bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic insights into nanoparticle surface-bacterial membrane interactions in overcoming antibiotic resistance
Authors: Modi Suraj Kumar , Gaur Smriti , Sengupta Mrittika , Singh Manu Smriti
Published: April 2023

Antimicrobial Resistance (AMR) raises a serious concern as it contributes to the global mortality by 5 million deaths per year. The overall impact pertaining to significant membrane changes, through broad spectrum drugs have rendered the bacteria resistant over the years. The economic expenditure due to increasing drug resistance poses a global burden on healthcare community and must be dealt with immediate effect. Nanoparticles (NP) have demonstrated inherent therapeutic potential or can serve as nanocarriers of antibiotics against multidrug resistant (MDR) pathogens. These carriers can mask the antibiotics and help evade the resistance mechanism of the bacteria. The targeted delivery can be fine-tuned through surface functionalization of Nanocarriers using aptamers, antibodies etc. This review covers various molecular mechanisms acquired by resistant bacteria towards membrane modification. Mechanistic insight on ‘NP surface-bacterial membrane’ interactions are crucial in deciding the role of NP as therapeutic. Finally, we highlight the potential accessible membrane targets for designing smart surface-functionalized nanocarriers which can act as bacteria-targeted robots over the existing clinically available antibiotics. As the bacterial strains around us continue to evolve into resistant versions, nanomedicine can offer promising and alternative tools in overcoming AMR.
Light conditions during Atlantic salmon embryogenesis affect key neuropeptides in the melanocortin system during transition from endogenous to exogenous feeding
Authors: Norland Sissel , Gomes Ana S. , Rønnestad Ivar , Helvik Jon Vidar , Eilertsen Mariann
Published: April 2023

During the first feeding period, fish will adapt to exogenous feeding as their endogenous source of nutrients is depleted. This requires the development of a functional physiological system to control active search for food, appetite, and food intake. The Atlantic salmon (Salmo salar) melanocortin system, a key player in appetite control, includes neuronal circuits expressing neuropeptide y (npya), agouti-related peptide (agrp1), cocaine- and amphetamine-regulated transcript (cart), and proopiomelanocortin (pomca). Little is known about the ontogeny and function of the melanocortin system during early developmental stages. Atlantic salmon [0–730 day degrees (dd)] were reared under three different light conditions (DD, continuous darkness; LD, 14:10 Light: Dark; LL, continuous light) before the light was switched to LD and the fish fed twice a day. We examined the effects of different light conditions (DDLD, LDLD, and LLLD) on salmon growth, yolk utilization, and periprandial responses of the neuropeptides npya1, npya2, agrp1, cart2a, cart2b, cart4, pomca1, and pomca2. Fish were collected 1 week (alevins, 830 dd, still containing yolk sac) and 3 weeks (fry, 991 dd, yolk sac fully consumed) into the first feeding period and sampled before (−1 h) and after (0.5, 1.5, 3, and 6 h) the first meal of the day. Atlantic salmon reared under DDLD, LDLD, and LLLD had similar standard lengths and myotome heights at the onset of first feeding. However, salmon kept under a constant light condition during endogenous feeding (DDLD and LLLD) had less yolk at first feeding. At 830 dd none of the neuropeptides analyzed displayed a periprandial response. But 2 weeks later, and with no yolk remaining, significant periprandial changes were observed for npya1, pomca1, and pomca2, but only in the LDLD fish. This suggests that these key neuropeptides serve an important role in controlling feeding once Atlantic salmon need to rely entirely on active search and ingestion of exogenous food. Moreover, light conditions during early development did not affect the size of salmon at first feeding but did affect the mRNA levels of npya1, pomca1, and pomca2 in the brain indicating that mimicking natural light conditions (LDLD) better stimulates appetite control.
Advances on intelligent algorithms for scientific computing: an overview
Authors: Hua Cheng , Cao Xinwei , Liao Bolin , Li Shuai
Published: April 2023

The field of computer science has undergone rapid expansion due to the increasing interest in improving system performance. This has resulted in the emergence of advanced techniques, such as neural networks, intelligent systems, optimization algorithms, and optimization strategies. These innovations have created novel opportunities and challenges in various domains. This paper presents a thorough examination of three intelligent methods: neural networks, intelligent systems, and optimization algorithms and strategies. It discusses the fundamental principles and techniques employed in these fields, as well as the recent advancements and future prospects. Additionally, this paper analyzes the advantages and limitations of these intelligent approaches. Ultimately, it serves as a comprehensive summary and overview of these critical and rapidly evolving fields, offering an informative guide for novices and researchers interested in these areas.
Application of a Hermite-based measure of non-Gaussianity to normality tests and independent component analysis
Authors: Jain Parul , Knight Bruce W. , Victor Jonathan D.
Published: April 2023

