bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical evaluation of different posterior fixation techniques for treating thoracolumbar burst fractures of osteoporosis old patients: a finite element analysis
Authors: Zhang Guodong , Du Yukun , Jiang Guangzong , Kong Weiqing , Li Jianyi , Zhu Zhongjiao , Xi Yongming
Published: November 2023

Objective: To investigate the biomechanical characteristics of different posterior fixation techniques in treatment of osteoporotic thoracolumbar burst fractures by finite element analysis.

Methods: The Dicom format images of T10-L5 segments were obtained from CT scanning of a volunteer, and transferred to the Geomagic Studio software, which was used to build digital models. L1 osteoporotic burst fracture and different posterior fixation techniques were simulated by SolidWorks software. The data of ROM, the maximum displacement of fixed segment, ROM of fractured L1 vertebrae, the stress on the screws and rods as well as on fractured L1 vertebrae under different movement conditions were collected and analysed by finite element analysis.

Results: Among the four groups, the largest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae occurred in CBT, and the corresponding data was 1.3°, 2.57 mm and 1.37°, respectively. While the smallest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae was found in LSPS, and the corresponding data was 0.92°, 2.46 mm and 0.89°, respectively. The largest stress of screws was 390.97 Mpa, appeared in CBT, and the largest stress of rods was 84.68 MPa, appeared in LSPS. The stress concentrated at the junction area between the root screws and rods. The maximum stress on fractured vertebrae was 93.25 MPa, appeared in CBT and the minimum stress was 56.68 MPa, appeared in CAPS. And the stress of fractured vertebrae concentrated in the middle and posterior column of the fixed segment, especially in the posterior edge of the superior endplate.

Conclusion: In this study, long-segment posterior fixation (LSPF) provided with the greatest stability of fixed segment after fixation, while cortical bone screw fixation (CBT) provided with the smallest stability. Cement-augmented pedicle screw-rod fixation (CAPS) and combined using cortical bone screw and pedicle screw fixation (CBT-PS) provided with the moderate stability. CBT-PS exhibited superiority in resistance of rotational torsion for using multiple connecting rods. CAPS and CBT-PS maybe biomechanically superior options for the surgical treatment of burst TL fractures in osteoporotic patients.
Exosomal non-coding RNAs in glioma progression: insights into tumor microenvironment dynamics and therapeutic implications
Authors: Marangon Davide , Lecca Davide
Published: November 2023

Gliomas are the most common and deadly types of brain tumors, known for their extensive genetic and epigenetic variability, which poses considerable challenges for pharmacological treatment. Glioma heterogeneity is also related to their intricate and dynamic tumor microenvironment (TME), which comprises a diverse array of cell types, including immune cells, vascular cells, glial cells, and neural precursors, collectively influencing tumor behavior and progression. A pivotal aspect of this intercellular communication relies on the exchange of extracellular vesicles (EVs), which contain and transfer complex molecular cargoes typical of their cells of origin, such as proteins, lipids, carbohydrates, metabolites, and non-coding RNAs (ncRNAs), that encompass microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Glioma cells actively release EVs loaded with specific ncRNAs that can target genes and other ncRNAs in recipient cells residing within the TME. Among these recipient cells, prominent players include tumor-associated macrophages and microglia (TAMs), non-neoplastic astrocytes and endothelial cells. The intricate interplay between EVs derived from glioma cells and these recipient cells significantly contributes to the establishment of a tumor-permissive microenvironment, promoting tumor cell proliferation, migration, angiogenesis, and invasion, by targeting various downstream pathways. This review critically examines the current understanding of the intricate interplay between glioma, exosomal ncRNAs, and various components of the glioma TME. By shedding light on the roles of ncRNAs in mediating intercellular communication, this review underscores their significance in orchestrating TME transformation and highlights their potential as novel therapeutic targets for effectively tackling glioma progression.
Virtual immediate feedback with POCUS in Belize
Authors: Mulye Anita , Bhasin Ajay , Borger Bonita , Fant Colleen
Published: November 2023

Point of care ultrasound (POCUS) is a portable and accessible tool that has immense potential in low- and middle-income countries (LMIC) for diagnostic accuracy and medical education. We implemented a hybrid in-person and virtual training curriculum to teach providers in Belize the basic techniques of lung ultrasound in the diagnosis of pneumonia. Between August 2021 and June 2022, a total of eleven lung scans were performed at Hillside Clinic for patients presenting with respiratory complaints. Deidentified images were shared via the ButterflyIQ web platform to POCUS experts in the United States. We found that training was solidified through virtual, immediate feedback using the common interfaces Butterfly iQ + and WhatsApp to share images and guide diagnostic reasoning. The aim of this review study is to share our experience and challenges in the implementation of a POCUS training curriculum in an LMIC, provide an example of training methodology that can be effective, and discuss how this can be implemented and modified for clinicians in similar settings.
Exploring lncRNAs associated with human pancreatic islet cell death induced by transfer of adoptive lymphocytes in a humanized mouse model
Authors: Hossain Md Munir , Roat Regan , Christopherson Jenica , Free Colette , Ansarullah  , James Brian , Guo Zhiguang
Published: November 2023

Background

Long noncoding RNA (lncRNA)-mediated posttranscriptional and epigenetic landscapes of gene regulation are associated with numerous human diseases. However, the regulatory mechanisms governing human β-cell function and survival remain unknown. Owing to technical and ethical constraints, studying the direct role of lncRNAs in β-cell function and survival in humans in vivo is difficult. Therefore, we utilized humanized mice with human islets to investigate lncRNA expression using whole transcriptome shotgun sequencing. Our study aimed to characterize lncRNAs that may be crucial for human islet cell function and survival.

