bluuebunny/crossref_metadata_2025 huggingface dataset:
Model for predicting immunotherapy based on M2 macrophage infiltration in TNBC
Authors: Wu Haoming , Feng Jikun , Zhong Wenjing , Zouxu Xiazi , Xiong Zhengchong , Huang Weiling , Zhang Chao , Wang Xi , Yi Jiarong
Published: March 2023

Introduction

Compared to other types of breast cancer, triple-negative breast cancer (TNBC) does not effectively respond to hormone therapy and HER2 targeted therapy, showing a poor prognosis. There are currently a limited number of immunotherapeutic drugs available for TNBC, a field that requires additional development.

Methods

Co-expressing genes with M2 macrophages were analyzed based on the infiltration of M2 macrophages in TNBC and the sequencing data in The Cancer Genome Atlas (TCGA) database. Consequently, the influence of these genes on the prognoses of TNBC patients was analyzed. GO analysis and KEGG analysis were performed for exploring potential signal pathways. Lasso regression analysis was conducted for model construction. The TNBC patients were scored by the model, and patients were divided into high- and low-risk groups. Subsequently, the accuracy of model was further verified using GEO database and patients information from the Cancer Center of Sun Yat-sen University. On this basis, we analyzed the accuracy of prognosis prediction, correlation with immune checkpoint, and immunotherapy drug sensitivity in different groups.

Results

Our findings revealed that OLFML2B, MS4A7, SPARC, POSTN, THY1, and CD300C genes significantly influenced the prognosis of TNBC. Moreover, MS4A7, SPARC, and CD300C were finally determined for model construction, and the model showed good accuracy in prognosis prediction. And 50 immunotherapy drugs with therapeutic significance in different groups were screened, which were assessed possible immunotherapeutics that have potential application and demonstrated the high precision of our prognostic model for predictive analysis.

Conclusion

MS4A7, SPARC, and CD300C, the three main genes used in our prognostic model, offer good precision and clinical application potential. Fifty immune medications were assessed for their ability to predict immunotherapy drugs, providing a novel approach to immunotherapy for TNBC patients and a more reliable foundation for applying drugs in subsequent treatments.
Seismic airgun sound propagation in shallow water of the East Siberian shelf and its prediction with the measured source signature
Authors: Han Dong-Gyun , Kim Sookwan , Landrø Martin , Son Wuju , Lee Dae Hyeok , Yoon Young Geul , Choi Jee Woong , Yang Eun Jin , Choi Yeonjin , Jin Young Keun , Hong Jong Kuk , Kang Sung-Ho , Rhee Tae Siek , Shin Hyoung Chul , La Hyoung Sul
Published: March 2023

Seismic airgun sound was measured with an autonomous passive acoustic recorder as a function of distance from 18.6 to 164.2 km in shallow water (<70 m) at the continental shelf of the East Siberian Sea in September 2019. The least-square regression curves were derived in the zero-to-peak sound pressure level, sound exposure level, and band level in a frequency range between 10 and 300 Hz using the initial amplitude scaled from the near-field hydrophone data. In addition, propagation modeling based on the parabolic equation with the measured source spectrum was performed for range-dependent bathymetry, and the results were compared with the band level of the measurements. The sediment structure of the measurement area was a thin layer of iceberg-scoured postglacial mud overlying a fast bottom with high density based on grounding events of past ice masses. The observed precursor arrivals, modal dispersion, and rapid decrease in spectrum level at low frequencies can be explained by the condition of the high-velocity sediment. Our results can be applied to studies on the inversion of ocean boundary conditions and measurement geometry and basic data for noise impact assessment.
Genome, biology and stability of the Thurquoise phage – A new virus from the Bastillevirinae subfamily
Authors: Węglewska Martyna , Barylski Jakub , Wojnarowski Filip , Nowicki Grzegorz , Łukaszewicz Marcin
Published: March 2023

Bacteriophages from the Bastillevirinae subfamily (Herelleviridae family) have proven to be effective against bacteria from the Bacillus genus including organisms from the B. cereus group, which cause food poisoning and persistent contamination of industrial installations. However, successful application of these phages in biocontrol depends on understanding of their biology and stability in different environments. In this study, we isolated a novel virus from garden soil in Wrocław (Poland) and named it ‘Thurquoise’. The genome of that phage was sequenced and assembled into a single continuous contig with 226 predicted protein-coding genes and 18 tRNAs. The cryo-electron microscopy revealed that Thurquoise has complex virion structure typical for the Bastillevirinae family. Confirmed hosts include selected bacteria from the Bacillus cereus group–specifically B. thuringiensis (isolation host) and B. mycoides, but susceptible strains display different efficiency of plating (EOP). The eclipse and latent periods of Thurquoise in the isolation host last ~ 50 min and ~ 70 min, respectively. The phage remains viable for more than 8 weeks in variants of the SM buffer with magnesium, calcium, caesium, manganese or potassium and can withstand numerous freeze–thaw cycles if protected by the addition of 15% glycerol or, to a lesser extent, 2% gelatine. Thus, with proper buffer formulation, this virus can be safely stored in common freezers and refrigerators for a considerable time. The Thurquoise phage is the exemplar of a new candidate species within the Caeruleovirus genus in the Bastillevirinae subfamily of the Herelleviridae family with a genome, morphology and biology typical for these taxa.
Rhizosphere microbial community assembly and association networks strongly differ based on vegetation type at a local environment scale
Authors: Liu Luxian , Ma Liya , Zhu Mengmeng , Liu Bo , Liu Xu , Shi Yu
Published: March 2023

Introduction

Rhizosphere microbes perform critical functions for their hosts, and their structure is strongly influenced by vegetation type. Although studies on the effects of vegetation on rhizosphere microbial community structure have been conducted at large and global environment scales, studies at local environment scales would eliminate numerous external factors such as climate and soil type, while highlighting the potential influence of local vegetation type.