In the analysis of neural data, measures of non-Gaussianity are generally applied in two ways: as tests of normality for validating model assumptions and as Independent Component Analysis (ICA) contrast functions for separating non-Gaussian signals. Consequently, there is a wide range of methods for both applications, but they all have trade-offs. We propose a new strategy that, in contrast to previous methods, directly approximates the shape of a distribution via Hermite functions. Applicability as a normality test was evaluated via its sensitivity to non-Gaussianity for three families of distributions that deviate from a Gaussian distribution in different ways (modes, tails, and asymmetry). Applicability as an ICA contrast function was evaluated through its ability to extract non-Gaussian signals in simple multi-dimensional distributions, and to remove artifacts from simulated electroencephalographic datasets. The measure has advantages as a normality test and, for ICA, for heavy-tailed and asymmetric distributions with small sample sizes. For other distributions and large datasets, it performs comparably to existing methods. Compared to standard normality tests, the new method performs better for certain types of distributions. Compared to contrast functions of a standard ICA package, the new method has advantages but its utility for ICA is more limited. This highlights that even though both applications—normality tests and ICA—require a measure of deviation from normality, strategies that are advantageous in one application may not be advantageous in the other. Here, the new method has broad merits as a normality test but only limited advantages for ICA.
Quantitative optical coherence microscopy of neuron morphology in human entorhinal cortex
Authors: Wang Hui , Gong Dayang , Augustinack Jean C. , Magnain Caroline
Published: April 2023

Introduction

The size and shape of neurons are important features indicating aging and the pathology of neurodegenerative diseases. Despite the significant advances of optical microscopy, quantitative analysis of the neuronal features in the human brain remains largely incomplete. Traditional histology on thin slices bears tremendous distortions in three-dimensional reconstruction, the magnitude of which are often greater than the structure of interest. Recently development of tissue clearing techniques enable the whole brain to be analyzed in small animals; however, the application in the human remains challenging.

Methods

In this study, we present a label-free quantitative optical coherence microscopy (OCM) technique to obtain the morphological parameters of neurons in human entorhinal cortex (EC). OCM uses the intrinsic back-scattering property of tissue to identify individual neurons in 3D. The area, length, width, and orientation of individual neurons are quantified and compared between layer II and III in EC.

Results

The high-resolution mapping of neuron size, shape, and orientation shows significant differences between layer II and III neurons in EC. The results are validated by standard Nissl staining of the same samples.

Discussion

The quantitative OCM technique in our study offers a new solution to analyze variety of neurons and their organizations in the human brain, which opens new insights in advancing our understanding of neurodegenerative diseases.
Amygdala neurocircuitry at the interface between emotional regulation and narcolepsy with cataplexy
Authors: Sardar Haniyyah , Goldstein-Piekarski Andrea N. , Giardino William J.
Published: April 2023

Narcolepsy is a sleep disorder characterized by chronic and excessive daytime sleepiness, and sudden intrusion of sleep during wakefulness that can fall into two categories: type 1 and type 2. Type 1 narcolepsy in humans is widely believed to be caused as a result of loss of neurons in the brain that contain the key arousal neuropeptide Orexin (Orx; also known as Hypocretin). Patients with type 1 narcolepsy often also present with cataplexy, the sudden paralysis of voluntary muscles which is triggered by strong emotions (e.g., laughter in humans, social play in dogs, and chocolate in rodents). The amygdala is a crucial emotion-processing center of the brain; however, little is known about the role of the amygdala in sleep/wake and narcolepsy with cataplexy. A collection of reports across human functional neuroimaging analyses and rodent behavioral paradigms points toward the amygdala as a critical node linking emotional regulation to cataplexy. Here, we review the existing evidence suggesting a functional role for the amygdala network in narcolepsy, and build upon a framework that describes relevant contributions from the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and the extended amygdala, including the bed nucleus of stria terminalis (BNST). We propose that detailed examinations of amygdala neurocircuitry controlling transitions between emotional arousal states may substantially advance progress in understanding the etiology of narcolepsy with cataplexy, leading to enhanced treatment opportunities.
Applying a nutrition security lens to the Dietary Guidelines for Americans to address metabolic health
Authors: Volek Jeff S. , Clinthorne Jonathan , S. Yancy Jr William
Published: April 2023

Nutrition security - access to food that promotes well-being and prevents or treats disease, particularly among racial and ethnic minority populations, lower income populations, and rural and remote populations - is a national priority. Leading causes of death and disability in America, such as heart disease, stroke, cancer, and diabetes that disproportionately affect minorities are linked to preventable diet-related risk factors. Mounting evidence indicates that adherence to a lower-carbohydrate dietary pattern is associated with weight maintenance, improved blood glucose and insulin control, lower blood pressure, reduced markers of inflammation, and a more favorable lipid profile. Additionally, prior concerns regarding the higher fat and cholesterol content of this dietary pattern are less founded in modern research. The inclusion of a lower-carbohydrate option that meets all essential nutrient requirements aligns with the contemporary movement toward more flexibility and precision nutrition. Most important, a lower-carbohydrate option positions the Dietary Guidelines for Americans to more accurately reflect the current scientific evidence and more effectively address the metabolic health of the nation. Further, it has the potential to improve nutrition security by addressing metabolic diseases that disproportionately affect people from historically marginalized racial, ethnic, socioeconomic, and cultural backgrounds. Given that most American adults are living with at least one diet-related chronic metabolic disease, updating the Dietary Guidelines for Americans to recognize and reflect the poor health status of the general population is prudent and urgent.
Impact of obesity on all-cause and cause-specific mortality among critically ill men and women: a cohort study on the eICU database
Authors: Li Shan , Zhang Wei , Fu Zhiqing , Liu Hongbin
Published: April 2023

Background

The effect of obesity on intensive care unit outcomes among critically ill patients and whether there are sex differences have not been well investigated. We sought to determine the association between obesity and 30-day all-cause and cause-specific mortality among critically ill men and women.

