bluuebunny/crossref_metadata_2025 huggingface dataset:
A meta-analysis of the association between vitamin D supplementation and the risk of acute respiratory tract infection in the healthy pediatric group
Authors: Fang Qiongyan , Wu Yingting , Lu Jie , Zheng Huaiyu
Published: June 2023

No previous meta-analysis had explored the association between vitamin D supplementation in healthy pediatrics and the risk of acute respiratory tract infections (ARTIs). Thus, we meta-analyzed the current evidence in this regard to provide sufficient knowledge about this risk-benefit ratio for vitamin D supplementation in this specific age group. We searched seven databases for randomized controlled trials (RCTs) that investigated the effect of vitamin D supplementation and ARTIs risk on a healthy pediatric population (0–18 years old). Meta-analysis was performed through R software. We included eight RCTs after the screening of 326 records according to our eligibility criteria. There were comparable infection rates between Vitamin D and placebo groups (OR = 0.98, 95% CI = 0.90–1.08, P-value = 0.62), with no significant heterogeneity among the included studies (I2 = 32%; P-value = 0.22). Moreover, there was no significant difference between the two vitamin D regimens (OR = 0.85, 95% CI = 0.64–1.12, P-value = 0.32), with no considerable heterogeneity among the included studies (I2 = 37%; P-value = 0.21). However, there was a significant reduction in Influenza A rates in the high-dose vitamin D group compared to the low dose one (OR = 0.39, 95% CI = 0.26–0.59, P-value < 0.001), with no heterogeneity among the included studies (I2 = 0%; P-value = 0.72). Only two studies of 8,972 patients reported different side effects, with overall acceptable safety profile. Regardless of the dosing regimen used or the type of infection, in the healthy pediatric group, there is no evident benefit of using vitamin D to prevent or reduce the ARTI rates.
Structural and physicochemical properties of bracken fern (Pteridium aquilinum) starch
Authors: Li Kehu , Zhang Tongze , Ren Huanhuan , Zhao Wei , Hong Siqi , Ge Yongyi , Li Xiaoqiong , Corke Harold
Published: June 2023

Introduction

Bracken fern (Pteridium aquilinum) starch is a non-mainstream, litter-researched starch, thus the starch characteristics remain largely unknown.

Methods

The structural and physicochemical properties of two bracken starches were systematically investigated, by use of various techniques that routinely applied in starch analysis.

Results and Discussion

The starches had amylose contents of 22.6 and 24.7%, respectively. The starch granules possessed C-type polymorph with D (4,3) ranging from 18.6 to 24.5 μm. During gelatinization event, the bracken starches showed lower viscosity than typical for rice starch, and lower gelatinization temperature than typical for cereal starches. After gelatinization event, bracken starches formed much softer and sticky gel than rice and potato starch. The molecular weight and branching degree (indexed by Mw, Mn and Rz values) of bracken starches were much higher than starches of many other sources. The branch chain length distributions showed that the bracken starches were structurally similar to some rice varieties (e. g. BP033, Beihan 1#), as reflected by proportions of A, B1, B2, and B3 chains. Notable differences in some starch traits between the two bracken starches were recorded, e. g. amylose content, gel hardness, gelatinization temperature and traits of structural properties. This study provides useful information on the utilization of bracken starch in both food and non-food industries.
RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer
Authors: Shang Peipei , Lu Jiongjiong , Song Feihong , Zhao Yijun , Hong Weipeng , He Yuange , Shen Weidong , Geng Li
Published: June 2023

Background

Colorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC.

Methods

Samples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.

Results

This study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.

Conclusion

Collectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.
Pathological complete response to long-course neoadjuvant alectinib in lung adenocarcinoma with EML4-ALK rearrangement: report of two cases and systematic review of case reports
Authors: Shi Liang , Gao Shuhong , Tong Li , Meng Qiyi , Zhou Shijie , Yu Daping , Dong Yujie , Liu Zhe
Published: June 2023

Objective

Despite the promising efficacy and tolerability of alectinib in treating advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC), the role of alectinib in neoadjuvant setting remains understudied in ALK-rearranged resectable lung cancer.