Methods

Here, we compared rhizosphere microbial communities using 54 samples under three vegetation types (herb, shrubs, and arbors, with bulk soil as the control) at the campus of Henan University. 16S rRNA and ITS amplicons were sequenced using Illumina high throughput sequencing.

Results and Discussion

Rhizosphere bacterial and fungal community structures were influenced considerably by vegetation type. Bacterial alpha diversity under herbs was significantly different from that under arbors and shrubs. The abundance of phyla such as Actinobacteria was extremely higher in bulk soil than in the rhizosphere soils. Herb rhizosphere harbored more unique species than other vegetation type soils. Furthermore, bacterial community assembly in bulk soil was more dominated by deterministic process, whereas the rhizosphere bacterial community assembly was dominated by stochasticity and the construction of fungal communities was all dominated by deterministic processes. In addition, rhizosphere microbial networks were less complex than bulk soil networks, and their keystone species differed based on vegetation type. Notably, bacterial community dissimilarities were strongly correlated with plant phylogenetic distance. Exploring rhizosphere microbial community patterns under different vegetation types could enhance our understanding of the role of rhizosphere microbes in ecosystem function and service provision, as well as basic information that could facilitate plant and microbial diversity conservation at the local environment scale.
Accuracy-speed-stability trade-offs in a targeted stepping task are similar in young and older adults
Authors: Muijres Wouter , Arnalsteen Sylvie , Daenens Cas , Afschrift Maarten , De Groote Friedl
Published: March 2023

Introduction

Stepping accuracy, speed, and stability are lower in older compared to young adults. Lower stepping performance in older adults may be due to larger accuracy-speed-stability trade-offs because of reduced ability to simultaneously fulfill these task-level goals. Our goal was to evaluate whether trade-offs are larger in older compared to young adults in a targeted stepping task. Since sensorimotor function declines with age, our secondary goal was to evaluate whether poorer sensorimotor function was associated with larger trade-offs.

Methods

Twenty-five young (median 22 years old) and 25 older (median 70 years old) adults stepped into projected targets in conditions with various levels of accuracy, speed, and stability requirements. We determined trade-offs as the change in performance, i.e., foot placement error, step duration, and mediolateral center of pressure path length, between each of these conditions and a control condition. To assess age-related differences in the magnitude of trade-offs, we compared the change in performance between age groups. Associations between trade-offs and measures of sensorimotor function were tested using correlations.

Results

We found an accuracy-speed and an accuracy-stability trade-off in both young and older adults, but trade-offs were not different between young and older adults. Inter-subject differences in sensorimotor function could not explain inter-subject differences in trade-offs.

Conclusion

Age-related differences in the ability to combine task-level goals do not explain why older adults stepped less accurate and less stable than young adults. However, lower stability combined with an age-independent accuracy-stability trade-off could explain lower accuracy in older adults.
Differences in clinical and biological factors between patients with PFO-related stroke and patients with PFO and no cerebral vascular events
Authors: Badea Raluca Ştefania , Ribigan Athena Cristina , Grecu Nicolae , Terecoasǎ Elena , Antochi Florina Anca , Bâldea Mihǎilǎ Sorina , Tiu Cristina , Popescu Bogdan Ovidiu
Published: March 2023

Background

While stroke is one of the most dissected topics in neurology, the primary prevention of PFO-related stroke in young patients is still an unaddressed subject. We present a study concerning clinical, demographic, and laboratory factors associated with stroke and transient ischemic attack in patients with patent foramen ovale (PFO), as well as comparing PFO-patients with and without cerebrovascular ischemic events (CVEs).

Patients and methods

Consecutive patients with PFO-associated CVEs were included in the study; control group was selected from patients with a PFO and no history of stroke. All participants underwent peripheral routine blood analyses, as well as, on treating physician's recommendations, screening for thrombophilia.

Results

Ninety-five patients with CVEs and 41 controls were included. Females had a significantly lower risk of CVEs than males (p = 0.04). PFO size was similar between patients and controls. Patients with CVEs had more often hypertension (n = 33, 34.7%), p = 0.007. No significant differences were found between the two groups with regard to routine laboratory tests and thrombophilia status. Hypertension and gender were identified in a binomial logistic regression model as independent predictors for CVEs, but with an area under the ROC curve of 0.531, suggesting a very poor level of discrimination between the two groups.

