bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-chain fatty acids abrogate Japanese encephalitis virus-induced inflammation in microglial cells via miR-200a-3p/ZBTB20/IKβα axis
Authors: Majumdar Atreye , Siva Venkatesh Indira Priya , Swarup Vivek , Basu Anirban
Published: June 2024

Japanese encephalitis virus (JEV), a member of the Flaviviridae family, is a leading cause of viral encephalitis in humans. Survivors of this infection often develop lifelong neurological sequelae. Short-chain fatty acids (SCFAs) produced in the gut are vital mediators of the gut-brain axis. We aimed to study microRNA-based mechanisms of SCFAs in an
in vitro
model of JEV infection. N9 microglial cells were pretreated with SCFA cocktail before JEV infection. Cytokine bead analysis, immunoblotting, and PCR were performed to analyze relevant inflammatory markers. microRNA sequencing was performed using Illumina Hiseq, and bioinformatics tools were used for differentially expressed (DE) miRNAs and weighted gene co-expression network analysis (WGCNA). microRNA mimic/inhibitor experiments and luciferase assay were performed to study miRNA-target interaction. A significant reduction in monocyte chemoattractant protein (MCP1) and tumor necrosis factor alpha (TNFα) along with reduced expression of phospho-nuclear factor kappa B (phospho-NF-κB) was observed in SCFA conditions. Significant attenuation of histone deacetylase activity and protein expression was recorded. miRNA sequencing revealed 160 DE miRNAs in SCFA + JEV-treated cells at 6 h post-infection. WGCNA revealed miR-200a-3p, a hub miRNA significantly upregulated in SCFA conditions. Transcription factor ZBTB20 was bioinformatically predicted and validated as a gene target for miR-200a-3p. Further miRNA mimic/inhibitor assay demonstrated that miR-200-3p regulated ZBTB20 along with Iκβα that possibly dampened NF-κB signal activation downstream.

IMPORTANCE

The gut-brain axis plays a pivotal role in the physiological state of an organism. Gut microbiota-derived metabolites are known to play a role in brain disorders including neuroviral infections. Short-chain fatty acids (SCFAs) appear to quench inflammatory markers in Japanese encephalitis virus-infected microglial cells
in vitro
. Mechanistically, we demonstrate the interaction between miR-200a-3p and ZBTB20 in regulating the canonical nuclear factor kappa B (NF-κB) signaling pathway via transcriptional regulation of Iκβα. Findings of this study pave the way to a better understanding of SCFA mechanisms that can be used to develop strategies against viral neuroinflammation.
Effects of an inoculant containing Lentilactobacillus hilgardii (CNCM-I-4785) on the microbiome, fermentation, and aerobic stability of corn silage stored for long term at different incubation temperatures
Authors: Drouin P. , da Silva É.B. , Scuderi R.A. , Tremblay J. , Castex M. , Apper E.
Published: June 2024

Whole-plant corn untreated (Control) or treated with an inoculant ( Lentilactobacillus buchneri, Lentilactobacillus hilgardii, and Pediococcus pentosaceus, INO) was ensiled for 210 days in mini-silos at constant (MS-C) or variable temperature (MS-V) or for 220 days in bunkers. Bunker samples were collected at 50 (D50) and 150 (D150) cm below silo surface. Samples from MS-V and MS-C had similar pH and concentrations of lactic acid, propionic acid, 1,2-propanediol, and ethanol, but different acetic acid content ( P = 0.009). Additionally, MS-V exhibited greater bacterial ( P = 0.002) and fungal ( P = 0.011) richness than MS-C. Inoculation decreased ( P < 0.001) lactic acid levels while increasing ( P < 0.05) acetic acid, 1,2-propanediol, and fungal richness in both mini-silos and bunker. In bunkers, samples collected from D50 had a lower aerobic stability ( P < 0.05) than D150, but inoculation increased ( P < 0.05) aerobic stability compared to Control, regardless of sampling depth. The storage temperature of mini-silos did not markedly impact the fermentation profile or fungal community. Overall, inoculation increased acetic acid production and fungal diversity in mini-silos, regardless of the storage temperature, and in bunkers, irrespective of sampling the depth, improving the aerobic stability of D50 and D150 bunker silages after long-term ensiling.
Ab-initio investigation of electronic and optical properties of vanadium pentoxide (V2O5)
Authors: Dhaked Khushbu , Shukla Rimpy , Sharma Krishna S. , Sharma Ramphal
Published: June 2024

