prognostic factor for a variety of cardiovascular diseases. However, its prevalence and prognostic value in hypertensive patients is still unclear. The present study sought to determine the prevalence and prognostic value of malnutrition in hypertensive patients in a community setting.

Methods

We included 9,949 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) (2005–2014). The Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Naples Prognostic Score (NPS) were applied to assess the nutritional status of participants. A Cox regression model was established to examine the association between malnutrition and cardiovascular and all-cause mortality.

Results

In all, 19.9, 3.9, and 82.9% hypertensive patients were considered to have malnutrition as evaluated by the CONUT, NRI, and NPS, respectively. Malnutrition assessed by CONUT and NRI was independently associated with cardiovascular mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.41 (1.04–1.91) and 5.79 (2.34–14.29) for CONUT; 2.60 (1.34–5.07) and 3.30 (1.66–6.56) for NRI (all P < 0.05), and for all-cause mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.48 (1.30–1.70) and 4.87 (3.40–6.98) for CONUT; 1.72 (1.24–2.39) and 2.60 (1.96–3.44) for NRI (all P < 0.01). Naples Prognostic Score could only independently predict all-cause mortality.

Conclusions

Malnutrition was common among hypertensive patients and was closely associated with both long-term cardiovascular and all-cause mortality.
Association Between Egg Consumption and Dementia Risk in the EPIC-Spain Dementia Cohort
Authors: Margara-Escudero Hernando J. , Zamora-Ros Raul , de Villasante Izar , Crous-Bou Marta , Chirlaque María-Dolores , Amiano Pilar , Mar Javier , Barricarte Aurelio , Ardanaz Eva , Huerta José María
Published: February 2022

Background

Current evidence suggests that egg composition might have potential neuroprotective effects. Our aim was to determine the association between egg consumption and the risk of dementia in a Mediterranean population.

Methods

This study was carried out in 3 centers from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort, i.e., 25,015 participants aged 30–70 years, recruited in 1992–1996, and followed up for a mean of 21.5 years.

Results

A total of 774 incident dementia cases were diagnosed and validated, of which 518 were Alzheimer's disease (AD). Data on egg consumption were estimated using a validated dietary history questionnaire at recruitment. Cox proportional hazards models, adjusted for confounders, were used in the analyses. No association was observed between egg consumption and either total dementia [hazard ratio between extreme quartiles (HRQ4vs.Q1: 1.05; 95% CI 0.85–1.31; p-trend = 0.93)] or AD (HRQ4vs.Q1 0.93; 95% CI 0.72–1.21; p-trend = 0.50) risks. After dividing the population by adherence to the relative Mediterranean diet (rMED) score, a borderline inverse association was found between egg intake and both total dementia (HRQ4vs.Q1: 0.52; 95% CI 0.30–0.90; p-trend = 0.10) and AD (HRQ4vs.Q1: 0.52; 95% CI 0.27–1.01; p-trend = 0.13) risks within participants with low adherence to rMED score. However, no association was observed in participants with medium and high adherence to rMED score.

Conclusion

This prospective study suggests that egg consumption is associated with a reduced risk of dementia, and specifically of AD, in the adult population with low adherence to rMED score; whereas it has no impact in subjects with moderate and high MD adherence.
Establishing a Macrophage Phenotypic Switch-Associated Signature-Based Risk Model for Predicting the Prognoses of Lung Adenocarcinoma
Authors: Chen Jun , Zhou Chao , Liu Ying
Published: February 2022

Background

Tumor-associated macrophages are important components of the tumor microenvironment, and the macrophage phenotypic switch has been shown to correlate with tumor development. However, the use of a macrophage phenotypic switch-related gene (MRG)-based prognosis signature for lung adenocarcinoma (LADC) has not yet been investigated.

Methods

In total, 1,114 LADC cases from two different databases were collected. The samples from TCGA were used as the training set (N = 490), whereas two independent datasets (GSE31210 and GSE72094) from the GEO database were used as the validation sets (N = 624). A robust MRG signature that predicted clinical outcomes of LADC patients was identified through multivariate COX and Lasso regression analysis. Gene set enrichment analysis was applied to analyze molecular pathways associated with the MRG signature. Moreover, the fractions of 22 immune cells were estimated using CIBERSORT algorithm.

