bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volatile organic compounds produced by Bacillus velezensis L1 as a potential biocontrol agent against postharvest diseases of wolfberry
Authors: Ling Lijun , Luo Hong , Yang Caiyun , Wang Yuanyuan , Cheng Wenting , Pang Mingmei , Jiang Kunling 
Published: August 2022

Volatile organic compounds (VOCs) produced by antagonistic microorganisms have good biocontrol prospects against postharvest diseases. Infection caused by Alternaria iridiaustralis and 10 other significant fungal diseases can be successfully inhibited by VOCs produced by an identified and screened endophytic strain L1 (Bacillus velezensis). This study revealed the in vivo and in vitro biocontrol effects of VOCs released by B. velezensis L1 on A. iridiaustralis, a pathogenic fungus responsible for rot of wolfberry fruit. The inhibition rates of VOCs of B. velezensis L1 on the mycelial growth of A. iridiaustralis in vitro were 92.86 and 90.30%, respectively, when the initial inoculum concentration on the plate was 1 × 109 colony forming unit (CFU)/ml. Spore germination and sporulation were 66.89 and 87.96%, respectively. VOCs considerably decreased the wolfberry’s disease index and decay incidence in vivo. Scanning electron microscopy revealed that the morphological and structural characteristics of A. iridiaustralis could be altered by VOCs. Ten VOCs were identified through headspace-gas chromatography-ion mobility spectrometry. Pure chemical tests revealed that 2.3-butanedione had the strongest antifungal effects, totally inhibiting A. iridiaustralis in wolfberry fruit at a 60 μl/L concentration. The theory underpinning the potential application of VOCs from B. velezensis is provided herein. This is also the first study to document the antifungal capabilities of the B. velezensis strain on postharvest wolfberry fruit.GRAPHICAL ABSTRACT
Machine Learning and Deep Learning CT-Based Models for Predicting the Primary Central Nervous System Lymphoma and Glioma Types: A Multicenter Retrospective Study
Authors: Lu Guang , Zhang Yuxin , Wang Wenjia , Miao Lixin , Mou Weiwei 
Published: August 2022

Purpose and BackgroundDistinguishing primary central nervous system lymphoma (PCNSL) and glioma on computed tomography (CT) is an important task since treatment options differ vastly from the two diseases. This study aims to explore various machine learning and deep learning methods based on radiomic features extracted from CT scans and end-to-end convolutional neural network (CNN) model to predict PCNSL and glioma types and compare the performance of different models.MethodsA total of 101 patients from five Chinese medical centers with pathologically confirmed PCNSL and glioma were analyzed retrospectively, including 50 PCNSL and 51 glioma. After manual segmentation of the region of interest (ROI) on CT scans, 293 radiomic features of each patient were extracted. The radiomic features were used as input, and then, we established six machine learning models and one deep learning model and three readers to identify the two types of tumors. We also established a 2D CNN model using raw CT scans as input. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models.ResultsThe cohort was split into a training (70, 70% patients) and validation cohort (31,30% patients) according to the stratified sampling strategy. Among all models, the MLP performed best, with an accuracy of 0.886 and 0.903, sensitivity of 0.914 and 0.867, specificity of 0.857 and 0.937, and AUC of 0.957 and 0.908 in the training and validation cohorts, respectively, which was significantly higher than the three primary physician's diagnoses (ACCs ranged from 0.710 to 0.742, p &lt; 0.001 for all) and comparable with the senior radiologist (ACC 0.839, p = 0.988). Among all the machine learning models, the AUC ranged from 0.605 to 0.821 in the validation cohort. The end-to-end CNN model achieved an AUC of 0.839 and an ACC of 0.840 in the validation cohort, which had no significant difference in accuracy compared to the MLP model (p = 0.472) and the senior radiologist (p = 0.470).ConclusionThe established PCNSL and glioma prediction model based on deep neural network methods from CT scans or radiomic features are feasible and provided high performance, which shows the potential to assist clinical decision-making.
Busulfan and thiotepa as a conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma: A study of the Korean Multiple Myeloma Working Party (KMMWP-1801 study)
Authors: Song Ga-Young , Jung Sung-Hoon , Kim Jin Seok , Eom Hyeon Seok , Moon Joon Ho , Yhim Ho-Young , Kim Kihyun , Min Chang-Ki , Lee Je-Jung 
Published: August 2022