Methods

Adult participants who had body mass index (BMI) measurements were included from the eICU database. Participants were divided into six groups according to BMI (kg/m2) categories (underweight, <18.5; normal weight, 18.5–24.9; overweight, 25–29.9; class I obesity, 30–34.9; class II obesity, 35–39.9; class III obesity, ≥40). A multivariable adjusted logistic model was conducted with odds ratios (ORs) and 95% confidence intervals (CIs). A cubic spline curve based on the generalized additive model was used to represent the nonlinear association. Stratified analysis and sensitivity analysis were also performed.

Results

A total of 160,940 individuals were included in the analysis. Compared with the class I obesity category, the underweight and normal weight categories had higher all-cause mortality, and the multivariable adjusted ORs were 1.62 (95% CI: 1.48–1.77) and 1.20 (95% CI: 1.13–1.27) for the general population, 1.76 (95% CI: 1.54–2.01) and 1.22 (95% CI: 1.13–1.32) for men, and 1.51 (95% CI: 1.33–1.71) and 1.16 (95% CI: 1.06–1.27) for women, respectively. Accordingly, multivariable adjusted ORs for the class III obesity category were 1.14 (95% CI: 1.05–1.24) for the general population, 1.18 (95% CI: 1.05–1.33) for men, and 1.10 (95% CI: 0.98–1.23) for women. With cubic spline curves, the association between BMI and all-cause mortality was U-shaped or reverse J-shaped. Similar findings were observed for cause-specific mortality, with the underweight category associated with a higher risk of mortality. Class III obesity increased the risk of cardiovascular death among men (OR 1.51; 95% CI: 1.23–1.84) and increased the risk of other-cause death among women (OR 1.33; 95% CI: 1.10–1.61).

Conclusion

The obesity paradox appears to be suitable for all-cause and cause-specific mortality among critically ill men and women. However, the protective effect of obesity cannot be extended to severely obese individuals. The association between BMI and cardiovascular mortality was sex-specific and was more pronounced among men than among women.
Full-thickness chest wall resection for malignant chest wall tumors and postoperative problems
Authors: Asanuma Kunihiro , Tsujii Masaya , Hagi Tomohito , Nakamura Tomoki , Kita Kouji , Shimamoto Akira , Kataoka Takeshi , Takao Motoshi , Sudo Akihiro
Published: April 2023

Background

Chest wall malignant tumor (including primary and metastatic lesions) is rare, representing less than 5% of all thoracic malignancies. Local control of chest wall malignancies requires wide resection with tumor-free margins. These requirements increase the risk of thoracic cavity failure and subsequent pulmonary failure. The restoration strategy for chest wall defects comprises chest wall reconstruction and soft-tissue coverage. Various reconstruction methods have been used, but both evidence and guidelines for chest wall reconstruction remain lacking. The purposes of this study were to collate our institutional experience, evaluate the outcomes of full-thickness chest wall resection and reconstruction for patients with chest wall malignant tumor, and identify problems in current practice for chest wall reconstruction with a focus on local control, complications, pulmonary function and scoliosis.

Methods

Participants comprised 30 patients with full-thickness chest wall malignant tumor who underwent chest wall resection and reconstruction between 1997 and 2021 in Mie University Hospital. All patients underwent chest wall resection of primary, recurrent or metastatic malignant tumors. A retrospective review was conducted for 32 operations.

Results

Recurrence was observed after 5 operations. Total 5-year recurrence-free survival (RFS) rate was 79.3%. Diameter ≥5 cm was significantly associated with poor RFS. The postoperative complication rate was 18.8%. Flail chest was observed with resection of ≥3 ribs in anterior and lateral resections or with sternum resection without polyethylene methylmethacrylate reconstruction. Postoperative EFV1.0% did not show any significant decrease. Postoperative %VC decreased significantly with resection of ≥4 ribs or an area of >70 cm2. Postoperative scoliosis was observed in 8 of 28 patients. Posterior resection was associated with a high prevalence of scoliosis (88.9%).

Conclusion

With chest wall reconstruction, risks of pulmonary impairment, flail chest and scoliosis were significantly increased. New strategies including indications for rigid reconstruction are needed to improve the outcomes of chest wall reconstruction.
The development and validation of a patient-reported outcome measure to assess financial hardship among older cancer survivors in China: hardship and recovery with distress survey
Authors: Liu Li , Zhang Aihua , Su Mingzhu , Sun Xiaojie , Shao Di , Cheng Joyce , Yao Nengliang (Aaron)
Published: April 2023

Background

Financial hardship has been described as a patient’s economic experiencefollowing cancer-related treatment. Standardized patient-reported outcome measures(PROM) to assess this distress has not been well-studied, especially among older cancer survivors.

Objective

The aim of this study was to develop and validate PROM for assessing the financial hardship of older cancer survivors in China.

Methods

Items were generated using qualitative interviews and literature review. Items were screened based on Delphi expert consultation and patients’ opinions. Item response theory (IRT) and classical test theory (CTT) were used to help reduce items. Retained items formed a pilot instrument that was subjected to psychometric testing. A cut-off score for the new instrument for predicting poor quality of life was identified by receiver operating characteristic (ROC) analysis.