DFT is used for making first-principles calculations of electronic and optical properties of V2O5 in its orthorhombic phase, by employing Augmented Plane Waves[Formula: see text][Formula: see text][Formula: see text]local orbital method with Generalized Gradient Approximation and Perdew–Burke–Ernzerhof potential to account for exchange–correlation interactions. The stability of the material is checked through the calculation of cohesive energy and Bader charge analysis is done to find out the electronic charges on different atoms in the unit cell. A DOS gap of about 2.1[Formula: see text]eV and a direct band gap of about 1.85[Formula: see text]eV just above the Fermi level is found to occur on using DFT, which is lower than the experimental value of 2.77[Formula: see text]eV. On using the DFT[Formula: see text][Formula: see text][Formula: see text]U method, with [Formula: see text][Formula: see text]eV for Vanadium, a DOS gap of about 2.8[Formula: see text]eV and an indirect band gap of about 3.0[Formula: see text]eV are found to occur, which are closer to the experimental result, showing that the DFT+U method better accounts for electronic properties of V2O5. The optical properties, such as dielectric function, reflectivity, absorption coefficient, optical conductivity, refractive index, extinction coefficient and electron energy loss function also investigated for V2O5 by using DFT.
Microstructure and mechanical property of Zr-4 alloys brazed with Ag–Cu–Ti filler metal
Authors: Bai Yujie , Wang Yao , Liu Yi , Li Yuanxing
Published: June 2024

Zr-4 alloys were vacuum brazed using Ag–Cu–Ti filler metal. The effect of brazing temperature on the microstructure evolution, shear strength and corresponding fracture behavior of the brazed joints was investigated. The typical phases at the brazing temperature of 800, 840 and 930∘C were inferred to be three different microstructures, i.e., a mixture of (Cu, Ti) phases and Ag-rich phase, Ag-rich phase and brittle intermetallic compound (IMC) AgZr, and a uniformly mixed morphology of CuZr and AgZr. And the width of the whole brazed seam increased from 78.4[Formula: see text][Formula: see text]m to 118.8[Formula: see text][Formula: see text]m. Meanwhile, the shear strength of the brazed joints first increased and then decreased followed by a small increase. The maximum shear strength of 138[Formula: see text]MPa was obtained at the treatment of 800∘C for 10[Formula: see text]min. The fracture morphology exhibited typical brittle fracture characteristics, and the cracks initiated from the interface of the brazed joints, and propagated into the intermediate zones.
Bacterial Quality and Molecular Detection of Food Poisoning Virulence Genes Isolated from Nasser Lake Fish, Aswan, Egypt
Authors: Elbarbary Nady Khairy , Dandrawy Mohamed K. , Hadad Ghada , Abdelhaseib Maha , Osman Amna A. A. , Alenazy Rawaf , Elbagory Ibrahim , Abdelmotilib Neveen M. , Elnoamany Fagelnour , Ibrahim Ghada A. , Gomaa Reda A.
Published: June 2024

The microbial analysis of fish is critical for ensuring overall health. Uncooked fish can serve as a conduit for transmitting several types of microbes; the current investigation sought to assess the bacterial levels in various kinds of fish from Nasser Lake, Aswan, Egypt, considered the chief source of potable water in Egypt. Two hundred and fifty fish samples, including 50 of each Oreochromis niloticus, Sander lucioperca, Lates niloticus, Clarias gariepinus, and Mormyrus kannume, from Nasser Lake, Aswan, Egypt, were collected to detect the bacterial load, isolation, and identification of Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio parahaemolyticus and their virulence genes. The findings revealed that Oreochromis niloticus and Clarias gariepinus exhibited higher bacterial loads than other fish species. Incidences of bacterial contamination among examined fishes were 28.8%, 20.4%, and 16% for Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio parahaemolyticus, respectively. Additionally, PCR analysis detected the presence of aerA (60%) and Act (40%) genes in A. hydrophila, rpoB (70%) and LasB (30%) genes in P. aeruginosa, and ToxR (70%) and tdh (50%) genes in V. parahaemolyticus. The study suggested that the bacterial contamination levels in Oreochromis niloticus and Clarias gariepinus could be notably more significant than in other species that could potentially be harmful to the consumers, especially considering the identification of particular bacteria known to cause foodborne illnesses. Further recommendations emphasized that regular monitoring and assessments are required to preserve their quality.
DNA barcode based phylogeographic analysis of the Aricia anteros (Freyer, 1838) species complex (Lepidoptera: Lycaenidae) with description of a new subspecies from SE Europe
Authors: LUKHTANOV VLADIMIR A. , BOTMAN ROMAN V. , GAGARINA ANASTASIA V.
Published: June 2024