Methods

Human β-cell death was induced in humanized mice engrafted with functional human islets. Using these humanized mice harboring human islets with induced β-cell death, we investigated lncRNA expression through whole transcriptome shotgun sequencing. Additionally, we systematically identified, characterized, and explored the regulatory functions of lncRNAs that are potentially important for human pancreatic islet cell function and survival.

Results

Human islet cell death was induced in humanized mice engrafted with functional human islets. RNA sequencing analysis of isolated human islets, islet grafts from humanized mice with and without induced cell death, revealed aberrant expression of a distinct set of lncRNAs that are associated with the deregulated mRNAs important for cellular processes and molecular pathways related to β-cell function and survival. A total of 10 lncRNA isoforms (SCYL1-1:22, POLG2-1:1, CTRB1-1:1, SRPK1-1:1, GTF3C5-1:1, PPY-1:1, CTRB1-1:5, CPA5-1:1, BCAR1-2:1, and CTRB1-1:4) were identified as highly enriched and specific to human islets. These lncRNAs were deregulated in human islets from donors with different BMIs and with type 2 diabetes (T2D), as well as in cultured human islets with glucose stimulation and induced cell death induced by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the medium used to culture islets with cytokines.

Conclusion

Islet-enriched and specific human lncRNAs are deregulated in human islet grafts and cultured human islets with induced cell death. These lncRNAs may be crucial for human β-cell function and survival and could have an impact on identifying biomarkers for β-cell loss and discovering novel therapeutic targets to enhance β-cell function and survival.
Energy development in rural China toward a clean energy system: utilization status, co-benefit mechanism, and countermeasures
Authors: Yin Shi , Zhao Zheng
Published: November 2023

In order to promote the construction of a clean, low-carbon, and diversified modern rural new energy system, this study examines the development, utilization, connection, and system construction of rural new energy in China. This is done through the classification, integration, and systematic analysis of official statistical data and materials from recent years. Utilizing descriptive statistical analysis, the study holds great theoretical and practical significance. The findings indicate the following: 1) overall, the development of new energy in China’s rural areas is progressing well. However, there is an increasing contradiction between supply and consumption. 2) The new energy industry is experiencing overall growth, accompanied by increasing policy support. Despite this, the industry’s driving effect is not substantial. 3) The development of new energy production equipment in rural areas is lagging, resulting in insufficient cleanliness of energy consumption. There is still a significant gap compared to the goal requirements of agricultural and rural modernization. 4) During the process of rural new energy connection and development, there exists a lack of strong connections between the various subjects of interest. The interest relationship is consequently unstable, necessitating the improvement of a closely-knit interest community. Taking the issue of rural new energy development as its starting point, this paper thoroughly explores the mechanisms driving rural new energy connection. It delves into the interest relationship between the different stakeholders and provides guidelines for optimizing rural new energy system construction. Ultimately, this research aims to contribute to rural revitalization, facilitate the realization of the “double carbon” goal, and establish a modern rural new energy system.
Influences of human activity and climate change on growing-season soil moisture in the Qinghai–Tibet grasslands from 2000 to 2020
Authors: Xiao Jianyu , Yu Chengqun , Fu Gang
Published: November 2023

Soil moisture (SM) serves as a vital indicator reflecting environmental water conditions, but significant uncertainties still persist regarding how human activity and climate change affect SM. In this study, we quantified the influences of human activity and climate change on growing-season SM in the Qinghai–Tibet grasslands from 2000 to 2020. Climate change led to a decline in spatially mean SM at a rate of −0.01 and −0.06 g g−1 year−1 at 0–10 and 10–20 cm, respectively. Nonetheless, climate change caused the soil to become wetter in 39.97% and 22.29% areas at 0–10 and 10–20 cm, respectively. Human activity resulted in a decline in spatially mean SM by 36% and 21% at 0–10 and 10–20 cm, respectively. Nonetheless, human activity caused soil to become wetter in 2.82% areas at 0–10 cm and 30.03% areas at 10–20 cm. Therefore, both climate change and human activity have contributed to a pattern where the whole Qinghai–Tibet grasslands became drier while specific parts became wetter during the last 20 years. In addition to temperature and precipitation change, we should also pay attention to the response of SM to radiation change.
Reclassifying variations of unknown significance in diseases affecting Saudi Arabia’s population reveal new associations
Authors: Al Eissa Mariam M. , Alotibi Raniah S. , Alhaddad Bader , Aloraini Taghrid , Samman Manar S. , AlAsiri Abdulrahman , Abouelhoda Mohamed , AlQahtani Amerh S.
Published: November 2023

Introduction: Physicians face diagnostic dilemmas upon reports indicating disease variants of unknown significance (VUS). The most puzzling cases are patients with rare diseases, where finding another matched genotype and phenotype to associate their results is challenging. This study aims to prove the value of updating patient files with new classifications, potentially leading to better assessment and prevention.

