bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice
Authors: Yoo Ye-Eun , Yoo Taesun , Kang Hyojin , Kim Eunjoon
Published: October 2022

Shank2 is an abundant excitatory postsynaptic scaffolding protein that has been implicated in various neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), intellectual disability, attention-deficit/hyperactivity disorder, and schizophrenia. Shank2-mutant mice show ASD-like behavioral deficits and altered synaptic and neuronal functions, but little is known about how different brain regions and gene dosages affect the transcriptomic phenotypes of these mice. Here, we performed RNA-Seq-based transcriptomic analyses of the prefrontal cortex, hippocampus, and striatum in adult Shank2 heterozygous (HT)- and homozygous (HM)-mutant mice lacking exons 6–7. The prefrontal cortical, hippocampal, and striatal regions showed distinct transcriptomic patterns associated with synapse, ribosome, mitochondria, spliceosome, and extracellular matrix (ECM). The three brain regions were also distinct in the expression of ASD-related and ASD-risk genes. These differential patterns were stronger in the prefrontal cortex where the HT transcriptome displayed increased synaptic gene expression and reverse-ASD patterns whereas the HM transcriptome showed decreased synaptic gene expression and ASD-like patterns. These results suggest brain region- and gene dosage-differential transcriptomic changes in Shank2-mutant mice.
Folate receptor-positive circulating tumor cells predict survival and recurrence patterns in patients undergoing resection for pancreatic cancer
Authors: Cheng Hao , Yang Jun , Fu Xu , Mao Liang , Chu Xuehui , Lu Chenglin , Li Gang , Qiu Yudong , He Wei
Published: October 2022

Objective

To evaluate the prognostic impact of folate receptor (FR)-positive circulating tumor cells (FR+ CTCs) for patients with pancreatic cancer (PC).

Background

Risk stratification before surgery for PC patients remains challenging as there are no reliable prognostic markers currently. FR+ CTCs, detected by ligand-targeted polymerase chain reaction (LT-PCR), have shown excellent diagnostic value for PC in our previous study and prognostic value in a variety of cancer types.

Methods

Peripheral blood samples from 44 consecutive patients diagnosed with PC were analyzed for FR+ CTCs. 25 patients underwent tumor resection and were assigned to the surgical group. 19 patients failed to undergo radical resection because of local advance or distant metastasis and were assigned to the non-surgical group. The impact of CTCs on relapse and survival were explored.

Results

For the prognostic stratification, the optimal cut-off value of CTCs analyzed by receiver operating characteristic (ROC) curve was 14.49 folate units (FU)/3 ml. High CTC levels (> 14.49 FU/3 ml) were detected in 52.0% (13/25) of the patients in the surgical group and 63.2% (12/19) in the non-surgical group. In the surgical group, median disease-free survival (DFS) for patients with high CTC levels versus low CTC levels (< 14.49 FU/3 ml) was 8.0 versus 26.0 months (P = 0.008). In multivariable analysis, CTCs were an independent risk factor for DFS (HR: 4.589, P = 0.012). Concerning the recurrence patterns, patients with high CTC levels showed a significantly frequent rate of distant and early recurrence (P = 0.017 and P = 0.011). CTC levels remained an independent predictor for both distant (OR: 8.375, P = 0.014) and early recurrence (OR: 8.412, P = 0.013) confirmed by multivariable logistic regression. However, CTCs did not predict survival in the non-surgical group (P = 0.220).

Conclusion

FR+ CTCs in resected PC patients could predict impaired survival and recurrence patterns after surgery. Preoperative CTC levels detected by LT-PCR may help guide treatment strategies and further studies in a larger cohort are warranted.
Metabolic features of myeloma cells in the context of bone microenvironment: Implication for the pathophysiology and clinic of myeloma bone disease
Authors: Raimondi Vincenzo , Toscani Denise , Marchica Valentina , Burroughs-Garcia Jessica , Storti Paola , Giuliani Nicola
Published: October 2022

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) into the bone marrow (BM). The complex interaction between the BM microenvironment and MM PCs can lead to severe impairment of bone remodeling. Indeed, the BM microenvironment exerts a critical role in the survival of malignant PCs. Growing evidence indicates that MM cells have several metabolic features including enhanced glycolysis and an increase in lactate production through the upregulation of glucose transporters and enzymes. More recently, it has been reported that MM cells arehighly glutamine addicted. Interestingly, these metabolic changes in MM cells may affect BM microenvironment cells by altering the differentiation process of osteoblasts from mesenchymal stromal cells. The identification of glutamine metabolism alterations in MM cells and bone microenvironment may provide a rationale to design new therapeutic approaches and diagnostic tools. The osteolytic lesions are the most frequent clinical features in MM patients, often characterized by pathological fractures and acute pain. The use of the newer imaging techniques such as Magnetic Resonance Imaging (MRI) and combined Positron Emission Tomography (PET) and Computerized Tomography (CT) has been introduced into clinical practice to better define the skeletal involvement. Currently, the PET/CT with 18F-fluorodeoxyglucose (FDG) is the diagnostic gold standard to detect active MM bone disease due to the high glycolytic activity of MM cells. However, new tracers are actively under investigation because a portion of MM patients remains negative at the skeletal level by 18F-FDG. In this review, we will summarize the existing knowledge on the metabolic alterations of MM cells considering their impact on the BM microenvironment cells and particularly in the subsequent formation of osteolytic bone lesions. Based on this, we will discuss the identification of possible new druggable targets and the use of novel metabolic targets for PET imaging in the detection of skeletal lesions, in the staging and treatment response of MM patients.
Cerebral glucose changes after chemotherapy and their relation to long-term cognitive complaints and fatigue
Authors: Schroyen Gwen , Schramm Georg , Van Weehaeghe Donatienne , Leenaerts Nicolas , Vande Casteele Thomas , Blommaert Jeroen , Koole Michel , Smeets Ann , Van Laere Koen , Sunaert Stefan , Deprez Sabine
Published: October 2022

