bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid whole genome sequencing methods for RNA viruses
Authors: Misu Masayasu , Yoshikawa Tomoki , Sugimoto Satoko , Takamatsu Yuki , Kurosu Takeshi , Ouji Yukiteru , Yoshikawa Masahide , Shimojima Masayuki , Ebihara Hideki , Saijo Masayuki
Published: February 2023

RNA viruses are the etiological agents of many infectious diseases. Since RNA viruses are error-prone during genome replication, rapid, accurate and economical whole RNA viral genome sequence determination is highly demanded. Next-generation sequencing (NGS) techniques perform whole viral genome sequencing due to their high-throughput sequencing capacity. However, the NGS techniques involve a significant burden for sample preparation. Since to generate complete viral genome coverage, genomic nucleic acid enrichment is required by reverse transcription PCR using virus-specific primers or by viral particle concentration. Furthermore, conventional NGS techniques cannot determine the 5′ and 3′ terminal sequences of the RNA viral genome. Therefore, the terminal sequences are determined one by one using rapid amplification of cDNA ends (RACE). However, since some RNA viruses have segmented genomes, the burden of the determination using RACE is proportional to the number of segments. To date, there is only one study attempting whole genome sequencing of multiple RNA viruses without using above mentioned methods, but the generated sequences’ accuracy compared to the reference sequences was up to 97% and did not reach 100% due to the low read depth. Hence, we established novel methods, named PCR-NGS and RCA-NGS, that were optimized for an NGS machine, MinION. These methods do not require nucleic acid amplification with virus-specific PCR primers, physical viral particle enrichment, and RACE. These methods enable whole RNA viral genome sequencing by combining the following techniques: (1) removal of unwanted DNA and RNA other than the RNA viral genome by nuclease treatment; (2) the terminal of viral genome sequence determination by barcoded linkers ligation; (3) amplification of the viral genomic cDNA using ligated linker sequences-specific PCR or an isothermal DNA amplification technique, such as rolling circle amplification (RCA). The established method was evaluated using isolated RNA viruses with single-stranded, double-stranded, positive-stranded, negative-stranded, non-segmented or multi-segmented genomes. As a result, all the viral genome sequences could be determined with 100% accuracy, and these mean read depths were greater than 2,500×, at least using either of the methods. This method should allow for easy and economical determination of accurate RNA viral genomes.
Anatomic and neurochemical analysis of the palpal olfactory system in the red flour beetle Tribolium castaneum, HERBST
Authors: Trebels Björn , Dippel Stefan , Anders Janet , Ernst Clara , Goetz Brigitte , Keyser Tim , Rexer Karl Heinz , Wimmer Ernst A. , Schachtner Joachim
Published: February 2023

The paired antennal lobes were long considered the sole primary processing centers of the olfactory pathway in holometabolous insects receiving input from the olfactory sensory neurons of the antennae and mouthparts. In hemimetabolous insects, however, olfactory cues of the antennae and palps are processed separately. For the holometabolous red flour beetle Tribolium castaneum, we could show that primary processing of the palpal and antennal olfactory input also occurs separately and at distinct neuronal centers. While the antennal olfactory sensory neurons project into the antennal lobes, those of the palps project into the paired glomerular lobes and the unpaired gnathal olfactory center. Here we provide an extended analysis of the palpal olfactory pathway by combining scanning electron micrographs with confocal imaging of immunohistochemical staining and reporter expression identifying chemosensory and odorant receptor-expressing neurons in the palpal sensilla. In addition, we extended the anatomical characterization of the gnathal olfactory center by 3D reconstructions and investigated the distribution of several neuromediators. The similarities in the neuromediator repertoire between antennal lobes, glomerular lobes, and gnathal olfactory center underline the role of the latter two as additional primary olfactory processing centers.
Aberrant hippocampus and amygdala morphology associated with cognitive deficits in schizophrenia
Authors: Peterson Bradley S. , Kaur Tejal , Sawardekar Siddhant , Colibazzi Tiziano , Hao Xuejun , Wexler Bruce E. , Bansal Ravi
Published: February 2023

Background

Working memory deficits are thought to be a primary disturbance in schizophrenia. We aimed to identify differences in morphology of the hippocampus and amygdala in patients with schizophrenia compared with healthy controls (HCs), and in patients who were either neuropsychologically near normal (NPNN) or neuropsychologically impaired (NPI). Morphological disturbances in the same subfields of the hippocampus and amygdala, but of greater magnitude in those with NPI, would strengthen evidence for the centrality of these limbic regions and working memory deficits in the pathogenesis of schizophrenia.

Methods

We acquired anatomical MRIs in 69 patients with schizophrenia (18 NPNN, 46 NPI) and 63 age-matched HC participants. We compared groups in hippocampus and amygdala surface morphologies and correlated morphological measures with clinical symptoms and working memory scores.

Results

Schizophrenia was associated with inward deformations of the head and tail of the hippocampus, protrusion of the hippocampal body, and widespread inward deformations of the amygdala. In the same regions where we detected the effects of schizophrenia, morphological measures correlated positively with the severity of symptoms and inversely with working memory performance. Patients with NPI displayed a similar pattern of anatomical abnormality compared to patients with NPNN.