Results

Qualitative interviews and literature review generated 135 items, which were reduced to 60 items because of redundancy. Following Delphi expert consultation and patients’ evaluation, 24 items with high importance were extracted. Sixteen items were selected due to satisfactory statistical analysis based on CTT and IRT. Ten items were retained and comprised 2 domains after loadings in exploratory factor analysis (EFA). Internal consistency was satisfactory (α = 0.838). Test-retest reliability was good (intraclass correlation, 0.909). The ROC analysis suggested that the cut-off of 18.5 yielded an acceptable sensitivity and specificity.

Conclusions

The PROM for Hardship and Recovery with Distress Survey (HARDS) consists of 10 items that specifically reflect the experiences of financial hardship among older Chinese cancer survivors, and it also showed good reliability and validity in clinical settings.
Fetal oxygenation in the last weeks of pregnancy evaluated through the umbilical cord blood gas analysis
Authors: Filippi Luca , Scaramuzzo Rosa Teresa , Pascarella Francesca , Pini Alessandro , Morganti Riccardo , Cammalleri Maurizio , Bagnoli Paola , Ciantelli Massimiliano
Published: April 2023

Introduction

Embryo and fetus grow and mature over the first trimester of pregnancy in a dynamic hypoxic environment, where placenta development assures an increased oxygen availability. However, it is unclear whether and how oxygenation changes in the later trimesters and, more specifically, in the last weeks of pregnancy.

Methods

Observational study that evaluated the gas analysis of the umbilical cord blood collected from a cohort of healthy newborns with gestational age ≥37 weeks. Umbilical venous and arterial oxygen levels as well as fetal oxygen extraction were calculated to establish whether oxygenation level changes over the last weeks of pregnancy. In addition, fetal lactate, and carbon dioxide production were analyzed to establish whether oxygen oscillations may induce metabolic effects in utero.

Results

This study demonstrates a progressive increase in fetal oxygenation levels from the 37th to the 41st weeks of gestation (mean venous PaO2 approximately from 20 to 25 mmHg; p < 0.001). This increase is largely attributable to growing umbilical venous PaO2, regardless of delivery modalities. In neonates born by vaginal delivery, the increased oxygen availability is associated with a modest increase in oxygen extraction, while in neonates born by cesarean section, it is associated with reduced lactate production. Independently from the type of delivery, carbon dioxide production moderately increased. These findings suggest a progressive shift from a prevalent anaerobic metabolism (Warburg effect) towards a growing aerobic metabolism.

Conclusion

This study confirms that fetuses grow in a hypoxic environment that becomes progressively less hypoxic in the last weeks of gestation. The increased oxygen availability seems to favor aerobic metabolic shift during the last weeks of intrauterine life; we hypothesize that this environmental change may have implications for fetal maturation during intrauterine life.
Clinical features and pathogen distributions of microbiological-based protracted bacterial bronchitis in children of different ages in Northeast China
Authors: Chen Ning , Zhang Han , Feng Yong
Published: April 2023

Background

Protracted bacterial bronchitis (PBB) is often diagnosed clinically according to chronic wet cough, which can be resolved by appropriate antibiotics. Though rarely performed in PBB diagnosis, bacterial cultures by sputum or bronchoalveolar lavage (BAL) fluid can provide etiological features, which may be different in western countries and different areas of China. This study aimed to investigate the clinical and etiological features and outcomes in children of different ages with PBB in northeast China.

Methods

We retrospectively analyzed children diagnosed with PBB by positive BAL fluid or sputum bacterial cultures between 2017 and 2021. Children were divided into three age groups: <1 year (infants), 1–5 years (younger children), and ≥6 years (older children). Clinical characteristics, chest radiographic findings, bronchoscopy findings, microbiological findings, treatment strategies, and outcomes were reviewed and compared among the age groups. Factors associated with remission during follow-up were examined using logistic regression.

Results

A total of 45 children with PBB were included, consisting of 24 (53.3%) infants. The infants were often boys and had a shorter cough duration, a lower proportion of expectoration, a greater proportion of wheezing, and less bronchial wall thickening on high-resolution computed tomography compared to older children (P < 0.05). No significant differences were found among the age groups regarding macroscopic findings, except for a higher proportion of tracheobronchial malacia in infants than in older children (P = 0.013). The most commonly cultured bacteria were Haemophilus influenzae (42.2%), followed by Streptococcus pneumoniae (22.2%) and Klebsiella pneumoniae (20.0%). Compared to older children, infants had a higher remission (P = 0.009) and relatively lower relapse rates (P = 0.059). Short duration of cough (OR = 0.58, 95% CI: 0.34–0.99, P = 0.046) and absence of recurrent cephalosporins before diagnosis (OR = 0.05, 95% CI: 0.00–0.73, P = 0.028) were associated with remission.

