bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 vaccines based on viral nanoparticles displaying a conserved B-cell epitope show potent immunogenicity and a long-lasting antibody response
Authors: Affonso de Oliveira Jessica Fernanda , Zhao Zhongchao , Xiang Yi , Shin Matthew D. , Villaseñor Kathleen Elizabeth , Deng Xinyi , Shukla Sourabh , Chen Shaochen , Steinmetz Nicole F.
Published: April 2023

The COVID-19 pandemic caused by SARS-CoV-2 sparked intensive research into the development of effective vaccines, 50 of which have been approved thus far, including the novel mRNA-based vaccines developed by Pfizer and Moderna. Although limiting the severity of the disease, the mRNA-based vaccines presented drawbacks, such as the cold chain requirement. Moreover, antibody levels generated by these vaccines decline significantly after 6 months. These vaccines deliver mRNA encoding the full-length spike (S) glycoprotein of SARS-CoV-2, but must be updated as new strains and variants of concern emerge, creating a demand for adjusted formulations and booster campaigns. To overcome these challenges, we have developed COVID-19 vaccine candidates based on the highly conserved SARS CoV-2, 809-826 B-cell peptide epitope (denoted 826) conjugated to cowpea mosaic virus (CPMV) nanoparticles and bacteriophage Qβ virus-like particles, both platforms have exceptional thermal stability and facilitate epitope delivery with inbuilt adjuvant activity. We evaluated two administration methods: subcutaneous injection and an implantable polymeric scaffold. Mice received a prime–boost regimen of 100 μg per dose (2 weeks apart) or a single dose of 200 μg administered as a liquid formulation, or a polymer implant. Antibody titers were evaluated longitudinally over 50 weeks. The vaccine candidates generally elicited an early Th2-biased immune response, which stimulates the production of SARS-CoV-2 neutralizing antibodies, followed by a switch to a Th1-biased response for most formulations. Exceptionally, vaccine candidate 826-CPMV (administered as prime-boost, soluble injection) elicited a balanced Th1/Th2 immune response, which is necessary to prevent pulmonary immunopathology associated with Th2 bias extremes. While the Qβ-based vaccine elicited overall higher antibody titers, the CPMV-induced antibodies had higher avidity. Regardless of the administration route and formulation, our vaccine candidates maintained high antibody titers for more than 50 weeks, confirming a potent and durable immune response against SARS-CoV-2 even after a single dose.
Four new suomilides isolated from the cyanobacterium Nostoc sp. KVJ20 and proposal of their biosynthetic origin
Authors: Schneider Yannik K.-H. , Liaimer Anton , Isaksson Johan , Wilhelmsen Oda S. B. , Andersen Jeanette H. , Hansen Kine Ø. , Hansen Espen H.
Published: April 2023

The suomilide and the banyasides are highly modified and functionalized non-ribosomal peptides produced by cyanobacteria of the order Nostocales. These compound classes share several substructures, including a complex azabicyclononane core, which was previously assumed to be derived from the amino acid tyrosine. In our study we were able to isolate and determine the structures of four suomilides, named suomilide B – E (1–4). The compounds differ from the previously isolated suomilide A by the functionalization of the glycosyl group. Compounds 1–4 were assayed for anti-proliferative, anti-biofilm and anti-bacterial activities, but no significant activity was detected. The sequenced genome of the producer organism Nostoc sp. KVJ20 enabled us to propose a biosynthetic gene cluster for suomilides. Our findings indicated that the azabicyclononane core of the suomilides is derived from prephenate and is most likely incorporated by a proline specific non-ribosomal peptide synthetase-unit.
Differences in soil physicochemical properties and rhizosphere microbial communities of flue-cured tobacco at different transplantation stages and locations
Authors: Zhao Leifeng , He Yuansheng , Zheng Yuanxian , Xu Yinlian , Shi Shoujie , Fan Meixun , Gu Shaolong , Li Guohong , Tianli Wajie , Wang Jiming , Li Junying , Deng Xiaopeng , Liao Xiaolin , Du Jun , Nian Fuzhao
Published: April 2023