Discussion and conclusions

There is little difference between patients with PFO with and without CVEs in terms of PFO size and routine laboratory analyses. While still a controversial topic in the specialty literature, classic first-level thrombophilic mutations are not a risk factor for stroke in patients with PFO. Hypertension and male gender were identified as factors associated with a higher risk of stroke in the setting of PFO.
Oxytocin receptors in the Magel2 mouse model of autism: Specific region, age, sex and oxytocin treatment effects
Authors: Gigliucci Valentina , Busnelli Marta , Santini Francesca , Paolini Camilla , Bertoni Alessandra , Schaller Fabienne , Muscatelli Françoise , Chini Bice
Published: March 2023

The neurohormone oxytocin (OXT) has been implicated in the regulation of social behavior and is intensively investigated as a potential therapeutic treatment in neurodevelopmental disorders characterized by social deficits. In the Magel2-knockout (KO) mouse, a model of Schaaf-Yang Syndrome, an early postnatal administration of OXT rescued autistic-like behavior and cognition at adulthood, making this model relevant for understanding the actions of OXT in (re)programming postnatal brain development. The oxytocin receptor (OXTR), the main brain target of OXT, was dysregulated in the hippocampus of Magel2-KO adult males, and normalized upon OXT treatment at birth. Here we have analyzed male and female Magel2-KO brains at postnatal day 8 (P8) and at postnatal day 90 (P90), investigating age, genotype and OXT treatment effects on OXTR levels in several regions of the brain. We found that, at P8, male and female Magel2-KOs displayed a widespread, substantial, down-regulation of OXTR levels compared to wild type (WT) animals. Most intriguingly, the postnatal OXT treatment did not affect Magel2-KO OXTR levels at P8 and, consistently, did not rescue the ultrasonic vocalization deficits observed at this age. On the contrary, the postnatal OXT treatment reduced OXTR levels at P90 in male Magel2-KO in a region-specific way, restoring normal OXTR levels in regions where the Magel2-KO OXTR was upregulated (central amygdala, hippocampus and piriform cortex). Interestingly, Magel2-KO females, previously shown to lack the social deficits observed in Magel2-KO males, were characterized by a different trend in receptor expression compared to males; as a result, the dimorphic expression of OXTR observed in WT animals, with higher OXTR expression observed in females, was abolished in Magel2-KO mice. In conclusion, our data indicate that in Magel2-KO mice, OXTRs undergo region-specific modifications related to age, sex and postnatal OXT treatment. These results are instrumental to design precisely-timed OXT-based therapeutic strategies that, by acting at specific brain regions, could modify the outcome of social deficits in Schaaf-Yang Syndrome patients.
The immediate effects of iTBS on the muscle activation pattern under challenging balance conditions in the patients with chronic low back pain: A preliminary study
Authors: Yang Jiajia , Fu Ruochen , Hao Zengming , Lin Nanhe , Cheng Xue , Ma Jinjin , Zhang Yushu , Li Yan , Lo Wai Leung Ambrose , Yu Qiuhua , Wang Chuhuai
Published: March 2023

Background

The patients with chronic low back pain (CLBP) showed impaired postural control, especially in challenging postural task. The dorsolateral prefrontal cortex (DLPFC) is reported to involve in the complex balance task, which required considerable attentional control. The effect of intermittent theta burst stimulation (iTBS) over the DLPFC to the capacity of postural control of CLBP patients is still unknown.

Methods

Participants diagnosed with CLBP received a single-session iTBS over the left DLPFC. All the participants completed the postural control tasks of single-leg (left/right) standing before and after iTBS. The activation changes of the DLPFC and M1 before and after iTBS were recorded by functional near-infrared spectroscopy (fNIRS). The activation pattern of the trunk [transversus abdominis (TrA), superficial lumbar multifidus (SLM)] and leg [tibialis anterior (TA), gastrocnemius medialis (GM)] muscles including root mean square (RMS) and co-contraction index (CCI) during single-leg standing were measured by surface electromyography (sEMG) before and after the intervention. The paired t-test was used to test the difference before and after iTBS. Pearson correlation analyses were performed to test the relationship between the oxyhemoglobin concentration and sEMG outcome variables (RMS and CCI).

Results

Overall, 20 participants were recruited. In the right-leg standing condition, compared with before iTBS, the CCI of the right TrA/SLM was significantly decreased (t = −2.172, p = 0.043), and the RMS of the right GM was significantly increased (t = 4.024, p = 0.001) after iTBS. The activation of the left DLPFC (t = 2.783, p = 0.012) and left M1 (t = 2.752, p = 0.013) were significantly decreased and the relationship between the left DLPFC and M1 was significant after iTBS (r = 0.575, p = 0.014). Correlation analysis showed the hemoglobin concentration of M1 was negatively correlated with the RMS of the right GM (r = −0.659, p = 0.03) and positively correlated between CCI of the right TrA/SLM (r = 0.503, p = 0.047) after iTBS. There was no significant difference in the brain or muscle activation change in the left leg-standing condition between before and after iTBS.