Conclusion

Our findings indicate that anatomical abnormalities of the hippocampus relate to working memory performance and clinical symptoms in persons with schizophrenia. Moreover, NPNN and NPI patients may lie on a continuum of severity, both in terms of working memory abilities and altered brain structure, with NPI patients being more severe than NPNN patients in both domains.
The highest region of muscle spindle abundance should be the optimal target of botulinum toxin A injection to block muscle spasms in rats
Authors: Yu Jie , Li Yunshan , Yang Lu , Li Yi , Zhang Shibin , Yang Shengbo
Published: February 2023

Purpose

The effective relief of muscle spasticity requires prompt solutions in rehabilitation medicine. This study aimed to reveal that the highest region of muscle spindle abundance is the optimal target of botulinum toxin A (BTX-A) injections for relieve muscle spasm.

Methods

Sixty adult, male Sprague–Dawley rats with lower limbs spasm caused by stroke after modeling, weighing (200 ± 20) g, were included in this study. The modelrats were divided into four groups: muscle spasm model group (group A), model rats treated with BTX-A injections into the middle of the muscle belly (group B), model rats treated with BTX-A injections into the center of the intramuscular nerve-dense region (INDR) (group C), and model rats treated with BTX-A injection into the center of the highest region of muscle spindle abundance (HRMSA) (group D). Groups B, C, and D were further divided into two subgroups: the 3rd and 6th days after BTX-A injection. The rats in each group were assigned modified Ashworth scale scores (MAS), and the changes in gastrocnemius muscle tone, wet muscle weight, and cross-sectional area of muscle fiber were detected.

Results

Muscle spindle abundance was the highest in the upper part of the INDR. Group B experienced no significant changes in MAS, muscle tone, wet muscle weight, or cross-sectional area of the muscle fiber. Conversely, groups C and D experienced a decrease in these indicators. Group C experienced the most significant decrease in wet muscle weight and cross-sectional area of muscle fibers. Group D experienced the most notable decrease in MAS and muscle tone. There were no significant differences in the indicators between the 3rd and 6th days after BTX-A injections in group B and there were significant differences in the improvement in the indicators between the two subgroups in groups C and D, with group D experiencing more notable intersubgroup differences.

Conclusion

The efficacy of BTX-A injections into the HRMSA is significantly superior to that of conventional BTX-A injections into the middle of the belly muscle or the INDR in the treatment of muscle spasms. Hence, HRMSA should be the optimal target of BTX-A to relieve muscle spasms.
Theta phase coherence in visual mismatch responses involved in access processing to visual awareness
Authors: Kurita Yuki , Urakawa Tomokazu , Araki Osamu
Published: February 2023

Introduction: The electroencephalographic brain response to a deviation from the preceding sequential regularity of visual events, called visual mismatch negativity (vMMN), is well known to reflect automatic visual change detection. Our preliminary study showed a significant correlation between the enhancement of the vMMN amplitude and facilitation of perceptual alternation in binocular rivalry when the deviant stimulus was presented unconsciously. This implies that the vMMN is relevant to access processing, in which the unconscious stimulus is consciously perceived. Recent studies have reported that theta band oscillation evoked by a deviant stimulus is involved in evoking vMMN. However, it has not been clarified whether theta band oscillation associated with vMMN is also relevant to access processing.

Methods: We analyzed the correlations between event-related spectral perturbation (ERSP) and inter-trial phase coherence (ITPC) in the theta band and the proportion of perceptual alternation from before to after the presentation of deviation in the same experimental paradigm as in our previous study.

Results: We found that an increase in ITPC in the theta band tended to correlate with facilitation of perceptual alternation in binocular rivalry when the deviant was presented unconsciously, but there was no significant correlation in ERSP.

Discussion: The results suggest that theta phase coherence underlying the visual mismatch process is relevant to the access processing.
A systematic comparison of deep learning methods for EEG time series analysis
Authors: Walther Dominik , Viehweg Johannes , Haueisen Jens , Mäder Patrick
Published: February 2023

Analyzing time series data like EEG or MEG is challenging due to noisy, high-dimensional, and patient-specific signals. Deep learning methods have been demonstrated to be superior in analyzing time series data compared to shallow learning methods which utilize handcrafted and often subjective features. Especially, recurrent deep neural networks (RNN) are considered suitable to analyze such continuous data. However, previous studies show that they are computationally expensive and difficult to train. In contrast, feed-forward networks (FFN) have previously mostly been considered in combination with hand-crafted and problem-specific feature extractions, such as short time Fourier and discrete wavelet transform. A sought-after are easily applicable methods that efficiently analyze raw data to remove the need for problem-specific adaptations. In this work, we systematically compare RNN and FFN topologies as well as advanced architectural concepts on multiple datasets with the same data preprocessing pipeline. We examine the behavior of those approaches to provide an update and guideline for researchers who deal with automated analysis of EEG time series data. To ensure that the results are meaningful, it is important to compare the presented approaches while keeping the same experimental setup, which to our knowledge was never done before. This paper is a first step toward a fairer comparison of different methodologies with EEG time series data. Our results indicate that a recurrent LSTM architecture with attention performs best on less complex tasks, while the temporal convolutional network (TCN) outperforms all the recurrent architectures on the most complex dataset yielding a 8.61% accuracy improvement. In general, we found the attention mechanism to substantially improve classification results of RNNs. Toward a light-weight and online learning-ready approach, we found extreme learning machines (ELM) to yield comparable results for the less complex tasks.
The clinicopathological features of ganglioglioma with CD34 expression and BRAF mutation in patients with epilepsy
Authors: Xie Ming-Guo , Wang Xiong-Fei , Qiao Jiao , Zhou Jian , Guan Yu-Guang , Li Tian-Fu , Qi Xue-Ling , Luan Guo-Ming
Published: February 2023

