bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review
Authors: Stainer Anna , Tonutti Antonio , De Santis Maria , Amati Francesco , Ceribelli Angela , Bongiovanni Gabriele , Torrisi Chiara , Iacopino Antonio , Mangiameli Giuseppe , Aliberti Stefano , Selmi Carlo
Published: March 2023

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular features. Our current understanding of the mechanisms and predictors of RA-ILD is limited despite the demonstration that an early identification of progressive fibrosing forms is crucial to provide timely treatment with antifibrotic therapies. While high resolution computed tomography is the gold standard technique for the diagnosis and follow-up of RA-ILD, it has been hypothesized that serum biomarkers (including novel and rare autoantibodies), new imaging techniques such as ultrasound of the lung, or the application of innovative radiologic algorithms may help towards predicting and detecting early forms of diseases. Further, while new treatments are becoming available for idiopathic and connective tissue disease-associated forms of lung fibrosis, the treatment of RA-ILD remains anecdotal and largely unexplored. We are convinced that a better understanding of the mechanisms connecting RA with ILD in a subgroup of patients as well as the creation of adequate diagnostic pathways will be mandatory steps for a more effective management of this clinically challenging entity.
Relationship between fibrinogen level and advanced colorectal adenoma among inpatients: A retrospective case-control study
Authors: Wang Huijie , Zheng Huanwei , Cao Xu , Meng Ping , Liu Jinli , Wang Zhichao , Zhang Teng , Zuo Haiying
Published: March 2023

Objective

This study was to explore the relationship between fibrinogen and advanced colorectal adenoma among inpatients.

Methods

From April 2015 to June 2022, 3738 participants (566 case subjects and 3172 control subjects) who underwent colonoscopies enrolled, and smooth curve fitting and logistic regression models were applied to explore the association between fibrinogen and advanced colorectal adenoma. In addition, sensitivity and subgroup analyses were performed to assess the stability of the results.

Results

Compared with lower fibrinogen quantile 1 (< 2.4 g/L), the adjusted OR values for fibrinogen and advanced colorectal adenoma in quantile 2 (2.4–2.75 g/L), quantile 3 (2.76–3.15 g/L), and quantile 4 (≥3.16 g/L) were 1.03 (95% confidence interval [CI]: 0.76–1.41), 1.37 (95% CI: 1.01–1.85), and 1.43 (95% CI: 1.06–1.94), respectively. A linear relationship between fibrinogen and advanced colorectal adenoma was observed. Sensitivity and subgroup analyses showed stable results.

Conclusion

Complements the evidence that fibrinogen was positively associated with advanced adenomas, suggesting that fibrinogen may play a role in the adenoma-carcinoma sequence.
Nutrient optimization for indigenous microbial consortia of a Bhagyam oil field: MEOR studies
Authors: Sharma Neha , Lavania Meeta , Koul Vatsala , Prasad Dhruva , Koduru Nitish , Pandey Amitabh , Raj Rahul , Kumar M. Suresh , Lal Banwari
Published: March 2023

The microbial enhanced oil recovery (MEOR) method is an eco-friendly and economical alternative technology. The technology involves a variety of uncertainties, and its success depends on controlling microbial growth and metabolism. This study is one of a kind that showed successful tertiary recovery of crude oil through indigenous microbial consortia. In this study, a medium was optimized to allow ideal microbial growth under reservoir conditions through RSM. Once the nutrient recipe was optimized, the microbial metabolites were estimated through gas chromatography. The maximum amount of methane gas (0.468 mM) was produced in the TERIW174 sample. The sequencing data set showed the presence of Methanothermobacter sp. and Petrotoga sp. In addition, these established consortia were analyzed for their toxicity, and they appeared to be safe for the environment. Furthermore, a core flood study showed efficient recovery that was ~25 and 34% in TERIW70 and TERIW174 samples, respectively. Thus, both the isolated consortia appeared to be suitable for the field trials.
Molecular analysis of clinical Citrobacter spp. isolates: Acquisition of the Yersinia high-pathogenicity island mediated by ICEkp in C. freundii
Authors: Zhang Guangcun , Zhao Qiang , Ye Kun , Ye Liyan , Ma Yanning , Yang Jiyong
Published: March 2023

Background

Studies on Citrobacter spp. are limited, hindering our understanding of its species evolution and medical relevance.

Methods

A total of 164 clinical Citrobacter spp. isolates were collected from 2017 to 2020 and identified by VITEK MALDI-TOF MS or VITEK-2 Gram-Negative Identification Card. All isolates were further analyzed by whole-genome sequencing using a HiSeq sequencer. All sequences were processed using different modules of the PGCGAP integrated package: Prokka and fastANI were used for annotation and average nucleotide identification (ANI), respectively. Antibiotic resistance and virulence genes were identified by searching CARD, ResFinder, and VFDB databases, respectively. Strains were identified using Ribosomal Multi-locus Sequence Typing (rMLST) classification based on 53 ribosome protein subunits (rps). The evolutionary relationship was analyzed using kSNP3 and visualized by iTOL editor v1_1. Genetic environments were compared by BLAST and visualized by Easyfig 2.2.5. The pathogenicity of some Citrobacter freundii isolates was confirmed by Galleria mellonella larvae infection test.