Methodology: We recruited retrospective phenotypic and genotypic data from King Saud Medical City, Riyadh, Kingdom of Saudi Arabia. Between September 2020 and December 2021, 1,080 patients’ genetic profiles were tested in a College of American Pathologists accredited laboratory. We excluded all confirmed pathogenic variants, likely pathogenic variants and copy number variations. Finally, we further reclassified 194 VUS using different local and global databases, employing in silico prediction to justify the phenotype–genotype association.

Results: Of the 194 VUS, 90 remained VUS, and the other 104 were reclassified as follows: 16 pathogenic, 49 likely pathogenic, nine benign, and 30 likely benign. Moreover, most of these variants had never been observed in other local or international databases.

Conclusion: Reclassifying the VUS adds value to understanding the causality of the phenotype if it has been reported in another family or population. The healthcare system should establish guidelines for re-evaluating VUS, and upgrading VUS should reflect on individual/family risks and management strategies.
Semaphorin 7a aggravates TGF-β1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma
Authors: Peng Haiying , Sun Fei , Jiang Yunxiu , Guo Zihan , Liu Xinyi , Zuo Anli , Lu Degan
Published: November 2023

Background

TGF-β1 can induce epithelial-mesenchymal transition (EMT) in primary airway epithelial cells (AECs). Semaphorin7A (Sema7a) plays a crucial role in regulating immune responses and initiating and maintaining transforming growth factor β1 TGF-β1-induced fibrosis.

Objective

To determine the expression of Sema7a, in serum isolated from asthmatics and non-asthmatics, the role of Sema7a in TGF-β1 induced proliferation, migration and airway EMT in human bronchial epithelial cells (HBECs) in vitro.

Methods

The concentrations of Sema7a in serum of asthmatic patients was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Sema7a and integrin-β1 were examined using conventional western blotting and real-time quantitative PCR (RT-PCR). Interaction between the Sema7a and Integrin-β1 was detected using the Integrin-β1 blocking antibody (GLPG0187). The changes in EMT indicators were performed by western blotting and immunofluorescence, as well as the expression levels of phosphorylated Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) were analyzed by western blot and their mRNA expression was determined by RT-PCR.

Results

We described the first differentially expressed protein of sema7a, in patients with diagnosed bronchial asthma were significantly higher than those of healthy persons (P<0.05). Western blotting and RT-PCR showed that Sema7a and Integrin-β1 expression were significantly increased in lung tissue from the ovalbumin (OVA)-induced asthma model. GLPG0187 inhibited TGF-β1-mediated HBECs EMT, proliferation and migration, which was associated with Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) phosphorylation.

Conclusion

Sema7a may play an important role in asthma airway remodeling by inducing EMT. Therefore, new therapeutic approaches for the treatment of chronic asthma, could be aided by the development of agents that target the Sema7a.
Analysis of vaccine responses after anti-CD20 maintenance in B-cell lymphoma in the Balearic Islands. A single reference center experience
Authors: Gutierrez Antonio , Alonso Aser , Garcia-Recio Marta , Perez Sandra , Garcia-Maño Lucia , Martinez-Serra Jordi , Ros Teresa , Garcia-Gasalla Mercedes , Ferrer Joana , Vögler Oliver , Alemany Regina , Salar Antonio , Sampol Antonia , Bento Leyre
Published: November 2023

Introduction

The use of maintenance approaches with anti-CD20 monoclonal antibodies has improved the outcomes of B-cell indolent lymphomas but may lead to significant peripheral B-cell depletion. This depletion can potentially hinder the serological response to neoantigens.

Methods

Our objective was to analyze the effect of anti-CD20 maintenance therapy in a reliable model of response to neoantigens: SARS-CoV-2 vaccine responses and the incidence/severity ofCOVID-19 in a reference hospital.

Results

In our series (n=118), the rate of vaccination failures was 31%. Through ROC curve analysis, we determined a cutoff for SARS-CoV-2 vaccine serologic response at 24 months from the last anti-CD20 dose. The risk of severe COVID-19 was notably higher within the first 24months following the last anti-CD20 dose (52%) compared to after this period (just 18%) (p=0.007). In our survival analysis, neither vaccine response nor hypogammaglobulinemia significantly affected OS. While COVID-19 led to a modest mortality rate of 2.5%, this figure was comparable to the OS reported in the general immunocompetent population. However, most patients with hypogammaglobulinemia received intravenous immunoglobulin therapy and all were vaccinated. In conclusion, anti-CD20 maintenance therapy impairs serological responses to SARS-CoV-2 vaccines.