Rhizosphere microbiota play an important role in regulating soil physical and chemical properties and improving crop production performance. This study analyzed the relationship between the diversity of rhizosphere microbiota and the yield and quality of flue-cured tobacco at different transplant times (D30 group, D60 group and D90 group) and in different regions [Linxiang Boshang (BS) and Linxiang ZhangDuo (ZD)] by high-throughput sequencing technology. The results showed that there were significant differences in the physicochemical properties and rhizosphere microbiota of flue-cured tobacco rhizosphere soil at different transplanting times, and that the relative abundance of Bacillus in the rhizosphere microbiota of the D60 group was significantly increased. RDA and Pearson correlation analysis showed that Bacillus, Streptomyces and Sphingomonas were significantly correlated with soil physical and chemical properties. PIGRUSt2 function prediction results showed that compared with the D30 group, the D60 group had significantly increased metabolic pathways such as the superpathway of pyrimidine deoxyribonucleoside salvage, allantoin degradation to glyoxylate III and pyrimidine deoxyribonucleotides de novo biosynthesis III metabolic pathways. The D90 group had significantly increased metabolic pathways such as ubiquitol-8 biosynthesis (prokaryotic), ubiquitol-7 biosynthesis (prokaryotic) and ubiquitol-10 biosynthesis (prokaryotic) compared with the D60 group. In addition, the yield and quality of flue-cured tobacco in the BS region were significantly higher than those in the ZD region, and the relative abundance of Firmicutes and Bacillus in the rhizosphere microbiota of flue-cured tobacco in the BS region at the D60 transplant stage was significantly higher than that in the ZD region. In addition, the results of the hierarchical sample metabolic pathway abundance map showed that the PWY-6572 metabolic pathway was mainly realized by Paenibacillus, and that the relative abundance of flue-cured tobacco rhizosphere microbiota (Paenibacillus) participating in PWY-6572 in the D60 transplant period in the BS region was significantly higher than that in the ZD region. In conclusion, different transplanting periods of flue-cured tobacco have important effects on soil physical and chemical properties and rhizosphere microbial communities. There were significant differences in the rhizosphere microbiota and function of flue-cured tobacco in different regions, which may affect the performance and quality of this type of tobacco.
A biotroph sets the stage for a necrotroph to play: ‘Candidatus Phytoplasma solani’ infection of sugar beet facilitated Macrophomina phaseolina root rot
Authors: Duduk Nataša , Vico Ivana , Kosovac Andrea , Stepanović Jelena , Ćurčić Živko , Vučković Nina , Rekanović Emil , Duduk Bojan
Published: April 2023

‘Candidatus Phytoplasma solani’ (stolbur phytoplasma) is associated with rubbery taproot disease (RTD) of sugar beet (Beta vulgaris L.), while Macrophomina phaseolina is considered the most important root rot pathogen of this plant in Serbia. The high prevalence of M. phaseolina root rot reported on sugar beet in Serbia, unmatched elsewhere in the world, coupled with the notorious tendency of RTD-affected sugar beet to rot, has prompted research into the relationship between the two diseases. This study investigates the correlation between the occurrence of sugar beet RTD and the presence of root rot fungal pathogens in a semi-field ‘Ca. P. solani’ transmission experiment with the cixiid vector Reptalus quinquecostatus (Dufour), in addition to naturally infected sugar beet in the open field. Our results showed that: (i) Reptalus quinquecostatus transmitted ‘Ca. P. solani’ to sugar beet which induced typical RTD root symptoms; (ii) Macrophomina phaseolina root rot was exclusively present in ‘Ca. P. solani’-infected sugar beet in both the semi-field experiment and naturally infected sugar beet; and that (iii) even under environmental conditions favorable to the pathogen, M. phaseolina did not infect sugar beet, unless the plants had been previously infected with phytoplasma.
Identification and analysis of the secretome of plant pathogenic fungi reveals lifestyle adaptation
Authors: Jia Mingxuan , Gong Xiaodong , Fan Mengmeng , Liu Haoran , Zhou He , Gu Shouqin , Liu Yuwei , Dong Jingao
Published: April 2023

The secretory proteome plays an important role in the pathogenesis of phytopathogenic fungi. However, the relationship between the large-scale secretome of phytopathogenic fungi and their lifestyle is not fully understood. In the present study, the secretomes of 150 plant pathogenic fungi were predicted and the characteristics associated with different lifestyles were investigated. In total, 94,974 secreted proteins (SPs) were predicted from these fungi. The number of the SPs ranged from 64 to 1,662. Among these fungi, hemibiotrophic fungi had the highest number (average of 970) and proportion (7.1%) of SPs. Functional annotation showed that hemibiotrophic and necrotroph fungi, differ from biotrophic and symbiotic fungi, contained much more carbohydrate enzymes, especially polysaccharide lyases and carbohydrate esterases. Furthermore, the core and lifestyle-specific SPs orthogroups were identified. Twenty-seven core orthogroups contained 16% of the total SPs and their motif function annotation was represented by serine carboxypeptidase, carboxylesterase and asparaginase. In contrast, 97 lifestyle-specific orthogroups contained only 1% of the total SPs, with diverse functions such as PAN_AP in hemibiotroph-specific and flavin monooxygenases in necrotroph-specific. Moreover, obligate biotrophic fungi had the largest number of effectors (average of 150), followed by hemibiotrophic fungi (average of 120). Among these effectors, 4,155 had known functional annotation and pectin lyase had the highest proportion in the functionally annotated effectors. In addition, 32 sets of RNA-Seq data on pathogen-host interactions were collected and the expression levels of SPs were higher than that of non-SPs, and the expression level of effector genes was higher in biotrophic and hemibiotrophic fungi than in necrotrophic fungi, while secretase genes were highly expressed in necrotrophic fungi. Finally, the secretory activity of five predicted SPs from Setosphearia turcica was experimentally verified. In conclusion, our results provide a foundation for the study of pathogen-host interaction and help us to understand the fungal lifestyle adaptation.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
Authors: Pardo Mònica , Gregorio Sara , Montalban Enrica , Pujadas Lluís , Elias-Tersa Alba , Masachs Núria , Vílchez-Acosta Alba , Parent Annabelle , Auladell Carme , Girault Jean-Antoine , Vila Miquel , Nairn Angus C. , Manso Yasmina , Soriano Eduardo
Published: April 2023