Results

A total of 14 species of Citrobacter spp. were identified from 164 isolates. However, 27 and 11 isolates were incorrectly identified as C. freundii and Citrobacter braakii by MALDI-TOF MS, respectively. In addition, MS also failed to identify Citrobacter portucalensis. The virulence genes mainly encoded proteins related to flagella and iron uptake systems. Citrobacter koseri isolates (n = 28) contained two iron uptake systems, coding yersiniabactin and aerobactin, respectively. C. braakii isolates (n = 32), like Salmonella, carried Vi capsule polysaccharide synthesis genes. The yersiniabactin gene clusters identified in five C. freundii isolates are located on various ICEkp elements and have not been reported previously. Moreover, ICEkp-carrying C. freundii showed diverse pathogenic features.

Conclusion

Conventional methods have significant defects in identifying Citrobacter spp. ICEkp-like elements-mediated acquirement of the Yersinia high-pathogenicity island was identified for the first time in C. freundii.
Antiviral immune response reveals host-specific virus infections in natural ant populations
Authors: Viljakainen Lumi , Fürst Matthias A. , Grasse Anna V. , Jurvansuu Jaana , Oh Jinook , Tolonen Lassi , Eder Thomas , Rattei Thomas , Cremer Sylvia
Published: March 2023

Hosts can carry many viruses in their bodies, but not all of them cause disease. We studied ants as a social host to determine both their overall viral repertoire and the subset of actively infecting viruses across natural populations of three subfamilies: the Argentine ant (Linepithema humile, Dolichoderinae), the invasive garden ant (Lasius neglectus, Formicinae) and the red ant (Myrmica rubra, Myrmicinae). We used a dual sequencing strategy to reconstruct complete virus genomes by RNA-seq and to simultaneously determine the small interfering RNAs (siRNAs) by small RNA sequencing (sRNA-seq), which constitute the host antiviral RNAi immune response. This approach led to the discovery of 41 novel viruses in ants and revealed a host ant-specific RNAi response (21 vs. 22 nt siRNAs) in the different ant species. The efficiency of the RNAi response (sRNA/RNA read count ratio) depended on the virus and the respective ant species, but not its population. Overall, we found the highest virus abundance and diversity per population in Li. humile, followed by La. neglectus and M. rubra. Argentine ants also shared a high proportion of viruses between populations, whilst overlap was nearly absent in M. rubra. Only one of the 59 viruses was found to infect two of the ant species as hosts, revealing high host-specificity in active infections. In contrast, six viruses actively infected one ant species, but were found as contaminants only in the others. Disentangling spillover of disease-causing infection from non-infecting contamination across species is providing relevant information for disease ecology and ecosystem management.
Mobile genetic element-encoded putative DNA primases composed of A-family polymerase—SSB pairs
Authors: Rice Phoebe A.
Published: March 2023

Mobile genetic elements can encode a wide variety of genes that support their own stability and mobility as well as genes that provide accessory functions to their hosts. Such genes can be adopted from host chromosomes and can be exchanged with other mobile elements. Due to their accessory nature, the evolutionary trajectories of these genes can differ from those of essential host genes. The mobilome therefore provides a rich source of genetic innovation. We previously described a new type of primase encoded by S. aureus SCCmec elements that is composed of an A-family polymerase catalytic domain in complex with a small second protein that confers single-stranded DNA binding. Here we use new structure prediction methods in conjunction with sequence database searches to show that related primases are widespread among putative mobile genetic elements in the Bacillota. Structure predictions show that the second protein adopts an OB fold (common among single-stranded DNA binding (SSB) proteins) and these predictions were far more powerful than simple sequence comparisons in identifying its homologs. The protein-protein interaction surface varies among these polymerase—SSB complexes appear to have arisen repeatedly by exploiting partial truncations of the polymerase’s N-terminal accessory domains.
Advances of multi-omics applications in hepatic precancerous lesions and hepatocellular carcinoma: The role of extracellular vesicles
Authors: Lu Xiaona , Li Yuyao , Li Yue , Zhang Xuemei , Shi Jia , Feng Hai , Gao Yueqiu , Yu Zhuo
Published: March 2023

Due to the lack of distinct early symptoms and specific biomarkers, most patients with hepatocellular carcinoma (HCC) are usually diagnosed at advanced stages, rendering the treatment ineffective and useless. Therefore, recognition of the malady at precancerous lesions and early stages is particularly important for improving patient outcomes. The interest in extracellular vesicles (EVs) has been growing in recent years with the accumulating knowledge of their multiple cargoes and related multipotent roles in the modulation of immune response and tumor progression. By virtue of the rapid advancement of high-throughput techniques, multiple omics, including genomics/transcriptomics, proteomics, and metabolomics/lipidomics, have been widely integrated to analyze the role of EVs. Comprehensive analysis of multi-omics data will provide useful insights for discovery of new biomarkers and identification of therapeutic targets. Here, we review the attainment of multi-omics analysis to the finding of the potential role of EVs in early diagnosis and the immunotherapy in HCC.
Structural and oxidative investigation of a recombinant high-yielding fetal hemoglobin mutant
Authors: Kettisen Karin , Nyblom Maria , Smeds Emanuel , Fago Angela , Bülow Leif
Published: March 2023