Results

An eight MRG-based signature comprising CTSL, ECT2, HCFC2, HNRNPK, LRIG1, OSBPL5, P4HA1, and TUBA4A was used to estimate the LADC patients’ overall survival. The MRG model was capable of distinguishing high-risk patients from low-risk patients and accurately predict survival in both the training and validation cohorts. Subsequently, the eight MRG-based signature and other features were used to construct a nomogram to better predict the survival of LADC patients. Calibration plots and decision curve analysis exhibited good consistency between the nomogram predictions and actual observation. ROC curves displayed that the signature had good robustness to predict LADC patients’ prognostic outcome.

Conclusions

We identified a phenotypic switch-related signature for predicting the survival of patients with LADC.
Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules
Authors: Xie Shaonan , Li Shaoteng , Deng Huiyan , Han Yaqing , Liu Guangjie , Liu Qingyi
Published: February 2022

Background

Synchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis.

Methods

SMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients’ need to undergo whole-body PET/CT and brain MRI examination.

Results

A total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted.

Conclusion

For SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.
Is Quantification of Measurable Clonal Plasma Cells in Stem Cell Grafts (gMRD) Clinically Meaningful?
Authors: Cengiz Seval Guldane , Beksac Meral
Published: February 2022

With the introduction of more effective novel therapies, the prognosis of multiple myeloma (MM) has improved significantly over the past decade, resulting with a significant proportion of patients achieving durable remissions that may reach even more than 10 years. Several studies demonstrated that the real prognostic value of complete remission (CR) relies on sustained undetectable minimal residual disease (MRD). Additionally, advances in MRD detection methods used for the detection of clonal plasma cells (cPC) inside or outside the bone marrow have also improved the value of MRD. The use of peripheral blood for MRD detection could be an effective method that overcomes the spatial heterogeneity and invasive intervention with recurrent bone marrow aspirations. During the last two decades, many groups have investigated the role of circulating plasma cells (CPCs) at diagnosis. As also presented by multiple groups during the recent ASH 2021 annual meeting, CPCs are becoming recognized as an independent prognostic factor. In addition, measurement of post-induction residual plasma cells in the stem cell graft is identified as another option for MRD assessment. Earlier studies in the era of less intensive induction regimens attempts to analyze the level of CPC contamination in the graft was shown to contribute to myeloma relapse and progression. According to these recent results, higher graft purity has been found to be in concordance with deeper responses. As expected, graft minimal residual disease (gMRD) may reflect the efficacy of induction as an additional response assessment tool. Although gMRD is a non-invasive approach, it has not gained sufficient support for routine use. In view of the hurdles related to monoclonal protein assessments, high-sensitivity cellular component measurement continues to possess its value as an end point for therapeutic efficacy. In this review, we will present a structural framework for MRD testing in peripheral blood stem cell autografts in MM and review the clinical integration into MM management.
A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis
Authors: Leite Carlos Heli Bezerra , Lopes Carlos Diego Holanda , Leite Caio Abner Vitorino Gonçalves , Terceiro Dulce Andrade , Lima Gabriel Silva , Freitas Jéssica Andrade , Cunha Fernando Queiroz , Almeida Paulo Roberto Carvalho , Wong Deysi Viviana Tenazoa , Lima-Júnior Roberto César Pereira
Published: February 2022

Background

Radiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.

Objective

The present study then aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis.

Material/Methods

C57BL/6 male mice were subjected to HDR (radiation source: iridium-192 [Ir-192]) through a cylindrical propylene tube inserted 2 cm far from the anal verge into the rectum. The animals received radiation doses once a day for three consecutive days (fractions of 9.5 Grays [Gy]), 3.0 mm far from the applicator surface. The sham group received only the applicator with no radiation source. The survival rate was recorded, and a colonoscopy was performed to confirm the tissue lesion development. Following euthanasia, samples of the rectum were collected for histopathology, cytokines dosage (IL-6 and KC), and immunohistochemical analysis (TNF-α and COX-2).

Results

HDR significantly reduced animals’ survival ten days post first radiation exposure (14% survival vs. 100% in the non-irradiated group). Day seven was then used for further investigation. Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P < 0.05 vs. the control group). The tissue damage was accompanied by an inflammatory response, marked by increased KC and IL-6 tissue levels, and immunostaining for TNF-α and COX-2 (P < 0.05 vs. control group).

Conclusions

We established a novel animal model of actinic proctitis induced by HDR brachytherapy, marked by inflammatory damage and low animal mortality.
A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects
Authors: Ferini Gianluca , Castorina Paolo , Valenti Vito , Illari Salvatore Ivan , Sachpazidis Ilias , Castorina Luigi , Marrale Maurizio , Pergolizzi Stefano
Published: February 2022

Introduction

Metastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit–risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models.