Conclusions

Infants are more prone to PBB, with increased wheezing. Gram-negative bacilli infections are common in infants in northeast China. Older children with PBB should be carefully assessed, treated and followed up, particularly those with long duration of cough and poor response to antibiotic treatments.
Effects of low-dose combined olanzapine and sertraline on negative and depressive symptoms in treatment-resistant outpatients with acute exacerbated schizophrenia
Authors: Lang Xiaoe , Zang Xiaocui , Yu Feng , Xiu Meihong
Published: April 2023

Background: Treatment-resistant schizophrenia (TRS) is a major clinical challenge. Current antipsychotic medications do not adequately address negative and depressive symptoms in patients with TRS, and novel treatments are thus needed. This study examines the efficacy of low-dose combined olanzapine (OLA) and sertraline on depressive and negative symptoms in patients with TRS.

Methods: A total of 34 TRS outpatients with acutely exacerbated schizophrenia were randomly assigned to OLA monotherapy (12.5–20 mg/day) (control group) or low-dose combined OLA (7.5–10 mg/day) and sertraline (50–100 mg/day) (OS group). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of treatment in weeks 4, 8, 12, and 24. Depressive symptoms and social functioning were also assessed.

Results: Compared to the control group, the OS group showed significant improvements in depressive and negative symptoms over time. In addition, the low-dose combination of OLA and sertraline significantly improved social functioning compared with OLA monotherapy. There were no significant between-group differences in psychotic symptom improvement. However, the reduction in Hamilton Depression Rating Scale total score and PANSS negative subscore were not associated with improvements in social functioning, suggesting that these effects of combined treatment are independent.

Conclusion: Low-dose combined OLA and sertraline may be effective in the treatment of negative and depressive symptoms compared with standard OLA monotherapy in patients with TRS who are experiencing an acute exacerbation of schizophrenia.

Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04076371].
Effects of elexacaftor/tezacaftor/ivacaftor therapy on mental health of patients with cystic fibrosis
Authors: Piehler Linus , Thalemann Ralf , Lehmann Christine , Thee Stephanie , Röhmel Jobst , Syunyaeva Zulfiya , Stahl Mirjam , Mall Marcus A. , Graeber Simon Y.
Published: April 2023

Introduction: The CFTR modulator drug elexacaftor/tezacaftor/ivacaftor (ETI) was shown to improve CFTR function and clinical symptoms in patients with cystic fibrosis (CF) with at least one F508del allele. Recently, some case reports suggested potential side effects of ETI on mental health with an increase in depressive symptoms and even suicide attempts in patients with CF. However, the general effects of this triple combination therapy on the mental health status of patients with CF remain largely unknown.

Methods: We, therefore, performed a prospective, observational study in a real-life setting and investigated the relationship between initiation of ETI therapy and changes in mental health in adult patients with CF. We assessed Cystic Fibrosis Questionnaire-Revised (CFQ-R), Patient Health Questionnaire-9 (PHQ-9), Beck’s Depression Inventory – Fast Screen (BDI-FS) and Generalized Anxiety Disorder 7-item Scale (GAD-7) at baseline and 8–16 weeks after initiation of ETI.

Results: In total, 70 adult patients with CF with at least one F508del allele and a median age of 27.9 years were recruited. After initiation of ETI, the CFQ-R respiratory domain score improved by 27.9 (IQR 5.6 to 47.2; p < 0.001). The PHQ-9 score of depressive symptoms decreased by 1.0 (IQR -3.0 to 0.3; p < 0.05) with an increase of 16.9% in the group with a minimal score after initiation of ETI and a decrease in the groups of mild (−11.3%) or moderate (−5.7%) scores compared to baseline. The BDI-FS score of depressive symptoms decreased from 1.0 (IQR 0.0–2.0) at baseline to 0.0 (IQR 0.0 to 2.0; p < 0.05) after initiation of ETI. The group with a minimal BDI-FS score increased by 8.0% after initiation of ETI, whereas the groups with mild (−4.9%), moderate (−1.6%) or severe (−1.6%) scores decreased compared to baseline. The GAD-7 score of anxiety symptoms did not change after initiation of ETI compared to baseline (0.0; IQR -2.0. to 0.0; p = 0.112).

Conclusion: Initiation of ETI improves symptoms of depression in adult patients with CF with at least one F508del allele. However, symptoms of anxiety do not change after short-term therapy with ETI.
Potential prognostic and immunotherapeutic value of calponin 1: A pan-cancer analysis
Authors: Zhou Hengli , Ke Junyu , Liu Changhua , Zhu Menglu , Xiao Bijuan , Wang Qi , Hou Rui , Zheng Yueer , Wu Yongqiang , Zhou Xingting , Chen Xinlin , Pan Huafeng
Published: April 2023

Background: Emerging evidence has suggested a pro-oncogenic role of calponin 1 (CNN1) in the initiation of a variety of cancers. Despite this, CNN1 remains unknown in terms of its effects and mechanisms on angiogenesis, prognosis, and immunology in cancer.

Materials and Methods: The expression of CNN1 was extracted and analyzed using the TIMER, UALCAN, and GEPIA databases. Meanwhile, we analyzed the diagnostic value of CNN1 by using PrognoScan and Kaplan–Meier plots. To elucidate the value of CNN1 in immunotherapy, we used the TIMER 2.0 database, TISIDB database, and Sangerbox database. Gene set enrichment analysis (GSEA) was used to analyze the expression pattern and bio-progression of CNN1 and the vascular endothelium growth factor (VEGF) in cancer. The expressions of CNN1 and VEGF in gastric cancer were confirmed using immunohistochemistry. We used Cox regression analysis to investigate the association between pathological characteristics, clinical prognosis, and CNN1 and VEGF expressions in patients with gastric cancer.