Purpose

To investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints.

Experimental design

Using [18F]-FDG-PET/CT whole-body scans, we retrospectively quantified relative cerebral glucose metabolism before and after neoadjuvant chemotherapy in a cohort of patients treated for non-metastatic breast cancer (2009-2019). Self-report of cognitive complaints and fatigue were prospectively assessed 7 ± 3 years after therapy. Metabolic changes were estimated with i) robust mixed-effects modelling in regions-of-interest (frontal, parietal, temporal, occipital, and insular cortex) and ii) general-linear modelling of whole-brain voxel-wise outcomes. iii) The association between metabolic changes and self-reported outcomes was evaluated using linear regression-analysis.

Results

Of the 667 screened patients, 263 underwent PET/CT before and after chemotherapy and 183 (48 ± 9 years) met the inclusion criteria. After chemotherapy, decreased frontal and increased parietal and insular metabolism were observed (|ß|>0.273, pFDR<0.008). Separately, additional increased occipital metabolism after epiribucin+ cyclophosphamide (EC) and temporal metabolism after EC+ fluorouracil chemotherapy were observed (ß>0.244, pFDR≤0.048). Voxel-based analysis (pcluster-FWE<0.001) showed decreased metabolism in the paracingulate gyrus (-3.2 ± 3.9%) and putamen (3.1 ± 4.1%) and increased metabolism in the lateral cortex (L=2.9 ± 3.1%) and pericentral gyri (3.0 ± 4.4%). Except for the central sulcus, the same regions showed changes in EC, but not in FEC patients. Of the 97 self-reported responders, 23% and 27% experienced extreme fatigue and long-term cognitive complaints, respectively, which were not associated with metabolic changes.

Conclusion

Both hyper- and hypometabolism were observed after chemotherapy for breast cancer. Combined with earlier findings, this study could support inflammatory mechanisms resulting in relative hypermetabolism, mainly in the parietal/occipital cortices. As early metabolic changes did not precede long-term complaints, further research is necessary to identify vulnerable patients.
18F-DCFPyL PET/CT in advanced high-grade epithelial ovarian cancer: A prospective pilot study
Authors: Metser Ur , Kulanthaivelu Roshini , Chawla Tanya , Johnson Sarah , Avery Lisa , Hussey Douglas , Veit-Haibach Patrick , Bernardini Marcus , Hogen Liat
Published: October 2022

Objectives

Glutamate carboxypeptidase-II (GCP-II), a zinc metalloenzyme that resides in cell membrane, has been reported as overexpressed in the neovasculature of ovarian cancers. The study objective was to determine whether GCP-II targeted imaging with 18F-DCFPyL PET/CT can detect disease sites in women with advanced high-grade serous ovarian cancer (HGSOC).

Materials and methods

Twenty treatment-naïve women with advanced HGSOC were recruited (median age 60 years). Prior to commencing therapy (primary cytoreductive surgery [n=9] or neoadjuvant chemotherapy [n=11]), subjects underwent routine staging with contrast-enhanced abdominopelvic CT (=CT), followed by 18F-DCFPyL PET/CT (=PET). CT and PET were reported independently using a standardized reporting template assessing 25 sites. The performance of PET was compared to CT in all subjects and to surgery and surgical histopathology in 9 patients who underwent primary cytoreductive surgery.

Results

Of the 25 sites assessed in 20 patients, CT detected disease in 292/500 (58.4%) locations and PET detected disease in 171/500 (34.2%). Compared to CT the sensitivity (95% CI) of PET to detect disease in the upper abdomen, the gastrointestinal tract or the peritoneum was 0.29 (0.20,0.40), 0.21 (0.11,0.33) and 0.74 (0.64,0.82), respectively. In the surgical cohort, 220 sites in 9 patients were evaluated. The sensitivity and specificity of CT and PET were 0.85 versus 0.54 (p<0.001) and 0.73 versus 0.93 (p<0.001), respectively.

Conclusion

Although 18F-DCFPyL has higher specificity than CT in detecting advanced HGSOC tumor sites, it detects less disease sites than CT, especially in the upper abdomen and along the gastrointestinal tract, likely limiting its clinical utility.