In addition to neuronal migration, brain development, and adult plasticity, the extracellular matrix protein Reelin has been extensively implicated in human psychiatric disorders such as schizophrenia, bipolar disorder, and autism spectrum disorder. Moreover, heterozygous reeler mice exhibit features reminiscent of these disorders, while overexpression of Reelin protects against its manifestation. However, how Reelin influences the structure and circuits of the striatal complex, a key region for the above-mentioned disorders, is far from being understood, especially when altered Reelin expression levels are found at adult stages. In the present study, we took advantage of complementary conditional gain- and loss-of-function mouse models to investigate how Reelin levels may modify adult brain striatal structure and neuronal composition. Using immunohistochemical techniques, we determined that Reelin does not seem to influence the striatal patch and matrix organization (studied by μ-opioid receptor immunohistochemistry) nor the density of medium spiny neurons (MSNs, studied with DARPP-32). We show that overexpression of Reelin leads to increased numbers of striatal parvalbumin- and cholinergic-interneurons, and to a slight increase in tyrosine hydroxylase-positive projections. We conclude that increased Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders.
Neurotypicals with higher autistic traits have delayed visual processing of an approaching life-sized avatar’s gait: an event-related potentials study
Authors: Inokuchi Ryo , Ichikawa Hiroko , Yamamoto Masataka , Takemura Hiroshi
Published: April 2023

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which is reportedly related to difficulties in the visual processing of human motion, such as biological motion and gestures. Moreover, neurotypical (here, we mention it as individuals without a diagnosis) adults with autistic traits are clumsier than those without autistic traits when passing by others. It is still unclear whether the clumsiness derived from atypical visual processing of another’s approaching gait motion. We aim to address this question by investigating the association between autistic traits in neurotypical adults and the visual processing of an approaching life-sized avatar’s gait.

Methods

We clarified a typical visual motion processing and autistic traits in daily life in 26 neurotypical adults by analyzing the subthreshold autism trait questionnaire (SATQ) score, a 24-item self-report scale of ASD, and event-related potentials (ERPs) in response to walking motion of a passing avatar. Videos of walking life-sized virtual avatars approaching and retreating were presented as visual stimuli.

Results and discussion

The association between the participants’ SATQ scores and the latencies and amplitudes of the ERPs was examined. ERP components (N170 and P200) components were identified at T5 and T6 electrodes. Participants reporting higher SATQ scores had longer latencies of P200 at T6 and lower amplitudes of P200 at T5 and T6 electrodes for the approaching avatar than those reporting lower SATQ scores. These findings indicate that adults with autistic traits have delayed and less sensitive visual processing of the approaching avatar. It suggests that while passing another person, these individuals have atypical visual processing of their approach. This study may contribute to elucidating autistic traits from the perspective of visual processing in an environment simulating daily life.
Profiles of cognitive impairment in chronic heart failure—A cluster analytic approach
Authors: Göpfert Dennis , Traub Jan , Sell Roxane , Homola György A. , Vogt Marius , Pham Mirko , Frantz Stefan , Störk Stefan , Stoll Guido , Frey Anna
Published: April 2023

Background

Cognitive impairment is a major comorbidity in patients with chronic heart failure (HF) with a wide range of phenotypes. In this study, we aimed to identify and compare different clusters of cognitive deficits.

Methods

The prospective cohort study “Cognition.Matters-HF” recruited 147 chronic HF patients (aged 64.5 ± 10.8 years; 16.2% female) of any etiology. All patients underwent extensive neuropsychological testing. We performed a hierarchical cluster analysis of the cognitive domains, such as intensity of attention, visual/verbal memory, and executive function. Generated clusters were compared exploratively with respect to the results of cardiological, neurological, and neuroradiological examinations without correction for multiple testing.

Results

Dendrogram and the scree plot suggested three distinct cognitive profiles: In the first cluster, 42 patients (28.6%) performed without any deficits in all domains. Exclusively, the intensity of attention deficits was seen in the second cluster, including 55 patients (37.4%). A third cluster with 50 patients (34.0%) was characterized by deficits in all cognitive domains. Age (p = 0.163) and typical clinical markers of chronic HF, such as ejection fraction (p = 0.222), 6-min walking test distance (p = 0.138), NT-proBNP (p = 0.364), and New York Heart Association class (p = 0.868) did not differ between clusters. However, we observed that women (p = 0.012) and patients with previous cardiac valve surgery (p = 0.005) prevailed in the “global deficits” cluster and the “no deficits” group had a lower prevalence of underlying arterial hypertension (p = 0.029). Total brain volume (p = 0.017) was smaller in the global deficit cluster, and serum levels of glial fibrillary acidic protein were increased (p = 0.048).

Conclusion

Apart from cognitively healthy and globally impaired HF patients, we identified a group with deficits only in the intensity of attention. Women and patients with previous cardiac valve surgery are at risk for global cognitive impairment when suffering HF and could benefit from special multimodal treatment addressing the psychosocial condition.
Soccer heading immediately alters brain function and brain-muscle communication
Authors: Parr Johnny V. V. , Uiga Liis , Marshall Ben , Wood Greg
Published: April 2023

Introduction

There is growing evidence of a link between repetitive soccer heading and the increased incidence of neurodegenerative disease. Even a short bout of soccer heading has been shown to impair cognitive performance and disrupt movement control. However, a greater understanding of the mechanisms behind these immediate impairments is needed. The current study attempted to identify how a short bout of soccer heading alters brain function and brain-muscle communication during a movement task.

