bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to Mediterranean Diet of Breastfeeding Mothers and Fatty Acids Composition of Their Human Milk: Results From the Italian MEDIDIET Study
Authors: Di Maso Matteo , Bravi Francesca , Ferraroni Monica , Agostoni Carlo , Eussen Simone R. B. M. , Decsi Tamás , Quitadamo Pasqua A. , Tonetto Paola , Peila Chiara , Profeti Claudio , Salvatori Guglielmo , Kazmierska Iwona , Decarli Adriano , Vacca Elisabetta , Bertino Enrico , Stahl Bernd , Moro Guido E.
Published: June 2022

Background and Aims

The content of fatty acids (FA) in human milk may be influenced by maternal nutrition. We evaluated the role of a Mediterranean diet in influencing the content of FA in human milk among 282 breastfeeding mothers participating in the MEDIDIET study.

Materials and Methods

Mediterranean Diet Score (MDS), a composite index, was used to evaluate adherence to the Mediterranean diet. It includes 9 components (i.e., vegetables, fruit, cereals, legumes, monounsaturated to saturated FA ratio – MUFA/SFA, fish, dairy products, meat, and alcohol) and therefore potentially ranges from 0 (no adherence) to 9 (complete adherence) points. None of the mothers obtained the highest score due to the low alcohol consumption in the study population. Mothers were categorized in approximate tertiles of adherence: 0–3 (34.4%), 4 (26.2%), and 5–8 points (39.4%). The mean content of FA across categories of MDS was compared using ANOVA and test for trend.

Results

A high adherence of breastfeeding mothers to the Mediterranean diet was associated with lower content of SFA in human milk (42.58 ± 4.36 for MDS = 0–3, 42.58 ± 4.89 for MDS = 4, and 40.92 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend = 0.02). Conversely, a high adherence was associated with higher content of MUFA in human milk (43.27 ± 4.27 for MDS = 0–3, 43.27 ± 4.47 for MDS = 4, and 45.24 ± 5.22% of fats for MDS = 5–8 points; p ANOVA and p for trend < 0.01), ω-3 FA (1.07 ± 0.25 for MDS = 0–3, 1.22 ± 0.49 for MDS = 4, and 1.31 ± 0.51% of fats for MDS = 5–8 points; p ANOVA and p for trend < 0.01), and the major types of ω-3 FA (i.e., α-linolenic acid – ALA, eicosapentaenoic acid – EPA, docosahexaenoic acid – DHA, docosapentaenoic acid – DPA). These associations were mainly driven by the adherence to the vegetables, MUFA/SFA, fish, and dairy products components of the Mediterranean diet.

Conclusion

A high adherence to the Mediterranean diet was associated with human milk showing a lower content of SFA and higher content of MUFA and ω-3 FA, including DHA. The Mediterranean diet may contribute in human milk production with higher content of specific FA which is directly involved in infant’s neural and visual development, as reported by previous studies.
Effect of Steam Explosion on Structural Characteristics of β−Conglycinin and Morphology, Chemical Compositions of Soybean Meal
Authors: Kong Feng , Zeng Qinghua , Li Yue , Guo Xingfeng
Published: June 2022

In this study, steam explosion was applied as a means to degrade β-conglycinin. We investigated changes in morphology, the chemical composition of soybean meal, and the structural characteristics of β-conglycinin. The results showed that steam explosion at 0.7 MPa for 8 min could effectively decrease the β-conglycinin content of soybean meal while the histamine content was not increased. The structural characteristics of soybean meal proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and X-ray diffraction (XRD). Steam explosion caused the degradation of high weight proteins and reduced the band density of α’, α, and β subunits in β-conglycinin. The micro-surface of soybean meal seemed to be in the cracked or puffed stage and the color became brown or dark after steam explosion. Steam explosion facilitated the dissolution of water-extractable arabinoxylans, which are 4.81 fold higher than that of native soybean meal. Phytic acid was exposed to the hydrothermal environment of the steam explosion process and consequently degraded by 12.95–24.69%. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of soybean meal extract was gradually increased from 20.70 to 33.71% with the rising of treated pressure from 0.3 to 0.7 MPa, which was 1.11–1.81 fold of native extract. The steam explosion may be a new modification technology that could decrease antigenicity, and steam-exploded soybean meal (0.7 MPa, 8 min) with lower β-conglycinin and phytic acid content that could be widely used in food products.
Impact of Heating Temperature and Fatty Acid Type on the Formation of Lipid Oxidation Products During Thermal Processing
Authors: Zhuang Yuan , Dong Jun , He Xiaomei , Wang Junping , Li Changmo , Dong Lu , Zhang Yan , Zhou Xiaofei , Wang Hongxun , Yi Yang , Wang Shuo
Published: June 2022