Conclusion

Intermittent theta burst stimulation over the left DLPFC seems to be able to improve the muscle activation pattern during postural control ability in challenging postural task, which would provide a new approach to the treatment of CLBP.
Cellular signaling impacts upon GABAergic cortical interneuron development
Authors: Pai Emily Ling-Lin , Stafford April M. , Vogt Daniel
Published: March 2023

The development and maturation of cortical GABAergic interneurons has been extensively studied, with much focus on nuclear regulation via transcription factors. While these seminal events are critical for the establishment of interneuron developmental milestones, recent studies on cellular signaling cascades have begun to elucidate some potential contributions of cell signaling during development. Here, we review studies underlying three broad signaling families, mTOR, MAPK, and Wnt/beta-catenin in cortical interneuron development. Notably, each pathway harbors signaling factors that regulate a breadth of interneuron developmental milestones and properties. Together, these events may work in conjunction with transcriptional mechanisms and other events to direct the complex diversity that emerges during cortical interneuron development and maturation.
Acute effects of fresh versus dried Hayward green kiwifruit on sleep quality, mood, and sleep-related urinary metabolites in healthy young men with good and poor sleep quality
Authors: Kanon Alexander P. , Giezenaar Caroline , Roy Nicole C. , McNabb Warren C. , Henare Sharon J.
Published: March 2023

Background and aims

Daily kiwifruit (KF) consumption has been associated with improved sleep quality, but underlying physiological mechanisms are unknown. This study examined acute effects of fresh and dried green KF, compared with a water control, on sleep quality, mood, and urinary serotonin and melatonin metabolite concentrations.

Methods

24 men (age: 29 ± 1 years, body mass index: 24 ± 1 kg/m2) with poor (n = 12) or good (n = 12) sleep quality participated in a randomized, single-blind crossover study. One of three treatments was consumed with a standardized evening meal; (1) the flesh of two fresh green KF, (2) dried green KF powder (including skin; equivalent to dry matter of two fresh KF) mixed with water, or (3) a water control, in their own home. Subjective and objective sleep quality, mood, waking urinary 5-hydroxyindoleacetic acid (5-HIAA), 6-sulfatoxymelatonin (aMT6s), vitamin C and B-vitamin concentrations were determined.

Results

Regardless of sleep quality group, compared to control, morning sleepiness, alertness upon awakening, and vigor were improved (p < 0.05) after dried KF consumption. Compared to control, both fresh and dried KF treatments tended (p < 0.1) toward improved esteem and total mood disturbance. Both KF treatments increased (fresh +1.56 ± 0.4 ng/g, p = 0.001; dried: +1.30 ± 0.4 ng/g, p = 0.004) urinary concentration of the serotonin metabolite 5-HIAA compared to the control (4.32 ± 0.4 ng/g). In poor sleepers, ease of awakening improved by 24% after dried KF consumption (p = 0.005) and tended to improve by 13% after fresh KF intake (p = 0.052) compared to the control. Good sleepers tended toward 9% improved ratings of getting to sleep with fresh KF (p = 0.053) compared to the control. Poor sleepers had lower amounts of some B-vitamins compared to good sleepers (p < 0.05).

Conclusion

Consumption of dried or fresh KF with a standard evening meal, was associated with improved aspects of sleep quality and mood, possibly mediated through changes in serotonin metabolism.

Clinical trial registration

[www.anzctr.org.au], identifier [ACTRN12621000046808].

Graphical Abstract
Compositional analysis of natural pomegranate peel powder dried by different methods and nutritional and sensory evaluation of cookies fortified with pomegranate peel powder
Authors: Muhammad Ali , Dayisoylu Kenan Sinan , Pei Jinjin , Khan Muhammad Rafiullah , Salman Muhammad , Ahmad Rafiq , Ullah Hakim , Noor Gul Rah
Published: March 2023

Introduction

Fortification of cereal products with natural plant extract is an interesting approach to fulfill the dietary requirement of the people.

Materials and methods

Peels of pomegranate (rich source of natural compounds) were cut into small pieces and dried in three different methods such as solar drying (SOD), oven drying (OD), and sun drying (SUD). The fine powder was prepared and proximate compositions (protein, ash, moisture, fats, fiber, and carbohydrates), minerals (zinc, iron, calcium, and potassium), total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity (DPPH) of the pomegranate peel powder (PP) were evaluated. Fine wheat flour (FWF) was fortified with different concentrations (3, 6, 8, 10, and 12 g) of PP powder, cookies were prepared and all the above analysis along with physical parameters (weight, width, thickness, spread ration) and sensory analysis were conducted. Cookies without PP powder were served as control.

Results and discussion

Results showed that a SOD was the best for drying PP powder in terms of compositional analysis. Addition of PP powder significantly (P < 0.05) enhanced the nutritional value, minerals profile and physical attributes of the fortified cookies. Sensory analysis of fortified cookies indicated that the cookies were acceptable to the sensory panel. Therefore, in conclusion, PP powder dried by SOD method could be used commercially in baking industries to provide nutritional enriched cookies to fulfill the dietary requirements of the people.
Assessment of lipid composition and eicosapentaenoic acid/docosahexaenoic acid bioavailability in fish oil obtained through different enrichment methods
Authors: Song Rongzhen , Li Wen , Deng Shanggui , Zhao Yueliang , Tao Ningping
Published: March 2023