Clinical trial registration

ClinicalTrials.gov, NCT03811899.
Automated multimodal fluorescence microscopy for hyperplex spatial-proteomics: Coupling microfluidic-based immunofluorescence to high resolution, high sensitivity, three-dimensional analysis of histological slides
Authors: Furia Laura , Pelicci Simone , Perillo Federica , Bolognesi Maddalena M. , Pelicci Pier Giuseppe , Facciotti Federica , Cattoretti Giorgio , Faretta Mario
Published: October 2022

In situ multiplexing analysis and in situ transcriptomics are now providing revolutionary tools to achieve the comprehension of the molecular basis of cancer and to progress towards personalized medicine to fight the disease. The complexity of these tasks requires a continuous interplay among different technologies during all the phases of the experimental procedures. New tools are thus needed and their characterization in terms of performances and limits is mandatory to reach the best resolution and sensitivity. We propose here a new experimental pipeline to obtain an optimized costs-to-benefits ratio thanks to the alternate employment of automated and manual procedures during all the phases of a multiplexing experiment from sample preparation to image collection and analysis. A comparison between ultra-fast and automated immunofluorescence staining and standard staining protocols has been carried out to compare the performances in terms of antigen saturation, background, signal-to-noise ratio and total duration. We then developed specific computational tools to collect data by automated analysis-driven fluorescence microscopy. Computer assisted selection of targeted areas with variable magnification and resolution allows employing confocal microscopy for a 3D high resolution analysis. Spatial resolution and sensitivity were thus maximized in a framework where the amount of stored data and the total requested time for the procedure were optimized and reduced with respect to a standard experimental approach.
The prognostic role of circulating tumor cells in gastric cancer: A meta-analysis
Authors: Li Zuxi , Song Meijuan , Han Shangjun , Jin Chuanwei , Yang Jing
Published: October 2022

Objective

We conducted a meta-analysis to evaluate the relationship between circulating tumor cells (CTC) and the prognosis of patients with gastric cancer.

Materials and methods

The cohort studies reporting on the relationship between CTC and prognosis of gastric cancer were collected from Pubmed, Cochrane, Embase, CNKI, WanFang Data, and VIP databases. The two researchers independently screened the literature, extracted the data, and evaluated the bias risk of the included literature. The data were analyzed by Revman software (Review Manager version 5.4).

Result

A total of 14 retrospective cohort studies with 1053 patients were included. The results showed that the overall survival time (OS) and progression-free survival time (PFS) of CTC-positive patients were shorter compared to CTC-negative patients. Taking into consideration the critical value of CTC positive patients, country of origin, sample size, treatment mode, and study time, the subgroup analysis showed that CTC-positive was related to the shortening of OS in patients with gastric cancer. Based on the subgroup analysis of the factors such as CTC positive critical value < 2.8, sample size ≥ 75, mixed therapy, longer study duration, country, and immunofluorescence detection of CTC, it was found that OS in CTC positive group was shorter than that in CTC-negative group (all P<0.05), while the critical value of positive CTC ≥ 2.8, sample size ≥ 75, choice of treatment only for operation or non-operation, short study time and molecular detection of CTC were not associated with OS (all P>0.05). In addition, CTC-positive patients had a more advanced TNM staging, poorer tumor differentiation, and earlier distant metastasis.

Conclusion

CTC can be used as a prognostic indicator of gastric cancer. Gastric cancer patients with positive CTC may have a poorer prognosis compared to those with CTC-negative tumors.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022323155.
Comparing outcomes between culture-positive and culture-negative septic shock in a PICU: A retrospective cohort study
Authors: Huang Haixin , Chen Jian , Dang Hongxing , Liu Chengjun , Fu Yue-qiang
Published: October 2022

Background

We assessed the outcomes and characteristics of culture-negative septic shock (CNSS) and culture-positive septic shock (CPSS) in pediatric intensive care unit (PICU).

Methods

We performed a retrospective study on the data of children admitted to the PICU due to septic shock between January 2018 and December 2021. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay (LOS) of hospital, the need for mechanical ventilation (MV) and continue renal replacement therapy (CRRT).

Results

Overall, 238 patients were enrolled. 114 patients (47.9%) had positive cultures (60 blood samples, 41 sputum samples, 17 pus samples, and 19 others), 18 of whom were cultured positive at two sites, 1 at three sites, and 3 had two different types of bacteria at same site. The in-hospital mortality was 47.1%. There were no significant differences in the in-hospital mortality (47.6% vs. 46.5%, P = 0.866), PRISM-III score (10 vs. 12, P = 0.409), PIM-3 score (0.08 vs. 0.07, P = 0.845), pSOFA score (10 vs. 10, P = 0.677) or the need for MV (64.5% vs. 68.4%, P = 0.524) and CRRT (29.8% vs. 34.2%, P = 0.470) between the CNSS group and the CPSS group. The Procalcitonin (8.89 ng/ml vs. 28.39 ng/ml, P = 0.001) and C-reactive protein (28 mg/L vs. 58 mg/L, P = 0.001) levels were significantly lower in the CNSS group than in the CPSS group, while WBC count (9.03 × 109/L vs. 5.02 × 109/L, P = 0.002) and serum sodium (137 mmol/L vs. 132 mmol/L, P = 0.001) was significantly higher in CNSS. The LOS of hospital was significantly longer (16 days vs. 11 days, P = 0.011) in the CPSS group than in the CNSS group, while the LOS of PICU (5 days vs. 4 days, P = 0.094) stay was not significantly different.