BackgroundAutologous stem cell transplantation (ASCT) remains the standard of care for patients with newly diagnosed multiple myeloma (MM). Several attempts to improve the efficacy of conditioning regimens have been conducted in MM, but no more effective regimen than conventional high-dose melphalan has been introduced.ObjectiveIn this study, the efficacy and toxicity of busulfan and thiotepa (BuTT) and those of high-dose melphalan (HD-MEL) were compared retrospectively as a conditioning regimen for ASCT in patients with MM.Study designIncluded in the analysis were 114 patients who received BuTT and 114 patients who received HD-MEL treatment between March 2008 and May 2020. The BuTT regimen consisted of intravenous thiotepa 5 mg/kg once a day from days 7 to 6, followed by intravenous busulfan 3.2 mg/kg once a day from days 5 to 3. The HD-MEL conditioning regimen consisted of melphalan 100 mg/m2 once a day from days 3 to 2.ResultsThe overall response rate after ASCT did not differ between BuTT and HD-MEL (94.7% in BuTT vs. 97.4% in HD-MEL, p = 0.333). After a median follow-up of 47.6 months, progression-free survival (PFS) tended to be longer in the BuTT group (median PFS, 41.5 months vs. 30.3 months; hazard ratio (HR), 0.706; 95% confidence interval (CI), 0.497–1.004, p = 0.053). In the subgroup analysis of patients who did not proceed to maintenance or consolidation treatment after ASCT, the difference in PFS became more significant (median PFS, 41.5 months vs. 24.4 months; HR, 0.621; 95% CI, 0.388–0.993; p = 0.047). Additionally, the BuTT group had fewer adverse events, such as grade 3 or 4 stomatitis and diarrhea, than the HD-MEL group (stomatitis, 10.5% vs. 23.7%, p = 0.013; diarrhea, 10.5% vs. 25.4%, p = 0.005). There was no difference in the occurrence of venous-occlusive disease (2.6% in BuTT vs. 0.9% in HD-MEL, p = 0.622).ConclusionOur study results suggest that BuTT is an effective alternative conditioning regimen with reduced toxicity in patients with newly diagnosed MM.
A review of key strategies to address the shortage of analgesics and sedatives in pediatric intensive care
Authors: Castro Roberta Esteves Vieira de , Rodríguez-Rubio Miguel , Magalhães-Barbosa Maria Clara de , Prata-Barbosa Arnaldo , Holbrook Jaimee , Kamat Pradip , Stormorken Anne 
Published: August 2022

ImportanceTargeted analgosedation is a challenge in critically ill children, and this challenge becomes even more significant with drug shortages.ObservationsPublished guidelines inform the provision of analgosedation in critically ill children. This review provides insights into general approaches using these guidelines during drug shortages in Pediatric Intensive Care Units as well as strategies to optimize both pharmacological and non-pharmacological approaches in these situations.Conclusions and relevanceConsidering that drug shortages are a recurrent worldwide problem, this review may guide managing these drugs in critically ill children in situations of scarcity, such as in pandemics or disasters.
The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis
Authors: Yuan Weiwei , Huang Jinxi , Hou Shanshan , Li Huahua , Bie Liangyu , Chen Beibei , Li Gaofeng , Zhou Yang , Chen Xiaobing 
Published: August 2022