Objective

The aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated gangliogliomas (GG) with CD34 expression and BRAFV600E mutation.

Methods

Clinical data of patients who underwent epilepsy surgery for GG were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAFV600E mutation in GG.

Results

A total of 208 patients with GG had immunohistochemical detection of CD34 expression (positive/negative: 184/24), and among them, 89 patients had immunohistochemical detection of BRAFV600E mutation (positive/negative: 54/35). By univariate and multivariate analyses, seizure aura (p = 0.025), concordance of ictal electroencephalogram (EEG) findings (p = 0.045) and medial temporal tumor (p = 0.030) were found to be related to CD34 expression, but only hospitalization time (p = 0.042) was different for BRAF-mutated status. In addition, drug-resistant epilepsy (p = 0.040) and concordance of interictal EEG findings (p = 0.009) were found to be associated with tumor progression-free survival (PFS) in univariate analysis, but only concordance of interictal EEG findings was with significance in multivariate analysis. However, CD34 expression or BRAFV600E mutation in GG was not found to be associated with surgical outcomes of seizure control and tumor PFS.

Conclusion

The CD34 expression or BRAFV600E mutation in GG may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence.
Association between magnesium intake and the risk of anemia among adults in the United States
Authors: Huang Jungao , Xu Jing , Ye Ping , Xin Xiaoqin
Published: February 2023

Background

Magnesium deficiency is related to an increased risk of anemia, but epidemiological evidence supporting this association remains scarce. The purpose of the present survey was to evaluate the relationship between dietary magnesium intake and the risk of anemia.

Methods

In total, 13,423 participants aged 20–80 years were enrolled using data from the National Health and Nutrition Examination Survey 2011–2016. Magnesium consumption was evaluated using 24 h dietary recalls. Multivariable generalized linear models were developed to demonstrate the association between dietary magnesium intake and the prevalence of anemia.

Results

An inverse association between dietary magnesium intake and the risk of anemia was detected based on a full adjustment model. We evaluated magnesium intake as a categorical variable (five quartiles). Compared with the lowest value, the highest multivariate adjusted odds ratio (95% confidence interval) for anemia was 0.64 (0.46–0.89). Stratified analyses revealed a reverse relationship between magnesium intake and anemia in women. However, no significant association was observed in men (pfor trend = 0.376). A similar reverse association was found among the older group (aged ≥60 years).

Conclusion

Magnesium deficiency is closely related to a higher rate of anemia occurrence, especially among women and older Americans. Further larger-scale prospective studies are required to confirm these conclusions.
Causal effects of fatty acids on atopic dermatitis: A Mendelian randomization study
Authors: Lin Jia-Ying , Ma Liang-Juan , Yuan Jin-Ping , Yu Pei , Bai Bing-Xue
Published: February 2023

Background

Some evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach.

Methods

We evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the FADS genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD.

Results

Mendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 ORIVW: 0.92, 95% confidence interval [CI]: 0.87–0.98; p = 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84–0.98; p = 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through FADS cluster, highlighting the significance of the FADS gene in the fatty acids synthesis pathway in the development of AD.

Conclusion

Our studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.
USDA Nutrition Evidence Systematic Review’s collaborative approach for conducting systematic reviews: Promoting diversity of expertise while managing potential conflicts of interest
Authors: Obbagy Julie , Raghavan Ramkripa , Cole Natasha Chong , English Laural K. , Higgins Molly , Spahn Joanne M. , Bahnfleth Charlotte L. , Callahan Emily , Fultz Amanda , Kim Julia H. , Kingshipp Brittany J. , Nevins Julie E. H. , Scinto-Madonich Sara R. , Webster Allison , Stoody Eve
Published: February 2023