Conclusion

Compared with children with CNSS, children with CPSS had higher PCT and CRP levels, but lower WBC count. Children with CPSS had longer LOS of hospital. However, positive or negative culture results were not associated with in-hospital mortality, the LOS of PICU, the need for MV or CRRT in children with septic shock.
Efficacy and determinants of vacuum bell treatment in preschool children with pectus excavatum
Authors: Luo Dengke , Cheng Kaisheng , Yuan Miao , Xu Chang , He Taozhen
Published: October 2022

Objective

The outcome of vacuum bell (VB) treatment for preschool patients with pectus excavatum (PE) is poorly understood. We aim to investigate the short-term treatment effect of VB with a three-dimensional scanner and assess the clinical and demographic factors that might influence treatment outcomes.

Methods

We conducted a chart review study to review the records of preschool patients with PE who received VB treatment in a tertiary hospital from January 1, 2021, through January 1, 2022. Demographic data and chest wall deformity assessments were recorded at follow-up, including the anterior chest wall depths and depth ratio (DR). The demographic and clinical factors influencing treatment outcomes were tested using a logistic regression model.

Results

139 patients who accepted vacuum bell treatment were included in the final study analysis, with a mean age of 4.6 years and a BMI of 14.9. Forty-three patients (30.9%) with a depth of less than 3 mm met the termination criteria and showed cosmetic results. The changes in depths (P < 0.001) and DR (P < 0.001) were statistically significant in 55 patients with three or four follow-ups. Multifactor logistic regression analysis showed that initial depth (OR 0.69, 95% CI 0.58–0.84, P < 0.001) and treatment period (OR 1.58, 95% CI 1.23–2.04, P < 0.001) were independent predictors of achieving complete correction.

Conclusion

VB is an effective treatment modality in preschool patients in the short-term follow-up, which is influenced by the depth of depression and the duration of treatment. However, further prospective studies are needed to confirm these results.
Developmental defects of enamel in children born preterm
Authors: Halperson Elinor , Shafir Salome , Fux-Noy Avia , Ram Diana , Eventov-Friedman Smadar
Published: October 2022

Introduction

To investigate manifestations of developmental defects of enamel (DDE) in children born preterm (PT), and to explore possible neonatal morbidities related to DDE manifestation and severity.

Methods

A cohort study of 52 children born before gestational week 32 and treated in the neonatal intensive care unit; and 55 children born at full term (FT) as a control group. All the children had a dental examination at age 1–4 years by a professional pediatric dentist. DDE was defined as an alteration in the enamel surface.

Results

DDE were observed in 23 (44%) and 6 (11%) children, in the PT and FT groups, respectively, odds ratio (OR) = 6.47. The OR for damaged anterior teeth was 12.87 times higher in the PT group. DDE of molars was diagnosed in 19% and 11% of the respective groups. In the PT group, the OR of DDE was 4.1 higher among those with than without respiratory distress. The risk for DDE was 5.7 higher in those who received surfactant than in those who did not. Ventilation length, both invasive and non-invasive, was significantly related to DEE.

Conclusions

DDE was higher in children born PT than FT. The DDE rate was lower than expected based on current literature, and considering the overall increase in survival; this suggests improvement in treatments affecting DEE. Respiratory distress syndrome, surfactant administration reflecting the need for intubation, longer ventilation and local oral trauma were risk factors for DDE. We recommend routine dental examinations in follow up of children born PT, particularly those exposed to assisted ventilation.
Risk factors and prediction score model for unplanned readmission among neonates with NRDS under one year of age: A retrospective cohort study
Authors: Yue Weihong , Wei Hong , Chen Feng , Chen Xinhong , Xu Zhen-E , Hu Ya
Published: October 2022

Objective

This study aimed to analyze the risk factors and establish a prediction score model for unplanned readmission among neonates with neonatal respiratory distress syndrome (NRDS) for respiratory problems under one year of age.

Methods

This retrospective cohort study enrolled 230 neonates with NRDS who were admitted between January 2020 and December 2020. The infants were classified into two subgroups based on whether they were readmitted for respiratory problems under one year of age: readmit group and non-readmit group. Readmission risk factors for NRDS were analyzed by logistic regression and a prediction score model was generated.

Results

Among the 230 enrolled infants, 51 (22%) were readmitted, and 179 (78%) were not readmitted. In univariate analysis, compared with non-readmit group infants, readmit group infants had a significantly younger birth gestational age (31.9 ± 2.3 vs. 32.8 ± 2.5 weeks, p = 0.012), lower birth weight (1,713.7 ± 501.3 g vs. 1,946.8 ± 634.4 g, p = 0.007), older age at discharge (41.7 vs. 31.7 days, p = 0.012), higher proportion of necrotizing enterocolitis (NEC) (31% vs. 16%, p = 0.016), higher rate of blood transfusion (39% vs. 25%, p = 0.049), higher rate of postnatal dexamethasone (DEX) administration (28% vs. 9.5%, p = 0.001), and higher rate of home oxygen therapy (HOT) (57% vs. 34%, p = 0.003). Moreover, readmit group infants had significantly longer antibiotic days usage (12.0 vs. 10.0 days, p = 0.026) and a longer duration of hospital stay (41.0 vs. 31.0 days, p = 0.012) than non-readmit group infants. The multivariate logistic regression analysis showed that taking readmission as a target variable, postnatal DEX administration (OR: 2.689, 95% CI: 1.168–6.189, p = 0.020), HOT (OR: 2.071, 95% CI: 1.060–4.046, p = 0.033), and NEC (OR: 2.088, 95% CI: 0.995–4.380, p = 0.051) could be regarded as risk factors for readmission. A scoring model predicting readmission was administered with a positive predictive value of 0.651 (95% CI: 0.557–0.745, p = 0.002), with a sensitivity of 0.412 and a specificity of 0.888 at a cut-off of 3.5 points, which were evaluated on the receiver operating characteristic curve.