Discussion

We report for the first time that patients during maintenance therapy and up to 24 months after the last anti-CD20 dose are at a higher risk of vaccine failure and more severe cases of COVID-19. Nevertheless, with close monitoring, intravenous immunoglobulin supplementation or proper vaccination, the impact on survival due to the lack of serological response in this high-risk population can be mitigated, allowing for the benefits of anti-CD20 maintenance therapy, even in the presence of hypogammaglobulinemia.
Diabetes and bacterial co-infection are two independent risk factors for respiratory syncytial virus disease severity
Authors: Sivgin Hakan , Cetin Sirin , Ulgen Ayse , Li Wentian
Published: November 2023

Diabetes mellitus (DM) is common among older adults hospitalized with lower respiratory tract infection, yet information on the impact of DM on disease severity is limited. This study retrospectively analyzed 46 Turkish patients infected with respiratory syncytial virus (RSV), with information on their comorbidities, co-infection status, and symptoms. Patients are grouped into four severity levels from mild to severe, according to lung parenchymal infiltration status and oxygen level. Similar to previously published studies, we found that comorbidities of diabetes, heart failure, hypertension, co-infection of any type, bacterial co-infection, and age are associated with the disease severity. Cough is the most common symptom (89%) followed by fever (26%) and myalgia, dyspnea, and weakness (around 20%). Using a second-order analysis (two-variable regression), we identified two independent risks for disease severity, the first is represented by diabetes, and the second is represented by bacterial co-infection. We observed two patients whose more severe symptoms were not associated with an older age, but associated with a combination of diabetes and bacterial co-infection. To confirm the true causality from the statistical correlation, further studies are needed.
Assessment of the antifungal efficacy of whey fermentate alone or in combination with citrus extract to control Aspergillus flavus mold in semi-moist pet food for dogs
Authors: Kiprotich Samuel , Dhakal Janak , Rasmussen Cynthia , Aldrich Greg
Published: November 2023

Semi-moist pet foods contain moisture levels ranging from 15 to 40%, making them ideal for mold growth and mycotoxin production. To control spoilage, synthetic mold inhibitors such as potassium sorbate have been used, but consumers prefer “natural” preservatives. Whey fermentate (WPF) is an efficient antifungal, but it requires large doses. Therefore, the objective of this study was to determine the antifungal effect of WPF alone or in combination with citrus extract oil (CEX) against Aspergillus flavus in semi-moist pet food. Nutritionally complete semi-moist pet foods were produced with WPF alone [0.25, 0.5, and 1.0% (w/w)] and in combination with CEX; 0.25% WPF+ 0.015% CEX, 0.25% WFP+ 0.15% CEX, 0.5% WPF+ 0.015% CEX, and 0.5% WFP+ 0.15% CEX (w/w). The negative control (NC) contained no antifungal additive and the positive control (PC) had potassium sorbate (0.1% w/w). The semi-moist pet food was thermally formed and was cut into 3 cm × 3 cm square pieces. Individual food pieces were inoculated with 0.1 mL of Aspergillus flavus (ATCC 204304) to achieve a final concentration of ~5.0 log CFU/piece. The inoculated pieces were individually incubated at 25°C. Fungal analysis was performed on day 3, 6, 9, 12, 15, 18, 21, 24, and 28 by surface plating on Potato Dextrose Agar (PDA) followed by incubation at 25°C for 72 h. The total log reductions were calculated by subtracting the initial inoculum from the final log counts on day 28. Higher log reductions of Aspergillus flavus (p < 0.05) were observed when WPF at 0.25 and 0.5% was combined with 0.15% CEX compared to when 0.015% CEX was used individually. All treatments were different from the NC (p < 0.05). Citrus extract at 0.15% potentiated the antifungal effect of WPF at 0.5% to give a similar log reduction (p > 0.05) to WPF at 1.0% in the food. In conclusion, CEX potentiated the antifungal efficacy and reduced the dose of WPF required to control Aspergillus flavus in semi-moist dog food.
Prevalence and genomic characterization of Salmonella isolates from commercial chicken eggs retailed in traditional markets in Ghana
Authors: Archer Edward W. , Chisnall Tom , Tano-Debrah Kwaku , Card Roderick M. , Duodu Samuel , Kunadu Angela Parry-Hanson
Published: November 2023