The complex of taxa closely related to Aricia anteros includes the species A. anteros sensu stricto, A. crassipuncta, A. bassoni, and A. vandarbani. All of them are sometimes considered as subspecies of a single polytypic species. Representatives of this complex are found in the Balkan Peninsula, Asia Minor, the Levant, the Caucasus, Transcaucasia, and Northern and Western Iran. In addition, an isolated population of A. anteros occurs in the Northern Black Sea region. In this work, based on DNA barcodes of all species and main populations of the complex, we show the existence of seven differentiated mitochondrial lineages: anteros (predominant in the Balkans), crassipuncta (predominant in Asia Minor), bassoni (the Levant), vandarbani (Talysh Mts), varicolor (Zagros Mts), dombaiensis (the Caucasus) and kalmius (Kalmius River basin in the Northern Black Sea region). The taxa of the A. anteros species complex are allopatric, except for A. anteros s.s. and A. crassipuncta, which have a mosaic distribution in eastern Anatolia and Transcaucasia. On the Balkan Peninsula, within the species A. anteros s.s, both the anteros and the crassipuncta mitochondrial haplogroups are found. This pattern is likely a consequence of interspecific hybridization and mitochondrial introgression. Based on mitochondrial DNA, the taxon A. crassipuncta mehmetcik from SE Anatolia is indistinguishable from A. crassipuncta crassipuncta, and the taxon varicolor from Central Iran is closer to the geographically distant European A. anteros than to the Anatolian A. crassipuncta. The geographically isolated and genetically differentiated population from the Kalmius River basin in the Northern Black Sea region is described here as a new subspecies.
First record of the genus Bradybatus Germar (Coleoptera, Curculionidae, Anthonomini) from China with description of a new species
Authors: LI YIZHE , LÜ HEYU , JIANG CHUNYAN , ZHANG RUNZHI
Published: June 2024

The genus Bradybatus Germar, 1823 is reported from China for the first time. A new species is described and illustrated under the name Bradybatus (Bradybatus) keerqinensis Lü and Zhang sp. n. from Inner Mongolia Autonomous Region, China. This new species can be easily distinguished from other species of Bradybatus by the large body size, black color, pronotum length/width ratio about 1.21–1.27 without longitudinal stripe, elytra length/width ratio about 1.85–2.00 without oblique or transverse band, and pedon uniformly curved C-shaped (in lateral view), sides subparallel (in dorsal view), with distinctly narrow apex. An identification key to all known species of the subgenus Bradybatus is updated. The biological characteristics of the species are also provided.
Perioperative Sleep Disturbance in Surgical Patients: A Concept Analysis
Authors: Yuan Xi , Ju Zhengyu , Zhang Xinmei , Yin Xuequn
Published: June 2024

To investigate and define the concept of perioperative sleep disturbance (PSD) among surgical patients, with the goal of aiding clinical practice and research. Walker and Avant’s eight-step approach of concept analysis was applied. A systematic search of English literature was conducted in the following databases: PubMed, Web of Science, and CINAHL, with a time restriction from 2010 to August 2023. Based on the 54 eligible studies, the attributes of PSD in surgical patients were identified as individualized symptom manifestation, difficulty initiating and/or maintaining sleep, and altered sleep patterns. The antecedents included poor psychological state, inaccurate perception, surgery and/or anesthesia-related physiological changes, and environmental interference. PSD in surgical patients was found to result in physical discomfort, psychological disorder, impaired neurocognitive function, and prolonged recovery. A clearly defined and distinguishable concept of PSD in surgical patients was achieved through concept analysis, which provides a conceptual basis for future development in both clinical practice and related research.
A systematic review of multi-output prediction model for indoor environment and heating, ventilation, and air conditioning energy consumption in buildings
Authors: Jiang Kaiyun , Shi Tianyu , Yu Haowei , Mahyuddin Norhayati , Lu Shifeng
Published: June 2024