In this study, we analyzed the eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) lipid composition of fish oil obtained through enzymatic treatment, fractional distillation and silica gel column purification, and further assessed EPA/DHA bioavailability. Lipid subclass composition information was obtained through ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), and bioavailability tests were performed using the Caco-2 cell monolayer model. Results showed that enzymatic treatment improved the incorporation of EPA/DHA as diacylglycerol (DG) while silica gel column chromatography enriched the content of EPA/DHA as phosphatidylglycerol (PG) (12.58%) and phosphatidylethanolamine (PE) (4.99%). Furthermore, increasing the purity of EPA/DHA could improve its bioavailability and after 24 incubation, binding forms of triglyceride (TG) was superior to ethyl ester (EE) (p < 0.05) at the same purity level. Those findings are helpful to provide research basis for exploring the bioactivity of fish oil.
Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer
Authors: Curtis Aaron A. , Yu Yajun , Carey Megan , Parfrey Patrick , Yilmaz Yildiz E. , Savas Sevtap
Published: March 2023

Background

Interactions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes.

Objectives

In this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction networks that predict the 5-year recurrence risk in a cohort of stage I-III colorectal cancer patients.

Methods

423 patients recruited to the Newfoundland Familial Colorectal Cancer Registry were included. Five Wnt family member proteins (Wnt1, Wnt2, Wnt5a, Wnt5b, and Wnt11) were selected. The BioGRID database was used to identify the proteins interacting with each of these proteins. Genotypes of the SNPs located in the interaction network genes were retrieved from a genome-wide SNP genotype data previously obtained in the patient cohort. The GMDR 0.9 program was utilized to examine 1-, 2-, and 3-SNP interactions using a 5-fold cross validation step. Top GMDR 0.9 models were assessed by permutation testing and, if significant, prognostic associations were verified by multivariable logistic regression models.

Results

GMDR 0.9 has identified novel 1, 2, and 3-way SNP interactions associated with 5-year recurrence risk in colorectal cancer. Nine of these interactions were multi loci interactions (2-way or 3-way). Identified interaction models were able to distinguish patients based on their 5-year recurrence-free status in multivariable regression models. The significance of interactions was the highest in the 3-SNP models. Several of the identified SNPs were eQTLs, indicating potential biological roles of the genes they were associated with in colorectal cancer recurrence.

Conclusions

We identified novel interacting genetic variants that associate with 5-year recurrence risk in colorectal cancer. A significant portion of the genes identified were previously linked to colorectal cancer pathogenesis or progression. These variants and genes are of interest for future functional and prognostic studies. Our results provide further evidence for the utility of GMDR models in identifying novel prognostic biomarkers and the biological importance of the Wnt pathways in colorectal cancer.
Amino acid metabolic reprogramming in tumor metastatic colonization
Authors: Wang Zihao , Wu Xingyun , Chen Hai-Ning , Wang Kui
Published: March 2023

Metastasis is considered as the major cause of cancer death. Cancer cells can be released from primary tumors into the circulation and then colonize in distant organs. How cancer cells acquire the ability to colonize in distant organs has always been the focus of tumor biology. To enable survival and growth in the new environment, metastases commonly reprogram their metabolic states and therefore display different metabolic properties and preferences compared with the primary lesions. For different microenvironments in various colonization sites, cancer cells must transfer to specific metabolic states to colonize in different distant organs, which provides the possibility of evaluating metastasis tendency by tumor metabolic states. Amino acids provide crucial precursors for many biosynthesis and play an essential role in cancer metastasis. Evidence has proved the hyperactivation of several amino acid biosynthetic pathways in metastatic cancer cells, including glutamine, serine, glycine, branched chain amino acids (BCAAs), proline, and asparagine metabolism. The reprogramming of amino acid metabolism can orchestrate energy supply, redox homeostasis, and other metabolism-associated pathways during cancer metastasis. Here, we review the role and function of amino acid metabolic reprogramming in cancer cells colonizing in common metastatic organs, including lung, liver, brain, peritoneum, and bone. In addition, we summarize the current biomarker identification and drug development of cancer metastasis under the amino acid metabolism reprogramming, and discuss the possibility and prospect of targeting organ-specific metastasis for cancer treatment.
Response to selpercatinib in a patient with RET fusion-positive pulmonary large-cell neuroendocrine carcinoma: A case report
Authors: Arora Aakriti , Zaemes Jacob , Ozdemirli Metin , Kim Chul
Published: March 2023

Large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of non-small-cell lung cancer associated with a poor prognosis. LCNEC is genetically heterogeneous, and studies have revealed distinct molecular subtypes of LCNEC, which may have therapeutic implications. Herein, we present a case of a patient with stage IV LCNEC harboring a KIF5B–RET fusion whose disease responded to the selective RET inhibitor selpercatinib both extra- and intra-cranially, highlighting the importance of comprehensive molecular testing in LCNEC for selection of optimal treatment.
Anomaly detection in radiotherapy plans using deep autoencoder networks
Authors: Huang Peng , Shang Jiawen , Xu Yingjie , Hu Zhihui , Zhang Ke , Dai Jianrong , Yan Hui
Published: March 2023

Purpose

Treatment plans are used for patients under radiotherapy in clinics. Before execution, these plans are checked for safety and quality by human experts. A few of them were identified with flaws and needed further improvement. To automate this checking process, an unsupervised learning method based on an autoencoder was proposed.