Thermal treatment of lipids rich in fatty acids contributes to the formation of lipid oxidation products (LOPs), which have potentially harmful effects on human health. This study included soybean oil (SO), palm oil (PO), olive oil (OO), and lard oil (LO) as the research objects, with an aim to investigate the impact of heating temperature and fatty acid type on the generation of LOPs (α-dicarbonyl compounds, malondialdehyde (MDA), α,β-unsaturated aldehydes, and 16 volatile aldehydes). Results showed that LOPs increased significantly (p < 0.05) with the increase in temperature (100 ~ 200°C). Furthermore, the amount of 2,3-butanedione (159.53 μg/g), MDA (3.15 μg/g), 4-hydroxy-hexenal (3.03 μg/g), 2-butenal (292.18%), 2-pentenal (102.26%), hexanal (898.72%), and 2,4-heptadienal (E, E) (2182.05%) were more at 200°C in SO rich in polyunsaturated fatty acids (PUFAs) than other oils. Results from heat map analysis indicated that the 2, 4-heptadienal, and glyoxal related to the myristic acid of oil. Moreover, the MDA was in close association with PUFAs. Based on the effect of temperature and fatty acid type on the generation of LOPs, this study could serve as a control method to reduce harmful LOPs.
A Pilot Study of Radiomics Models Combining Multi-Probe and Multi-Modality Images of 68Ga-NOTA-PRGD2 and 18F-FDG PET/CT for Differentiating Benign and Malignant Pulmonary Space-Occupying Lesions
Authors: Xie Fei , Zheng Kun , Liu Linwen , Jin Xiaona , Fu Lilan , Zhu Zhaohui
Published: June 2022

Background

This is a pilot study of radiomics based on 68Ga-NOTA-PRGD2 [NOTA-PEG4-E[c(RGDfK)]2)] and 18F-FDG PET/CT to (i) evaluate the diagnostic efficacy of radiomics features of 68Ga-NOTA-PRGD2 PET in the differential diagnosis of benign and malignant pulmonary space-occupying lesions and (ii) compare the diagnostic efficacy of multi-modality and multi-probe images.

Methods

We utilized a dataset of 48 patients who participated in 68Ga-NOTA-PRGD2 PET/CT and 18F-FDG PET/CT clinical trials to extract image features and evaluate their diagnostic efficacy in the differentiation of benign and malignant lesions by the Mann-Whitney U test. After feature selection with sequential forward selection, random forest models were developed with tenfold cross-validation. The diagnostic performance of models based on different image features was visualized by receiver operating characteristic (ROC) curves and compared by permutation tests.

Results

Fourteen of the 68Ga-NOTA-PRGD2 PET features between benign and malignant pulmonary space-occupying lesions had significant differences (P<0.05, Mann-Whitney U test). Eighteen of the 68Ga-NOTA-PRGD2 PET features demonstrated higher AUC values than all CT features in the differential diagnosis of pulmonary lesions. The AUC value (0.908) ​​of the three-modal feature model was significantly higher (P<0.05, permutation test) than those of the single- and dual-modal models.

Conclusion

68Ga-NOTA-PRGD2 PET features have better diagnostic capacity than CT features for pulmonary space-occupying lesions. The combination of multi-modality and multi-probe images can improve the diagnostic efficiency of models. Our preliminary clinical hypothesis of using radiomics based on 68Ga-NOTA-PRGD2 PET images and multimodal images as a diagnostic tool warrants further validation in a larger multicenter sample size.
AX-Unet: A Deep Learning Framework for Image Segmentation to Assist Pancreatic Tumor Diagnosis
Authors: Yang Minqiang , Zhang Yuhong , Chen Haoning , Wang Wei , Ni Haixu , Chen Xinlong , Li Zhuoheng , Mao Chengsheng
Published: June 2022

Image segmentation plays an essential role in medical imaging analysis such as tumor boundary extraction. Recently, deep learning techniques have dramatically improved performance for image segmentation. However, an important factor preventing deep neural networks from going further is the information loss during the information propagation process. In this article, we present AX-Unet, a deep learning framework incorporating a modified atrous spatial pyramid pooling module to learn the location information and to extract multi-level contextual information to reduce information loss during downsampling. We also introduce a special group convolution operation on the feature map at each level to achieve information decoupling between channels. In addition, we propose an explicit boundary-aware loss function to tackle the blurry boundary problem. We evaluate our model on two public Pancreas-CT datasets, NIH Pancreas-CT dataset, and the pancreas part in medical segmentation decathlon (MSD) medical dataset. The experimental results validate that our model can outperform the state-of-the-art methods in pancreas CT image segmentation. By comparing the extracted feature output of our model, we find that the pancreatic region of normal people and patients with pancreatic tumors shows significant differences. This could provide a promising and reliable way to assist physicians for the screening of pancreatic tumors.
Present and Future Perspective on PLK1 Inhibition in Cancer Treatment
Authors: Chiappa Michela , Petrella Serena , Damia Giovanna , Broggini Massimo , Guffanti Federica , Ricci Francesca
Published: June 2022

Polo-like kinase 1 (PLK1) is the principle member of the well conserved serine/threonine kinase family. PLK1 has a key role in the progression of mitosis and recent evidence suggest its important involvement in regulating the G2/M checkpoint, in DNA damage and replication stress response, and in cell death pathways. PLK1 expression is tightly spatially and temporally regulated to ensure its nuclear activation at the late S-phase, until the peak of expression at the G2/M-phase. Recently, new roles of PLK1 have been reported in literature on its implication in the regulation of inflammation and immunological responses. All these biological processes are altered in tumors and, considering that PLK1 is often found overexpressed in several tumor types, its targeting has emerged as a promising anti-cancer therapeutic strategy. In this review, we will summarize the evidence suggesting the role of PLK1 in response to DNA damage, including DNA repair, cell cycle progression, epithelial to mesenchymal transition, cell death pathways and cancer-related immunity. An update of PLK1 inhibitors currently investigated in preclinical and clinical studies, in monotherapy and in combination with existing chemotherapeutic drugs and targeted therapies will be discussed.
Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme
Authors: Xie Pan , Yan Han , Gao Ying , Li Xi , Zhou Dong-Bo , Liu Zhao-Qian
Published: June 2022

Background

Glioblastoma multiforme (GBM), the most prevalent and aggressive of primary malignant central nervous system tumors (grade IV), has a poor clinical prognosis. This study aimed to assess and predict the survival of GBM patients by establishing an m6A-related lncRNA signaling model and to validate its validity, accuracy and applicability.