Heating, ventilation and air conditioning (HVAC) systems could significantly impact indoor environmental quality, particularly in terms of thermal comfort and indoor air quality. Achieving a high-quality indoor environment poses challenges to the energy consumption of HVAC systems. Thus, balancing thermal comfort, indoor air quality (IAQ) and energy consumption becomes a challenging task. Currently, indoor environment prediction methods are considered effective solutions to address this issue. However, the published literature usually concentrates on single aspects like thermal comfort, air quality or energy consumption, with multi-aspect prediction methods being rare. The present work reviews research spanning the last decade that employs machine learning methods for predicting indoor environments and HVAC energy consumption through separate and multi-output predictive models. Separate predictive models focus on HVAC systems’ impact on the indoor environment, while multi-output models consider the interplay of various outputs. This article gives a thorough insight into machine learning prediction models’ workflow, detailing data collection, feature selection and model optimization for each research goal. A systematic assessment of methods for data collection of diverse prediction targets, machine learning algorithms and validation approaches for different prediction models is presented. This review highlights the complexities of data management, model development and validation, enriching the knowledge base in indoor environmental quality optimization.
Barriers and Facilitators of Taking a Lifestyle History and Referral to Lifestyle Interventions in Mental Health
Authors: Koomen L. E. M. , Deenik J. , Cahn W.
Published: June 2024

Background: Lifestyle interventions can improve mental and physical health in patients with mental illness, but implementing these in clinical practice seems difficult. Purpose: Investigate barriers and facilitators for mental health professionals (MHPs) in taking lifestyle histories and referring to lifestyle interventions. Methods: A cross-sectional national online survey among MHPs. All mental health care institutions, hospital psychiatry departments, associations for nurse specialists, and independent working psychiatrists’ organizations in the Netherlands were invited to participate. Ordinal regression analyses were performed to study factors associated with barriers. Results: 1524 MHPs participated. Barriers were time constraints (45.3%), lack of referral possibilities (33.2%), patient disinterest (25.4%) and lack of knowledge about: effect (25.5%), availability of interventions (57.5%), lifestyle (16.9%), and reimbursement (41.5%). Facilitators included more referral possibilities (44.9%), integration of lifestyle into clinical routine (48.3%), a dedicated tool (41.5%), organizational commitment (41.2%) and lifestyle as standard treatment component (40.3%), and more knowledge about: referral possibilities (51.4%), effect (38.1%), and reimbursement (48.1%). Older MHPs, those who consider their own lifestyle important, and those working in organizations where lifestyle interventions are available experienced fewer barriers. Conclusions: Organizations should prioritize lifestyle psychiatry by educating staff, integration into clinical routine, and increasing the availability and reimbursements of interventions.
Intrapartum maternal glycaemic control for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis
Authors: Ulyatt Caitlyn M. , Roberts Lily F. , Crowther Caroline A. , Harding Jane E. , Lin Luling
Published: June 2024

Background

Neonatal hypoglycaemia is the most common metabolic disorder in infants, and may be influenced by maternal glycaemic control. This systematic review evaluated the effect of intrapartum maternal glycaemic control on neonatal hypoglycaemia.

Methods

We included randomised controlled trials (RCTs), quasi-RCTs, non-randomised studies of interventions, and cohort or case-control studies that examined interventions affecting intrapartum maternal glycaemic control compared to no or less stringent control. We searched four databases and three trial registries to November 2023. Quality assessments used Cochrane Risk of Bias 1 or the Effective Public Health Practice Project Quality Assessment Tool. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Meta-analysis was performed using random-effects models analysed separately for women with or without diabetes. The review was registered prospectively on PROSPERO (CRD42022364876).

Results

We included 46 studies of women with diabetes and five studies of women without diabetes: one RCT, 32 cohort and 18 case-control studies (11,273 participants). For women with diabetes, the RCT showed little to no difference in the incidence of neonatal hypoglycaemia between tight versus less tight intrapartum glycaemic control groups (76 infants, RR 1.00 (0.45, 2.24), p = 1.00, low certainty evidence). However, 11 cohort studies showed tight intrapartum glycaemic control may reduce neonatal hypoglycaemia (6,152 infants, OR 0.44 (0.31, 0.63), p < 0.00001, I2 = 58%, very low certainty evidence). For women without diabetes, there was insufficient evidence to determine the effect of tight intrapartum glycaemic control on neonatal hypoglycaemia.

Conclusions

Very uncertain evidence suggests that tight intrapartum glycaemic control may reduce neonatal hypoglycaemia in infants of women with diabetes. High-quality RCTs are required.
Examining the etiological factors resulting in retinal detachment following prophylactic vitrectomy in the context of acute retinal necrosis syndrome
Authors: Nie Yu-hong , Zhang Yu , Chen Zhen , Xing Yi-qiao
Published: June 2024

Objective

The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome.

Methods

A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery.

Results

This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels.

Conclusion

RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.
Prognostic and predictive value of examined lymph node count in stage III colorectal cancer: a population based study
Authors: Wei Ran , Zheng Zifan , Li Qinghai , Qian Yan , Wu Chong , Li Yin , Wang Mian , Chen Jianhui , He Weiling
Published: June 2024

Background

The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood.