Background and Objective: Triptolide (TP), one of the fat-soluble components extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F. (TWHF), possesses strong antitumor bioactivities, but its dose-dependent side effects restrict its wide application. This study was designed to investigate whether inflammatory factors increased the antitumor effects of the nontoxic dose of TP on gastric cancer cells and tried to explore the possible molecular mechanisms.Method: AGS and MKN45 cells were treated with different doses of TP and TNF-α. Cell viability and apoptosis were detected in vitro. In addition, NF-κB mediated prosurvival signals and cytoprotective proteins, especially FLICE-inhibitory protein (FLIP), were detected to determine their effects on TP/TNF-α–induced apoptosis. Moreover, the function of lncRNA H19/miR-204-5p/NF-κB/FLIP axis was investigated in vitro, and the antigastric cancer effect of TP plus TNF-α was proved in the mice xenograft model.Result:In vitro experimental results showed that TP pretreatment promoted apoptosis in AGS and MKN45 cells upon TNF-α exposure. TP/TNF-α–mediated apoptosis was partly mediated by the inhibitory effect of NF-κB–mediated FLIP expression. Oncogene H19 lying in the upstream pathway of NF-κB played a vital role upon TNF-α exposure, and bioinformatics analysis proved that H19 participated in TP/TNF-α–induced apoptosis via binding of miR-204-5p. Lastly, a low dose of TP and TNF-α inhibited the tumor weight and tumor volume of AGS and MKN45 cells in vivo.Conclusion: TP pretreatment increased apoptosis in TNF-α–stimulated gastric cancer cells, which are dependent on the disruption of the H19/miR-204-5p/NF-κB/FLIP axis. Cotreatment of TP and TNF-α is a better option for enhancing the anticancer effect and lowering the side effect of TP.
Linezolid resistance in multidrug-resistant mycobacterium tuberculosis: A systematic review and meta-analysis
Authors: Azimi Taher , Khoshnood Saeed , Asadi Arezoo , Heidary Mohsen , Mahmoudi Hassan , Kaviar Vahab Hassan , Hallajzadeh Masoume , Nasiri Mohammad Javad 
Published: August 2022

Introduction: Linezolid (LNZ) is an effective antibiotic to treat patients with multidrug-resistant tuberculosis (MDR-TB) treatment failure. M. tuberculosis strains resistant to isoniazid and rifampin are defined as MDR-TB. In recent years, resistance to LNZ among MDR-TB cases has been reported in several different countries. In this study, we performed a systematic review and meta-analysis to investigate the prevalence of LNZ resistance among MDR-TB isolates.Methods: The databases of Embase, PubMed/Medline, and Web of Science were searched systematically from January 2000 to April 2021. Statistical analyses were performed by using Comprehensive Meta-Analysis software. Heterogeneity was reported by using the t-squared statistic and Q-statistic. Begg’s rank correlation in combination with the funnel plot were used to evaluate any possible publication bias.Results: In total, 25 studies were selected for meta-analysis from 14 different countries; the majority was from China (n = 5) and Turkey (n = 4). Moreover, 7,366 patients were infected with MDR M. tuberculosis. Among the study population, 98 patients were co-infected with HIV, and 18 patients with hepatitis C virus (HCV). Furthermore, 28 cases had diabetes, and139 cases were alcohol abuser. Overall, 4,956 MDR M. tuberculosis strains were isolated from TB patients. The pooled frequency of LNZ resistance among the clinical isolates of MDR M. tuberculosis was 4.2% (95%). Begg’s (p = 0.72) test showed no evidence of publication bias.Conclusion: LNZ resistance among MDR M. tuberculosis isolates is increasing. On the other hand, long-term treatment of MDR-TB cases with LNZ alone is associated with several adverse effects. Thus, it is recommended that newer anti-TB drugs, including bedaquiline and delamanid, in combination with linezolid could increase its effectiveness and decrease toxicities. However, more studies should be done in this field.
The mechanism of action of a novel neuroprotective low molecular weight dextran sulphate: New platform therapy for neurodegenerative diseases like Amyotrophic Lateral Sclerosis
Authors: Logan Ann , Belli Antonio , Di Pietro Valentina , Tavazzi Barbara , Lazzarino Giacomo , Mangione Renata , Lazzarino Giuseppe , Morano Inés , Qureshi Omar , Bruce Lars , Barnes Nicholas M. , Nagy Zsuzsanna 
Published: August 2022