Human fetal hemoglobin (HbF) is an attractive starting protein for developing an effective agent for oxygen therapeutics applications. This requires that HbF can be produced in heterologous systems at high levels and in a homogeneous form. The introduction of negative charges on the surface of the α-chain in HbF can enhance the recombinant production yield of a functional protein in Escherichia coli. In this study, we characterized the structural, biophysical, and biological properties of an HbF mutant carrying four additional negative charges on each α-chain (rHbFα4). The 3D structure of the rHbFα4 mutant was solved with X-ray crystallography at 1.6 Å resolution. Apart from enabling a higher yield in recombinant protein production in E. coli, we observed that the normal DNA cleavage activity of the HbF was significantly lowered, with a four-time reduced rate constant for the rHbFα4 mutant. The oxygen-binding properties of the rHbFα4 mutant were identical to the wild-type protein. No significant difference between the wild-type and rHbFα4 was observed for the investigated oxidation rates (autoxidation and H2O2-mediated ferryl formation). However, the ferryl reduction reaction indicated some differences, which appear to be related to the reaction rates linked to the α-chain.
Crosstalk between the endocannabinoid and mid-brain dopaminergic systems: Implication in dopamine dysregulation
Authors: Kibret Berhanu Geresu , Canseco-Alba Ana , Onaivi Emmanuel S. , Engidawork Ephrem
Published: March 2023

Endocannabinoids (eCBs) and the expanded endocannabinoid system (ECS)-“endocannabinoidome”, consists of the endogenous ligands, eCBs, their canonical and non-canonical receptor subtypes, and their synthesizing and metabolizing enzymes. This system modulates a wide range of body functions and acts as a retrograde signaling system within the central nervous system (CNS) by inhibition of classical transmitters, and plays a vital modulatory function on dopamine, a major neurotransmitter in the CNS. Dopamine is involved in different behavioral processes and contributes to different brain disorders—including Parkinson’s disease, schizophrenia, and drug addiction. After synthesis in the neuronal cytosol, dopamine is packaged into synaptic vesicles until released by extracellular signals. Calcium dependent neuronal activation results in the vesicular release of dopamine and interacts with different neurotransmitter systems. The ECS, among others, is involved in the regulation of dopamine release and the interaction occurs either through direct or indirect mechanisms. The cross-talk between the ECS and the dopaminergic system has important influence in various dopamine-related neurobiological and pathologic conditions and investigating this interaction might help identify therapeutic targets and options in disorders of the CNS associated with dopamine dysregulation.
Iterative transfer learning for automatic collective motion tuning on multiple robot platforms
Authors: Abpeikar Shadi , Kasmarik Kathryn , Garratt Matt
Published: March 2023

This paper proposes an iterative transfer learning approach to achieve swarming collective motion in groups of mobile robots. By applying transfer learning, a deep learner capable of recognizing swarming collective motion can use its knowledge to tune stable collective motion behaviors across multiple robot platforms. The transfer learner requires only a small set of initial training data from each robot platform, and this data can be collected from random movements. The transfer learner then progressively updates its own knowledge base with an iterative approach. This transfer learning eliminates the cost of extensive training data collection and the risk of trial-and-error learning on robot hardware. We test this approach on two robot platforms: simulated Pioneer 3DX robots and real Sphero BOLT robots. The transfer learning approach enables both platforms to automatically tune stable collective behaviors. Using the knowledge-base library the tuning procedure is fast and accurate. We demonstrate that these tuned behaviors can be used for typical multi-robot tasks such as coverage, even though they are not specifically designed for coverage tasks.
Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology
Authors: Diab Rim , Pilotto Federica , Saxena Smita
Published: March 2023

The proper functioning of the cell clearance machinery is critical for neuronal health within the central nervous system (CNS). In normal physiological conditions, the cell clearance machinery is actively involved in the elimination of misfolded and toxic proteins throughout the lifetime of an organism. The highly conserved and regulated pathway of autophagy is one of the important processes involved in preventing and neutralizing pathogenic buildup of toxic proteins that could eventually lead to the development of neurodegenerative diseases (NDs) such as Alzheimer’s disease or Amyotrophic lateral sclerosis (ALS). The most common genetic cause of ALS and frontotemporal dementia (FTD) is a hexanucleotide expansion consisting of GGGGCC (G4C2) repeats in the chromosome 9 open reading frame 72 gene (C9ORF72). These abnormally expanded repeats have been implicated in leading to three main modes of disease pathology: loss of function of the C9ORF72 protein, the generation of RNA foci, and the production of dipeptide repeat proteins (DPRs). In this review, we discuss the normal physiological role of C9ORF72 in the autophagy-lysosome pathway (ALP), and present recent research deciphering how dysfunction of the ALP synergizes with C9ORF72 haploinsufficiency, which together with the gain of toxic mechanisms involving hexanucleotide repeat expansions and DPRs, drive the disease process. This review delves further into the interactions of C9ORF72 with RAB proteins involved in endosomal/lysosomal trafficking, and their role in regulating various steps in autophagy and lysosomal pathways. Lastly, the review aims to provide a framework for further investigations of neuronal autophagy in C9ORF72-linked ALS-FTD as well as other neurodegenerative diseases.
The factors influencing postoperative efficacy of anterior clinoidal meningioma treatment and an analysis of best-suited surgical strategies
Authors: Chen Li-Hua , Xia Yong , Wei Fan , Sun Kai , Huang Hong-Zhi , Xu Ru-Xiang
Published: March 2023

Objective

To explore the influence of the type of anterior clinoidal meningioma on surgical strategy planning, surgical approach selection, and postoperative efficacy.