Methods

First, features were extracted from the treatment plan by human experts. Then, these features were assembled and used for model learning. After network optimization, a reconstruction error between the predicted and target signals was obtained. Finally, the questionable plans were identified based on the value of the reconstruction error. A large value of the reconstruction error indicates a longer distance from the standard distribution of normal plans. A total of 576 treatment plans for breast cancer patients were used for the test. Among them, 19 were questionable plans identified by human experts. To evaluate the performance of the autoencoder, it was compared with four baseline detection algorithms, namely, local outlier factor (LOF), hierarchical density-based spatial clustering of applications with noise (HDBSCAN), one-class support vector machine (OC-SVM), and principal component analysis (PCA).

Results

The results showed that the autoencoder achieved the best performance than the other four baseline algorithms. The AUC value of the autoencoder was 0.9985, while the second one was 0.9535 (LOF). While maintaining 100% recall, the average accuracy and precision of the results by the autoencoder were 0.9658 and 0.5143, respectively. While maintaining 100% recall, the average accuracy and precision of the results by LOF were 0.8090 and 0.1472, respectively.

Conclusion

The autoencoder can effectively identify questionable plans from a large group of normal plans. There is no need to label the data and prepare the training data for model learning. The autoencoder provides an effective way to carry out an automatic plan checking in radiotherapy.
Vertebral body tethering: An alternative to posterior spinal fusion in idiopathic scoliosis?
Authors: Hammad Ahmad M. , Balsano Massimo , Ahmad Alaaeldin A.
Published: March 2023

Introduction

Skeletally immature patient with adolescent idiopathic scoliosis (AIS) whose curves continue to progress despite bracing should be treated surgically. Vertebral body tethering (VBT) is a non-fusion, compression-based, growth preserving alternative to posterior spinal fusion (PSF) based on the concept of ‘growth modulation’ to prevent possible functional complications secondary to fusion while correcting scoliotic deformity. This review aims to shed light on the indications of VBT, short- and medium-term outcomes, describe the surgical technique and associated complications, and to compare its efficacy to that of PSF.

Methods

A review of peer-reviewed literature on VBT as a surgical technique, its indications, outcomes, complications, and comparison with other surgical interventions to correct AIS was conducted in December 2022.

Results

Indications remain controversial and mainly include stage of skeletal maturity based on radiographic markers, curve location, magnitude and flexibility, and presence of secondary curve. Assessment of VBT clinical success should not be restricted to improvement in radiographic parameters but should include functional results and patient-centered outcomes, improved body image and pain, and durability of outcomes. In contrast to fusion, VBT seems to be associated with preserved spinal growth, shorter recovery, potentially better functional outcomes, less motion loss but possibly less curve correction.

Discussion

Yet still, with VBT there exists a risk of overcorrection, construct breakage or failure of procedure which require revision and at times conversion to PSF. Patient and family preferences must be accounted for acknowledging gaps in knowledge, attributes and drawbacks of each intervention.
Artesunate inhibits airway remodeling in asthma via the MAPK signaling pathway
Authors: Zhang Mengyuan , Lin Jiangtao , Zhang Jingyuan , Zhao Ruiheng , Wan Jingxuan , Nong Ying
Published: March 2023

Background: Artesunate (ART), is a semi-synthetic water-soluble artemisinin derivative extracted from the plant Artemisia annua, which is often used to treating malaria. In vivo and in vitro studies suggested it may help decrease inflammation and attenuate airway remodeling in asthma. However, its underlying mechanism of action is not elucidated yet. Herein, an attempt is made to investigate the ART molecular mechanism in treating asthma.

Methods: The BALB/c female mice sensitized via ovalbumin (OVA) have been utilized to establish the asthma model, followed by carrying out ART interventions. Lung inflammation scores by Haematoxylin and Eosin (H&E), goblet cell hyperplasia grade by Periodic Acid-Schiff (PAS), and collagen fibers deposition by Masson trichrome staining have been utilized for evaluating how ART affected asthma. RNA-sequencing (RNA-seq) analyses were performed to identify differentially expressed genes (DEGs). The DEGs were analyzed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Protein-Protein interaction (PPI) function analyses. Hub clusters were found by Cytoscape MCODE. Subsequently, Real-Time quantitative PCR (RT-qPCR) verified the mRNA expression profiles of DEGs. Finally, immunohistochemistry (IHC) and western blots have validated the relevant genes and potential pathways.

Results: ART considerably attenuated inflammatory cell infiltration, mucus secretion, and collagen fibers deposition. KEGG pathway analysis revealed that the ART played a protective role via various pathways including the mitogen-activated protein kinase (MAPK) pathway as one of them. Moreover, ART could alleviate the overexpression of found in inflammatory zone 1(FIZZ1) as revealed by IHC and Western blot analyses. ART attenuated OVA-induced asthma by downregulating phosphorylated p38 MAPK.