Methods

RNA sequencing data and clinical data of GBM patients were obtained from TCGA data. First, m6A-associated lncRNAs were screened and lncRNAs associated with overall survival in GBM patients were obtained. Subsequently, the signal model was established using LASSO regression analysis, and its accuracy and validity are further verified. Finally, GO enrichment analysis was performed, and the influence of this signature on the immune regulation response and anticancer drug sensitivity of GBM patients was discussed.

Results

The signature constructed by four lncRNAs AC005229.3, SOX21-AS1, AL133523.1, and AC004847.1 is obtained. Furthermore, the signature proved to be effective and accurate in predicting and assessing the survival of GBM patients and could function independently of other clinical characteristics (Age, Gender and IDH1 mutation). Finally, Immunosuppression-related factors, including APC co-inhibition, T-cell co-inhibition, CCR and Check-point, were found to be significantly up-regulated in GBM patients in the high-risk group. Some chemotherapeutic drugs (Doxorubicin and Methotrexate) and targeted drugs (AZD8055, BI.2536, GW843682X and Vorinostat) were shown to have higher IC50 values in patients in the high-risk group.

Conclusion

We constructed an m6A-associated lncRNA risk model to predict the prognosis of GBM patients and provide new ideas for the treatment of GBM. Further biological experiments can be conducted on this basis to validate the clinical value of the model.
Assessing Pain Research: A Narrative Review of Emerging Pain Methods, Their Technosocial Implications, and Opportunities for Multidisciplinary Approaches
Authors: Berger Sara E. , Baria Alexis T.
Published: June 2022

Pain research traverses many disciplines and methodologies. Yet, despite our understanding and field-wide acceptance of the multifactorial essence of pain as a sensory perception, emotional experience, and biopsychosocial condition, pain scientists and practitioners often remain siloed within their domain expertise and associated techniques. The context in which the field finds itself today—with increasing reliance on digital technologies, an on-going pandemic, and continued disparities in pain care—requires new collaborations and different approaches to measuring pain. Here, we review the state-of-the-art in human pain research, summarizing emerging practices and cutting-edge techniques across multiple methods and technologies. For each, we outline foreseeable technosocial considerations, reflecting on implications for standards of care, pain management, research, and societal impact. Through overviewing alternative data sources and varied ways of measuring pain and by reflecting on the concerns, limitations, and challenges facing the field, we hope to create critical dialogues, inspire more collaborations, and foster new ideas for future pain research methods.
How to Choose the Correct Drug in Severe Pediatric Asthma
Authors: Bush Andrew
Published: June 2022

When a child with severe asthma (asthma defined clinically for the purposes of this review as wheeze, breathlessness, and chest tightness sometimes with cough) does not respond to treatment, it is important to be sure that an alternative or additional diagnosis is not being missed. In school age children, the next step is a detailed protocolized assessment to determine the nature of the problem, whether within the airway or related to co-morbidities or social/environmental factors, in order to personalize the treatment. For example, those with refractory difficult asthma due to persistent non-adherence may benefit from using budesonide and formoterol combined in a single inhaler [single maintenance and reliever treatment (SMART)] as both a reliever and preventer. For those with steroid-resistant Type 2 airway inflammation, the use of biologicals such as omalizumab and mepolizumab should be considered, but for mepolizumab at least, there is a paucity of pediatric data. Protocols are less well developed in preschool asthma, where steroid insensitive disease is much more common, but the use of two simple measurements, aeroallergen sensitization, and peripheral blood eosinophil count, allows the targeted use of inhaled corticosteroids (ICSs). There is also increasing evidence that chronic airway infection may be important in preschool wheeze, increasing the possibility that targeted antibiotics may be beneficial. Asthma in the first year of life is not driven by Type 2 inflammation, so beyond avoiding prescribing ICSs, no evidence based recommendations can be made. In the future, we urgently need to develop objective biomarkers, especially of risk, so that treatment can be targeted effectively; we need to address the scandal of the lack of data in children compared with adults, precluding making evidence-based therapeutic decisions and move from guiding treatment by phenotypes, which will change as the environment changes, to endotype based therapy.
Reference Values for and Correlation Analysis of the Anogenital Distance of Chinese Han Full-Term Singleton Neonates
Authors: Cao Wei , Ding Xiaowei , Dong Zhiya , Tang Haiting
Published: June 2022

Background

Anogenital distance (AGD) is a biomarker used for the evaluation of fetal androgen action. The disruption of fetal androgen action can affect the development of the reproductive system and adversely affect future reproductive functions. However, AGD may differ by race. Currently, there is a lack of data regarding the evaluation of AGD in large Han Chinese samples.

Objective

AGD for neonates in Shanghai, China, was measured, and relevant factors that influenced AGD were analyzed.