Methods

Sixty soccer players were exposed to either an acute bout (i.e., 20 balls thrown underarm) of soccer heading (n = 30) or a control condition where participants (n = 30) headed soccer balls in virtual reality (VR). Before and after heading, we measured cognitive performance on the King-Devick test, as well as electromyography (EMG), electroencephalography (EEG) and brain-muscle communication (i.e., corticomuscular coherence; CMC) during a force precision task.

Results

Following the heading protocol, the VR group improved their cognitive performance whereas the Heading group showed no change. Both groups displayed more precise force contractions at post-test. However, the VR group displayed elevated frontal theta activity and global increases in alpha and beta activity during the contraction task, whereas the Heading group did not. Contrary to our expectations, the Heading group displayed elevated CMC, whereas the VR group showed no change.

Discussion

Our findings indicate a short bout of soccer heading may impair cognitive function and disrupt the organization of efficient neural processes that typically accompany motor skill proficiency. Soccer heading also induced corticomuscular hyperconnectivity, which could represent compensatory brain-muscle communication and an inefficient allocation of increased task-related neuromuscular resources. These initial findings offer insights to the mechanisms behind the impairments experienced after a short bout of repetitive soccer heading.
STDP-based adaptive graph convolutional networks for automatic sleep staging
Authors: Zhao Yuan , Lin Xianghong , Zhang Zequn , Wang Xiangwen , He Xianrun , Yang Liu
Published: April 2023

Automatic sleep staging is important for improving diagnosis and treatment, and machine learning with neuroscience explainability of sleep staging is shown to be a suitable method to solve this problem. In this paper, an explainable model for automatic sleep staging is proposed. Inspired by the Spike-Timing-Dependent Plasticity (STDP), an adaptive Graph Convolutional Network (GCN) is established to extract features from the Polysomnography (PSG) signal, named STDP-GCN. In detail, the channel of the PSG signal can be regarded as a neuron, the synapse strength between neurons can be constructed by the STDP mechanism, and the connection between different channels of the PSG signal constitutes a graph structure. After utilizing GCN to extract spatial features, temporal convolution is used to extract transition rules between sleep stages, and a fully connected neural network is used for classification. To enhance the strength of the model and minimize the effect of individual physiological signal discrepancies on classification accuracy, STDP-GCN utilizes domain adversarial training. Experiments demonstrate that the performance of STDP-GCN is comparable to the current state-of-the-art models.
Investigating the influence of an adjustable zoned air mattress on sleep: a multinight polysomnography study
Authors: Wei Yu , Zhu Yongpeng , Zhou Yihan , Yu Xiaokang , Lin Huiping , Ruan Lijun , Lei Hua , Luo Yuxi
Published: April 2023

Introduction

A comfortable mattress should improve sleep quality. In this study, we sought to investigate the specific sleep parameters that could be affected by a mattress and explore any potential differences between the effects felt by each sex.

Methods

A total of 20 healthy young adults (10 females and 20 males; 22.10 ± 1.25 years) participated in the experiments. A smart adjustable zoned air mattress was designed to maintain comfortable support, and an ordinary mattress was used for comparison. The participants individually spent four nights on these two mattresses in four orders for polysomnography (PSG) scoring. Sleep architecture, electroencephalogram (EEG) spectrum, and heart rate variability (HRV), which reflect the central and autonomic nervous activities, were used to compare the difference between the two mattresses.

Results

An individual difference exited in sleep performance. The modes of influence of the mattresses were different between the sexes. The adjustable air mattress and the increase in experimental nights improved female participants' sleep efficiency, while male participants exhibited a smaller response to different mattresses. With an increasing number of experiment nights, both sexes showed increased REM and decreased N2 proportions; the N3 sleep proportion decreased in the male participants, and the heart rate decreased in both sexes. The performance of the EEG spectrum supports the above results. In addition, the adjustable air mattress weakened automatic nerve activity during N3 sleep in most participants. The female participants appeared to be more sensitive to mattresses. Experiment night was associated with psychological factors. There were differences in the results for this influence between the sexes.

Conclusion

This study may shed some light on the differences between the ideal sleep environment of each sex.
Functional and effective connectivity analysis of drug-resistant epilepsy: a resting-state fMRI analysis
Authors: Bacon Eric Jacob , Jin Chaoyang , He Dianning , Hu Shuaishuai , Wang Lanbo , Li Han , Qi Shouliang
Published: April 2023

Objective

Epilepsy is considered as a neural network disorder. Seizure activity in epilepsy may disturb brain networks and damage brain functions. We propose using resting-state functional magnetic resonance imaging (rs-fMRI) data to characterize connectivity patterns in drug-resistant epilepsy.

Methods

This study enrolled 47 participants, including 28 with drug-resistant epilepsy and 19 healthy controls. Functional and effective connectivity was employed to assess drug-resistant epilepsy patients within resting state networks. The resting state functional connectivity (FC) analysis was performed to assess connectivity between each patient and healthy controls within the default mode network (DMN) and the dorsal attention network (DAN). In addition, dynamic causal modeling was used to compute effective connectivity (EC). Finally, a statistical analysis was performed to evaluate our findings.