Salmonella enterica are important foodborne bacterial pathogens globally associated with poultry. Exposure to Salmonella-contaminated eggs and egg-related products is a major risk for human salmonellosis. Presently, there is a huge data gap regarding the prevalence and circulating serovars of Salmonella in chicken eggs sold in Ghana. In this study, 2,304 eggs (pools of six per sample unit) collected from informal markets in Accra, Kumasi and Tamale, representing the three ecological belts across Ghana, were tested for Salmonella. Antimicrobial susceptibility testing and Whole Genome Sequencing (WGS) of the isolates were performed using standard microdilution protocols and the Illumina NextSeq platform, respectively. The total prevalence of Salmonella was 5.5% with a higher rate of contamination in eggshell (4.9%) over egg content (1.8%). The serovars identified were S. Ajiobo (n = 1), S. Chester (n = 6), S. Hader (n = 7), S. enteritidis (n = 2); and S. I 4:b:- (n = 8). WGS analysis revealed varied sequence types (STs) that were serovar specific. The S. I 4:b:- isolates had a novel ST (ST8938), suggesting a local origin. The two S. enteritidis isolates belonged to ST11 and were identified with an invasive lineage of a global epidemic clade. All isolates were susceptible to ampicillin, azithromycin, cefotaxime, ceftazidime, gentamicin, meropenem, and tigecycline. The phenotypic resistance profiles to seven antimicrobials: chloramphenicol (13%), ciprofloxacin (94%), and nalidixic acid (94%), colistin (13%), trimethoprim (50%) sulfamethoxazole (50%) and tetracycline (50%) corresponded with the presence of antimicrobial resistance (AMR) determinants including quinolones (gyrA (D87N), qnrB81), aminoglycosides (aadA1), (aph(3“)-Ib aph(6)-Id), tetracyclines (tet(A)), phenicols (catA1), trimethoprim (dfrA14 and dfrA1). The S. enteritidis and S. Chester isolates were multidrug resistant (MDR). Several virulence factors were identified, notably cytolethal distending toxin (cdtB gene), rck, pef and spv that may promote host invasion and disease progression in humans. The findings from this study indicate the presence of multidrug resistant and virulent strains of Salmonella serovars in Ghanaian chicken eggs, with the potential to cause human infections. This is a critical baseline information that could be used for Salmonella risk assessment in the egg food chain to mitigate potential future outbreaks.
Lactoferrin-based food supplements trigger toxin production of enteropathogenic Bacillus cereus
Authors: Jugert Clara-Sophie , Didier Andrea , Jessberger Nadja
Published: November 2023

Lactoferrin is an iron-binding glycoprotein exhibiting antibacterial, antiviral, antifungal, antiparasitic, antiinflammatory, antianaemic and anticarcinogenic properties. While its inhibitory effects against bacterial pathogens are well investigated, little is known about its influence on the production and/or mode of action of bacterial toxins. Thus, the present study aimed to determine the impact of food supplements based on bovine lactoferrin on Bacillus cereus enterotoxin production. First, strain-specific growth inhibition of three representative isolates was observed in minimal medium with 1 or 10 mg/mL of a lactoferrin-based food supplement, designated as product no. 1. Growth inhibition did not result from iron deficiency. In contrast to that, all three strains showed increased amounts of enterotoxin component NheB in the supernatant, which corresponded with cytotoxicity. Moreover, lactoferrin product no. 1 enhanced NheB production of further 20 out of 28 B. cereus and Bacillus thuringiensis strains. These findings again suggested a strain-specific response toward lactoferrin. Product-specific differences also became apparent comparing the influence of further six products on highly responsive strain INRA C3. Highest toxin titres were detected after exposure to products no. 7, 1 and 2, containing no ingredients except pure bovine lactoferrin. INRA C3 was also used to determine the transcriptional response toward lactoferrin exposure via RNA sequencing. As control, iron-free medium was also included, which resulted in down-regulation of eight genes, mainly involved in amino acid metabolism, and in up-regulation of 52 genes, mainly involved in iron transport, uptake and utilization. In contrast to that, 153 genes were down-regulated in the presence of lactoferrin, including genes involved in flagellar assembly, motility, chemotaxis and sporulation as well as genes encoding regulatory proteins, transporters, heat and cold shock proteins and virulence factors. Furthermore, 125 genes were up-regulated in the presence of lactoferrin, comprising genes involved in sporulation and germination, nutrient uptake, iron transport and utilization, and resistance. In summary, lactoferrin exposure of B. cereus strain-specifically triggers an extensive transcriptional response that considerably exceeds the response toward iron deficiency and, despite down-regulation of various genes belonging to the PlcR-regulon, ultimately leads to an increased level of secreted enterotoxin by a mechanism, which has yet to be elucidated.
Detection of cell-free histones in the cerebrospinal fluid of pediatric central nervous system malignancies by imaging flow cytometry
Authors: Buzova Diana , Frohlich Jan , Zapletalova Danica , Raffaele Marco , Lo Re Oriana , Tsoneva Desislava K. , Sterba Jaroslav , Cerveny Jan , Vinciguerra Manlio
Published: November 2023

Introduction: Pediatric brain tumours (PBT) are one of the most common malignancies during childhood, with variable severity according to the location and histological type. Certain types of gliomas, such a glioblastoma and diffuse intrinsic pontine glioma (DIPG), have a much higher mortality than ependymoma and medulloblastoma. Early detection of PBT is essential for diagnosis and therapeutic interventions. Liquid biopsies have been demonstrated using cerebrospinal fluid (CSF), mostly restricted to cell free DNA, which display limitations of quantity and integrity. In this pilot study, we sought to demonstrate the detectability and robustness of cell free histones in the CSF.

Methods: We collected CSF samples from a pilot cohort of 8 children with brain tumours including DIPG, medulloblastoma, glioblastoma, ependymoma and others. As controls, we collected CSF samples from nine children with unrelated blood malignancies and without brain tumours. We applied a multichannel flow imaging approach on ImageStream(X) to image indiviual histone or histone complexes on different channels.

Results: Single histones (H2A, macroH2A1.1, macroH2A1.2 H2B, H3, H4 and histone H3 bearing the H3K27M mutation), and histone complexes are specifically detectable in the CSF of PBT patients. H2A and its variants macroH2A1.1/macroH2A1/2 displayed the strongest signal and abundance, together with disease associated H3K27M. In contrast, mostly H4 is detectable in the CSF of pediatric patients with blood malignancies.