Patients and methods

We conducted a retrospective analysis of the clinical data of 63 cases, including data on visual function, extent of tumor resection, and postoperative follow-up. Grade I and II approaches were selected according to the type of tumor. A univariate analysis of the factors influencing the extent of tumor resection, postoperative visual function, and postoperative relapse and complications was conducted.

Results

Simpson Grade I–II total resection was seen in 48 cases (76.2%), with an overall relapse/progression rate of 12.7%. The tumor type and texture and the relationship between the tumors and adjacent structures were the main factors influencing total tumor resection (P < 0.01). The overall postoperative visual acuity improvement, stabilization rate, and deterioration rate were 76.2, 15.9, and 7.9%, respectively. Postoperative visual acuity level was significantly correlated with preoperative visual acuity level and tumor type (P < 0.01).

Conclusions

Determining the type of tumor at a preoperative level and whether the optic canal and cavernous sinus are invaded can aid in the planning of detailed individualized surgical strategies.
Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs
Authors: Tyagi Sidharth , Sarveswaran Nivedita , Higerd-Rusli Grant P. , Liu Shujun , Dib-Hajj Fadia B. , Waxman Stephen G. , Dib-Hajj Sulayman D.
Published: March 2023

Non-addictive treatment of chronic pain represents a major unmet clinical need. Peripheral voltage-gated sodium (NaV) channels are an attractive target for pain therapy because they initiate and propagate action potentials in primary afferents that detect and transduce noxious stimuli. NaV1.7 sets the gain on peripheral pain-signaling neurons and is the best validated peripheral ion channel involved in human pain, and previous work has shown that it is transported in vesicles in sensory axons which also carry Rab6a, a small GTPase known to be involved in vesicular packaging and axonal transport. Understanding the mechanism of the association between Rab6a and NaV1.7 could inform therapeutic modalities to decrease trafficking of NaV1.7 to the distal axonal membrane. Polybasic motifs (PBM) have been shown to regulate Rab-protein interactions in a variety of contexts. In this study, we explored whether two PBMs in the cytoplasmic loop that joins domains I and II of human NaV1.7 were responsible for association with Rab6a and regulate axonal trafficking of the channel. Using site-directed mutagenesis we generated NaV1.7 constructs with alanine substitutions in the two PBMs. Voltage-clamp recordings showed that the constructs retain wild-type like gating properties. Optical Pulse-chase Axonal Long-distance (OPAL) imaging in live sensory axons shows that mutations of these PBMs do not affect co-trafficking of Rab6a and NaV1.7, or the accumulation of the channel at the distal axonal surface. Thus, these polybasic motifs are not required for interaction of NaV1.7 with the Rab6a GTPase, or for trafficking of the channel to the plasma membrane.
Economic and health impacts of the Change4Life Food Scanner app: Findings from a randomized pilot and feasibility study
Authors: Mahdi Sundus , Buckland Nicola J. , Chilcott Jim
Published: March 2023

Introduction

The UK Government developed the Change4Life Food Scanner app to provide families with engaging feedback on the nutritional content of packaged foods. There is a lack of research exploring the cost-effectiveness of dietary health promotion apps.

Methods

Through stakeholder engagement, a conceptual model was developed, outlining the pathway by which the Food Scanner app leads to proximal and distal outcomes. The conceptual model informed the development of a pilot randomized controlled trial which investigated the feasibility and acceptability of evaluating clinical outcomes in children and economic effectiveness of the Food Scanner app through a cost-consequence analysis. Parents of 4–11 years-olds (n = 126) were randomized into an app exposure condition (n = 62), or no intervention control (n = 64). Parent-reported Child Health Utility 9 Dimension (CHU9D) outcomes were collected alongside child healthcare resource use and associated costs, school absenteeism and parent productivity losses at baseline and 3 months follow up. Results for the CHU9D were converted into utility scores based on UK adult preference weights. Sensitivity analysis accounted for outliers and multiple imputation methods were adopted for the handling of missing data.

Results

64 participants (51%) completed the study (intervention: n = 29; control: n = 35). There was a mean reduction in quality adjusted life years between groups over the trial period of –0.004 (SD = 0.024, 95% CI: –0.005; 0.012). There was a mean reduction in healthcare costs of –£30.77 (SD = 230.97; 95% CI: –£113.80; £52.26) and a mean reduction in workplace productivity losses of –£64.24 (SD = 241.66, 95% CI: –£147.54; £19.07) within the intervention arm, compared to the control arm, over the data collection period. Similar findings were apparent after multiple imputation.