Results

The FC analysis revealed significant connectivity changes in patients giving 64.3% (18/28) and 78.6% (22/28) for DMN and DAN, respectively. Statistical analysis of FC was significant between the medial prefrontal cortex, posterior cingulate cortex, and bilateral inferior parietal cortex for DMN. For DAN, it was significant between the left and the right intraparietal sulcus and the frontal eye field. For the DMN, the patient group showed significant EC connectivity in the right inferior parietal cortex and the medial prefrontal cortex for the DMN. There was also bilateral connectivity between the medial prefrontal cortex and the posterior cingulate cortex, as well as between the left and right inferior parietal cortex. For DAN, patients showed significant connectivity in the right frontal eye field and the right intraparietal sulcus. Bilateral connectivity was also found between the left frontal eye field and the left intraparietal sulcus, as well as between the right frontal eye field and the right intraparietal sulcus. The statistical analysis of the EC revealed a significant result in the medial prefrontal cortex and the right intraparietal cortex for the DMN. The DAN was found significant in the left frontal eye field, as well as the left and right intraparietal sulcus.

Conclusion

Our results provide preliminary evidence to support that the combination of functional and effective connectivity analysis of rs-fMRI can aid in diagnosing epilepsy in the DMN and DAN networks.
Physiological ischemic training improves cardiac function through the attenuation of cardiomyocyte apoptosis and the activation of the vagus nerve in chronic heart failure
Authors: Zhu Xiuhua , Wang Shenrui , Cheng Yihui , Gu Hongmei , Zhang Xiu , Teng Meiling , Zhang Yingjie , Wang Jiayue , Hua Wenjie , Lu Xiao
Published: April 2023

Purpose

This study investigated the functional outcomes of patients with chronic heart failure (CHF) after physiological ischemic training (PIT), identified the optimal PIT protocol, evaluated its cardioprotective effects and explored the underlying neural mechanisms.

Methods

Patients with CHF were randomly divided into experimental group (n = 25, PIT intervention + regular treatment) and control group (n = 25, regular treatment). The outcomes included the left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) and cardiopulmonary parameters. LVEF and cardiac biomarkers in CHF rats after various PIT treatments (different in intensity, frequency, and course of treatment) were measured to identify the optimal PIT protocol. The effect of PIT on cardiomyocyte programmed cell death was investigated by western blot, flow cytometry and fluorescent staining. The neural mechanism involved in PIT-induced cardioprotective effect was assessed by stimulation of the vagus nerve and muscarinic M2 receptor in CHF rats.

Results

LVEF and VO2max increased while BNP decreased in patients subjected to PIT. The optimal PIT protocol in CHF rats was composed of five cycles of 5 min ischemia followed by 5 min reperfusion on remote limbs for 8 weeks. LVEF and cardiac biomarker levels were significantly improved, and cardiomyocyte apoptosis was inhibited. However, these cardioprotective effects disappeared after subjecting CHF rats to vagotomy or muscarinic M2 receptor inhibition.

Conclusion

PIT improved functional outcomes in CHF patients. The optimal PIT protocol required appropriate intensity, reasonable frequency, and adequate treatment course. Under these conditions, improvement of cardiac function in CHF was confirmed through cardiomyocyte apoptosis reduction and vagus nerve activation.
Application of artificial intelligence for automatic cataract staging based on anterior segment images: comparing automatic segmentation approaches to manual segmentation
Authors: Gan Fan , Liu Hui , Qin Wei-Guo , Zhou Shui-Lian
Published: April 2023

Purpose

Cataract is one of the leading causes of blindness worldwide, accounting for >50% of cases of blindness in low- and middle-income countries. In this study, two artificial intelligence (AI) diagnosis platforms are proposed for cortical cataract staging to achieve a precise diagnosis.

Methods

A total of 647 high quality anterior segment images, which included the four stages of cataracts, were collected into the dataset. They were divided randomly into a training set and a test set using a stratified random-allocation technique at a ratio of 8:2. Then, after automatic or manual segmentation of the lens area of the cataract, the deep transform-learning (DTL) features extraction, PCA dimensionality reduction, multi-features fusion, fusion features selection, and classification models establishment, the automatic and manual segmentation DTL platforms were developed. Finally, the accuracy, confusion matrix, and area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the performance of the two platforms.

Results

In the automatic segmentation DTL platform, the accuracy of the model in the training and test sets was 94.59 and 84.50%, respectively. In the manual segmentation DTL platform, the accuracy of the model in the training and test sets was 97.48 and 90.00%, respectively. In the test set, the micro and macro average AUCs of the two platforms reached >95% and the AUC for each classification was >90%. The results of a confusion matrix showed that all stages, except for mature, had a high recognition rate.

Conclusion

Two AI diagnosis platforms were proposed for cortical cataract staging. The resulting automatic segmentation platform can stage cataracts more quickly, whereas the resulting manual segmentation platform can stage cataracts more accurately.
Medial and dorsal lateral septum involving social disruption stress-primed escalation in acid-induced writhes
Authors: Liao Yi-Han , Sun Li-Han , Su Yi-Chi , Yao Wei-Jen , Yu Lung
Published: April 2023

Introduction

Stress may cause prospective escalations in abdominal pain magnitude and accumbal TRPV1 expression, while central neural circuits mediating these stress effects remain unclear.