Results: CNN1 expression was higher in normal tissues than it was in tumor tissues of most types of cancers. However, the expression level rebounds during the development of tumors. High levels of CNN1 indicate a poor prognosis for 11 tumors, which include stomach adenocarcinoma (STAD). There is a relationship between CNN1 and tumor-infiltrating lymphocytes (TILs), and the marker genes NRP1 and TNFRSF14 of TILs are significantly related to CNN1 expression in gastric cancers. The GSEA results confirmed the lower expression of CNN1 in tumors when compared to normal tissues. However, CNN1 again showed an increasing trend during tumor development. In addition, the results also suggest that CNN1 is involved in angiogenesis. The immunohistochemistry results validated the GSEA result (take gastric cancer as an example). Cox analysis suggested that high CNN1 expression and high VEGF expression are closely associated with poor clinical prognosis.

Conclusion: Our study has shown that CNN1 expression is aberrantly elevated in various cancers and positively correlates with angiogenesis and the immune checkpoint, contributing to cancer progression and poor prognosis. These results suggest that CNN1 could serve as a promising candidate for pan-cancer immunotherapy.
Mass production of ultra-pure NaI powder for COSINE-200
Authors: Shin KeonAh , Choe JunSeok , Gileva Olga , Iltis Alain , Kim Yena , Kim Yeongduk , Lee Cheolho , Lee Eunkyung , Lee HyunSu , Lee Moo Hyun
Published: April 2023

COSINE-200 is the next phase experiment of the ongoing COSINE-100 that aims to unambiguously verify the annual modulation signals observed by the DAMA experiment and to reach the world competitive sensitivity on the low-mass dark matter search. To achieve the physics goal of the COSINE-200, the successful production of the low-background NaI(Tl) detectors is crucial and it must begin from the mass production of the ultra-low background NaI powder. A clean facility for mass-producing the pure-NaI powder has been constructed at the Center for Underground Physics (CUP) in Korea. Two years of operation determined efficient parameters of the mass purification and provided a total of 480 kg of the ultra-pure NaI powder in hand. The potassium concentration in the produced powders varied from 5.4 to 11 ppb, and the maximum production capacity of 35 kg per 2 weeks was achieved. Here, we report our operational practice with the mass purification of the NaI powder, which includes raw powder purification, recycling of the mother solution, and recovery of NaI from the residual melt after crystal growth.
Real-world effects of once-daily inhaled steroid (fluticasone furoate) combined with long-acting beta-2 agonist (vilanterol) and long-acting muscarinic antagonist (umeclidinium) on lung function tests of asthma patients in Japan
Authors: Umeda Akira , Shimada Hisato , Yamane Tateki , Mochizuki Taichi , Inoue Yasushi , Tsushima Kenji , Miyagawa Kazuya , Mochida Atsumi , Takeda Hiroshi , Okada Yasumasa , Masaki Katsunori , Matsusaka Masako , Fukunaga Koichi
Published: April 2023

Background: The Japanese drug use system allowed the once-daily use of inhaled corticosteroid fluticasone furoate (FF) combined with a long-acting beta-2 agonist vilanterol (VI) and a long-acting muscarinic antagonist umeclidinium (UMEC) against asthma on 18 February 2021. We investigated the real-world effects of these drugs (FF/UMEC/VI) mainly on lung function tests.

Methods: This was an open-label, uncontrolled, within-group time-series (before-after) study. Prior asthma treatment (inhaled corticosteroid with/without a long-acting beta-2 agonist with/without a long-acting muscarinic antagonist) was switched to FF/UMEC/VI 200/62.5/25 μg. Subjects were evaluated by lung function tests prior to, and 1–2 months after, initiation of FF/UMEC/VI 200/62.5/25 μg. Patients were asked questions regarding the asthma control test and preference for drugs.

Results: Overall, 114 asthma outpatients (97% Japanese) were enrolled from February 2021 to April 2022: 104 subjects completed the study. Forced expiratory volume in 1 s, peak flow, and asthma control test score of FF/UMEC/VI 200/62.5/25 μg-treated subjects were significantly increased (p < 0.001, p < 0.001, and p < 0.01, respectively). In contrast with FF/VI 200/25 μg, instantaneous flow at 25% of the forced vital capacity and expiratory reserve volume were significantly increased by FF/UMEC/VI 200/62.5/25 μg (p < 0.01, p < 0.05, respectively). Sixty-six percent of subjects declared they wanted to continue FF/UMEC/VI 200/62.5/25 μg in the future. Adverse effects, mainly local, were seen in 30% of patients, but no serious adverse effects were seen.