Conclusion: ART exerted a protective function in a multitarget and multi-pathway on asthma. FIZZ1 was a possible target for asthma airway remodeling. The MARK pathway was one of the key pathways by which ART protected against asthma.
Structure-function relationships in the sodium chloride cotransporter
Authors: Moreno Erika , Pacheco-Alvarez Diana , Chávez-Canales María , Elizalde Stephanie , Leyva-Ríos Karla , Gamba Gerardo
Published: March 2023

The thiazide sensitive Na+:Cl− cotransporter (NCC) is the principal via for salt reabsorption in the apical membrane of the distal convoluted tubule (DCT) in mammals and plays a fundamental role in managing blood pressure. The cotransporter is targeted by thiazide diuretics, a highly prescribed medication that is effective in treating arterial hypertension and edema. NCC was the first member of the electroneutral cation-coupled chloride cotransporter family to be identified at a molecular level. It was cloned from the urinary bladder of the Pseudopleuronectes americanus (winter flounder) 30 years ago. The structural topology, kinetic and pharmacology properties of NCC have been extensively studied, determining that the transmembrane domain (TM) coordinates ion and thiazide binding. Functional and mutational studies have discovered residues involved in the phosphorylation and glycosylation of NCC, particularly on the N-terminal domain, as well as the extracellular loop connected to TM7-8 (EL7-8). In the last decade, single-particle cryogenic electron microscopy (cryo-EM) has permitted the visualization of structures at high atomic resolution for six members of the SLC12 family (NCC, NKCC1, KCC1-KCC4). Cryo-EM insights of NCC confirm an inverted conformation of the TM1-5 and TM6-10 regions, a characteristic also found in the amino acid-polyamine-organocation (APC) superfamily, in which TM1 and TM6 clearly coordinate ion binding. The high-resolution structure also displays two glycosylation sites (N-406 and N-426) in EL7-8 that are essential for NCC expression and function. In this review, we briefly describe the studies related to the structure-function relationship of NCC, beginning with the first biochemical/functional studies up to the recent cryo-EM structure obtained, to acquire an overall view enriched with the structural and functional aspects of the cotransporter.
Evaluation of pea genotype PI180693 partial resistance towards aphanomyces root rot in commercial pea breeding
Authors: Kälin Carol , Kolodinska Brantestam Agnese , Arvidsson Anna-Kerstin , Dubey Mukesh , Elfstrand Malin , Karlsson Magnus
Published: March 2023

The cultivation of vining pea (Pisum sativum) faces a major constraint with root rot diseases, caused by a complex of soil-borne pathogens including the oomycetes Aphanomyces euteiches and Phytophtora pisi. Disease resistant commercial varieties are lacking but the landrace PI180693 is used as a source of partial resistance in ongoing pea breeding programs. In this study, the level of resistance and their interaction with A. euteiches virulence levels of six new back-crossed pea breeding lines, deriving from the cross between the susceptible commercial cultivar Linnea and PI180693, were evaluated for their resistance towards aphanomyces root rot in growth chamber and green house tests. Resistance towards mixed infections by A. euteiches and P. pisi and commercial production traits were evaluated in field trials. In growth chamber trials, pathogen virulence levels had a significant effect on plant resistance, as resistance was more consistent against A. euteiches strains exhibiting high or intermediate virulence compared with lowly virulent strains. In fact, line Z1701-1 showed to be significantly more resistant than both parents when inoculated with a lowly virulent strain. In two separate field trials in 2020, all six breeding lines performed equally well as the resistant parent PI180693 at sites only containing A. euteiches, as there were no differences in disease index. In mixed infections, PI180693 exhibited significantly lower disease index scores than Linnea. However, breeding lines displayed higher disease index scores compared with PI180693, indicating higher susceptibility towards P. pisi. Data on seedling emergence from the same field trials suggested that PI180693 was particularly sensitive towards seed decay/damping off disease caused by P. pisi. Furthermore, the breeding lines performed equally well as Linnea in traits important for green pea production, again emphasizing the commercial potential. In summary, we show that the resistance from PI180693 interacts with virulence levels of the pathogen A. euteiches and is less effective towards root rot caused by P. pisi. Our results show the potential use of combining PI180693 partial resistance against aphanomyces root rot with commercially favorable breeding traits in commercial breeding programs.
Responses of wheat kernel weight to diverse allelic combinations under projected climate change conditions
Authors: Wang Keyi , Shi Liping , Zheng Bangyou , He Yong
Published: March 2023

Introduction

In wheat, kernel weight (KW) is a key determinant of grain yield (GY). However, it is often overlooked when improving wheat productivity under climate warming. Moreover, little is known about the complex effects of genetic and climatic factors on KW. Here, we explored the responses of wheat KW to diverse allelic combinations under projected climate warming conditions.

Methods

To focus on KW, we selected a subset of 81 out of 209 wheat varieties with similar GY, biomass, and kernel number (KN) and focused on their thousand-kernel weight (TKW). We genotyped them at eight kompetitive allele-specific polymerase chain reaction markers closely associated with TKW. Subsequently, we calibrated and evaluated the process-based model known as Agricultural Production Systems Simulator (APSIM-Wheat) based on a unique dataset including phenotyping, genotyping, climate, soil physicochemistry, and on-farm management information. We then used the calibrated APSIM-Wheat model to estimate TKW under eight allelic combinations (81 wheat varieties), seven sowing dates, and the shared socioeconomic pathways (SSPs) designated SSP2-4.5 and SSP5-8.5, driven by climate projections from five General Circulation Models (GCMs) BCC-CSM2-MR, CanESM5, EC-Earth3-Veg, MIROC-ES2L, and UKESM1-0-LL.