Methods

Using retrograde tracing methods, we first demonstrated the existence of a medial septal-dorsal lateral septal -accumbal circuit very likely involving social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 level. An intersectional viral strategy and virus-carrying hM3Dq and hM4Di DREADDs were, then, employed to selectively modulate GABAergic and cholinergic neuronal activity in medial and dorsal lateral septum.

Results

Exciting medial septal GABAergic neuron was found to prevent social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 and PKCε expressions. Likewise, inactivating dorsal lateral septal cholinergic neurons was also effective in abolishing these stress-primed escalations. Inactivating GABAergic neuron in non-stressed animals’ medial septum was found to reproduce the stress-primed effects in causing heightened acid-induced writhes and accumbal TRPV1 and PKCε levels.

Discussion

These results, taken together, prompt us to conclude that social disruption stress may produce plastic changes in a newly-identified medial septal-dorsal lateral septal-accumbal circuit. Moreover, medial septal GABAergic hypoactivity and dorsal lateral septal cholinergic hyperactivity are, at least, two likely causes reflecting such stress-produced escalations in abdominal pain magnitude and pain transduction-related protein over-expression in nucleus accumbens.
Concurrent sintilimab with sequential chemoradiotherapy for unresectable, stage III non-small cell lung cancer: a retrospective study
Authors: Tang Shi , Cong Xiaofeng , Zheng Dan , Chen Chen , Liu Zengguang , Gao Jie , Zhang Huimin , Zhang Youhao , Liu Ziling
Published: April 2023

Background

Concurrent programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors with sequential chemoradiotherapy (SCRT) have been reported in only a limited number of studies involving patients with unresectable stage III non-small-cell lung cancer (NSCLC). A retrospective study was conducted to systematically analyze the efficacy and safety of the emerging therapy among Chinese patients.

Materials and methods

We included patients with unresectable, stage III NSCLC who received concurrent sintilimab with chemotherapy or chemotherapy alone for 3-6 cycles, followed by radical radiotherapy at the First Hospital of Jilin University from Dec 15, 2019, to Jul 15, 2022. The primary end point was the objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), 12-month and 18-month PFS rates, the duration of response (DoR), and safety.

Results

The retrospective study involved 77 patients, of which 49 receiving concurrent sintilimab with SCRT were assigned to cohort A, and 28 receiving SCRT alone were assigned to cohort B. The ORR was significantly higher in cohort A (79.6%, 95% CI 65.7–89.8) than in cohort B (35.7%, 95% CI 18.6–55.9) (p<0.001). Median PFS was significantly longer in cohort A than in cohort B (NR [95% CI 21.4–NR] vs. 16.0 months [13.0–22.5]; HR 0.375, 95% CI 0.192–0.735; p=0.003). The PFS rates at 12 and 18 months were 84.8% (95% CI 75.0–95.9) and 71.3% (95% CI 58.7–86.7) in cohort A and 75.0% (95% CI 60.6–92.9) and 38.3% (95% CI 23.7–61.7) in cohort B, respectively. Grade 3 or 4 adverse events (AEs) were reported in 19 patients (38.8%) and seven patients (25.0%) in two cohorts, respectively. Grade 3 or 4 pneumonitis or immune-mediated pneumonitis, radiation pneumonitis, and pneumonia occurred in five (10.2%), four (8.2%), and two (4.1%) cohort A patients, and zero, two (7.1%), and two (7.1%) cohort B patients, respectively. Only cohort A reported AE leading to death in one (2.0%) patient (immune-mediated pneumonitis).

Conclusion

Concurrent sintilimab with SCRT resulted in a significantly better ORR and longer PFS than SCRT alone, with manageable safety profiles in Chinese patients with unresectable stage III NSCLC.
Liquid biopsy in hematological malignancies: current and future applications
Authors: Talotta Donatella , Almasri Mohammad , Cosentino Chiara , Gaidano Gianluca , Moia Riccardo
Published: April 2023

The assessment of the cancer mutational profile is crucial for patient management, stratification, and therapeutic decisions. At present, in hematological malignancies with a solid mass, such as lymphomas, tumor genomic profiling is generally performed on the tissue biopsy, but the tumor may harbor genetic lesions that are unique to other anatomical compartments. The analysis of circulating tumor DNA (ctDNA) on the liquid biopsy is an emerging approach that allows genotyping and monitoring of the disease during therapy and follow-up. This review presents the different methods for ctDNA analysis and describes the application of liquid biopsy in different hematological malignancies. In diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), ctDNA analysis on the liquid biopsy recapitulates the mutational profile of the tissue biopsy and can identify mutations otherwise absent on the tissue biopsy. In addition, changes in the ctDNA amount after one or two courses of chemotherapy significantly predict patient outcomes. ctDNA analysis has also been tested in myeloid neoplasms with promising results. In addition to mutational analysis, liquid biopsy also carries potential future applications of ctDNA, including the analysis of ctDNA fragmentation and epigenetic patterns. On these grounds, several clinical trials aiming at incorporating ctDNA analysis for treatment tailoring are currently ongoing in hematological malignancies.
PI3K/AKT/mTOR pathway-derived risk score exhibits correlation with immune infiltration in uveal melanoma patients
Authors: Geng Yuxin , Geng Yulei , Liu Xiaoli , Chai Qiannan , Li Xuejing , Ren Taoran , Shang Qingli
Published: April 2023