Background: Acute and chronic neurodegenerative diseases represent an immense socioeconomic burden that drives the need for new disease modifying drugs. Common pathogenic mechanisms in these diseases are evident, suggesting that a platform neuroprotective therapy may offer effective treatments. Here we present evidence for the mode of pharmacological action of a novel neuroprotective low molecular weight dextran sulphate drug called ILB®. The working hypothesis was that ILB® acts via the activation of heparin-binding growth factors (HBGF).Methods: Pre-clinical and clinical (healthy people and patients with ALS) in vitro and in vivo studies evaluated the mode of action of ILB®. In vitro binding studies, functional assays and gene expression analyses were followed by the assessment of the drug effects in an animal model of severe traumatic brain injury (sTBI) using gene expression studies followed by functional analysis. Clinical data, to assess the hypothesized mode of action, are also presented from early phase clinical trials.Results: ILB® lengthened APTT time, acted as a competitive inhibitor for HGF-Glypican-3 binding, effected pulse release of heparin-binding growth factors (HBGF) into the circulation and modulated growth factor signaling pathways. Gene expression analysis demonstrated substantial similarities in the functional dysregulation induced by sTBI and various human neurodegenerative conditions and supported a cascading effect of ILB® on growth factor activation, followed by gene expression changes with profound beneficial effect on molecular and cellular functions affected by these diseases. The transcriptional signature of ILB® relevant to cell survival, inflammation, glutamate signaling, metabolism and synaptogenesis, are consistent with the activation of neuroprotective growth factors as was the ability of ILB® to elevate circulating levels of HGF in animal models and humans.Conclusion: ILB® releases, redistributes and modulates the bioactivity of HBGF that target disease compromised nervous tissues to initiate a cascade of transcriptional, metabolic and immunological effects that control glutamate toxicity, normalize tissue bioenergetics, and resolve inflammation to improve tissue function. This unique mechanism of action mobilizes and modulates naturally occurring tissue repair mechanisms to restore cellular homeostasis and function. The identified pharmacological impact of ILB® supports the potential to treat various acute and chronic neurodegenerative disease, including sTBI and ALS.
Integrative medicine in treating post-stroke depression: Study protocol for a multicenter, prospective, randomized, controlled trial
Authors: Chen Jing , Shen Ke , Fan Lijuan , Hu Hantong , Li Tieniu , Zhang Yiting , Gao Hong 
Published: August 2022

BackgroundPost-stroke depression (PSD) is one of the most common neuropsychiatric diseases in patients with stroke, and it can increase the disability rate, mortality, and recurrence rate of stroke. Currently, many clinical studies have indicated that traditional Chinese medicine (TCM), such as acupuncture and herbs, Western medicine, rehabilitation, repeated transcranial magnetic stimulation, and other treatment methods, are effective in treating PSD. However, no study has formulated a comprehensive treatment plan that integrates TCM, Western medicine, and rehabilitation for PSD. Thus, this trial aims to assess the efficacy and safety of integrative medicine for treating PSD.MethodsThis multicenter, prospective, randomized, controlled study aims to form a set of effective clinical treatment schemes that integrate TCM, Western medicine, and rehabilitation for PSD. A total of 202 participants recruited from four centers will be randomized into either the integrative medicine or standard care group. Standard care—basic treatment, general nursing care, and exercise therapy—will be provided to all participants. The integrative medicine group will also receive acupuncture, Chinese herbs, and repeated transcranial magnetic stimulation (rTMS). Participants will receive acupuncture and rTMS treatments five times per week for 4 weeks and will be administered Chinese herbs, basic treatment, general nursing care, and exercise therapy for 4 weeks. The primary outcomes include the Hamilton Depression Scale (HAMD), Self-Rating Depression Scale (SDS), and Activity of Daily Living Scale (ADL). And the secondary outcomes include the Montreal Cognitive Assessment Scale, the Fugl-Meyer Assessment (FMA) Scale, and the Pittsburgh Sleep Quality Index (PSQI). All outcome measures will be evaluated at baseline, week 4 (the end of the treatment courses), and week 8 (the end of follow-up). Safety assessments will be performed throughout the study.DiscussionThis study is expected to verify the efficacy and safety of integrative medicine for treating PSD, providing an evidence-based clinical reference for the future development of a standardized scheme.Clinical trial registrationClinicalTrials.gov, identifier: NCT05187975
The presence of psychological distress in healthcare workers across different care settings in Windsor, Ontario, during the COVID-19 pandemic: A cross-sectional study
Authors: Voth Jennifer , Jaber Lindsey , MacDougall Linda , Ward Leslee , Cordeiro Jennifer , Miklas Erica P. 
Published: August 2022