Methods

The AGD of full-term singleton neonates was measured within 3 days of birth, and the results were grouped according to gestational age and body weight at birth. In addition, relevant factors that influenced AGD were investigated.

Results

A total of 1,867 full-term singleton neonates were enrolled in this study. All the neonates were Han Chinese; among them, 986 were male, and 881 were female. Male AGD was 23.18 ± 3.17 mm, and female AGD was 11.65 ± 1.53 mm. Male AGD was 1.99 times longer than female AGD. With the increase in gestational age and body weight, AGD gradually increased. AGD was correlated with gestational age, body weight, and head circumference. The correlation between body weight at birth and AGD was highly significant.

Conclusion

This study, for the first time, reported AGD measurement data for Chinese Han neonates. The results indicated that AGD was correlated with gestational age, body weight, and head circumference. The correlation between body weight at birth and AGD was highly significant.
Gastrodin From Gastrodia elata Enhances Cognitive Function and Neuroprotection of AD Mice via the Regulation of Gut Microbiota Composition and Inhibition of Neuron Inflammation
Authors: Fasina Opeyemi B. , Wang Jianyu , Mo Jianxia , Osada Hiroyuki , Ohno Hiroshi , Pan Wensheng , Xiang Lan , Qi Jianhua
Published: June 2022

Gastrodin (Gas) is known to exhibit neuroprotective effects in Alzheimer’s disease (AD). However, the detailed mechanism of action is still unclear. In the present study, we focused on the microbiome–gut–brain axis to investigate the mechanism of action of Gas using a D-galactose (Dgal)–induced AD model. Gas reversed the memory dysfunction of Dgal-administered mice. Neurons in the cerebral cortex and hippocampus were reduced in the Dgal-administered group, and the decrease of neurons was suppressed in 90 and 210 mg/kg Gas treatment groups. 16S rRNA sequence analysis was carried out to explore the composition of gut microbiota in fecal samples of mice. Gas treatment had a positive correlation with Firmicutes and had a negative correlation with Cyanobacteria, Proteobacteria, and Deferribaceters. Importantly, the LPS and proinflammatory cytokines in the brain increased in Dgal-administered mice, but these parameters recovered to normal levels after oral administration of Gas. To determine whether the microbiota–gut–brain axis is involved in the neuroprotective effect of Gas, the mice were given antibiotic cocktail before and during the trial period to decrease the gut microbiota of mice. The antibiotic cocktail partially eliminated the neuroprotective effect of Gas by changing the gut microbiome composition. These results indicated that Gas improves the memory of the AD mouse model via partly targeting the microbiota–gut–brain axis and mitigating neuron inflammation.
Key Considerations for Phase 2 or 3 Clinical Study Design of Anti-Inflammatory Agent for COVID-19 Treatment
Authors: Park Yewon , Na Joo Young , Cho Joo-Youn , Oh Jaeseong , Rhee Su-jin
Published: June 2022

Purpose: Current understanding of COVID-19 disease progression suggests a major role for the “cytokine storm” as an important contributor to COVID-19 mortality. To prevent an exaggerated immune response and improve COVID-19 patient endpoints, anti-inflammatory therapeutics have been proposed as clinically useful in severe patients with COVID-19. The purpose of this study was to propose a clinical trial design for the development of anti-inflammatory agents for the treatment of COVID-19, taking into account the physiological and immunological process of COVID-19 and the treatment mechanism of anti-inflammatory agents.

Methods: We reviewed and analyzed the guidelines for the development of COVID-19 treatments and the treatment of COVID-19 by regulatory agencies and previously conducted clinical trials on anti-inflammatory drugs for COVID-19. Finally, after discussing with an advisory group, a synopsis was presented for an example protocol for a COVID-19 anti-inflammatory agent phase 2 or 3 study that considers the drug mechanism and the disease progression of COVID-19.

Results: A randomized, placebo-controlled, double-blind parallel-group design was suggested as a phase 2 or 3 trial design for developing an anti-inflammatory agent as a COVID-19 treatment. A key item of the example protocol specific to anti-inflammatory agents was the inclusion and exclusion criteria, taking into account the immunosuppressive effects of the drug, clinical time course of COVID-19 disease, and treatment guidelines for COVID-19. Time to recovery is the primary endpoint associated with clinical efficacy and is generally well accepted by many experts.

Conclusion: Through this suggested phase 2 or 3 study design of an anti-inflammatory drug for COVID-19, we provide a basis for a study design that can be utilized in clinical development by pharmaceutical companies which are developing a potential anti-inflammatory agent for COVID-19.
Emodin Ameliorates Acute Pancreatitis-Associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis
Authors: Wu Xiajia , Yao Jiaqi , Hu Qian , Kang Hongxin , Miao Yifan , Zhu Lv , Li Cong , Zhao Xianlin , Li Juan , Wan Meihua , Tang Wenfu
Published: June 2022

Objective: To investigate the protective effect of emodin in acute pancreatitis (AP)-associated lung injury and the underlying mechanisms.

Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into four groups: sham, AP, Ac-YVAD-CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed with H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot.

Results: Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally, emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory cytokines and lactate dehydrogenase. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention.

Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.
Antibiotic-Induced Neutropenia in Pediatric Patients: New Insights From Pharmacoepidemiological Analyses and a Systematic Review
Authors: Battini Vera , Mari Alessandra , Gringeri Michele , Casini Francesca , Bergamaschi Francesco , Mosini Giulia , Guarnieri Greta , Pozzi Marco , Nobile Maria , Zuccotti Gianvincenzo , Clementi Emilio , Radice Sonia , Fabiano Valentina , Carnovale Carla
Published: June 2022

Aim: to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide spectrum of treatment options and the occurrence of this relatively uncommon but potentially clinically relevant adverse event.

Methods: we carried out a pharmacoepidemiological analysis based on the FDA Adverse Event Reporting System (FAERS) database, a retrospective chart review and a systematic review of the literature, focusing on the time to onset (TTO) of this side effect, in the pediatric clinical setting.

Results: A total of 281 antibiotic-related neutropenia events, involving 11 categories of antibiotics, were included in the time to onset analysis. The median TTO ranged from 4 to 60 days after the start of the therapy. A shorter median TTO was found from the retrospective chart review [16 patients: median days (25th-75th percentiles) = 4 (3–5)], compared to 15 (9–18) vs. 10 (6–18) for literature (224 patients) and FAERS (41 cases), respectively. The Anatomical Therapeutic Chemical classes, J01X, J01F, J01E and J04A, and the median TTOs retrieved from more than one source revealed high accordance (p > 0.05), with J01X causing neutropenia in less than a week and J01F/J01E/J04A in more than 10 days. Antibiotics were discontinued in nearly 34% of cases. In FDA Adverse Event Reporting System reports, half of the patients experiencing neutropenia were hospitalized.

Conclusion: Whereas antibiotic associated neutropenia is benign in the majority of cases, yet it should not be neglected as, even if rarely, it may put children at higher risk of clinical consequences. Clinicians’ awareness of antibiotic-associated neutropenia and its mode of presentation contributes to the continuous process of monitoring safety of antibiotics.
Appropriateness and Associated Factors of Stress Ulcer Prophylaxis for Surgical Inpatients of Orthopedics Department in a Tertiary Hospital: A Cross-Sectional Study
Authors: Li Haiyan , Li Ning , Jia Xiaoni , Zhai Yuyao , Xue Xiaorong , Qiao Yi
Published: June 2022

Background: Stress ulcer prophylaxis (SUP) prescribed in patients admitted to surgical wards with a low risk of stress-related mucosal disease (SRMD) accounted for a considerable proportion of improper use of proton pump inhibitors (PPIs). This study aimed to analyze the appropriateness of SUP prescribing patterns and identify its associated factors in the orthopedics department of a tertiary hospital in the Northwestern China.

Methods: In this cross-sectional study, information regarding the demographic and clinical characteristics of 1,200 fracture inpatients who underwent surgical operations from January 2020 to August 2021 were collected from medical records. Established criteria were used to assess the appropriateness of the prescribing pattern for SUP, and the incidence of inappropriate SUP medication was calculated. Logistic regression analyses were used to identify factors associated with inappropriate SUP medication.

Results: Approximately, 42.4% of the study population was interpreted as inappropriate prescription of SUP. A total of 397 (33.1%) patients received SUP without a proper indication (overprescription), and the incidence of inappropriate SUP medication was calculated to be 43.11 per 100 patient-days. In addition, 112 (9.3%) inpatients for whom SUP was indicated did not receive SUP (underprescription). PPIs were prescribed in 96.1% of the inpatients who used acid suppression therapy (AST), and intravenous PPIs accounted for 95.3% thereof. In a multivariate logistic regression analysis, age above 65 years and prolonged hospitalization were associated with overprescription of SUP. Increased number of drugs excluding PPIs, the concurrent use of systemic corticosteroids, comorbidity of hypertension, and unemployed or retired status in inpatients were associated with a reduced likelihood of overprescription for SUP. Conversely, prolonged hospitalization, the concurrent use of systemic corticosteroids or anticoagulants, and unemployed status in inpatients were positively associated with underprescription of SUP.

Conclusion: There was a high prevalence of inappropriate SUP prescription among noncritically ill inpatients of fracture who underwent surgical operations. We delineated the associated factors with inappropriate SUP medication, which indicated that more information was required for clinicians about rationality and efficiency of their prescribing practices. Effective intervention strategies should be executed by clinical pharmacists to reduce improper SUP medication.
Frequency and Management of Adverse Drug Reactions Among Drug-Resistant Tuberculosis Patients: Analysis From a Prospective Study
Authors: Massud Asif , Syed Sulaiman Syed Azhar , Ahmad Nafees , Shafqat Muhammad , Chiau Ming Long , Khan Amer Hayat
Published: June 2022

Drug-resistant tuberculosis (DR-TB) management is often linked with a higher rate of adverse drug reactions (ADRs) needing effective and timely management of these ADRs, which, if left untreated, may result in a higher rate of loss to follow-up of drug-resistant patients.

Study objective: The study was aimed at prospectively identifying the nature, frequency, suspected drugs, and management approaches for ADRs along with risk factors of ADRs occurrence among DR-TB patients at Nishtar Medical University, Hospital, Multan, Pakistan.

Materials and Methods: The prospective study included all the DR-TB patients enrolled for treatment from January 2016 to May 2017 at the study site. Patients were evaluated for the treatment-induced ADRs as per standard criteria of the National Tuberculosis Program, Pakistan. Multivariate logistic regression was used to assess the independent variables associated with the occurrence of ADRs.