Methods

This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the “limma” package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration.

Results

Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment.

Conclusions

The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.
Effect of COVID-19 response work experience on turnover intention among employees of dedicated COVID-19 hospitals in Seoul
Authors: Park Eunyoung , You Chang Hoon , Joung Hyojee , Kwon Young Dae
Published: June 2024

Background

According to previous studies, stress and job burnout among medical personnel increased during the COVID-19 pandemic. This study analyzed the effect of the experience of COVID-19 response work on the intention of municipal hospital staffs to leave their workplaces during the pandemic.

Methods

The 3556 employees who had worked for more than 1 year at one of the eight Seoul Municipal Hospitals that either provided inpatient treatment for quarantined COVID-19 patients or operated as screening clinics were taken as the study population. In total, 1227 employees completed a web or mobile survey between October 21 and November 18, 2020. A chi-squared test was performed to confirm the difference in the distribution of turnover intention depending on whether the employees performed COVID-19 response tasks. Multiple logistic regression analyses were performed to determine the factors that affected the intention to leave.

Results

Of the 1227 respondents, 761 (62.0%) were frontline workers who were the first line of response to COVID-19. Experience with COVID-19 response tasks (OR = 1.59, p = 0.003) was significantly associated with the intention to leave. Additionally, the probability of turnover intention was significantly higher among workers aged 20–29 years (OR = 2.11, p = 0.038) and 40–49 years (OR = 1.57, p = 0.048), unmarried individuals (OR = 1.66, p = 0.005), doctors (OR = 2.41, p = 0.010), nurses (OR = 1.59, p = 0.036), and technical staff members (OR = 2.22, p = 0.009). High turnover intention was found among those who experienced high levels of burnout (OR = 2.03, p < 0.001) and those working in non-directly managed municipal hospitals (OR = 1.87, p = 0.018).

Conclusion

Employees directly involved in COVID-19 response work displayed higher turnover intention. Various personal, job, and organizational factors significantly influenced employees’ intentions to leave their positions in dedicated COVID-19 hospitals. These findings suggest the necessity of introducing management programs to aid workers who have experienced sudden changes in their duties and loss of autonomy while performing COVID-19 response tasks.
BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo
Authors: Yang Qihong , To Kenneth Kin Wah , Hu Guilin , Fu Kai , Yang Chuan , Zhu Shuangli , Pan Can , Wang Fang , Luo Kewang , Fu Liwu
Published: June 2024

Background

Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date. Here, we will investigate the effect of BI-2865, a pan-KRAS inhibitor, on reversing MDR induced by P-gp, BCRP and MRP1 in vitro and in vivo, and its reversal mechanisms will be explored.

Methods

The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts’ tumor were analyzed through LC-MS. Mechanisms of BI-2865 inhibiting P-gp substrate’s efflux were analyzed through the vanadate-sensitive ATPase assay, [125I]-IAAP-photolabeling assay and computer molecular docking. The effects of BI-2865 on P-gp expression and KRAS-downstream signaling were detected via Western blotting, Flow cytometry and/or qRT-PCR. Subcellular localization of P-gp was visualized by Immunofluorescence.

Results

We found BI-2865 notably fortified response of P-gp-driven MDR cancer cells to the administration of chemo-drugs including paclitaxel, vincristine and doxorubicin, while such an effect was not observed in their parental sensitive cells and BCRP or MRP1-driven MDR cells. Importantly, the mice vivo combination study has verified that BI-2865 effectively improved the anti-tumor action of paclitaxel without toxic injury. In mechanism, BI-2865 prompted doxorubicin accumulating in carcinoma cells by directly blocking the efflux function of P-gp, which more specifically, was achieved by BI-2865 competitively binding to the drug-binding sites of P-gp. What’s more, at the effective MDR reversal concentrations, BI-2865 neither varied the expression and location of P-gp nor reduced its downstream AKT or ERK1/2 signaling activity.

Conclusions

This study uncovered a new application of BI-2865 as a MDR modulator, which might be used to effectively, safely and specifically improve chemotherapeutic efficacy in the clinical P-gp mediated MDR refractory cancers.
Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis
Authors: Chen Chang-Ming , Yan Qiu-Long , Guo Ruo-Chun , Tang Fang , Wang Min-Hui , Yi Han-Zhi , Huang Chun-Xia , Liu Can , Wang Qiu-Yi , Lan Wei-Ya , Jiang Zong , Yang Yu-Zheng , Wang Guang-Yang , Zhang Ai-Qin , Ma Jie , Zhang Yan , You Wei , Ullah Hayan , Zhang Yue , Li Sheng-Hui , Yao Xue-Ming , Sun Wen , Ma Wu-Kai
Published: June 2024

Background/purpose(s)

The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation.