IntroductionFew studies have examined psychological distress in healthcare workers (HCWs) across the care continuum. This study describes distress levels reported by HCWs across care settings and factors associated with distress.MethodsA cross-sectional survey of HCWs from Windsor, Ontario, was conducted between May 30th, 2020, and June 30th, 2020. The survey included the Kessler Psychological Distress Scale (K10), sociodemographic, frontline status, perceptions of training, protection, support, respect among teams, and professional and personal stressors. Univariate analyses were used to compare across settings and multivariate logistic regression assessed factors associated with distress.ResultsFour hundred and three HCWs from the hospital (49.4%), community health and social service (18.4%), first responder (14.7%), primary care (7.9%), home (6.0%), and long-term care (LTC; 4.0%) participated in the survey. Common concerns included fear of transmitting COVID-19 to family, safety on the job, and balancing personal care with work demands. LTC and home-care HCWs reported greater concern about workload and staffing levels, whereas community health workers were more anxious about their financial security. Overall, 228 (74.2%) HCWs who completed the K10 reported high distress, with greater rates among hospital and LTC HCWs. Distress was more likely in HCWs who identified as female, younger than 55, perceived lower respect among team, and experienced greater worry about physical and mental health and managing high workloads.ConclusionResults showed a high degree of distress experienced by HCWs across care settings and the impact of the COVID-19 pandemic on personal and work-related stress. Promoting self-care and supportive and collaborative healthcare teams are promising avenues for mitigating symptoms of distress.
Exploring trajectories of depressive symptoms in North Korean defectors: A latent class mixed analysis
Authors: Kim Dahae , Park Sohee , An Ji Hyun , Kim Myung Hyun , Chang Hyein , Hong Jin Pyo 
Published: August 2022

BackgroundNorth Korean defectors (NKDs) are known to be vulnerable to depression due to the influence of various psychosocial factors during their settlement process. Therefore, this study aimed to explore different trajectories of depressive symptoms in NKDs and identify predictors of the worsening of depressive symptoms. In particular, the focus was on whether posttraumatic stress disorder (PTSD) functions as a significant predictor.MethodsParticipants consisted of 300 NKDs who settled in South Korea within 3 years of entering in the country. Five waves of longitudinal data collected from 2016 to 2019 were used. In this study, the North Korean Composite International Diagnostic Interview (NK-CIDI), a diagnostic interview tool, was conducted at baseline and depressive symptoms were measured at each wave. Trajectory identification was based on latent class mixed modeling. Logistic regression was used to extract the significant factors predicting a high/increasing depressive symptom trajectory.ResultsTwo trajectories of depressive symptoms were identified: “low/stable symptom” (76.7% of participants) and “high/increasing symptom” (23.3% of participants). Predictors of the high/increasing symptom group were being female and a low use of mental health services. Generalized anxiety disorder, social phobia, and alcohol dependence acted as significant predictors. Although PTSD was not a significant predictor, self-reported PTSD symptom scores were high in the high/increasing symptom group.ConclusionsIdentifying the trajectories of depressive symptoms in NKDs helps identify the risk factors of clinically vulnerable groups. In the process of establishing government-level interventions, it may be helpful to create a therapeutic environment. In addition, when evaluating initial psychiatric problems, it is important to primarily consider NKDs' anxiety levels and alcohol problems. There should also be an appropriate consideration of PTSD symptoms.