Discussion

Modest mean differences between study arms may have been due to the exploration of distal outcomes over a short follow-up period. The study was also disrupted due to the coronavirus pandemic, which may have confounded healthcare resource data. Although measures adopted were deemed feasible, the study highlighted difficulties in obtaining data on app development and maintenance costs, as well as the importance of economic modeling to predict long-term outcomes that may not be reliably captured over the short-term.

Clinical trial registration

https://osf.io/, identifier 62hzt.
Vinegar: A potential source of healthy and functional food with special reference to sugarcane vinegar
Authors: Chen Gan-Lin , Zheng Feng-Jin , Lin Bo , Yang Yu-Xia , Fang Xiao-Chun , Verma Krishan K. , Yang Li-Fang
Published: March 2023

Vinegar is one of the most widely used acidic condiments. Recently, rapid advances have been made in the area of vinegar research. Different types of traditional vinegar are available around the globe and have many applications. Vinegar can be made either naturally, through alcoholic and then acetic acid fermentation, or artificially, in laboratories. Vinegar is the product of acetic acid fermentation of dilute alcoholic solutions, manufactured by a two-step process. The first step is the production of ethanol from a carbohydrate source such as glucose, which is carried out by yeasts. The second step is the oxidation of ethanol to acetic acid, which is carried out by acetic acid bacteria. Acetic acid bacteria are not only producers of certain foods and drinks, such as vinegar, but they can also spoil other products such as wine, beer, soft drinks, and fruits. Various renewable substrates are used for the efficient biological production of acetic acid, including agro and food, dairy, and kitchen wastes. Numerous reports on the health advantages associated with vinegar ingredients have been presented. Fresh sugarcane juice was fermented with wine yeast and LB acetate bacteria to develop a high-quality original sugarcane vinegar beverage. To facilitate the current study, the bibliometric analysis method was adopted to visualize the knowledge map of vinegar research based on literature data. The present review article will help scientists discern the dynamic era of vinegar research and highlight areas for future research.
High-fat intake reshapes the circadian transcriptome profile and metabolism in murine meibomian glands
Authors: Zou Sen , Liu Jiangman , Si Hongli , Huang Duliurui , Qi Di , Pei Xiaoting , Lu Dingli , Huang Shenzhen , Li Zhijie
Published: March 2023

Background

Nutritional and food components reshape the peripheral clock and metabolism. However, whether food challenges affect the circadian clock and metabolism of meibomian glands (MGs) has not been fully explored. This study was designed to analyze alterations in the rhythmic transcriptome and metabolism of MGs of murine fed a balanced diet or a high-fat diet (HFD).

Methods

Male C57BL/6J mice were maintained on a 12/12 h light/dark cycle and fed ad libitum on normal chow (NC) or HFD for 4 weeks. MGs were collected from sacrificed animals at 3-h intervals throughout a 24-h circadian cycle. The circadian transcriptome of MGs was analyzed via bioinformatics approaches using high-throughput RNA sequencing (RNA-seq). In addition, circadian oscillations of lipid components in MGs were analyzed.

Results

Meibomian glands displayed robust transcriptome rhythmicity. HFD feeding significantly altered the circadian transcriptome profile of MGs—including composition and phase—and spatiotemporally affected the enriched signaling pathways. In addition, HFD feeding significantly altered the normal rhythmic oscillations of lipid components in MGs.

Conclusion

Our data show that HFD significantly affects MGs’ rhythmicity, which reveals a high sensitivity of MGs’ clocks to lipid composition in food.
Precise prediction of the sensitivity of platinum chemotherapy in SCLC: Establishing and verifying the feasibility of a CT-based radiomics nomogram
Authors: Su Yanping , Lu Chenying , Zheng Shenfei , Zou Hao , Shen Lin , Yu Junchao , Weng Qiaoyou , Wang Zufei , Chen Minjiang , Zhang Ran , Ji Jiansong , Wang Meihao
Published: March 2023

Objectives

To develop and validate a CT-based radiomics nomogram that can provide individualized pretreatment prediction of the response to platinum treatment in small cell lung cancer (SCLC).

Materials

A total of 134 SCLC patients who were treated with platinum as a first-line therapy were eligible for this study, including 51 patients with platinum resistance (PR) and 83 patients with platinum sensitivity (PS). The variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) were applied for feature selection and model construction. The selected texture features were calculated to obtain the radiomics score (Rad-score), and the predictive nomogram model was composed of the Rad-score and the clinical features selected by multivariate analysis. Receiver operating characteristic (ROC) curves, calibration curves, and decision curves were used to assess the performance of the nomogram.

Results

The Rad-score was calculated using 10 radiomic features, and the resulting radiomics signature demonstrated good discrimination in both the training set (area under the curve [AUC], 0.727; 95% confidence interval [CI], 0.627–0.809) and the validation set (AUC, 0.723; 95% CI, 0.562–0.799). To improve diagnostic effectiveness, the Rad-score created a novel prediction nomogram by combining CA125 and CA72-4. The radiomics nomogram showed good calibration and discrimination in the training set (AUC, 0.900; 95% CI, 0.844-0.947) and the validation set (AUC, 0.838; 95% CI, 0.534-0.735). The radiomics nomogram proved to be clinically beneficial based on decision curve analysis.