Conclusions

Postnatal DEX administration, HOT, and NEC were risk factors for readmission of NRDS. NRDS infants with a predictive score of 3.5 points or more were at high risk for unplanned readmission.
Applicability of the hour of life approach in hyperbilirubinemia among Filipino term infants
Authors: Villanueva-Uy Maria Esterlita T. , G. Uy Herbert , Amarillo Maria Lourdes E.
Published: October 2022

Background

Hyperbilirubinemia remains a common morbidity among infants. Additional research on bilirubin kinetics and associated risk factors will contribute to providing a more targeted management approach for the Filipino infant.

Objective

To develop a Filipino bilirubin nomogram by studying bilirubin patterns during the first 5 days of life.

Methodology

This prospective study recruited 1,412 stable, full-term infants (≥37 weeks age of gestation) born at the Philippine General Hospital (PGH). Using the Dräger-Minolta JM-103 jaundice meter, transcutaneous bilirubin (TcB) levels were determined at the 3rd, 6th, 12th, 24th, 36th, 48th, 72nd, 96th, and 120th hour of life (HOL). A bilirubin nomogram was created using the averages of 3 TcB forehead and sternal measurements at each time epoch. Simultaneous measurement of TcB and total serum bilirubin (TsB) on a subset of 106 infants was done to determine correlation.

Results

Correlation coefficients were high between TsB and forehead TcB (r2 = 0.88), and between TsB and sternal TcB (r2 = 0.91). The Filipino bilirubin nomogram reflected a steep rise until the 48th hour, followed by plateauing of values. Inadequate nursing and bilirubin levels at 12th and 48th HOL were risk factors for developing significant hyperbilirubinemia at 72nd HOL.

Conclusion

TcB is a reliable, non-invasive bilirubin screening tool. Among healthy, full-term, Filipino infants, their nomogram features a sudden increase in bilirubin values during the first 48 h, followed by a plateau. To aid in identification of infants at risk for significant hyperbilirubinemia, healthcare providers can assess breastfeeding adequacy and perform bilirubin screening at the 24th−48th HOL. Registration No. (RGAO-2016-0686).
Study on the relationship between nephrotic syndrome and atopic diseases in childhood
Authors: Zheng Yue , He Xuehui , Hou Ling , Wang Xiuli , Zhao Chengguang , Du Yue
Published: October 2022

Objective

The present study aimed to explore the relationship between nephrotic syndrome and atopic diseases in childhood.

Methods

From 2018 to 2019, 234 children with first-onset primary nephrotic syndrome (PNS) were selected for observation and long-term follow-up, and the clinical and laboratory data. To compare the levels of total serum IgE, histamine and bradykinin of the same children at the time of first onset, remission and relapse of PNS. The extent of podocyte foot process effacement was compared between the urinary protein negative-conversion group and the proteinuric group with the NS range. The correlation between the urine protein quantification and the extent of foot process effacement was also observed.

Results

(1) The mean age of 234 children with first-onset PNS was 4.82 ± 3.63 years, with a male to female ratio of 162/72. (2) There were 109 cases (46.58%) with concomitant atopic diseases (AD) and 151 cases (64.53%) with elevated levels of total serum IgE. There were 136 cases with recurrence during the follow-up, of which recurrence due to allergy-related factors was greater than that due to infection-related factors. (3) The total IgE and bradykinin serum levels were significantly higher in children with first-onset PNS and recurrent PNS compared with those in remission, and the differences were statistically significant (P < 0.05). The level of histamine in children with first-onset PNS was higher than that in children with remission (P < 0.05), and there was no significant difference in the level of histamine between children in the recurrence group and those in the remission group (P > 0.05). (4) There was no significant difference in the extent of foot process effacement between the urinary protein negative-conversion group and the proteinuric group with the NS range. There was no significant correlation between the proteinuria quantification and the extent of foot process effacement.