U.S. Department of Agriculture’s (USDA) Nutrition Evidence Systematic Review (NESR) Branch develops food-and nutrition-related systematic reviews and other evidence synthesis products. NESR has established itself as a key resource for the Federal government when making evidence-informed decisions related to public health nutrition, such as the development of the Dietary Guidelines for Americans. NESR’s systematic review methodology is rigorous, protocol-driven, and highly collaborative. NESR’s systematic reviews examine the complex interplay between diet and health with input and support from various collaborators, including Federal stakeholders, expert groups, and public stakeholders. Implementing NESR’s rigorous methodology ensures that the appropriate steps are taken to minimize conflict of interest, producing systematic reviews that are high-quality, trustworthy, and useful to end users who make decisions based on their findings. This article describes how NESR’s systematic review process leverages a diversity of expertise and experience, while managing potential conflicts of interest. It describes the groups who collaborate to conduct NESR systematic reviews, their expertise, and why their involvement is critical for ensuring the rigor and utility of NESR’s work.
Mitigation of Paeoniae Radix Alba extracts on H2O2-induced oxidative damage in HepG2 cells and hyperglycemia in zebrafish, and identification of phytochemical constituents
Authors: Zhang Lu , Deng Mei , Wang Si-yu , Ding Qiao , Liu Jia-hui , Xie Xing , Huang Yun-hong , Tu Zong-cai
Published: February 2023

Paeoniae Radix Alba (PRA), as a Traditional Chinese Medicine, is widely used in Chinese cuisine due to high health-benefits and nutrition, but the effect of different polarity of solvents on the extraction of antioxidant and hypoglycemic constituents, as well as the major active compounds remain unclear. In this research, 40, 70, and 95% ethanol were firstly applied to extract the polyphenols from PRA, the extraction yields, total phenolics, and total flavonoids content, free radical scavenging ability, α-glucosidase inhibition ability, and anti-glycation ability of extracts were evaluated spectroscopically. The oxidative damage protection, hypoglycemic activity, and alleviation on peripheral nerve damage were evaluated by H2O2-induced HepG2 cells and hyperglycemic zebrafish models. UPLC-QTOF-MS/MS was used to identify the major chemical constituents. The results showed that 40, 70, and 95% ethanol exhibited insignificant difference on the extraction of phenolics and flavonoids from PRA. All extracts showed promising DPPH⋅ and ABTS⋅+ scavenging ability, α-glucosidase inhibition and anti-glycation ability. In addition, PRA extracts could restore the survival rate of HepG2 cells induced by H2O2, and alleviate the oxidative stress by reducing the content of MDA and increasing the levels of SOD, CAT, and GSH-Px. The 70% ethanol extract could also mitigate the blood glucose level and peripheral motor nerve damage of hyperglycemic zebrafish. Thirty-five compounds were identified from 70% ethanol extract, gallotannins, gallic acid and its derivatives, and paeoniflorin and its derivatives were the dominant bioactive compounds. Above results could provide important information for the value-added application of PRA in functional food and medicinal industry.
Transarterial chemoembolization combined with lenvatinib versus transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Liu Jun-Ning , Li Ji-Jiang , Yan Shu , Zhang Guang-Nian , Yi Peng-Sheng
Published: February 2023

Background

The combination of tyrosine kinase inhibitors (TKIs) and transarterial chemoembolization (TACE) fulfills an important role in the treatment of unresectable hepatocellular carcinoma (uHCC). Among the combination therapies, both lenvatinib and sorafenib combined with TACE are recommended as first-¬line treatments for uHCC. However, at present, limited data are available concerning the efficacy and safety of these two combination therapies in uHCC.

Methods

A detailed systematic search for studies on lenvatinib plus TACE (LEN+TACE) and sorafenib plus TACE (SOR+TACE) was conducted in the online databases PubMed, Embase and The Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), time to progression (TTP), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.

Results

One randomized controlled trial and five cohort studies with 598 patients (LEN+TACE: 261, SOR+TACE: 337) were included in the meta-analysis. A higher rate of odds ratio (OR) for the objective response rate (ORR) [OR: 3.63; 95% confidence intervals (95% CI): 1.89-6.95; I squared statistic (I2) = 57%, P < 0.001] and disease control rate (DCR) (OR: 3.78; 95% CI: 2.00-7.16; I2 = 52%, P = 0.0001) were observed in the LEN+SOR group compared with the SOR+TACE group. The LEN+TACE group also had significant longer OS [hazard ratio (HR): 0.67; 95% CI: 0.52-0.85; I2 = 1%, P = 0.001], PFS (HR: 0.49; 95% CI: 0.38-0.62; I2 = 0%, P? 0.001) and TTP (HR: 0.62; 95% CI: 0.45-0.84; I2 = 0%, P = 0.002) compared with the SOR+TACE group. The incidence of hypertension (OR: 3.05; 95% CI: 1.45-6.39; P = 0.003) and proteinuria (OR: 5.25; 95% CI: 1.73-15.89; P = 0.003) were significantly higher in the LEN+TACE group than SOR+TACE group, while LEN+TACE group exhibited a lower rate of hand–foot–skin reaction (HFSR) (OR: 0.51; 95% CI: 0.27-0.95; P = 0.03) compared with the SOR+TACE group.

Conclusion

The combination therapy of LEN+TACE showed significant superiority compared with SOR+TACE in terms of its efficacy for patients with uHCC. SOR+TACE should be recommended as a replacement therapy when serious AEs occur during the administration of LEN+TACE as the combination therapy.
CNS efficacy of afatinib as first-line treatment in advanced non-small cell lung cancer patients with EGFR mutations
Authors: Kang Liping , Mai Jianliang , Liang Weiting , Zou Qihua , Huang Caiwen , Lin Yongbin , Liang Ying
Published: February 2023

Background

Afatinib is a potent, irreversible second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has demonstrated efficacy in advanced non-small cell lung cancer (NSCLC) patients harboring either common or uncommon EGFR mutations. However, data on its activity against brain metastases are limited. This study aimed to retrospectively evaluate the efficacy and safety of afatinib as first-line treatment for EGFR-mutant NSCLC patients with brain metastases.