Conclusion

We developed and validated a radiomics nomogram model for predicting the response to platinum in SCLC patients. The outcomes of this model can provide useful suggestions for the development of tailored and customized second-line chemotherapy regimens.
An MRI-based radiomics nomogram in predicting histologic grade of non-muscle-invasive bladder cancer
Authors: Li Longchao , Zhang Jing , Zhe Xia , Chang Hongzhi , Tang Min , Lei Xiaoyan , Zhang Li , Zhang Xiaoling
Published: March 2023

Background

Non-muscle-invasive bladder cancer (NMIBC) is categorized into high and low grades with different clinical treatments and prognoses. Thus, accurate preoperative evaluation of the histologic NMIBC grade through imaging techniques is essential.

Objectives

To develop and validate an MRI-based radiomics nomogram for individualized prediction of NMIBC grading.

Methods

The study included 169 consecutive patients with NMIBC (training cohort: n = 118, validation cohort: n = 51). A total of 3148 radiomic features were extracted, and one-way analysis of variance and least absolute shrinkage and selection operator were used to select features for building the radiomics score(Rad-score). Three models to predict NMIBC grading were developed using logistic regression analysis: a clinical model, a radiomics model and a radiomics–clinical combined nomogram model. The discrimination and calibration power and clinical applicability of the models were evaluated. The diagnostic performance of each model was compared by determining the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis.

Results

A total of 24 features were used to build the Rad-score. A clinical model, a radiomics model, and a radiomics–clinical nomogram model that incorporated the Rad-score, age, and number of tumors were constructed. The radiomics model and nomogram showed AUCs of 0.910 and 0.931 in the validation set, which outperformed the clinical model (0.745). The decision curve analysis also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model.

Conclusion

A radiomics–clinical combined nomogram model has the potential to be used as a non-invasive tool for the differentiating low-from high-grade NMIBCs.
Case report: POLE (P286R) mutation in a case of recurrent intestinal leakage and its treatment
Authors: Xiang Dang , Fu Gongbo , Chen Yitian , Chu Xiaoyuan
Published: March 2023

In recent years, although new drugs and molecular markers have been used to treat metastatic colorectal cancer, there has been little progress in the immunotherapy of advanced colon cancer. The development of sequencing and multiomics technology helps us classify patients more accurately, and then find patients who may benefit from immunotherapy. The development of this advanced technology and immunotherapy based on new targets may herald a new era in the treatment of metastatic colorectal cancer. It is well known that colorectal cancer with dmmr/msi-h phenotype is sensitive to immunotherapy, yet the POLE mutation is the MSS phenotype in colorectal tumors but is also an effective target for immunotherapy. This paper describes a case of recurrent intestinal leakage that required multiple surgical procedures. A high-grade colon adenocarcinoma was identified on surgical histopathology after 18 months, and bevacizumab combined with oxaliplatin and capecitabine proved ineffective against this cancer. An analysis of gene expression indicated that POLE (P286R) mutation, TMB 119.333 mutation per 100 MB, and immune checkpoint inhibitor treatment had a significant impact. This case reminds us that the existence of malignant tumors should be considered for patients with repeated intestinal leakage, and emphasizes the importance of gene detection in the treatment of malignant tumors and the significance of POLE mutations in colorectal cancer.
Ferroptosis open a new door for colorectal cancer treatment
Authors: Liang Hong , He Xia , Tong Yitong , Bai Niuniu , Pu Yushu , Han Ke , Wang Yi
Published: March 2023

Colorectal cancer (CRC) is the third highest incidence and the second highest mortality malignant tumor in the world. The etiology and pathogenesis of CRC are complex. Due to the long course of the disease and no obvious early symptoms, most patients are diagnosed as middle and late stages. CRC is prone to metastasis, most commonly liver metastasis, which is one of the leading causes of death in CRC patients. Ferroptosis is a newly discovered cell death form with iron dependence, which is driven by excessive lipid peroxides on the cell membrane. It is different from other form of programmed cell death in morphology and mechanism, such as apoptosis, pyroptosis and necroptosis. Numerous studies have shown that ferroptosis may play an important role in the development of CRC. For advanced or metastatic CRC, ferroptosis promises to open a new door in the setting of poor response to chemotherapy and targeted therapy. This mini review focuses on the pathogenesis of CRC, the mechanism of ferroptosis and the research status of ferroptosis in CRC treatment. The potential association between ferroptosis and CRC and some challenges are discussed.
A review on surgical treatment options in gliomas
Authors: Yang Zhongxi , Zhao Chen , Zong Shan , Piao Jianmin , Zhao Yuhao , Chen Xuan
Published: March 2023