Conclusion

There existed a high co-morbidity with AD in children with PNS, and allergy-related factors might be an important recurrence factor in children with PNS. The injury to the filtration barrier in MCD might not only be correlated with podocyte lesions but also with some serum permeability factors. Serum IgE, histamine, and bradykinin might be the plasma permeability factors in children with PNS.
EZH2: Its regulation and roles in immune disturbance of SLE
Authors: Yang Yiying , Liu Ke , Liu Meidong , Zhang Huali , Guo Muyao
Published: October 2022

The pathogenesis of systemic lupus erythematosus (SLE) is related to immune homeostasis imbalance. Epigenetic mechanisms have played a significant role in breaking immune tolerance. Enhancer of zeste homolog 2 (EZH2), the specific methylation transferase of lysine at position 27 of histone 3, is currently found to participate in the pathogenesis of SLE through affecting multiple components of the immune system. This review mainly expounds the mechanisms underlying EZH2-mediated disruption of immune homeostasis in SLE patients, hoping to provide new ideas in the pathogenesis of SLE and new targets for future treatment.
Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study
Authors: Zhou Ying-Yong , Yang Shu-Ting , Duan Kai-Ming , Bai Zhi-Hong , Feng Yun-Fei , Guo Qu-Lian , Cheng Zhi-Gang , Wu Hui , Shangguan Wang-Ning , Wu Xiao-Min , Wang Chun-Hui , Chai Xiao-Qing , Xu Guo-Hai , Liu Cun-Ming , Zhao Gao-Feng , Chen Chun , Gao Bao-An , Li Li-E , Zhang Min , Ouyang Wen , Wang Sai-Ying
Published: October 2022

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy.

Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam.

Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference −6.7 × 10%–6% to −5.1 × 10%–6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of −5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group.

Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer.

Clinical Trial Registration:clinicaltrials.gov, ChiCTR2000039753
The olfactory receptor OR51E2 activates ERK1/2 through the Golgi-localized Gβγ-PI3Kγ-ARF1 pathway in prostate cancer cells
Authors: Xu Xin , Khater Mostafa , Wu Guangyu
Published: October 2022

The olfactory receptor OR51E2 is ectopically expressed in prostate tissues and regulates prostate cancer progression, but its function and regulation in oncogenic mitogen-activate protein kinase (MAPK) activation are poorly defined. Here we demonstrate that β-ionone, an OR51E2 agonist, dose-dependently activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) in prostate cancer cells, with an EC50 value of approximate 20 μM and an efficiency comparable to other receptor agonists. We also find that CRISPR-Cas9-mediated knockout of Golgi-translocating Gγ9 subunit, phosphoinositide 3-kinase γ (PI3Kγ) and the small GTPase ADP-ribosylation factor 1 (ARF1), as well as pharmacological inhibition of Gβγ, PI3Kγ and Golgi-localized ARF1, each abolishes ERK1/2 activation by β-ionone. We further show that β-ionone significantly promotes ARF1 translocation to the Golgi and activates ARF1 that can be inhibited by Gγ9 and PI3Kγ depletion. Collectively, our data demonstrate that OR51E2 activates ERK1/2 through the Gβγ-PI3Kγ-ARF1 pathway that occurs spatially at the Golgi, and also provide important insights into MAPK hyper-activation in prostate cancer.
Silicon enhances plant resistance to Fusarium wilt by promoting antioxidant potential and photosynthetic capacity in cucumber (Cucumis sativus L.)
Authors: Sun Shuangsheng , Yang Zhengkun , Song Zhiyu , Wang Nannan , Guo Ning , Niu Jinghan , Liu Airong , Bai Bing , Ahammed Golam Jalal , Chen Shuangchen
Published: October 2022

Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Fo), is a severe soil-borne disease affecting cucumber production worldwide, particularly under monocropping in greenhouses. Silicon (Si) plays an important role in improving the resistance of crops to Fusarium wilt, but the underlying mechanism is largely unclear. Here, an in vitro study showed that 3 mmol·l-1 Si had the best inhibitory effect on the mycelial growth of F. oxysporum in potato dextrose agar (PDA) culture for 7 days. Subsequently, the occurrence of cucumber wilt disease and its mechanisms were investigated upon treatments with exogenous silicon under soil culture. The plant height, stem diameter, root length, and root activity under Si+Fo treatment increased significantly by 39.53%, 94.87%, 74.32%, and 95.11% compared with Fo only. Importantly, the control efficiency of Si+Fo was 69.31% compared with that of Fo treatment. Compared with Fo, the activities of peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) significantly increased by 148.92%, 26.47%, and 58.54%, while the contents of H2O2, O2·−, and malondialdehyde (MDA) notably decreased by 21.67%, 59.67%, and 38.701%, respectively, in roots of cucumber plants treated with Si + Fo. Compared with Fo treatment, the net photosynthesis rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), maximum RuBisCO carboxylation rates (Vcmax), maximum RuBP regeneration rates (Jmax), and activities of ribulose-1,5-bisphosphate carboxylase (RuBisCO), fructose-1,6-bisphosphatase (FBPase), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the expression of FBPA, TPI, SBPase, and FBPase in Si+Fo treatment increased significantly. Furthermore, Si alleviated stomatal closure and enhanced endogenous silicon content compared with only Fo inoculation. The study results suggest that exogenous silicon application improves cucumber resistance to Fusarium wilt by stimulating the antioxidant system, photosynthetic capacity, and stomatal movement in cucumber leaves. This study brings new insights into the potential of Si application in boosting cucumber resistance against Fusarium wilt with a bright prospect for Si use in cucumber production under greenhouse conditions.
DNA profiling with the 20K apple SNP array reveals Malus domestica hybridization and admixture in M. sieversii, M. orientalis, and M. sylvestris genebank accessions
Authors: Volk Gayle M. , Peace Cameron P. , Henk Adam D. , Howard Nicholas P.
Published: October 2022