Uveal melanoma (UVM) is a rare but highly aggressive intraocular tumor with a poor prognosis and limited therapeutic options. Recent studies have implicated the PI3K/AKT/mTOR pathway in the pathogenesis and progression of UVM. Here, we aimed to explore the potential mechanism of PI3K/AKT/mTOR pathway-related genes (PRGs) in UVM and develop a novel prognostic-related risk model. Using unsupervised clustering on 14 PRGs profiles, we identified three distinct subtypes with varying immune characteristics. Subtype A demonstrated the worst overall survival and showed higher expression of human leukocyte antigen, immune checkpoints, and immune cell infiltration. Further enrichment analysis revealed that subtype A mainly functioned in inflammatory response, apoptosis, angiogenesis, and the PI3K/AKT/mTOR signaling pathway. Differential analysis between different subtypes identified 56 differentially expressed genes (DEGs), with the major enrichment pathway of these DEGs associated with PI3K/AKT/mTOR. Based on these DEGs, we developed a consensus machine learning-derived signature (RSF model) that exhibited the best power for predicting prognosis among 76 algorithm combinations. The novel signature demonstrated excellent robustness and predictive ability for the overall survival of patients. Moreover, we observed that patients classified by risk scores had distinguishable immune status and mutation. In conclusion, our study identified a consensus machine learning-derived signature as a potential biomarker for prognostic prediction in UVM patients. Our findings suggest that this signature is correlated with tumor immune infiltration and may serve as a valuable tool for personalized therapy in the clinical setting.
Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA–GPGE Registry
Authors: Elonen Lotta , Wölfle Lena , de Laffolie Jan , Posovszky Carsten ,   the CEDATA–GPGE-Study-Group
Published: April 2023

Introduction

Pediatric patients with inflammatory bowel disease (IBD) are classified into Crohn's disease (CD), ulcerative colitis (UC), and unclassifiable (IBD-U). However, data provide evidence that ileal CD (L1) is distinct from colonic CD (L2). The aim of this study was to investigate the clinical features of isolated Crohn's colitis in a pediatric population.

Material and Methods

Children who were prospectively included in the CEDATA–GPGE registry on diagnosis were compared according to the diagnosis of CD with L2 vs. L1 and ileocolonic (L3) involvement pattern as well as IBD-U and UC. The clinical significance of L2 was investigated with regard to extraintestinal manifestations, treatment, surgery, and disease activity.

Results

Fifty-two patients with L2 CD at a median age of 13.4 years (±3.8 SD) were compared with 182 L1 (13.8 ± 2.9 SD), 782 with L3 (12.8 ± 3.3 SD), 653 with UC (12.7 ± 3.8 SD), and 111 patients with IBD-U (11.9 ± 4.7 SD). Bloody stools at diagnosis were more common in L2 (44%) than in L1 (19.7%) and L3 (28.8%), but not as common as in UC (66.5%) and IBD-U (61.3%). Fewer CD patients with L2 (10.2%) received exclusive enteral nutrition therapy (EEN) as induction than patients with L1 (34.3%) and L3 (33.3%). After induction therapy, 42.3% of patients with L2 received immunosuppressants and 21% biologicals during follow-up (L1 56.5/10.5%; L3 59/21%; CU 43.5/11.9%; IBD-U 26.1/12.6%). Extraintestinal manifestations were more frequent in L2 (23.1%) vs. L1 (18.7%), L3 (20.2%), CU (15.8%), and IBD-U (11.7%). The number of patients requiring surgery did not differ within the CD subgroups and was significantly lower in UC and IBD-U. Perianal fistula surgery was significantly more common in L2 (44%) than in L1 (4.8%) or L3 (21.7%). In addition, the frequency of surgery for perianal abscesses was also more frequent in L2 (55.6%) than in L1 (12.7%) or L3 (38.4%).

Conclusions

The consideration of pediatric Crohn's colitis as a distinct disease seems necessary as it is characterized by extraintestinal manifestations (EIMs) with mainly joint involvement and perianal fistulas or abscesses requiring surgery and biologic therapy. Thus, colonic Crohn's disease may have an influence on the therapeutic stratification and should be addressed in further studies.
JAK inhibitors in systemic juvenile idiopathic arthritis
Authors: He Tingyan , Xia Yu , Luo Ying , Yang Jun
Published: April 2023

Objective

Systemic juvenile idiopathic arthritis (SJIA) is characterized by excessive and inappropriate production of proinflammatory cytokines. Janus kinase inhibitors (JAKi) can block the downstream pathway of many cytokines. The use of JAKi in SJIA or macrophage activation syndrome (MAS) has only been described in a limited number of case reports. In this study, we aimed to assess the efficacy and potential adverse effects of JAKi in SJIA patients.

Methods

Patients with SJIA who received JAKi and underwent at least one assessment of efficacy and safety after JAKi initiation were eligible for this study. Data were collected retrospectively from inpatient or outpatient medical records at JAKi initiation, at 1, 3, 6, 9, and 12 months, after disease flare, after JAKi discontinuation, or at the last follow-up.