Results: Out of 271 DR-TB patients included in the final analysis, it was observed that 55 patients (20.3%) experienced at least three ADRs. A total of 50 (18.5%) patients experienced zero adverse effects, while 15 (5.5%), 33 (12.2%), and 53 (19.6%) patients experienced one, two, and four ADRs, respectively. Gastrointestinal disturbances (66.7%), nervous system disorders (59.4%), and electrolyte disturbances (55.7%) remained the highest reported ADRs during therapy, followed by arthralgia (49.1%), ototoxicity (24%), pruritic reactions/rash (12.9%), dyspnoea (12.5%), and tinnitus (8.8%). Pulmonary cavitation at the baseline visit (p-value 0.001, OR 3.419; 95% CI (1.694–6.902) was significantly associated with the occurrence of ADRs among DR-TB patients.

Conclusion: The frequency of ADRs was high among the study cohort; however, these were managed effectively. Patients with recognized risk factors for ADRs occurrence need continuous clinical management efforts.
Artesunate Therapy Alleviates Fracture-Associated Chronic Pain After Orthopedic Surgery by Suppressing CCL21-Dependent TREM2/DAP12 Inflammatory Signaling in Mice
Authors: Zhang Linlin , Li Nan , Zhang Haoyue , Wang Yigang , Gao Tianyu , Zhao Yuying , Wang Guolin , Yu Yonghao , Wang Chunyan , Li Yize
Published: June 2022

Chronic pain after bone fracture and orthopedic surgery is often refractory to most analgesics currently in use, thus emphasizing the urgent need for improved therapeutic medications. Chemokine-dependent neuroinflammation is critical for excitatory synaptic plasticity and central nociception sensitization. Recent studies have focused on the inhibition of inflammatory responses by artesunate, the first anti-malaria drug extracted from artemisinin. The present study investigated the analgesic effects and potential targets of artesunate in a mouse model of chronic pain induced by tibial fracture and orthopedic surgery. Three injections of artesunate were intrathecally administered on a daily basis from days 4 to 6 after fracture. We reported that repetitive exposure to artesunate (10 and 100 μg but not 1 μg) dose-dependently prevented fracture-induced mechanical and cold allodynia. Moreover, single intrathecal injection of artesunate (100 μg) alleviated the established chronic pain on day 14 after fracture surgery. Intraperitoneal artesunate (10 and 50 mg kg−1) therapy was effective against chronic fracture pain. Intriguingly, artesunate inhibited the upregulation of spinal chemokine CCL21, triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12) expressions and microglia activation in fracture mice. Furthermore, spinal CCL21 neutralization attenuated the severity of fracture-associated post-surgical pain. Exogenous CCL21-induced acute inflammatory pain was impaired by artesunate therapy. Additionally, the pharmacological blockage of TREM2 reduced recombinant CCL21-elicited behavioral hypernociception. The present findings demonstrate that artesunate therapy reduces the initiation and maintenance of fracture-associated chronic postoperative pain by inhibiting CCL21-dependent TREM2/DAP12 inflammatory signaling and microglia activation, thus suggesting that artesunate could emerge as a therapeutic strategy for fracture pain management.
Cortical Bone Thickness, Base Osteophyte Occurrence and Radiological Signs of Osteoarthritis in the Fingers of Male Elite Sport Climbers: A Cross-Sectional 10-Year Follow-Up Study
Authors: Pastor Torsten , Fröhlich Stefan , Pastor Tatjana , Spörri Jörg , Schweizer Andreas
Published: June 2022

Background: Sport climbing places high mechanical loads on fingers. In 2012, our research group demonstrated adaptations of climbers’ cortical bones with the presence of osteophytes compared to non-climbing controls.

Objectives: 1) To investigate 10-year changes in cortical bone thickness, base osteophyte occurrence and radiological signs of osteoarthritis in the fingers of elite male sport climbers with more than 25 years of climbing history and 2) to compare cortical bone thickness, base osteophyte occurrence and radiological signs of osteoarthritis between male sport climbers and age-matched controls at the 10-year follow-up.

Methods: All 31 elite sport climbers who participated in both the baseline and 10-year follow-up assessments (follow-up rate 100%) were examined by means of X-rays. Cortical bone thickness, presence of osteophytes and signs of osteoarthritis according to Kellgren-Lawrence were obtained and compared to the baseline values 10 years earlier and to age-matched controls at the follow-up (n = 15).

Results: Significantly increased cortical bone thickness over the past 10 years was observed in climbers (mean absolute difference with 95% CI:0.98 mm (0.77 mm, 1.19 mm); p <0.001). Moreover, compared to age-matched controls, climbers had significantly thicker cortical bone at the 10-year follow-up (mean absolute difference with 95% CI:0.86 mm (0.61 mm, 1.12 mm); p <0.001). In climbers, osteophytes and clear signs of osteoarthritis were mainly seen in DIP joints. Signs of osteoarthritis according to Kellgren-Lawrence were more prevalent than 10 years before in most joints. In lateral radiographs, base osteophytes were not significantly more prevalent than 10 years before in most of the joints. The percentage of climbers who had osteophytes in any DIP (PIP) joint increased from 93.5% (67.7%) at baseline to 100% (74.2%) at the 10-year follow-up. The percentage of climbers who had clear signs of osteoarthritis according to Kellgren-Lawrence in any DIP (PIP) joint increased from 12.9% (9.7%) at baseline to 74.2% (64.5%) at 10-year follow-up. Only a few such degenerative changes were found in age-matched controls.