Gliomas are one of the most common primary central nervous system tumors, and surgical treatment remains the principal role in the management of any grade of gliomas. In this study, based on the introduction of gliomas, we review the novel surgical techniques and technologies in support of the extent of resection to achieve long-term disease control and summarize the findings on how to keep the balance between cytoreduction and neurological morbidity from a list of literature searched. With modern neurosurgical techniques, gliomas resection can be safely performed with low morbidity and extraordinary long-term functional outcomes.
Immunotherapy for HER-2 positive breast cancer
Authors: Yang Tingting , Kang Lihua , Li Dan , Song Yanqiu
Published: March 2023

Immunotherapy is a developing treatment for advanced breast cancer. Immunotherapy has clinical significance for the treatment of triple-negative breast cancers and human epidermal growth factor receptor-2 positive (HER2+) breast cancers. As a proved effective passive immunotherapy, clinical application of the monoclonal antibodies trastuzumab, pertuzumab and T-DM1 (ado-trastuzumab emtansine) has significantly improved the survival of patients with HER2+ breast cancers. Immune checkpoint inhibitors that block programmed death receptor-1 and its ligand (PD-1/PD-L1) have also shown benefits for breast cancer in various clinical trials. Adoptive T-cell immunotherapies and tumor vaccines are emerging as novel approaches to treating breast cancer, but require further study. This article reviews recent advances in immunotherapy for HER2+ breast cancers.
Getting Recovery Right After Neck Dissection (GRRAND-F): Mixed-methods feasibility study to design a pragmatic randomised controlled trial
Authors: Smith Toby O. , Garrett Angela , Liu Tianshu , Morris Alana , Gallyer Victoria , Fordham Bethany A. , Dutton Susan J. , Chester-Jones Mae , Lamb Sarah E. , Winter Stuart Charles
Published: March 2023

Objective

To determine the feasibility of a randomised controlled trial to estimate the effectiveness and cost-effectiveness of a rehabilitation intervention following neck dissection (ND) after head and neck cancer (HNC).

Design

Two-arm, open, pragmatic, parallel, multicentre, randomised controlled feasibility trial.

Setting

Two UK NHS hospitals.

Participants

People who had HNC in whom a ND was part of their care. We excluded those with a life expectancy of six months or less, pre-existing, long-term neurological disease affecting the shoulder and cognitive impairment.

Intervention

Usual care (standard care supplemented with a booklet on postoperative self-management) was received by all participants. The GRRAND intervention programme consisted of usual care plus up to six individual physiotherapy sessions including neck and shoulder range of motion and progressive resistance exercises, advice and education. Between sessions, participants were advised to complete a home exercise programme.

Randomisation

1:1 randomisation. Allocation was based on minimisation, stratified by hospital site and spinal accessory nerve sacrifice. It was not possible to mask treatment received.

Main outcome measures

Primary: Participant recruitment, retention and fidelity to the study protocol and interventions from study participants and staff at six months post-randomisation (and 12 months for those reaching that time-point). Secondary: clinical measures of pain, function, physical performance, health-related quality of life, health utilisation and adverse events.

Results

36 participants were recruited and enrolled. The study achieved five of its six feasibility targets. These included consent - 70% of eligible participants were consented; intervention fidelity - 78% participants discharged completed the intervention sessions; contamination - none - no participants in the control arm received the GRRAND-F intervention and retention - 8% of participants were lost to follow-up. The only feasibility target that was not achieved was the recruitment target where only 36 of the planned 60 participants were recruited over 18 months. This was principally due to the COVID-19 pandemic which caused all research activity to be paused or reduced, with a subsequent reduction in.

Conclusions

Based on the findings a full-trial can now be designed to better understand whether this proposed intervention is effective.

Clinical Trial Registration

https://www.isrctn.com/ISRCTN1197999, identifier ISRCTN11979997.
Case report: Long-term voluntary Tyrosine Kinase Inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML): Molecular evidence of an immune surveillance
Authors: Imeri Jusuf , Desterke Christophe , Marcoux Paul , Chaker Diana , Oudrhiri Noufissa , Fund Xavier , Faivre Jamila , Bennaceur-Griscelli Annelise , Turhan Ali G.
Published: March 2023

The classical natural history of chronic myeloid leukemia (CML) has been drastically modified by the introduction of tyrosine kinase inhibitor (TKI) therapies. TKI discontinuation is currently possible in patients in deep molecular responses, using strict recommendations of molecular follow-up due to risk of molecular relapse, especially during the first 6 months. We report here the case of a patient who voluntarily interrupted her TKI therapy. She remained in deep molecular remission (MR4) for 18 months followed by detection of a molecular relapse at +20 months. Despite this relapse, she declined therapy until the occurrence of the hematological relapse (+ 4 years and 10 months). Retrospective sequential transcriptome experiments and a single-cell transcriptome RNA-seq analysis were performed. They revealed a molecular network focusing on several genes involved in both activation and inhibition of NK-T cell activity. Interestingly, the single-cell transcriptome analysis showed the presence of cells expressing NKG7, a gene involved in granule exocytosis and highly involved in anti-tumor immunity. Single cells expressing as granzyme H, cathepsin-W, and granulysin were also identified. The study of this case suggests that CML was controlled for a long period of time, potentially via an immune surveillance phenomenon. The role of NKG7 expression in the occurrence of treatment-free remissions (TFR) should be evaluated in future studies.
Is it feasible and ethical to randomize patients between surgery and non-surgical treatments for gastrointestinal cancers?
Authors: Rebelo Artur , Klose Johannes , Kleeff Jörg , Ronellenfitsch Ulrich
Published: March 2023

Background

In several settings in the treatment of gastrointestinal cancers, it is unclear if the addition of surgery to a multimodal treatment strategy, or in some circumstances its omission, lead to a better outcome for patients. In such situations of clinical equipoise, high-quality evidence from randomised-controlled trials is needed to decide which treatment approach is preferable.