Methods

Treatment-naive advanced NSCLC patients harboring EGFR mutations and brain metastases treated with afatinib were retrospectively reviewed to assess the central nervous system (CNS) efficacy and also the systematic benefits.

Results

Totally 43 patients with measurable or non-measurable brain metastases were enrolled in the CNS full analysis (cFAS) set. Among them, 23 patients with measurable brain metastases were included in the CNS evaluable for response (cEFR) set. The CNS ORR was 48.8% (95% CI, 33.3 - 64.5%) in the cFAS set and 82.6% (95% CI, 61.2 - 95.0%) in the cEFR set, respectively. CNS mDoR was 8.9 months (95% CI, 4.7 - 13.1 months) and CNS mPFS was 12.7 months (95% CI, 6.9 - 18.5 months) in the cFAS set. In the subgroup analysis stratified by EGFR mutation types, CNS ORR of cEFR set in the common mutation cohort was 100% (95% CI, 75.3 - 100%) and 60% (95% CI, 26.2 - 87.8%) in the uncommon mutation cohort (p = 0.024); CNS ORR of cFAS set was 57.7% (95% CI, 36.9 - 76.6%) and 35.3% (95% CI, 14.2 - 61.7%), respectively (p = 0.151). CNS mPFS was 14.4 months in patients with common mutations and 6.1 months in patients with uncommon mutations (hazard ratio, 0.47; 95% CI, 0.22 - 1.00; p = 0.045). Patients with common mutations showed a significantly lower cumulative incidence of CNS failure than uncommon mutation cohort (p = 0.0026). Most of patients experienced grade 1/2 treatment-related adverse events.

Conclusions

First-line afatinib demonstrated encouraging efficacy on brain metastases in NSCLC patients harboring either common or major uncommon EGFR mutations in a real-world setting, with manageable toxicities. Patients with common mutations showed better CNS outcomes than those with uncommon mutations.
Artificial-intelligence-based computed tomography histogram analysis predicting tumor invasiveness of lung adenocarcinomas manifesting as radiological part-solid nodules
Authors: Gao Jian , Qi Qingyi , Li Hao , Wang Zhenfan , Sun Zewen , Cheng Sida , Yu Jie , Zeng Yaqi , Hong Nan , Wang Dawei , Wang Huiyang , Yang Feng , Li Xiao , Li Yun
Published: February 2023

Background

Tumor invasiveness plays a key role in determining surgical strategy and patient prognosis in clinical practice. The study aimed to explore artificial-intelligence-based computed tomography (CT) histogram indicators significantly related to the invasion status of lung adenocarcinoma appearing as part-solid nodules (PSNs), and to construct radiomics models for prediction of tumor invasiveness.

Methods

We identified surgically resected lung adenocarcinomas manifesting as PSNs in Peking University People’s Hospital from January 2014 to October 2019. Tumors were categorized as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) by comprehensive pathological assessment. The whole cohort was randomly assigned into a training (70%, n=832) and a validation cohort (30%, n=356) to establish and validate the prediction model. An artificial-intelligence-based algorithm (InferRead CT Lung) was applied to extract CT histogram parameters for each pulmonary nodule. For feature selection, multivariate regression models were built to identify factors associated with tumor invasiveness. Logistic regression classifier was used for radiomics model building. The predictive performance of the model was then evaluated by ROC and calibration curves.

Results

In total, 299 AIS/MIAs and 889 IACs were included. In the training cohort, multivariate logistic regression analysis demonstrated that age [odds ratio (OR), 1.020; 95% CI, 1.004–1.037; p=0.017], smoking history (OR, 1.846; 95% CI, 1.058–3.221; p=0.031), solid mean density (OR, 1.014; 95% CI, 1.004–1.024; p=0.008], solid volume (OR, 5.858; 95% CI, 1.259–27.247; p = 0.037), pleural retraction sign (OR, 3.179; 95% CI, 1.057–9.559; p = 0.039), variance (OR, 0.570; 95% CI, 0.399–0.813; p=0.002), and entropy (OR, 4.606; 95% CI, 2.750–7.717; p<0.001) were independent predictors for IAC. The areas under the curve (AUCs) in the training and validation cohorts indicated a better discriminative ability of the histogram model (AUC=0.892) compared with the clinical model (AUC=0.852) and integrated model (AUC=0.886).

Conclusion

We developed an AI-based histogram model, which could reliably predict tumor invasiveness in lung adenocarcinoma manifesting as PSNs. This finding would provide promising value in guiding the precision management of PSNs in the daily practice.
Nomogram prediction model of postoperative pneumonia in patients with lung cancer: A retrospective cohort study
Authors: Jin Fan , Liu Wei , Qiao Xi , Shi Jingpu , Xin Rui , Jia Hui-Qun
Published: February 2023

Background

The prediction model of postoperative pneumonia (POP) after lung cancer surgery is still scarce.