Methods

We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples.

Results

Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA.

Conclusion

Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Graphical Abstract
Optimization of graphene polypyrrole for enhanced adsorption of moxifloxacin antibiotic: an experimental design approach and isotherm investigation
Authors: Ishaq Sara , Nadim Ahmed H. , Amer Sawsan M. , Elbalkiny Heba T.
Published: June 2024

The presence of antibiotics in water systems had raised a concern about their potential harm to the aquatic environment and human health as well as the possible development of antibiotic resistance. Herein, this study investigates the power of adsorption using graphene-polypyrrole (GRP-PPY) nanoparticles as a promising approach for the removal of Moxifloxacin HCl (MXF) as a model antibiotic drug. GRP-PPY nanoparticles synthesis was performed with a simple and profitable method, leading to the formation of high surface area particles with excellent adsorption properties. Characterization was assessed with various techniques, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET). Box-Behnken experimental design was developed to optimize the adsorption process. Critical parameters such as initial antibiotic concentration, nanoparticle concentration, and pH were investigated. The Freundlich isotherm model provided a good fit to the experimental data, indicating multilayer adsorption of MXF onto the GRP-PPY-NP. As a result, a high adsorption capacity of MXF (92%) was obtained in an optimum condition of preparing 30 μg/mL of the drug to be adsorbed by 1 mg/mL of GRP-PPY-NP in pH 9 within 1 h in a room temperature. Moreover, the regeneration and reusability of GRP-PPY-NP were investigated. They could be effectively regenerated for 3 cycles using appropriate desorption agents without significant loss in adsorption capacity. Overall, this study highlights the power of GRP-PPY-NP as a highly efficient adsorbent for the removal of MXF from wastewater as it is the first time to use this NP for a pharmaceutical product which shows the study's novelty, and the findings provide valuable insights into the development of sustainable and effective wastewater treatment technologies for combating antibiotic contamination in aquatic environments.
Health-SigQOLM is a versatile scale for measuring various aspects of health-related quality of life
Authors: Bujang Mohamad Adam , Lai Wei Hong , Ratnasingam Selvasingam , Tiong Xun Ting , Hon Yoon Khee , Yap Eileen Pin Pin , Jee Yvonne Yih Huan , Ahmad Nurul Fatma Diyana , Kim Alex Ren Jye , Husin Masliyana
Published: June 2024

Objective

The “Health” element is one of the elements in Significant Quality of Life Measure (SigQOLM) that measures quality of life and well-being of people. This study aims to evaluate the Health element (Health-SigQOLM) as a generic and dynamic scale to measure health-related quality of life (HRQOL) with a broader spectrum of coverage. This study used a secondary data that developed SigQOLM. Only the “Health” element with 33 items is used for analysis.

Results

The construct of Health-SigQOLM has a minimum factor loading of 0.425 with excellent model fit. The health status among healthcare workers is significantly associated with the Health-SigQOLM (p < 0.001). The Health-SigQOLM score can clearly distinguish between healthy people and those who have been afflicted with some diseases but have never been hospitalized due to disease progression or other associated complications (p = 0.002). The Health-SigQOLM is a generic and dynamic tool for assessing various aspects of health-related quality of life.
Evaluation of a multifaceted implementation strategy for semi-automated surveillance of surgical site infections after total hip or knee arthroplasty: a multicentre pilot study in the Netherlands
Authors: Brekelmans Manon , Hopmans Titia , van Mourik Maaike , de Greeff Sabine , Swillens Julie , van Rooden Stephanie
Published: June 2024

Introduction

To promote the nation-wide implementation of semi-automated surveillance (AS) of surgical site infection after hip and knee arthroplasty, the Dutch National Institute for Public Health and the Environment (RIVM) deployed a decentralised multifaceted implementation strategy. This strategy consisted of a protocol specifying minimum requirements for an AS system, supported by a user manual, education module, individual guidance for hospitals and user-group meetings. This study describes an effect evaluation and process evaluation of the implementation strategy for AS in five frontrunner hospitals.