The USDA-ARS National Plant Germplasm System (NPGS) apple collection in Geneva, NY, USA maintains accessions of the primary Malus domestica (Suckow) Borkh. progenitor species M. sieversii (Ledeb.) M. Roem., M. orientalis Uglitzk., and M. sylvestris (L.) Mill. Many of these accessions originated from seeds that were collected from wild populations in the species’ centers of diversity. Some of these accessions have fruit phenotypes that suggest recent M. domestica hybridization, which if true would represent crop contamination of wild species populations and mislabeled species status of NPGS accessions. Pedigree connections and admixture between M. domestica and its progenitor species can be readily identified with apple SNP array data, despite such arrays not being designed for these purposes. To investigate species purity, most (463 accessions) of the NPGS accessions labeled as these three progenitor species were genotyped using the 20K apple SNP array. DNA profiles obtained were compared with a dataset of more than 5000 unique M. domestica apple cultivars. Only 212 accessions (151 M. sieversii, 26 M. orientalis, and 35 M. sylvestris) were identified as “pure” species representatives because their DNA profiles did not exhibit genotypic signatures of recent hybridization with M. domestica. Twenty-one accessions (17 M. sieversii, 1 M. orientalis, and 3 M. sylvestris) previously labeled as wild species were instead fully M. domestica. Previously unrealized hybridization and admixture between wild species and M. domestica was identified in 230 accessions (215 M. sieversii, 9 M. orientalis, and 6 M. sylvestris). Among these species-mislabeled accessions, ‘Alexander’, ‘Gold Reinette’, ‘Charlamoff’, ‘Rosmarina Bianca’, and ‘King of the Pippins’ were the most frequently detected M. domestica parents or grandparents. These results have implications for collection management, including germplasm distribution, and might affect conclusions of previous research focused on these three progenitor species in the NPGS apple collection. Specifically, accessions received from the NPGS for breeding and genomics, genetics, and evolutionary biology research might not be truly representative of their previously assigned species.
Dynamic DNA methylation changes reveal tissue-specific gene expression in sugarcane
Authors: Xue Yajie , Zou Chengwu , Zhang Chao , Yu Hang , Chen Baoshan , Wang Haifeng
Published: October 2022

DNA methylation is an important mechanism for the dynamic regulation of gene expression and silencing of transposons during plant developmental processes. Here, we analyzed genome-wide methylation patterns in sugarcane (Saccharum officinarum) leaves, roots, rinds, and piths at single-base resolution. DNA methylation patterns were similar among the different sugarcane tissues, whereas DNA methylation levels differed. We also found that DNA methylation in different genic regions or sequence contexts plays different roles in gene expression. Differences in methylation among tissues resulted in many differentially methylated regions (DMRs) between tissues, particularly CHH DMRs. Genes overlapping with DMRs tended to be differentially expressed (DEGs) between tissues, and these DMR-associated DEGs were enriched in biological pathways related to tissue function, such as photosynthesis, sucrose synthesis, stress response, transport, and metabolism. Moreover, we observed many DNA methylation valleys (DMVs), which always overlapped with transcription factors (TFs) and sucrose-related genes, such as WRKY, bZIP, WOX, SPS, and FBPase. Collectively, these findings provide significant insights into the complicated interplay between DNA methylation and gene expression and shed light on the epigenetic regulation of sucrose-related genes in sugarcane.
Transcriptome mining of hormonal and floral integrators in the leafless flowers of three cymbidium orchids
Authors: Ahmad Sagheer , Yang Kang , Chen Guizhen , Huang Jie , Hao Yang , Tu Song , Zhou Yuzhen , Zhao Kai , Chen Jinliao , Shi Xiaoling , Lan Siren , Liu Zhongjian , Peng Donghui
Published: October 2022

Flowering is the most studied ornamental trait in orchids where long vegetative phase may span up to three years. Cymbidium orchids produce beautiful flowers with astonishing shapes and pleasant scent. However, an unusually long vegetative phase is a major drawback to their ornamental value. We observed that under certain culture conditions, three cymbidium species (Cymbidium ensifolium, C. goeringii and C. sinense) skipped vegetative growth phase and directly flowered within six months, that could be a breakthrough for future orchids with limited vegetative growth. Hormonal and floral regulators could be the key factors arresting vegetative phase. Therefore, transcriptomic analyses were performed for leafless flowers and normal vegetative leaves to ascertain differentially expressed genes (DEGs) related to hormones (auxin, cytokinin, gibberellin, abscisic acid and ethylene), floral integrators and MADS-box genes. A significant difference of cytokinin and floral regulators was observed among three species as compared to other hormones. The MADS-box genes were significantly expressed in the leafless flowers of C. sinense as compared to other species. Among the key floral regulators, CONSTANS and AGAMOUS-like genes showed the most differential expression in the leafless flowers as compared to leaves where the expression was negligible. However, CONSTANS also showed downregulation. Auxin efflux carriers were mainly downregulated in the leafless flowers of C. ensifolium and C. sinense, while they were upregulated in C. goeringii. Moreover, gibberellin and cytokinin genes were also downregulated in C. ensifolium and C. sinense flowers, while they were upregulated in C. goeringii, suggesting that species may vary in their responses. The data mining thus, outsources the valuable information to direct future research on orchids at industrial levels.
QTL mapping for seed morphology using the instance segmentation neural network in Lactuca spp
Authors: Seki Kousuke , Toda Yosuke
Published: October 2022