Conclusion: Once-daily FF/UMEC/VI 200/62.5/25 μg was effective against asthma without serious adverse events. This is the first report that demonstrated FF/UMEC/VI dilated peripheral airways using lung function tests. This evidence on drug effects may improve our understanding of pulmonary physiology and the pathophysiology of asthma.
Foliar application of putrescine alleviates terminal drought stress by modulating water status, membrane stability, and yield- related traits in wheat (Triticum aestivum L.)
Authors: Wasaya Allah , Rehman Iqra , Mohi Ud Din Atta , Hayder Bin Khalid Muhammad , Ahmad Yasir Tauqeer , Mansoor Javaid Muhammad , El-Hefnawy Mohamed , Brestic Marian , Rahman Md Atikur , El Sabagh Ayman
Published: April 2023

Drought stress is one of the major limitations to the growth and yield productivity of cereal crops. It severely impairs the early growing and grain -filling stages of wheat. Therefore, cost- effective and eco-friendly approaches for alleviating drought stress in cereal crops are in high demand. Polyamines, such as putrescine, have a significant effect on improving crop yield under drought- stress conditions. Therefore, the current study was executed with the aim of exploring the significance of putrescine in alleviating drought stress and improving yield- related traits in wheat. Two distinct wheat cultivars (Fakhar-e-Bhakkar and Anaj-2017) were treated with the foliar application of different concentrations (control, 0.5, 1.0, and 1.5 PPM) of putrescine (put) under two moisture conditions (well- watered and terminal drought stress). The results demonstrate that the imposition of terminal drought stress significantly reduces different physiological and yield- related traits of both wheat cultivars. The reduction of relative water content (RWC%), membrane stability index (MSI), leaf area, tillers per plant, biomass yield, number of spikelets per spike, 100-grain weight, grain yield per plant, and straw yield was greater in Anaj-2017 than in Fakhar-e-Bhakkar cultivar. The results further explain that the foliar application of increased concentrations of putrescine from 0.0 to 1.0 PPM gradually improved physiological and yield traits, whereas these traits declined with the application of putrescine at the highest dose (1.5 PPM). The exogenous application of 1.0 PPM putrescine improved the relative water content (19.76%), specific leaf area (41.47%), and leaf area ratio (35.84%) compared with the controlled treatment. A higher grain yield (28.0 g plant-1) and 100-grain weight (3.8 g) were obtained with the foliar application of 1.0 PPM putrescine compared with controlled treatments. The findings of this study confirm the protective role of putrescine against terminal drought stress. It is therefore recommended to use putrescine at a concentration of 1.0 PPM, which could help alleviate terminal drought stress and attain better wheat yield.
Re-shaping pruning improves the dynamic response of centuries-old olive trees to branch-shaker vibrations application
Authors: Camposeo Salvatore , Vicino Francesco , Vivaldi Gaetano Alessandro , Pascuzzi Simone
Published: April 2023

Introduction

The Mediterranean basin is home to centuries-old large olive trees; high-vigor cultivars are widespread, with training forms poorly adapted to mechanical harvesting by trunk/branch shakers. The significant quantity of leaves, the considerable tree height, and the presence of multiple dichotomous hanging branches reduce the transmission of vibrations applied by the branch-shaker machines. Thus, re-shaping pruning may improve the performance of this modern mechanical harvesting method by focusing on removing both the hanging branches and those forming dichotomies. The goal of this study was to evaluate the dynamic responses of large-sized olive trees to pruning (or not) through various field tests under different excitation forces. We hypothesized that more rational pruning could significantly increase vibration transmissions.

Methods

To assess the transmission of vibrations, tests were conducted before and after the pruning on representative trees. Tri-axial accelerometers packed in a small titanium housing were used. Trees were assessed before and after the re-shaping pruning. This study reports the first data about the dynamic behavior of centuries-old tree skeletons, in the context of very large-sized olive trees, while taking into account the effects of two different vibrations application modes: a realistic one represented by the system vibration head-tree, originated when the gripper of a shaking machine wrapped and fastened the main branch of the olive trees, and a more speculative one, represented by a single impulse of a short-duration force originated by a hammer.

Results

After pruning, spectral density increased 10 fold in the tertiary branches of pruned trees (ranging 1.0–10 m s−2) compared to that of not-pruned ones (ranging 0.1–1.0 m s−2) at frequency >50 Hz under vibration excitation. Moreover, vibrational decay times (120–150 ms) and amplitude (>10−1 m s−2) were higher under single-impulse excitation.

Discussion

A more rational pruning applied to ancient large-sized olive trees significantly increased the vibration transmission under both impulse and vibratory excitation forces, without affected their typical “look”. Moreover, these insights are helpful in turn in achieving maximum fruit-removal efficiency. These insights could be applied to various horticultural conditions which would improve the economic sustainability of monumental olive trees, a key portion of the Mediterranean landscape and cultural heritage.
Trans-cinnamaldehyde-related overproduction of benzoic acid and oxidative stress on Arabidopsis thaliana
Authors: López-González David , Ferradás Yolanda , Araniti Fabrizio , Graña Elisa , Hermida-Ramón José M. , González María Victoria , Teijeira Marta , Rey Manuel , Reigosa Manuel J. , Sánchez-Moreiras Adela M.
Published: April 2023

Introduction

Trans-cinnamaldehyde is a specialised metabolite that naturally occurs in plants of the Lauraceae family. This study focused on the phytotoxic effects of this compound on the morphology and metabolism of Arabidopsis thaliana seedlings.