Methods

To evaluate the effect of the implementation strategy, the achieved phase of implementation was determined in each frontrunner hospital at the end of the study period. The process evaluation consisted of (1) an evaluation of the feasibility of strategy elements, (2) an evaluation of barriers and facilitators for implementation and (3) an evaluation of the workload for implementation. Interviews were performed as a basis for a subsequent survey quantifying the results regarding the feasibility as well as barriers and facilitators. Workload was self-monitored per profession. Qualitative data were analysed using a framework analysis, whereas quantitative data were analysed descriptively.

Results

One hospital finished the complete implementation process in 240 person-hours. Overall, the elements of the implementation strategy were often used, positively received and overall, the strategy was rated effective and feasible. During the implementation process, participants perceived the relative advantage of AS and had sufficient knowledge about AS. However, barriers regarding complexity of AS data extraction, data-infrastructure, and validation, lack of capacity and motivation at the IT department, and difficulties with assigning roles and responsibilities were experienced.

Conclusion

A decentralised multifaceted implementation strategy is suitable for the implementation of AS in hospitals. Effective local project management, including clear project leadership and ownership, obtaining commitment of higher management levels, active involvement of stakeholders, and appropriate allocation of roles and responsibilities is important for successful implementation and should be facilitated by the implementation strategy. Sufficient knowledge about AS, its requirements and the implementation process should be available among stakeholders by e.g. an education module. Furthermore, exchange of knowledge and experiences between hospitals should be encouraged in user-group meetings.
A fast spectral recovery does not necessarily indicate post-fire forest recovery
Authors: Celebrezze Joe V. , Franz Madeline C. , Andrus Robert A. , Stahl Amanda T. , Steen-Adams Michelle , Meddens Arjan J. H.
Published: June 2024

Background

Climate change has increased wildfire activity in the western USA and limited the capacity for forests to recover post-fire, especially in areas burned at high severity. Land managers urgently need a better understanding of the spatiotemporal variability in natural post-fire forest recovery to plan and implement active recovery projects. In burned areas, post-fire “spectral recovery”, determined by examining the trajectory of multispectral indices (e.g., normalized burn ratio) over time, generally corresponds with recovery of multiple post-fire vegetation types, including trees and shrubs. Field data are essential for deciphering the vegetation types reflected by spectral recovery, yet few studies validate spectral recovery metrics with field data or incorporate spectral recovery into spatial models of post-fire vegetation recovery. We investigated relationships between spectral recovery and field measurements of post-fire recovery (16 to 27 years post-fire) from 99 plots in mixed conifer forests of the Blue Mountains, USA. Additionally, using generalized linear mixed effects models, we assessed the relative capacities of multispectral, climatic, and topographic data to predict field measurements of post-fire recovery.

Results

We found that a fast spectral recovery did not necessarily coincide with field measurements of forest recovery (e.g., density of regenerating seedlings, saplings, and young trees and % juvenile conifer cover). Instead, fast spectral recovery often coincided with increases in % shrub cover. We primarily attributed this relationship to the response of snowbrush ceanothus, an evergreen shrub that vigorously resprouts post-fire. However, in non-trailing edge forests—where it was cooler and wetter and fast-growing conifers were more common—rapid spectral recovery coincided with both increases in % shrub cover and forest recovery. Otherwise, spectral recovery showed potential to identify transitions to grasslands, as grass-dominated sites showcased distinctly slow spectral trajectories. Lastly, field measurements of post-fire forest recovery were best predicted when including post-fire climate and multispectral data in predictive models.

Conclusions

Despite a disconnect between a fast spectral recovery and forest recovery, our results suggest that including multispectral data improved models predicting the likelihood of post-fire forest recovery. Improving predictive models would aid land managers in identifying sites to implement active reforestation projects.

Graphical Abstract

Photo credit: J. Celebrezze
Molecular residual disease (MRD) detection using bespoke circulating tumor DNA (ctDNA) assays in localized soft tissue sarcoma (STS): A multicenter study.
Authors: Alshibany Aisha , Zhou Maggie , Warren Emilie AK , Ganjoo Kristen N. , Demicco Elizabeth , Feeney Jordan , Lee Jasmine , Shultz David Benjamin , Spickard Erik , Bui Nam , Cardona Kenneth , Salawu Abdulazeez , Abdul Razak Albiruni Ryan
Published: June 2024