Conclusion: An accumulation of repetitive climbing-related stress to the fingers of elite sport climbers over the career may induce lifelong mechano-adaptation of the cortical bone thickness of all phalanges. At the 10-year follow-up, a further significant increase in radiographic signs of osteoarthritic changes was observed.
High-Precision Wheat Head Detection Model Based on One-Stage Network and GAN Model
Authors: Zhang Yan , Li Manzhou , Ma Xiaoxiao , Wu Xiaotong , Wang Yaojun
Published: June 2022

Counting wheat heads is a time-consuming process in agricultural production, which is currently primarily carried out by humans. Manually identifying wheat heads and statistically analyzing the findings has a rigorous requirement for the workforce and is prone to error. With the advancement of machine vision technology, computer vision detection algorithms have made wheat head detection and counting feasible. To accomplish this traditional labor-intensive task and tackle various tricky matters in wheat images, a high-precision wheat head detection model with strong generalizability was presented based on a one-stage network structure. The model's structure was referred to as that of the YOLO network; meanwhile, several modules were added and adjusted in the backbone network. The one-stage backbone network received an attention module and a feature fusion module, and the Loss function was improved. When compared to various other mainstream object detection networks, our model outperforms them, with a mAP of 0.688. In addition, an iOS-based intelligent wheat head counting mobile app was created, which could calculate the number of wheat heads in images shot in an agricultural environment in less than a second.
Assessing Grapevine Biophysical Parameters From Unmanned Aerial Vehicles Hyperspectral Imagery
Authors: Matese Alessandro , Di Gennaro Salvatore Filippo , Orlandi Giorgia , Gatti Matteo , Poni Stefano
Published: June 2022

Over the last 50 years, many approaches for extracting plant key parameters from remotely sensed data have been developed, especially in the last decade with the spread of unmanned aerial vehicles (UAVs) in agriculture. Multispectral sensors are very useful for the elaboration of common vegetation indices (VIs), however, the spectral accuracy and range may not be enough. In this scenario, hyperspectral (HS) technologies are gaining particular attention thanks to the highest spectral resolution, which allows deep characterization of vegetative/soil response. Literature presents few papers encompassing UAV-based HS applications in vineyard, a challenging conditions respect to other crops due to high presence of bare soil, grass cover, shadows and high heterogeneity canopy structure with different leaf inclination. The purpose of this paper is to present the first contribution combining traditional and multivariate HS data elaboration techniques, supported by strong ground truthing of vine ecophysiological, vegetative and productive variables. Firstly the research describes the UAV image acquisition and processing workflow to generate a 50 bands HS orthomosaic of a study vineyard. Subsequently, the spectral data extracted from 60 sample vines were elaborated both investigating the relationship between traditional narrowband VIs and grapevine traits. Then, multivariate calibration models were built using a double approach based on Partial Least Square (PLS) regression and interval-PLS (iPLS), to evaluate the correlation performance between the biophysical parameters and HS imagery using the whole spectral range and a selection of more relevant bands applying a variable selection algorithm, respectively. All techniques (VIs, PLS and iPLS) provided satisfactory correlation performances for the ecophysiological (R2= 0.65), productive (R2= 0.48), and qualitative (R2= 0.63) grape parameters. The novelty of this work is represented by the first assessment of a UAV HS dataset with the expression of the entire vine ecosystem, from the physiological and vegetative state to grapes production and quality, using narrowband VIs and multivariate PLS regressions. A correct non-destructive estimation of key parameters in vineyard, above all physiological parameters which must be measured in a short time as they are extremely influenced by the variability of environmental conditions during the day, represents a powerful tool to support the winegrower in vineyard management.
MrERF, MrbZIP, and MrSURNod of Medicago ruthenica Are Involved in Plant Growth and Abiotic Stress Response
Authors: Wu Rina , Xu Bo , Shi Fengling
Published: June 2022

Abiotic stresses affect plant growth and productivity. The outstanding stress resistance of Medicago ruthenica makes it a desirable gene resource to improve the stress tolerance of other plants. The roles of three differently expressed genes [(DEGs) (MrERF, MrbZIP, and MrSURNod)] from M. ruthenica in stress resistance have not been fully elucidated. Therefore, we constructed their expression vectors, transformed them into tobacco, and subjected transgenic lines to abiotic stresses. Through comprehensive bioinformatics, transcriptomic, morphological, and physiological analyses of transgenic lines, we have revealed the critical role of these three DEGs in plant growth and abiotic stress response. The upregulation of genes enhanced the germination rate, biomass, root length number, etc. Additionally, the accumulation of osmolytes increased the activity of antioxidant enzymes. These genes are also associated with improved seed yield, increased branching, and early flowering, thereby shortening the growth period. Potentially, this is one of the ways for tobacco to cope with stress. Furthermore, the resistance of transgenic tobacco expressing MrERF or MrbZIP was better than that with MrSURNod. MrERF and MrbZIP can improve drought and salt tolerance of plants, whereas MrSURNod is beneficial in improving drought and cold resistance. Moreover, MrERF or MrbZIP can promote root elongation and increase the root number, whereas MrSURNod mainly promotes root elongation. This may be the reason why stress resistance conferred by MrSURNod is weaker than that associated with the other two genes. Overall, MrERF, MrbZIP, and MrSURNod positively modulate plant growth and stress tolerance.
Growth-Defense Trade-Offs Induced by Long-term Overgrazing Could Act as a Stress Memory
Authors: Qu Kairi , Cheng Yunxiang , Gao Kairu , Ren Weibo , Fry Ellen L. , Yin Jingjing , Liu Yaling
Published: June 2022