Results

The APSIM-Wheat model reliably simulated wheat TKW with a root mean square error (RMSE) of < 3.076 g TK-1 and R2 of > 0.575 (P < 0.001). The analysis of variance based on the simulation output showed that allelic combination, climate scenario, and sowing date extremely significantly affected TKW (P < 0.001). The impact of the interaction allelic combination × climate scenario on TKW was also significant (P < 0.05). Meanwhile, the variety parameters and their relative importance in the APSIM-Wheat model accorded with the expression of the allelic combinations. Under the projected climate scenarios, the favorable allelic combinations (TaCKX-D1b + Hap-7A-1 + Hap-T + Hap-6A-G + Hap-6B-1 + H1g + A1b for SSP2-4.5 and SSP5-8.5) mitigated the negative effects of climate change on TKW.

Discussion

The present study demonstrated that optimizing favorable allelic combinations can help achieve high wheat TKW. The findings of this study clarify the responses of wheat KW to diverse allelic combinations under projected climate change conditions. Additionally, the present study provides theoretical and practical reference for marker-assisted selection of high TKW in wheat breeding.
Precise control of water stress in the field reveals different response thresholds for forage yield and digestibility of maize hybrids
Authors: Main Oscar , Jacquemot Marie-Pierre , Griveau Yves , Guillaume Sophie , Demonceaux Claire , Lopez-Marnet Paul-Louis , Rey Sébastien , Fargier Sébastien , Sartre Pascal , Montagnier Christophe , Uijttewaal Anthony , Mangel Nathalie , Meunier Florence , Reymond Matthieu , Méchin Valérie , Coursol Sylvie
Published: March 2023

Introduction

With dwindling global freshwater supplies and increasing water stress, agriculture is coming under increasing pressure to reduce water use. Plant breeding requires high analytical capabilities. For this reason, near-infrared spectroscopy (NIRS) has been used to develop prediction equations for whole-plant samples, particularly for predicting dry matter digestibility, which has a major impact on the energy value of forage maize hybrids and is required for inclusion in the official French catalogue. Although the historical NIRS equations have long been used routinely in seed company breeding programmes, they do not predict all variables with the same accuracy. In addition, little is known about how accurate their predictions are under different water stress-environments.

Methods

Here, we examined the effects of water stress and stress intensity on agronomic, biochemical, and NIRS predictive values in a set of 13 modern S0-S1 forage maize hybrids under four different environmental conditions resulting from the combination of a northern and southern location and two monitored water stress levels in the south.

Results

First, we compared the reliability of NIRS predictions for basic forage quality traits obtained using the historical NIRS predictive equations and the new equations we recently developed. We found that NIRS predicted values were affected to varying degrees by environmental conditions. We also showed that forage yield gradually decreased as a function of water stress, whereas both dry matter and cell wall digestibilities increased regardless of the intensity of water stress, with variability among the tested varieties decreasing under the most stressed conditions.

Discussion

By combining forage yield and dry matter digestibility, we were able to quantify digestible yield and identify varieties with different strategies for coping with water stress, raising the exciting possibility that important potential selection targets still exist. Finally, from a farmer’s perspective, we were able to show that late silage harvest has no effect on dry matter digestibility and that moderate water stress does not necessarily result in a loss of digestible yield.
Identification of long noncoding RNAs involved in plumule-vernalization of Chinese cabbage
Authors: Dai Yun , Li Guoliang , Gao Xinyu , Wang Shaoxing , Li Ze , Song Chao , Zhang Shifan , Li Fei , Fang Zhiyuan , Sun Rifei , Zhang Hui , Zhang Shujiang
Published: March 2023

Vernalization is a phenomenon in which plants must undergo a period of continuous low temperatures to change from the vegetative growth stage to the reproductive growth stage. Chinese cabbage is a heading vegetable, and flowering time is an essential developmental trait. Premature vernalization leads to premature bolting, which causes a loss of product value and yield. While research into vernalization has provided a wealth of information, a complete understanding of the molecular mechanism for controlling vernalization requirements has not yet been elucidated. In this study, using high-throughput RNA sequencing, we analyzed the plumule-vernalization response of mRNA and long noncoding RNA in the bolting-resistant Chinese cabbage double haploid (DH) line ‘Ju Hongxin’ (JHX). A total of 3382 lncRNAs were identified, of which 1553 differentially expressed (DE) lncRNAs were characterized as plumule-vernalization responses. The ceRNA network revealed that 280 ceRNA pairs participated in the plumule-vernalization reaction of Chinese cabbage. Through identifying DE lncRNAs in Chinese cabbage and analyzing anti-, cis-, and trans-functional analysis, some candidate lncRNAs related to vernalization promoting flowering of Chinese cabbage and their regulated mRNA genes were found. Moreover, the expression of several critical lncRNAs and their targets was verified using qRT-PCR. Furthermore, we identified the candidate plumule-vernalization-related long noncoding RNAs that regulate BrFLCs in Chinese cabbage, which was interesting and different from previous studies and was a new discovery. Our findings expand the knowledge of lncRNAs in the vernalization of Chinese cabbage, and the identified lncRNAs provide rich resources for future comparative and functional studies.