Discussion: In conclusion, free histones and histone complexes are detectable with a strong signal in the CSF of children affected by brain tumours, using ImageStream(X) technology and may provide additive diagnostic and predictive information.
Short-term efficacy of stenting as a rescue therapy for acute atherosclerotic occlusion in anterior cerebral circulation
Authors: Wang Jianyi , Shang Suhang , Dun Wanghuan , Chen Chen , Gao Fan , Yu Jia , Han Jianfeng , Liu Fude
Published: November 2023

Purpose

The study aimed to explore the efficacy and safety of the Neuroform EZ stent in treating acute anterior circulation large artery occlusion.

Methods

The clinical data of 42 consecutive patients with acute anterior circulation large atherosclerotic occlusion who were treated with the Neuroform EZ stent from January 2018 to August 2019 in our stroke care center, including baseline characteristics, images, therapeutic condition, and follow-up data were retrospectively analyzed.

Results

There were 42 mechanical thrombectomy (MT) failure cases of intracranial atherosclerotic stenosis with rescue Neuroform EZ stent implantation, of which 78.6% (33/42) had a good prognosis and 88.1% (37/42) showed no re-stenosis at follow-up. The average time from puncture to recanalization is 79.50 ± 14.19 min. The successful rate of intraoperative stent release is 97.6%, while there is one case of stent displacement, three cases of thrombus escape, and six cases of hemorrhage.

Conclusion

Rescue therapy of the Neuroform EZ stent for acute anterior circulation large atherosclerotic occlusion can archive good short-term imaging and clinical results, while long-term follow-up is still needed to verify.
Impact of different chemotherapy regimens on intestinal mucosal injury assessed with bedside ultrasound: a study in 213 AML patients
Authors: Benedetti Edoardo , Traverso Ginevra , Pucci Giulia , Morganti Riccardo , Bramanti Emilia , Lippolis Piero , Susini Maria Chiara , Mazzantini Elisa , Giubbolini Rachele , Mavilia Fabrizio , Capochiani Enrico , Neri Emanuele , Arena Chiara , Cerri Francesca , De Simone Luigi , Valentini Katia , Stella Salvatore Massimo , Ricchiuto Vittorio , Bruno Benedetto , Galimberti Sara
Published: November 2023

Introduction

Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage.

Methods

In our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN).

Results and discussion

Overall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening.
Review time of oncology drugs and its underlying factors: an exploration in China
Authors: Zhu Xingyue , Liu Bao
Published: November 2023

Introduction: How the launch delay of drugs and other factors of interest can influence the length of the review period by drug agencies is still unknown, and understanding this can help better strike the trade-off related to review speed.

Methods: We included all new oncology drug applications submitted to China’s National Medical Product Administration (NMPA) between 1 January 2018 and 31 December 2021, and ultimately succeeded in achieving marketing approval. For each drug, the length of the NMPA review process and other major characteristics were collected, including the registration class, approval class, priority review designation, and launch delay relative to the United States, as well as the number of patients enrolled, comparator, and primary endpoint of the pivotal trials supporting the approval. Linear regression model was employed to analyze the effects of factors of interest on the NMPA review time.

Results: From 2018 to 2021, NMPA received 137 oncology applications that were ultimately approved. Half of the approvals [76 (55.5%)] were first licensed in the US, leaving a median launch delay of 2.71 years (IQR, 1.03–5.59) in China. In the pivotal studies, the median enrollment was 361 participants (IQR, 131–682), and the use of control groups [90 (65.7%)] and surrogate endpoints [101 (73.7%)] was prevalent. The median review time was 304 days (IQR, 253–376). Multivariate analysis for log-transformed review time showed that larger enrollment (> 92) was associated with a drop of 20.55% in review time (coefficient = −0.230; 95% CI, −0.404 to −0.055; p = 0.010); and a short delay (0 < delay ≤ 1.95 years) was associated with a drop of 17.63% in review time (coefficient = −0.194; 95% CI, −0.325 to −0.062; p = 0.004).

Discussion: The short launch delay relative to the US was one important driver to the review speed of NMPA, which might suggest its latent regulatory reliance on the other global regulator during the post-marketing period when new information on the drug’s clinical benefit was still lacking.
Associations between COVID-19 outcomes and asthmatic patients with inhaled corticosteroid
Authors: Yong Su-Boon , Gau Shuo-Yan , Li Chia-Jung , Tseng Chih-Wei , Wang Shiow-Ing , Wei James Cheng-Chung
Published: November 2023

Background: The impact of inhaled corticosteroid (ICS) in the interaction between asthma, COVID-19 and COVID-19 associated outcomes remain largely unknown. The objective of this study is to investigate the risk of COVID-19 and its related outcomes in patients with asthma using and not using inhaled corticosteroid (ICS).

Methods: We used the TriNetX Network, a global federated network that comprises 55 healthcare organizations (HCO) in the United States, to conduct a retrospective cohort study. Patients with a diagnosis of asthma with and without ICS between January 2020 and December 2022 were included. Propensity score matching was used to match the case cohorts. Risks of COVID-19 incidence and medical utilizations were evaluated.