Long-term overgrazing (OG) is one of the key drivers of global grassland degradation with severe loss of productivity and ecosystem functions, which may result in stress memory such as smaller stature of grassland plants. However, how the OG-induced stress memory could be regulated by phytohormones is unknown. In this study, we investigated the changes of four phytohormones of cloned offspring of Leymus chinensis that were developed from no-grazing (NG) plants and OG plants with a grazing history of 30 years. The concentrations of auxin (IAA) and gibberellic acid (GA) in OG plant leaves were 45% and 20% lower than control, respectively. Meanwhile, the level of abscisic acid (ABA) in OG leaves nearly doubled compared with that in NG leaves. The situation was quite similar in roots. Unexpectedly, no significant changes in the jasmonic acid (JA) level were observed between OG and NG plants. The changes in gene expression patterns between OG and NG plants were also investigated by transcriptomic analysis. In total, 302 differentially expressed genes (DEGs) were identified between OG and NG plants, which were mainly classified into the functions of synthesis, receptor, and signal transduction processes of phytohormones. The expression of 24 key genes related to the biosynthesis and signal transduction of IAA and GA was downregulated in OG plants. Among them, OASA1 and AO1 (regulating the biosynthesis of IAA and ABA, respectively) were reduced significantly by 88 and 92%, respectively. In addition, the content of secondary metabolites related to plant defense such as flavonoids and phenols was also increased in leaves. Taken together, the decrease of positive plant growth-related hormones (IAA and GA) together with the increase of plant stress-related hormones or factors (ABA, flavonoids, and phenols) induced the growth-defense trade-offs for L. chinensis adaptation to long-term OG stress. The findings reported in this study shed new light on the mechanism of plant–animal interaction in the grassland ecosystem and provide a deeper insight into optimizing grazing management and sustainable utilization of grassland.
The Impact of Positive Emotional Appeals on the Green Purchase Behavior
Authors: Wang Jianming , Yang Xincheng , He Zhengxia , Wang Jianguo , Bao Jing , Gao Jian
Published: June 2022

The practice of green consumption has become a common initiative of the international community. Existing studies have shown that emotional factors have an important impact on consumer behavior, but few scholars in the field of green consumption behavior have explored the relationship between positive emotions and green purchase behavior in specific dimensions. This study creatively put forward two dimensions and four kinds of positive emotional appeals which include the cherishing appeal, the yearning appeal, the proud appeal, and the admiring appeal. Through the conceptual model analysis based on the data, the effects of different four positive emotional appeals on consumers’ perceived green value, perceived green responsibility, and green purchase behaviors were confirmed. The results indicated that the four kinds of positive emotional appeals, perceived green value, perceived green responsibility, and green purchase behavior were positively correlated. Perceived green responsibility and perceived green value have significant mediating effect on the relationship between positive emotional appeals and green purchase behaviors. Middle doctrine significantly moderates the relationship between positive emotional appeals (Cherishing VS. Yearning) and perceived green value.
Top-Down Influence Leads to a Reduced Sense of Body Ownership in Individuals With Depersonalization Tendencies: A Focus on Full Body Illusion
Authors: Yamamoto Kazuki , Nakao Takashi
Published: June 2022

Sense of body ownership, that is, the feeling that “my body belongs to me,” has been examined by both the rubber hand illusion (RHI) and full body illusion (FBI). In a study that examined the relationship between RHI and depersonalization, a symptom in which people experience a lower sense of body ownership, people with a high depersonalization tendency experienced RHI through the bottom-up process of visual-tactile integration. Why is it that people with depersonalization feel a lower sense of body ownership over their bodies? Case studies of depersonalization suggest that the top-down cognition in people with depersonalization may make them less likely to feel a sense of body ownership. However, the top-down influence on the sense of body ownership in depersonalization has not yet been experimentally demonstrated. By incorporating top-down manipulation (e.g., instructing participants to regard a fake body as their own) into the FBI procedure, we aimed to clarify the cause of the reduced sense of body ownership in people with a high depersonalization tendency. The FBI procedure was conducted in a virtual reality environment using an avatar as a fake body. The avatar was presented from a third-person perspective, and visual-tactile stimuli were presented to create an illusion. To examine the degree of illusion, we measured the skin conductance responses to the fear stimulus presented after the visual-tactile stimuli presentation. The degree of depersonalization was measured using the Japanese version of the Cambridge Depersonalization Scale. To manipulate the top-down influence, we provided self-association instructions before the presentation of the visual-tactile stimuli. We predicted that the higher the degree of depersonalization, the lower the degree of illusion in the self-association instruction. The results showed that participants with a higher depersonalization tendency had a lower degree of illusion (rho = −0.424, p = 0.035) in the self-association condition. This indicates that in people with a high depersonalization tendency, top-down cognition of the body as their own leads to a decrease in the sense of body ownership.