Results

Ten patients with SJIA were included in the study. At the start of JAKi treatment, all patients presented with active disease; five showed variable adverse effects secondary to glucocorticoids. Seven patients received tofacitinib (one later switched to ruxolitinib). Of these, only two patients showed a complete response of persistent arthritis associated with tocilizumab; tofacitinib was used without a biological DMARD only in two patients, together with MTX, showing a partial response; three patients were nonresponders. Four patients with SJIA-related MAS or persistent hyperferritinemia were treated with ruxolitinib. Ruxolitinib allowed a good response on MAS parameters in three of them. All these four patients required an adjunction or switch to canakinumab later. The median decrease in the daily glucocorticoid dose between JAKi initiation and the last follow-up was 90.6% in patients with complete remission and 77.4% in other patients. Three patients discontinued glucocorticoid treatment after the introduction of JAKi. Severe adverse events, notably serious infection or thrombosis, were not observed during JAKi treatment.

Conclusion

JAKi may be an alternative or adjuvant agent for SJIA patients, especially in those with persistently active disease, glucocorticoid-related adverse reactions, or SJIA-MAS.
Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus
Authors: Elgharbawy Fawzia M. , Karim Mohammed Yousuf , Soliman Dina Sameh , Hassan Amel Siddik , Sudarsanan Anoop , Gad Ashraf
Published: April 2023

Background

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an increased risk of developing malignancies later in life.

Case presentation

We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.

Conclusion

We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.
Sanghuangporus sanghuang extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16/SIR-2.1
Authors: Dong Zhenghan , Wang Yachao , Hao Cuiting , Cheng Yuan , Guo Xi , He Yanyu , Shi Yueyue , Wang Shuang , Li Yunqi , Shi Wei
Published: April 2023

Sanghuangporus Sanghuang is a fungus species. As a traditional Chinese medicine, it is known for antitumor, antioxidant and anti-inflammatory properties. However, the antiaging effect of S. Sanghuang has not been deeply studied. In this study, the effects of S. Sanghuang extract (SSE) supernatants on the changes of nematode indicators were investigated. The results showed that different concentrations of SSE prolonged the lifespans of nematodes and substantially increased these by 26.41%. In addition, accumulations of lipofuscin were also visibly reduced. The treatment using SSE also played a role in increasing stress resistance, decreasing ROS accumulations and obesity, and enhancing the physique. RT–PCR analysis showed that the SSE treatment upregulated the transcription of daf-16, sir-2.1, daf-2, sod-3 and hsp-16.2, increased the expression of these genes in the insulin/IGF-1 signalling pathway and prolonged the lifespans of nematodes. This study reveals the new role of S. Sanghuang in promoting longevity and inhibiting stress and provides a theoretical basis for the application of S. Sanghuang in anti-ageing treatments.
Metabolomic and transcriptomic analyses of the flavonoid biosynthetic pathway in blueberry (Vaccinium spp.)
Authors: Li Yinping , Li Haifei , Wang Shiyao , Li Jing , Bacha Syed Asim Shah , Xu Guofeng , Li Jing
Published: April 2023

As a highly economic small fruit crop, blueberry is enjoyed by most people in terms of color, taste, and rich nutrition. To better understand its coloring mechanism on the process of ripening, an integrative analysis of the metabolome and transcriptome profiles was performed in three blueberry varieties at three developmental stages. In this study, 41 flavonoid metabolites closely related to the coloring in blueberry samples were analyzed. It turned out that the most differential metabolites in the ripening processes were delphinidin-3-O-arabinoside (dpara), peonidin-3-O-glucoside (pnglu), and delphinidin-3-O-galactoside (dpgal), while the most differential metabolites among different varieties were flavonols. Furthermore, to obtain more accurate and comprehensive transcripts of blueberry during the developmental stages, PacBio and Illumina sequencing technology were combined to obtain the transcriptome of the blueberry variety Misty, for the very first time. Finally, by applying the gene coexpression network analysis, the darkviolet and bisque4 modules related to flavonoid synthesis were determined, and the key genes related to two flavonoid 3′, 5′-hydroxylase (F3′5′H) genes in the darkviolet module and one bHLH transcription factor in the bisque4 module were predicted. It is believed that our findings could provide valuable information for the future study on the molecular mechanism of flavonoid metabolites and flavonoid synthesis pathways in blueberries.
Modulation of lignin biosynthesis for drought tolerance in plants
Authors: Choi Su Jeong , Lee Zion , Kim Sohyun , Jeong Eui , Shim Jae Sung
Published: April 2023

Lignin is a complex polymer that is embedded in plant cell walls to provide physical support and water protection. For these reasons, the production of lignin is closely linked with plant adaptation to terrestrial regions. In response to developmental cues and external environmental conditions, plants use an elaborate regulatory network to determine the timing and location of lignin biosynthesis. In this review, we summarize the canonical lignin biosynthetic pathway and transcriptional regulatory network of lignin biosynthesis, consisting of NAC and MYB transcription factors, to explain how plants regulate lignin deposition under drought stress. Moreover, we discuss how the transcriptional network can be applied to the development of drought tolerant plants.