11537

Background: Surgery and (neo)adjuvant radiotherapy (RT) are the mainstay curative treatments for localized STS. Despite treatment, up to 50% of STS patients experience metastatic relapse, and routine use of adjuvant systemic therapy (AST) remains controversial. The presence of ctDNA following curative-intent treatment of STS is a potential biomarker for MRD and may identify patients who are likely to benefit from AST. Given the genomic heterogeneity of STS, a histology-agnostic approach to ctDNA detection in this population is desirable. Methods: This multicentre prospective study enrolled patients with localized, high-risk (grade ≥ 2, size ≥ 5 cm) STS. Blood samples were collected at diagnosis, post- radiotherapy, post-surgery, and at serial longitudinal time points for up to 2 years. Standard radiologic follow-up was performed concurrently. Whole exome sequencing of tumor tissue was carried out to identify patient-specific, single nucleotide variants. Personalized, and tumor-informed multiplex PCR next-generation sequencing-based ctDNA (Signatera) assays were used to track ctDNA in serial plasma samples. The primary endpoint was ctDNA detection rate of >70% at diagnosis. Secondary endpoints were MRD detection after local therapy and correlation of ctDNA detection with disease relapse. Results: A total of 76 subjects (female n = 43; median age [range]: 58 [21- 84] years) were included in this study from Princess Margaret Cancer Center, Stanford University, and Emory University. The most common STS types observed were leiomyosarcoma (LMS, n = 28), liposarcoma (n = 14), (predominantly dedifferentiated [n = 6]), and myxofibrosarcoma (n = 11). Among 38 pts who had blood samples collected at baseline (time of surgery), ctDNA was positive in 30/38 (79%). A baseline sample prior to radiotherapy was collected in 24 pts. Following neoadjuvant radiotherapy, 8/24 pts (33%) who were ctDNA positive at baseline became ctDNA negative, while 29/30 became ctDNA-negative after surgical resection. Median follow-up was 19 months, and 19/76 pts (25%) experienced disease recurrence Among these 19 pts, ctDNA was detected in all pts with baseline studies. ctDNA was detected at or before radiologic recurrence in 9/19 pts (47%), predominantly LMS 4/9, with a median lead time of 64.8 days (range: 0-197 days). ctDNA was detected in 14/38 patients at baseline with no radiological recurrence during follow-up period. Conclusions: Personalized, tumor-informed ctDNA assays can detect MRD and has prognostic value after definitive therapy, surgery and (neo)adjuvant radiotherapy, in localized STS patients. Additional studies are ongoing to evaluate ctDNA as a predictive biomarker for benefit from AST in STS. Clinical trial information: NCT03818412 .
Symptom burden in adolescents and young adults with cancer: A subgroup analysis of the enhanced, EHR-facilitated cancer symptom control (E2C2) trial.
Authors: Storandt Michael H. , Jin Zhaohui , Kour Oudom , Ruddy Kathryn Jean , Pachman Deirdre R. , Kroenke Kurt , Griffin Joan M. , Austin Jessica , Chlan Linda L. , Cobran Ewan Kemar , Greenmyer Jacob , Grzegorczyk Veronica , Allen-Rhoades Wendy A , Ehlers Shawna L. , Wilder Smith Ashley , Mitchell Sandra A. , Shi Qian , Cheville Andrea L.
Published: June 2024

12065

Background: Incidence of cancer, including colorectal, breast, pancreas, kidney, and uterine cancer, is increasing in younger populations. Adolescents and young adults (AYA, defined as age 15-39) with cancer face unique challenges. This study aimed to characterize how symptom burden differs between AYA and non-AYA (aged 40+) patients with cancer. Methods: We performed a subgroup analysis of the E2C2 study, a cluster-randomized, pragmatic trial examining the effectiveness of routine symptom assessment and guideline-based management on patient-centered and healthcare utilization metrics during and following cancer treatment. Six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue (SPPADE)] were evaluated using 11-point numerical rating scales (NRS). Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of symptom burden among AYA patients (defined as age 18-39 in this study), using their first-reported NRS scores. Results: The E2C2 cohort included 2,598 AYA patients and 38,061 non-AYA patients who completed >1 SPPADE NRS on at least one survey. AYA patients were more likely than non-AYA patients to report severe anxiety ( p<0.0001) and depression ( p<0.0001) (Table). Non-AYA patients were more likely to report severe pain ( p=0.02179), fatigue ( p=0.0022), and physical function limitations ( p<0.0001). Sociodemographic differences were also noted. A higher proportion of AYA patients held a bachelor’s degree or higher (38% vs 28%), were employed (73% vs 37%), and lived in an urban setting (67% vs 56%), compared to non-AYA patients. Non-AYA patients were more likely to have government insurance (63% vs 21%) and to be married (72% vs 59%). Conclusions: AYA patients with cancer were more likely to report severe depression and anxiety compared to their counterparts age 40 and above, underscoring the need for targeted and tailored psycho-oncology care for this population. [Table: see text]