Methods

Retrospective analysis of patients with lung cancer who underwent surgery at The Fourth Hospital of Hebei Medical University from September 2019 to March 2020 was performed. All patients were randomly divided into two groups, training cohort and validation cohort at the ratio of 7:3. The nomogram was formulated based on the results of multivariable logistic regression analysis and clinically important factors associated with POP. Concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow goodness-of-fit test and decision curve analysis (DCA) were used to evaluate the predictive performance of the nomogram.

Results

A total of 1252 patients with lung cancer was enrolled, including 877 cases in the training cohort and 375 cases in the validation cohort. POP was found in 201 of 877 patients (22.9%) and 89 of 375 patients (23.7%) in the training and validation cohorts, respectively. The model consisted of six variables, including smoking, diabetes mellitus, history of preoperative chemotherapy, thoracotomy, ASA grade and surgery time. The C-index from AUC was 0.717 (95%CI:0.677-0.758) in the training cohort and 0.726 (95%CI:0.661-0.790) in the validation cohort. The calibration curves showed the model had good agreement. The result of DCA showed that the model had good clinical benefits.

Conclusion

This proposed nomogram could predict the risk of POP in patients with lung cancer surgery in advance, which can help clinician make reasonable preventive and treatment measures.
Novel considerations on EGFR-based therapy as a contributor to cancer cell death in NSCLC
Authors: Peng Weiwei , Yao Chengyun , Pan Qin , Zhang Zhi , Ye Jinjun , Shen Bo , Zhou Guoren , Fang Ying
Published: February 2023

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) represented by gefitinib and erlotinib are widely used in treating non-small cell lung cancer (NSCLC). However, acquired resistance to EGFR-TKI treatment remains a clinical challenge. In recent years, emerging research investigated in EGFR-TKI-based combination therapy regimens, and remarkable achievements have been reported. This article focuses on EGFR-TKI-based regimens, reviews the standard and novel application of EGFR targets, and summarizes the mechanisms of EGFR-TKI combinations including chemotherapy, anti-vascular endothelial growth factor monoclonal antibodies, and immunotherapy in the treatment of NSCLC. Additionally, we summarize clinical trials of EGFR-TKI-based combination therapy expanding indications to EGFR mutation-negative lung malignancies. Moreover, novel strategies are under research to explore new drugs with good biocompatibility. Nanoparticles encapsulating non-coding RNA and chemotherapy of new dosage forms drawn great attention and showed promising prospects in effective delivery and stable release. Overall, as the development of resistance to EGFR-TKIs treatment is inevitable in most of the cases, further research is needed to clarify the underlying mechanism of the resistance, and to evaluate and establish EGFR-TKI combination therapies to diversify the treatment landscape for NSCLC.
Potential use of TG68 - A novel thyromimetic - for the treatment of non-alcoholic fatty liver (NAFLD)-associated hepatocarcinogenesis
Authors: Caddeo Andrea , Serra Marina , Sedda Francesca , Bacci Andrea , Manera Clementina , Rapposelli Simona , Columbano Amedeo , Perra Andrea , Kowalik Marta Anna
Published: February 2023

Introduction

Several lines of evidence suggest that the thyroid hormone signaling pathway is altered in patients with NAFLD and that pharmacological strategies to target the thyroid hormone/thyroid hormone nuclear receptor axis (TH/THR) in the liver may exert beneficial effects. In this study, we investigated the effect of TG68, a novel THRβ agonist, on rat hepatic fat accumulation and NAFLD-associated hepatocarcinogenesis.

Methods

Male rats given a single dose of diethylnitrosamine (DEN) and fed a high fat diet (HFD) were co-treated with different doses of TG68. Systemic and hepatic metabolic parameters, immunohistochemistry and hepatic gene expression were determined to assess the effect of TG68 on THRβ activation.

Results

Irrespectively of the dose, treatment with TG68 led to a significant reduction in liver weight, hepatic steatosis, circulating triglycerides, cholesterol and blood glucose. Importantly, a short exposure to TG68 caused regression of DEN-induced preneoplastic lesions associated with a differentiation program, as evidenced by a loss of neoplastic markers and reacquisition of markers of differentiated hepatocytes. Finally, while an equimolar dose of the THRβ agonist Resmetirom reduced hepatic fat accumulation, it did not exert any antitumorigenic effect.

Discussion

The use of this novel thyromimetic represents a promising therapeutic strategy for the treatment of NAFLD-associated hepatocarcinogenesis.
Global research trends between gut microbiota and lung cancer from 2011 to 2022: A bibliometric and visualization analysis
Authors: Chen Haitao , Lai Yuebiao , Ye Chenxiao , Wu Changhong , Zhang Jiali , Zhang Zewei , Yao Qinghua
Published: February 2023

Background

An increasing number of studies have found that the gut microbiota was related to the occurrence and development of lung cancer. Nonetheless, publication trends and research hotspots in this field remain unknown. The study aimed to perform a bibliometric analysis to systematically identify publication trends and research hotspots in the field of gut microbiota and lung cancer research within a 12-year panorama.