Material and methods

To evaluate the phytotoxicity of trans-cinnamaldehyde, a dose-response curve was first performed for the root growth process in order to calculate the reference inhibitory concentrations IC50 and IC80 (trans-cinnamaldehyde concentrations inducing a 50% and 80% inhibition, respectively). Subsequently, the structure and ultrastructure of the roots treated with the compound were analysed by light and electron microscopy. Based on these results, the following assays were carried out to in depth study the possible mode of action of the compound: antiauxinic PCIB reversion bioassay, determination of mitochondrial membrane potential, ROS detection, lipid peroxidation content, hormone quantification, in silico studies and gene expression of ALDH enzymes.

Results

Trans-cinnamaldehyde IC50 and IC80 values were as low as 46 and 87 μM, reducing the root growth and inducing the occurrence of adventitious roots. At the ultrastructural level, the compound caused alterations to the mitochondria, which were confirmed by detection of the mitochondrial membrane potential. The morphology observed after the treatment (i.e., appearance of adventitious roots) suggested a possible hormonal mismatch at the auxin level, which was confirmed after PCIB bioassay and hormone quantification by GC-MS. The addition of the compound caused an increase in benzoic, salicylic and indoleacetic acid content, which was related to the increased gene expression of the aldehyde dehydrogenase enzymes that can drive the conversion of trans-cinnamaldehyde to cinnamic acid. Also, an increase of ROS was also observed in treated roots. The enzyme-compound interaction was shown to be stable over time by docking and molecular dynamics assays.

Discussion

The aldehyde dehydrogenases could drive the conversion of trans-cinnamaldehyde to cinnamic acid, increasing the levels of benzoic, salicylic and indoleacetic acids and causing the oxidative stress symptoms observed in the treated seedlings. This would result into growth and development inhibition of the trans-cinnamaldehyde-treated seedlings and ultimately in their programmed-cell-death.
Interactions between Verticillium dahliae and cotton: pathogenic mechanism and cotton resistance mechanism to Verticillium wilt
Authors: Zhu Yutao , Zhao Mei , Li Taotao , Wang Lianzhe , Liao Chunli , Liu Dongxiao , Zhang Huamin , Zhao Yanpeng , Liu Lisen , Ge Xiaoyang , Li Bingbing
Published: April 2023

Cotton is widely grown in many countries around the world due to the huge economic value of the total natural fiber. Verticillium wilt, caused by the soil-borne pathogen Verticillium dahliae, is the most devastating disease that led to extensive yield losses and fiber quality reduction in cotton crops. Developing resistant cotton varieties through genetic engineering is an effective, economical, and durable strategy to control Verticillium wilt. However, there are few resistance gene resources in the currently planted cotton varieties, which has brought great challenges and difficulties for breeding through genetic engineering. Further revealing the molecular mechanism between V. dahliae and cotton interaction is crucial to discovering genes related to disease resistance. In this review, we elaborated on the pathogenic mechanism of V. dahliae and the resistance mechanism of cotton to Verticillium wilt. V. dahliae has evolved complex mechanisms to achieve pathogenicity in cotton, mainly including five aspects: (1) germination and growth of microsclerotia; (2) infection and successful colonization; (3) adaptation to the nutrient-deficient environment and competition of nutrients; (4) suppression and manipulation of cotton immune responses; (5) rapid reproduction and secretion of toxins. Cotton has evolved multiple physiological and biochemical responses to cope with V. dahliae infection, including modification of tissue structures, accumulation of antifungal substances, homeostasis of reactive oxygen species (ROS), induction of Ca2+ signaling, the mitogen-activated protein kinase (MAPK) cascades, hormone signaling, and PAMPs/effectors-triggered immune response (PTI/ETI). This review will provide an important reference for the breeding of new cotton germplasm resistant to Verticillium wilt through genetic engineering.
Strength Back – A qualitative study on the co-creation of a positive psychology digital health intervention for spinal surgery patients
Authors: Van Der Horst Annemieke Y. , Bohlmeijer Ernst T. , Schreurs Karlein M. G. , Kelders Saskia M.
Published: April 2023

Introduction

Spinal surgery patients often experience pain as well as stress, anxiety or even depression before surgery, highlighting the need for better mental preparation before undergoing surgery. Acceptance and Commitment Therapy and positive psychology have proven effective in coping with chronic pain and providing long-term skills that enhance psychological flexibility and mental well-being.

The aim of this study is to develop a digital intervention (app) based on Acceptance and Commitment Therapy and positive psychology in co-creation with all stakeholders, including patients and professionals. The aim of the intervention is to increase psychological flexibility and positive skills of spinal surgery patients to promote long-term resilience.

Materials and methods

In this qualitative study, individual, semi-structured interviews were held with healthcare professionals (N = 9) and spinal surgery patients (N = 12) to identify contextual factors and needs for the app. Subsequently, three focus-group sessions were held with healthcare professionals and newly recruited patients to specify relevant values. Also, a first version of the app, named Strength Back, was developed using a participatory design.

Results

The interviews confirmed the need for information and digital support to cope with insecurity, anxiety and pain, both before and after surgery. Based on iterative steps in the focus-group sessions, thirteen modules were developed focusing on procedural information, pain education, psychological flexibility and mental well-being.

Discussion

The intervention Strength Back, containing information as well as Acceptance and Commitment Therapy and positive psychology exercises, has the potential to increase psychological flexibility, enhance well-being and improve postoperative recovery after spinal surgery.