Results: Out of 64,587 asthmatic patients with ICS and without ICS, asthmatic patients with ICS had a higher incidence of COVID-19 (Hazard ratio, HR: 1.383, 95% confidence interval, CI: 1.330–1.437). On the contrary, asthmatic patients with ICS revealed a significantly lower risk of hospitalization (HR: 0.664, 95% CI: 0.647–0.681), emergency department visits (HR: 0.774, 95% CI: 0.755–0.793), and mortality (HR:0.834, 95% CI:0.740–0.939). In addition, subgroup or sensitivity analyses were also conducted to examine the result of different vaccination status, disease severity, or COVID-19 virus variants.

Conclusion: For asthmatic patients using ICS, risk of COVID-19 was significantly higher than non-users. The observed association could provide potential guidance for primary care physicians regarding the risk of COVID-19 in asthmatic patients.
A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions
Authors: Shan Yu , Zhao Jianan , Wei Kai , Jiang Ping , Xu Lingxia , Chang Cen , Xu Linshuai , Shi Yiming , Zheng Yixin , Bian Yanqin , Zhou Mi , Schrodi Steven J. , Guo Shicheng , He Dongyi
Published: November 2023

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the immune system mistakenly attacks and damages the body’s tissues and organs. This excessive immune response leads to inflammation, tissue damage, and functional impairment. Therapeutic approaches typically involve medications that regulate immune responses, reduce inflammation, alleviate symptoms, and target specific damaged organs. Tripterygium wilfordii Hook. f., a traditional Chinese medicinal plant, has been widely studied in recent years for its application in the treatment of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Numerous studies have shown that preparations of Tripterygium wilfordii have anti-inflammatory, immunomodulatory, and immunosuppressive effects, which effectively improve the symptoms and quality of life of patients with autoimmune diseases, whereas the active metabolites of T. wilfordii have been demonstrated to inhibit immune cell activation, regulate the production of inflammatory factors, and modulate the immune system. However, although these effects contribute to reductions in inflammatory responses and the suppression of autoimmune reactions, as well as minimize tissue and organ damage, the underlying mechanisms of action require further investigation. Moreover, despite the efficacy of T. wilfordii in the treatment of autoimmune diseases, its toxicity and side effects, including its potential hepatotoxicity and nephrotoxicity, warrant a thorough assessment. Furthermore, to maximize the therapeutic benefits of this plant in the treatment of autoimmune diseases and enable more patients to utilize these benefits, efforts should be made to strengthen the regulation and standardized use of T. wilfordii.
A highly-compact and ultra-fast homogeneous electromagnetic calorimeter based on oriented lead tungstate crystals
Authors: Bandiera L. , Baryshevsky V. G. , Canale N. , Carsi S. , Cutini S. , Davì F. , De Salvador D. , Gianoli A. , Guidi V. , Haurylavets V. , Korjik M. , Lobko A. S. , Malagutti L. , Mazzolari A. , Montalto L. , Guarnieri P. Monti , Moulson M. , Negrello R. , Paternò G. , Presti M. , Rinaldi D. , Romagnoni M. , Selmi A. , Sgarbossa F. , Soldani M. , Sytov A. , Tikhomirov V. V. , Vallazza E.
Published: November 2023

Progress in high-energy physics has been closely tied to the development of high-performance electromagnetic calorimeters. Recent experiments have demonstrated the possibility to significantly accelerate the development of electromagnetic showers inside scintillating crystals typically used in homogeneous calorimeters based on scintillating crystals when the incident beam is aligned with a crystallographic axis to within a few mrad. In particular, a reduction of the radiation length has been measured when ultrarelativistic electron and photon beams were incident on a high-Z scintillator crystal along one of its main axes. Here, we propose the possibility to exploit this physical effect for the design of a new type of compact e.m. calorimeter, based on oriented ultra-fast lead tungstate (PWO-UF) crystals, with a significant reduction in the depth needed to contain electromagnetic showers produced by high-energy particles with respect to the state-of-the-art. We report results from tests of the crystallographic quality of PWO-UF samples via high-resolution X-ray diffraction and photoelastic analysis. We then describe a proof-of-concept calorimeter geometry defined with a Geant4 model including the shower development in oriented crystals. Finally, we discuss the experimental techniques needed for the realization of a matrix of scintillator crystals oriented along a specific crystallographic direction. Since the angular acceptance for e.m. shower acceleration depends little on the particle energy, while the decrease of the shower length remains pronounced at very high energy, an oriented crystal calorimeter will open the way for applications at the maximum energies achievable in current and future experiments. Such applications span from forward calorimeters, to compact beam dumps for the search for light dark matter, to source-pointing space-borne γ-ray telescopes, to decrease the size and the cost of the calorimeter needed to fully contain e.m. showers initiated by GeV to TeV particles.
Novel genetic resources associated with sucrose and stachyose content through genome-wide association study in soybean (Glycine max (L.) Merr.)
Authors: Lee Dongho , Lara Laura , Moseley David , Vuong Tri D. , Shannon Grover , Xu Dong , Nguyen Henry T.
Published: November 2023