Methods

Publications related to the gut microbiota and lung cancer between 1 January 2011 and 25 October 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. The online analytic tool of the WoSCC was used to analyze various bibliometric parameters. The bibliometrics website, CiteSpace, and VOSviewer were used to identify research trends and hotspots.

Results

A total of 375 publications related to the gut microbiota and lung cancer were extracted from WoSCC and identified for analysis. The number of annual publications has grown rapidly since 2018 and reached a peak in 2022. China was the most prolific country in this field, with 120 publications, followed by the United States (114), with the highest H-index of 31. Additionally, France ranked the highest with an average of 133 citations, while the leading institution and journal were the Unicancer and the International Journal of Molecular Sciences, respectively. Interestingly, Routy Bertrand was the most prolific author and also the most cited author in terms of H-index and citations. Reference and keyword burst detection indicated that the research hotspots mainly included 1) the gut microbiota directly affects the efficacy of immunotherapy for lung cancer, 2) the application of different gut bacteria on lung cancer, and 3) the mechanism of the gut microbiota on lung cancer.

Conclusion

The findings of this study revealed the general publication trends and evolving research hotspots in the field of gut microbiota and lung cancer at a global level. The research hotspots focused on the clinical application of the gut microbiota combined with immunotherapy in lung cancer and its mechanism. The findings of this study provide new perspectives on the field, which may shed light on a beneficial impact on further etiological studies, diagnosis, and treatment for lung cancer.
Vascular endothelial growth factor and risk of malignant brain tumor: A genetic correlation and two-sample Mendelian randomization study
Authors: Zhang Qiaoyun , Wu Guangheng , Zhang Xiaoyu , Zhang Jie , Jiang Mengyang , Zhang Yiqiang , Ding Lixiang , Wang Youxin
Published: February 2023

Objective

The relationship between vascular endothelial growth factor (VEGF) and the risk of malignant brain tumors has always been a concern in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders, coinheritability and reverse causality. We aimed to investigate the causal relationship between VEGF and different types of malignant brain tumors.

Methods

Using publicly available summary data from genome-wide association studies (GWAS) of VEGF (n=16,112) and different types of malignant brain tumors (n=174,097-174,646), we adopted a standard two-sample bidirectional Mendelian randomization (MR) to estimate potential causal associations of circulating VEGF levels and the risk of malignant brain tumors. Inverse variance weighted (IVW) was used as the primary analysis method to estimate causality. MR-Egger regression, weighted median (WM), penalty weighted median (PWM), MR robust adjusted profile score (MR.RAPS) and causal analysis using summary effect estimates (CAUSE) methods were used in sensitivity analyses to verify the robustness of the findings. Meanwhile, we applied the MR pleiotropy residual sum and outlier (MR-PRESSO) test and PhenoScanner tool to identify and remove potential horizontal pleiotropic single nucleotide polymorphisms (SNPs). Additionally, linkage disequilibrium score regression (LDSC) analysis was conducted to assess the coinheritability of exposure and outcome.

Results

A total of 6 (VEGF), 12 (malignant brain tumor), 13 (brain glioblastoma) and 12 (malignant neoplasm of meninges) SNPs were identified as valid instrumental variables. No evidence supported a causal relationship between circulating VEGF levels and the risk of malignant brain tumors (forwards: odds ratio (OR) = 1.277, 95% confidence interval (CI), 0.812~2.009; reversed: β = 0.005, 95% CI, -0.029~0.038), brain glioblastoma (forwards: OR (95% CI) = 1.278(0.463~3.528); reversed: β = 0.010, 95% CI, -0.002~0.022) and malignant neoplasm of meninges (forwards: OR (95% CI) = 0.831(0.486~1.421); reversed: β = 0.010, 95% CI, -0.030~0.050) using the main IVW method. Outliers and pleiotropy bias were not detected by sensitivity analyses and pleiotropy-robust methods in any estimates. LDSC failed to identify genetic correlations between VEGF and different types of malignant brain tumors.

Conclusions

Our findings reported no coinheritability and failed to provide evidence for causal associations between VEGF and the risk of different types of malignant brain tumors. However, certain subtypes of VEGF for which genetic predictors have not been identified may play a role and need to be further investigated.
A novel current steering method for targeted spinal cord stimulation
Authors: Mishra Lakshmi Narayan , Kulkarni Gaurav , Gadgil Mandar
Published: February 2023

Spinal Cord Stimulation (SCS) with leads embedded in the epidural space has become a recognized and effective clinical therapy for chronic pain relief. Leads with multiple electrodes placed close to the spinal cord allow targeted stimulation. This paper presents a novel current steering method to achieve targeted spinal cord stimulation by determining the optimal current sourced through a set of electrodes to maximize current density in a specified region of the spinal cord. The method provides a flexibility for personalized pain relief therapy, while minimizing stimulation in unwanted regions. The paper proposes a new optimization problem to achieve current steering. The optimization problem uses a solution of the Poisson equation evaluated using Finite Element Analysis (FEA) over a geometric model of the spinal cord and the embedded leads. The solution to the optimization problem determines the optimal current sourced through a set of electrodes to achieve a targeted stimulation.
Association between unmet social needs and healthy lifestyle parenting behaviors
Authors: Egan Kelsey A. , Luo Man , Perkins Meghan , Castro Ines , Sandel Megan , Kistin Caroline J. , Taveras Elsie M. , Fiechtner Lauren
Published: February 2023

Objective

To examine cross-sectional associations of food and housing security risks and healthy lifestyle parenting behaviors related to nutrition and physical activity among families with children with overweight/obesity.