Wild species of lettuce (Lactuca sp.) are thought to have first been domesticated for oilseed contents to provide seed oil for human consumption. Although seed morphology is an important trait contributing to oilseed in lettuce, the underlying genetic mechanisms remain elusive. Since lettuce seeds are small, a manual phenotypic determination required for a genetic dissection of such traits is challenging. In this study, we built and applied an instance segmentation-based seed morphology quantification pipeline to measure traits in seeds generated from a cross between the domesticated oilseed type cultivar ‘Oilseed’ and the wild species ‘UenoyamaMaruba’ in an automated manner. Quantitative trait locus (QTL) mapping following ddRAD-seq revealed 11 QTLs linked to 7 seed traits (area, width, length, length-to-width ratio, eccentricity, perimeter length, and circularity). Remarkably, the three QTLs with the highest LOD scores, qLWR-3.1, qECC-3.1, and qCIR-3.1, for length-to-width ratio, eccentricity, and circularity, respectively, mapped to linkage group 3 (LG3) around 161.5 to 214.6 Mb, a region previously reported to be associated with domestication traits from wild species. These results suggest that the oilseed cultivar harbors genes acquired during domestication to control seed shape in this genomic region. This study also provides genetic evidence that domestication arose, at least in part, by selection for the oilseed type from wild species and demonstrates the effectiveness of image-based phenotyping to accelerate discoveries of the genetic basis for small morphological features such as seed size and shape.
Application of time lags between light and temperature cycles for growth control based on the circadian clock of Lactuca sativa L. seedlings
Authors: Masuda Kosaku , Yamada Tatsuya , Kagawa Yuya , Fukuda Hirokazu
Published: October 2022

The circadian clock plays an important role in agriculture, especially in highly controlled environments, such as plant factories. However, multiple environmental factors have an extremely high degree of freedom, and it is difficult to experimentally search for the optimal design conditions. A recent study demonstrated that the effect of time lags between light and temperature cycles on plant growth could be predicted by the entrainment properties of the circadian clock in Arabidopsis thaliana. Based on this prediction, it was possible to control plant growth by adjusting the time lag. However, for application in plant factories, it is necessary to verify the effectiveness of this method using commercial vegetables, such as leaf lettuce. In this study, we investigated the entrainment properties of the circadian clock and the effect of the time lag between light and temperature cycles on circadian rhythms and plant growth in Lactuca sativa L. seedlings. For evaluation of circadian rhythms, we used transgenic L. sativa L. with a luciferase reporter in the experiment and a phase oscillator model in the simulation. We found that the entrainment properties for the light and temperature stimuli and the effects of time lags on circadian rhythm and growth were similar to those of A. thaliana. Moreover, we demonstrated that changes in growth under different time lags could be predicted by simulation based on the entrainment properties of the circadian clock. These results showed the importance of designing a cultivation environment that considers the circadian clock and demonstrated a series of methods to achieve this.
The “beauty premium” effect of voice attractiveness of long speech sounds in outcome-evaluation event-related potentials in a trust game
Authors: Shang Junchen , Liu Zhihui
Published: October 2022

Previous research suggested that people with attractive voices had an advantage in economic games, even if the voices were only presented for 400 ms. The present study investigated the influence of voice attractiveness on the cooperative trust behavior with longer exposure times to the voices. Event-related potentials (ERPs) were recorded during the feedback outcome evaluation. Participants heard a voice of the partner for 2,040 ms and decided whether to invest to the partner for a possibility to gain more money. The results showed that participants made more invest choices to the attractive partners, replicating the “beauty premium” effect of the attractive voices. Moreover, participants were more likely to invest to male partners. The ERP analysis for the outcome showed that the difference waves of feedback-related negativity (FRN) amplitude were smaller in the attractive voice condition than in the unattractive voice condition, suggesting that the rewarding effect of attractive voices weakened the frustrating feelings of the loss. In sum, the present study confirms that attractive voices with longer presentation durations facilitate cooperative behavior and modulate the processing of feedback evaluations.
Moral spillover in carbon offset judgments
Authors: Sörqvist Patrik , MacCutcheon Douglas , Holmgren Mattias , Haga Andreas , Västfjäll Daniel
Published: October 2022

Moral spillover occurs when a morally loaded behavior becomes associated with another source. In the current paper, we addressed whether the moral motive behind causing CO2 emissions spills over on to how much people think is needed to compensate for the emissions. Reforestation (planting trees) is a common carbon-offset technique. With this in mind, participants estimated the number of trees needed to compensate for the carbon emissions from vehicles that were traveling with various moral motives. Two experiments revealed that people think larger carbon offsets are needed to compensate for the emissions when the emissions are caused by traveling for immoral reasons, in comparison with when caused by traveling for moral reasons. Hence, moral motives influence people’s judgments of carbon-offset requirements even though these motives have no bearing on what is compensated for. Moreover, the effect was insensitive to individual differences in carbon literacy and gender and to the unit (kilograms or tons) in which the CO2 emissions were expressed to the participants. The findings stress the role of emotion in how people perceive carbon offsetting.