The nutritional value of soybean [Glycine max (L.) Merr.] for animals is influenced by soluble carbohydrates, such as sucrose and stachyose. Although sucrose is nutritionally desirable, stachyose is an antinutrient causing diarrhea and flatulence in non-ruminant animals. We conducted a genome-wide association study of 220 soybean accessions using 21,317 single nucleotide polymorphisms (SNPs) from the SoySNP50K iSelect Beadchip data to identify significant SNPs associated with sucrose and stachyose content. Seven significant SNPs were identified for sucrose content across chromosomes (Chrs.) 2, 8, 12, 17, and 20, while thirteen significant SNPs were identified for stachyose content across Chrs. 2, 5, 8, 9, 10, 13, 14, and 15. Among those significant SNPs, three sucrose-related SNPs on Chrs. 8 and 17 were novel, while twelve stachyose-related SNPs on Chrs. 2, 5, 8, 9, 10, 13, 14, and 15 were novel. Based on Phytozome, STRING, and GO annotation, 17 and 24 candidate genes for sucrose and stachyose content, respectively, were highly associated with the carbohydrate metabolic pathway. Among these, the publicly available RNA-seq Atlas database highlighted four candidate genes associated with sucrose (Glyma.08g361200 and Glyma.17g258100) and stachyose (Glyma.05g025300 and Glyma.13g077900) content, which had higher gene expression levels in developing seed and multiple parts of the soybean plant. The results of this study will extend knowledge of the molecular mechanism and genetic basis underlying sucrose and stachyose content in soybean seed. Furthermore, the novel candidate genes and SNPs can be valuable genetic resources that soybean breeders may utilize to modify carbohydrate profiles for animal and human usage.
Longitudinal associations between paternal mental health and child behavior and cognition in middle childhood
Authors: Jones Sherri Lee , Caccese Christina , Davis Kelsey P. , Lew Jimin , Elgbeili Guillaume , Herba Catherine M. , Barnwell Julia , Robert Cindy Hénault , Gavanski Isabella , Horsley Kristin , Fraser William D. , Da Costa Deborah , Séguin Jean R. , Nguyen Tuong-Vi , Montreuil Tina C.
Published: November 2023

Introduction

Paternal mental health has been associated with adverse consequences on offspring psychosocial development, and family environmental factors may partly explain those associations. To clarify this, we need comprehensive prospective studies, particularly in middle-childhood when the child enters school and is expected to make use of behavioral and cognitive skills as part of their interactions and learning.

Method

Using data from a sub-sample of the prospective 3D birth cohort study comprised of mother-father-child triads, and a follow-up of the parents and the children at 6–8 years of age (n = 61; 36 boys, 25 girls), we examined whether paternal anxious and depressive symptoms measured during the pregnancy period (i.e., prenatally) or concurrently when the child was assessed at 6–8 years old were associated with children's cognition/behavior.

Results

In contrast to our hypotheses, we found that greater prenatal paternal depressive symptoms predicted fewer child behavioral difficulties; and that greater concurrent childhood paternal depression or anxiety symptoms were associated with higher child full-scale IQ, controlling for the equivalent maternal mental health assessment and parental education. Father parenting perception did not mediate these associations, nor were they moderated by maternal mental health at the concurrent assessment, or paternal ratings of marital relationship quality.

Discussion

These findings suggest that higher symptoms of paternal mental health symptoms are associated with fewer child behavioral difficulties and higher cognitive performance in middle childhood. Potential clinical implications and future research directions are discussed.
Perceiving violence against healthcare workers in a child and adolescent emergency psychiatric ward in Hungary: a qualitative pilot study
Authors: Sófi Gyula , Törő Krisztina , Csikós Gábor , Fliegauf Gergely
Published: November 2023

Aim

Psychiatry is a challenging setting that requires extraordinary effort from the staff. Healthcare workers in the field of psychiatry face substantial levels of violence, making the identification of abuse risk factors a social concern. Both the conduct of the children and their relatives can pose potential harm. Our study delved into the criminological and psychiatric factors underlying violence against healthcare workers.

Methodology

We used qualitative, semi-structured, self-developed, online questionnaire involving 21 respondents. The participants were representing the staff composition of our department. The data set was coded in two phases using a multi-stage content analysis method. The results were compared with Hungarian and international literature.

Findings

Among the participants, 52% reported no instances of physical abuse. The most prevalent form of perceived non-contact abuse was threats, accounting for 38% of reported cases. The identified risk factors for abuse included the child’s psychiatric disorder, communication issues, parental behavior, and low socio-economic status. Psychological trauma was identified as the most severe consequence. The respondents’ opinion indicated that the most common cause of violence (52%) was attributed to the child’s mental disorder. Workers primarily deal with abuse through negative emotions, with 76% of them reporting feelings of victimization. Additionally, 43% believed that abuse cannot be avoided, while 19% emphasized the significance of worker competence.

Value

Our research can help to identify risk factors in child psychiatry wards and provide guidance for developing effective responses to violence against healthcare workers in Hungary, especially at our ward.