Methods

We surveyed 407 parents of children ages 6–12 years with overweight/obesity. Exposures were measures of food and housing insecurity risk. Outcomes were healthy lifestyle parenting behaviors related to nutrition and physical activity. Logistic regression models for each exposure-outcome relationship were adjusted for parental educational attainment, parental cohabitation status, household size, and household income.

Results

In multivariable-adjusted models, food insecurity was associated with significantly lower odds of parent modeling exercise {aOR 0.60 [95% confidence interval (CI): 0.37, 0.96]} and parent modeling eating healthy foods [aOR 0.42 (95% CI: 0.24, 0.73)]. Housing insecurity was associated with significantly lower odds of parent modeling exercise [aOR 0.57 (95% CI: 0.35, 0.95)].

Conclusions

Food insecurity and housing insecurity may be barriers to parents adopting and modeling healthy lifestyle parenting behaviors related to physical activity and nutrition.
Endoscopic percutaneous repair of laryngeal cleft
Authors: Tang XinYe , Yang Yang , Zhang ZhiHai , Sun Rong
Published: February 2023

Objective

The aim of this study was to describe a novel surgical technique of endoscopic percutaneous repair in pediatric patients with type 1, type 2 and type 3 laryngeal cleft (LC).

Methods

A retrospective study involving 12 patients with LC was performed at a tertiary pediatric hospital between February 2021 and June 2022. Endoscopic percutaneous repair was performed in all the patients. Information such as demographics, comorbidities, history of tracheostomy and the open approach for the repair, type of cleft and complications were analyzed.

Results

Twelve patients were diagnosed with LC. The median age of the patients at the time of surgery was 8.50 months (interquartile range, 49.50 months). Seven patients had tracheomalacia, four patients had subglottic stenosis, three patients had laryngomalacia. No surgical complications occurred in the 10 patients who underwent the primary procedure. For two patients who underwent a secondary procedure, endoscopic percutaneous repair failed again to heal the cleft. During the follow-up period after surgery, none of the patients had stridor, recurrent pneumonia, feeding difficulties, or dyspnea. Follow-up modified barium swallow postoperatively demonstrated no aspiration in 10 patients. Only the 2 patients with a secondary procedure had intermittent cough while taking large gulps of water. The cure rate of endoscopic percutaneous repairer was 83.3% (95% confidence interval: 73.9%–92.8%).

Conclusion

Endoscopic percutaneous repair should be considered as an alternative to the open transcervical approach and the traditional endoscopic approach for type 1, type 2 and type 3 LC.
Locomotor learning in infants at high risk for cerebral palsy: A study protocol
Authors: Prosser Laura A. , Skorup Julie , Pierce Samuel R. , Jawad Abbas F. , Fagg Andrew H. , Kolobe Thubi H. A. , Smith Beth A.
Published: February 2023

Background

Physical disability in individuals with cerebral palsy (CP) creates lifelong mobility challenges and healthcare costs. Despite this, very little is known about how infants at high risk for CP learn to move and acquire early locomotor skills, which set the foundation for lifelong mobility. The objective of this project is to characterize the evolution of locomotor learning over the first 18 months of life in infants at high risk for CP. To characterize how locomotor skill is learned, we will use robotic and sensor technology to provide intervention and longitudinally study infant movement across three stages of the development of human motor control: early spontaneous movement, prone locomotion (crawling), and upright locomotion (walking).

Study design

This longitudinal observational/intervention cohort study (ClinicalTrials.gov Identifier: NCT04561232) will enroll sixty participants who are at risk for CP due to a brain injury by one month post-term age. Study participation will be completed by 18 months of age. Early spontaneous leg movements will be measured monthly from 1 to 4 months of age using inertial sensors worn on the ankles for two full days each month. Infants who remain at high risk for CP at 4 months of age, as determined from clinical assessments of motor function and movement quality, will continue through two locomotor training phases. Prone locomotor training will be delivered from 5 to 9 months of age using a robotic crawl training device that responds to infant behavior in real-time. Upright locomotor training will be delivered from 9 to 18 months of age using a dynamic weight support system to allow participants to practice skills beyond their current level of function. Repeated assessments of locomotor skill, training characteristics (such as movement error, variability, movement time and postural control), and variables that may mediate locomotor learning will be collected every two months during prone training and every three months during upright training.

Discussion

This study will develop predictive models of locomotor skill acquisition over time. We hypothesize that experiencing and correcting movement errors is critical to skill acquisition in infants at risk for CP and that locomotor learning is mediated by neurobehavioral factors outside of training.

Project Number 1R01HD098364-01A1.

ClinicalTrials.gov Identifier: NCT04561232