Methods

We treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed.

Results

We observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system.

Conclusions

PET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system’s role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.
The Changing Landscape of Systemic Treatment for Cervical Cancer: Rationale for Inhibition of the TGF-β and PD-L1 Pathways
Authors: Birrer Michael J. , Fujiwara Keiichi , Oaknin Ana , Randall Leslie , Ojalvo Laureen S. , Valencia Christian , Ray-Coquard Isabelle
Published: February 2022

Cervical cancer is one of the most common and lethal cancers among women worldwide. Treatment options are limited in patients with persistent, recurrent, or metastatic cervical cancer, with <20% of women living >5 years. Persistent human papillomavirus (HPV) infection has been implicated in almost all cases of cervical cancer. HPV infection not only causes normal cervical cells to transform into cancer cells, but also creates an immunosuppressive environment for cancer cells to evade the immune system. Recent clinical trials of drugs targeting the PD-(L)1 pathway have demonstrated improvement in overall survival in patients with cervical cancer, but only 20% to 30% of patients show overall survival benefit beyond 2 years, and resistance to these treatments remains common. Therefore, novel treatment strategies targeting HPV infection–associated factors are currently being evaluated in clinical trials. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human immunoglobulin G1 monoclonal antibody that blocks PD-L1. Early clinical trials of bintrafusp alfa have shown promising results in patients with advanced cervical cancer.
Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside
Authors: Jafari Ameneh , Babajani Amirhesam , Sarrami Forooshani Ramin , Yazdani Mohsen , Rezaei-Tavirani Mostafa
Published: February 2022

Cancer is a multifaceted global health issue and one of the leading causes of death worldwide. In recent years, medical science has achieved great advances in the diagnosis and treatment of cancer. Despite the numerous advantages of conventional cancer therapies, there are major drawbacks including severe side effects, toxicities, and drug resistance. Therefore, the urgency of developing new drugs with low cytotoxicity and treatment resistance is increasing. Antimicrobial peptides (AMPs) have attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tumor cells with less toxicity to normal tissues. In this review, we present the structure, biological function, and underlying mechanisms of AMPs. The recent experimental studies and clinical trials on anticancer peptides in different cancer types as well as the challenges of their clinical application have also been discussed.
Clinical Efficacy and Safety of Traditional Medicine Preparations Combined With Chemotherapy for Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis
Authors: Hu Jiaqi , Jiang Juling , Liu Rui , Cheng Mengqi , Zhu Guanghui , He Shulin , Shi Bolun , Zhao Yuwei , He Zhongning , Yu Huibo , Zhang Xing , Zheng Honggang , Hua Baojin
Published: February 2022

Background

Traditional medicine preparations (TMPs) combined with chemotherapy is widely used for patients with advanced pancreatic cancer (APC); however, its efficacy and safety are still unclear. The purpose of this meta-analysis was to evaluate the clinical efficacy and safety of TMPs combined with chemotherapy for the treatment of APC.

Methods

A systematic search of eight electronic databases for randomized controlled trials (RCTs) was conducted from inception to October 15, 2021. Tumor response was identified as primary outcome, whereas quality of life (QoL), cancer biomarkers, and adverse drug reactions (ADRs) were identified as secondary outcomes. Quality of the evidence for each outcome was evaluated by GRADE profiler.

Results

In total, 31 RCTs involving 1,989 individuals were included. This meta-analysis showed that TMPs combined with chemotherapy significantly improved the objective response rate (ORR) (RR=1.64, 95% CI [1.43 to 1.88], p <0.00001), disease control rate (DCR) (RR=1.29, 95% CI [1.21 to 1.38], p <0.00001), and QoL (continuous data: SMD=0.81, 95% CI [0.44 to 1.18], p <0.0001, dichotomous data: RR=1.44, 95% CI [1.22 to 1.70], p<0.0001), compared to those with chemotherapy alone. In addition, the combined treatment group also had lower levels of CA19-9 (SMD=-0.46, 95% CI [-0.90 to -0.02], p=0.04) and CEA (SMD=-0.55, 95% CI [-0.93 to -0.17], p=0.004). Moreover, TMPs reduced the ADRs during chemotherapy.