Objective

In this article, we outline the importance of randomised trials comparing surgery with non-surgical therapies for specific scenarios in the treatment of gastrointestinal cancers. We explain the difficulties and solutions of designing these trials and recruiting patients in this context.

Methods

We performed a selective review based on a not systematic literature search in core databases, supplemented by browsing health information journals and citation searching. Only articles in English were selected. Based on this search, we discuss the results and methodological characteristics of several trials which randomised patients with gastrointestinal cancers between surgery and non-surgical treatments, highlighting their differences, advantages, and limitations.

Results and conclusions

Innovative and effective cancer treatment requires randomised trials, also comparing surgery and non-surgical treatments for defined scenarios in the treatment of gastrointestinal malignancies. Nevertheless, potential obstacles to designing and carrying out these trials must be recognised ahead of time to avoid problems before or during the trial.
Access to advanced cancer care services in the West Bank-occupied Palestinian territory
Authors: Mitwalli Suzan , Hammoudeh Weeam , Giacaman Rita , Harding Richard
Published: March 2023

Introduction

Universal Health Coverage (UHC) identifies the provision of palliative care for people with advanced disease as an essential health service. Palliative care is also stipulated as a human right under existing covenants. Oncology services provided by the Palestinian Authority under Israeli military occupation are limited to surgery and chemotherapy treatment. Our study aimed to describe the experiences of patients with advanced-stage cancer in the West Bank in accessing oncology services and meeting their health care needs.

Methodology

We conducted a qualitative study among adult patients diagnosed with advanced lung, colon, or breast cancer in three Palestinian governmental hospitals, and with oncologists. Thematic analysis was conducted on the verbatim interview transcripts.

Results

The sample consisted of 22 Palestinian patients (10 men and 12 women) and 3 practicing oncologists. The findings reveal that cancer care is fragmented, with limited access to the services needed. Patients face referral delays in accessing treatment which worsen their health condition in some cases. Some patients reported difficulties in getting Israeli permits to access radiotherapy treatment in East-Jerusalem, and others experienced interruptions of their chemotherapy treatment sessions due to the unavailability of chemotherapy medications caused by Israeli-side delays. Other reported problems were related to the Palestinian health system and service delivery and quality, including fragmentation of services, infrastructure issues, and unavailability of medications. Advanced diagnostic services and palliative care are almost absent at Palestinian governmental hospitals, and patients need to seek these services in the private sector.

Conclusion

The data demonstrate specific access restrictions to cancer care in the West Bank due to Israeli military occupation of Palestinian land. This affects all stages of the care pathway, from restricted diagnosis services, to limited treatment and then poor availability of palliative care. Cancer patients will continue to suffer if the root causes of these structural constraints are not addressed.
Is MRI-Linac helpful in SABR treatments for liver cancer?
Authors: Tallet Agnès , Boher Jean-Marie , Tyran Marguerite , Mailleux Hugues , Piana Gilles , Benkreira Mohamed , Fau Pierre , Salem Naji , Gonzague Laurence , Petit Claire , Darréon Julien
Published: March 2023

Objective

To determine the MRI-Linac added value over conventional image-guided radiation therapy (IGRT) in liver tumors Stereotactic ablative radiation therapy (SABR).

Materials and methods

We retrospectively compared the Planning Target Volumes (PTVs), the spared healthy liver parenchyma volumes, the Treatment Planning System (TPS) and machine performances, and the patients’ outcomes when using either a conventional accelerator (Versa HD®, Elekta, Utrecht, NL) with Cone Beam CT as the IGRT tool or an MR-Linac system (MRIdian®, ViewRay, CA).

Results

From November 2014 to February 2020, 59 patients received a SABR treatment (45 and 19 patients in the Linac and MR-Linac group, respectively) for 64 primary or secondary liver tumors. The mean tumor size was superior in the MR-Linac group (37,91cc vs. 20.86cc). PTV margins led to a median 74%- and 60% increase in target volume in Linac-based and MRI-Linac-based treatments, respectively. Liver tumor boundaries were visible in 0% and 72% of the cases when using CBCT and MRI as IGRT tools, respectively. The mean prescribed dose was similar in the two patient groups. Local tumor control was 76.6%, whereas 23.4% of patients experienced local progression (24.4% and 21.1% of patients treated on the conventional Linac and the MRIdian system, respectively). SABR was well tolerated in both groups, and margins reduction and the use of gating prevented ulcerous disease occurrence.

Conclusion

The use of MRI as IGRT allows for the reduction of the amount of healthy liver parenchyma irradiated without any decrease of the tumor control rate, which would be helpful for dose escalation or subsequent liver tumor irradiation if needed.