Conclusion

This systematic review suggests that TMPs combined with chemotherapy might be a potential option to enhance therapeutic effects and reduce ADRs during the treatment of APC. However, more high-quality randomized controlled trials with more participants are needed.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209825, identifier PROSPERO Number: CRD42021264938.
Effect of Abdominal Circumference on the Irradiated Bowel Volume in Pelvic Radiotherapy for Rectal Cancer Patients: Implications for the Radiotherapy-Related Intestinal Toxicity
Authors: Wang Gang , Wang Wenling , Jin Haijie , Dong Hongmin , Chen Weiwei , Li Xiaokai , Bai Saixi , Li Guodong , Chen Wanghua , Li Leilei , Chen Juan
Published: February 2022

Background

To effectively reduce the irradiated bowel volume so as to reduce intestinal toxicity from pelvic radiotherapy, treatment in the prone position with a full bladder on a belly board is widely used in pelvic radiotherapy for rectal cancer patients. However, the clinical applicable condition of this radiotherapy mode is unclear. The aim of this study was to preliminarily identify patients who were not eligible for this radiotherapy mode by analyzing the effect of abdominal circumference on the irradiated bowel volume.

Methods

From May 2014 to September 2019, 179 patients with locally advanced rectal cancer were retrospectively reviewed in our center. All patients received pelvic radiotherapy. Weight, height, AC, and body mass index (BMI) were used as the research objects, and the irradiated bowel volume at different dose levels (V10, V20, V30, V40, V50) was selected as the outcome variable. Multivariate linear regression and sensitivity analyses were used to evaluate the correlation between AC and irradiated bowel volume. Generalized additive model (GAM) and piecewise linear regression were used to further analyze the possible nonlinear relationship between them.

Results

Among the four body size indicators, AC showed a negative linear correlation with the irradiated bowel volume, which was the most significant and stable. In adjuvant radiotherapy patients, we further discovered the threshold effect between AC and irradiated bowel volume, as AC was greater than the inflection point (about 71 cm), irradiated bowel volume decreased rapidly with the increase in AC. t-test showed that in patients with small AC (<71 cm), the irradiated bowel volume was significantly higher than that of patients with medium-large AC (≥71 cm). Especially in patients with adjuvant radiotherapy, the mean irradiated bowel volume of patients with small AC was the highest in this study. Compared with adjuvant radiotherapy, in neoadjuvant radiotherapy, the mean difference of irradiated bowel volume between patients with medium-large AC and those with small AC was larger.

Conclusion

AC is an independent factor influencing the irradiated bowel volume and has a strong negative linear correlation with it. Patients with small AC may not benefit from this common mode of radiotherapy, especially in adjuvant radiotherapy.
LncRNA-AC068228.1 Is a Novel Prognostic Biomarker That Promotes Malignant Phenotypes in Lung Adenocarcinoma
Authors: Jiang Xiulin , Chen Min , Du Junyi , Bi Hong , Guo Xiang , Yang Chao , He Xu , Jin Zhixian
Published: February 2022

Background

The crucial roles played by lncRNA-AC068228.1 in primary malignant cancer remain poorly understood. This study aimed at examining the clinical significance and evaluating the biological function of AC068228.1 in lung adenocarcinoma (LUAD).

Methods

We used data obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Gene Expression Omnibus (GEO) database to examine the expression of AC068228.1 in LUAD patients, and the prognostic and diagnostic value of those levels. Functional experiments were conducted to determine the function of AC068228.1 on LUAD cells. Signaling pathway enrichment analysis of AC068228.1 was conducted using the clusterProfiler and Gene Set Enrichment Analysis (GSEA) software. We analyzed the correlation between AC068228.1 expression and immune infiltration level in LUAD using the single-sample gene set enrichment analysis (ssGSEA) method by the R package GSVA.

Results

AC068228.1 expression was significantly elevated in LUAD tissues compared with normal tissues. Higher expression of AC068228.1 was strongly correlated with adverse clinical outcomes and was identified as an independent prognostic marker for LUAD patients. GSEA and infiltration analysis confirmed that AC068228.1 expression was significantly correlated with immune cells infiltrating in LUAD. Knockdown of AC068228.1 inhibited the cell proliferation and cell migration of LUAD.

Conclusions

AC068228.1 was upregulated in LUAD and was significantly correlated with adverse clinical outcomes. Meanwhile, it was associated with immune cell infiltration and could be used as a promising diagnostic and prognostic biomarker for LUAD patients.