Methods

Our report concerns two cases of early-stage NSCLC with complete pathologic responses to off-label use of long-course neoadjuvant alectinib. PubMed, Web of Science, and Cochrane Library were searched comprehensively for ALK-positive resectable cases with neoadjuvant alectinib. The papers were chosen following PRISMA recommendations. Seven cases from the literature and two present cases were evaluated.

Results

Two cases with stage IIB (cT3N0M0) EML4-ALK lung adenocarcinoma received long-course (more than 30 weeks) of neoadjuvant alectinib followed by R0 lobectomy with the complete pathological response. In our systematic review, 74 studies were included in the original search. Application of the screening criteria resulted in 18 articles deemed eligible for full-text reading. Following the application of the exclusion criteria, out of six papers, seven cases were selected for inclusion in the final analysis and were included in the systematic review. None of the studies were included in the quantitative analysis.

Conclusion

We report two cases of lung adenocarcinoma with resectable ALK-positive that achieved pCR with long-course neoadjuvant alectinib. Our cases and a systematic review of the literature support the feasibility of neoadjuvant alectinib treatment for NSCLC. However, large clinical trials must be conducted in the future to determine the treatment course and efficacy of the neoadjuvant alectinib modality.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022376804.
Prognostic value of computed tomography radiomics features in patients with gastric neuroendocrine neoplasm
Authors: Yang Zhi-hao , Han Yi-jing , Cheng Ming , Wang Rui , Li Jing , Zhao Hui-ping , Gao Jian-bo
Published: June 2023

Purpose

The present study aimed to investigate the clinical prognostic significance of radiomics signature (R-signature) in patients with gastric neuroendocrine neoplasm (GNEN).

Methods and Materials

A retrospective study of 182 patients with GNEN who underwent dual-phase enhanced computed tomography (CT) scanning was conducted. LASSO-Cox regression analysis was used to screen the features and establish the arterial, venous and the arteriovenous phase combined R-signature, respectively. The association between the optimal R-signature with the best prognostic performance and overall survival (OS) was assessed in the training cohort and verified in the validation cohort. Univariate and multivariate Cox regression analysis were used to identify the significant factors of clinicopathological characteristics for OS. Furthermore, the performance of a combined radiomics-clinical nomogram integrating the R-signature and independent clinicopathological risk factors was evaluated.

Results

The arteriovenous phase combined R-signature had the best performance in predicting OS, and its C-index value was better than the independent arterial and venous phase R-signature (0.803 vs 0.784 and 0.803 vs 0.756, P<0.001, respectively). The optimal R-signature was significantly associated with OS in the training cohort and validation cohort. GNEN patients could be successfully divided into high and low prognostic risk groups with radiomics score median. The combined radiomics-clinical nomogram combining this R-signature and independent clinicopathological risk factors (sex, age, treatment methods, T stage, N stage, M stage, tumor boundary, Ki67, CD56) exhibited significant prognostic superiority over clinical nomogram, R-signature alone, and traditional TNM staging system (C-index, 0.882 vs 0.861, 882 vs 0.803, and 0.882 vs 0.870 respectively, P<0.001). All calibration curves showed remarkable consistency between predicted and actual survival, and decision curve analysis verified the usefulness of the combined radiomics-clinical nomogram for clinical practice.

Conclusions

The R-signature could be used to stratify patients with GNEN into high and low risk groups. Furthermore, the combined radiomics-clinical nomogram provided better predictive accuracy than other predictive models and might aid clinicians with therapeutic decision-making and patient counseling.
Adjuvant composite cold atmospheric plasma therapy increases antitumoral effect of doxorubicin hydrochloride
Authors: Kniazeva Volha , Tzerkovsky Dzmitry , Baysal Ömür , Kornev Alexander , Roslyakov Evgeny , Kostevitch Serhei
Published: June 2023

Introduction

Cancer is a global health concern, with a significant impact on mortality rates. Despite advancements in targeted antitumor drugs, the development of new therapies remains challenging due to high costs and tumor resistance. The exploration of novel treatment approaches, such as combined chemotherapy, holds promise for improving the effectiveness of existing antitumor agents. Cold atmospheric plasma has demonstrated antineoplastic effects in preclinical studies, but its potential in combination with specific ions for lymphosarcoma treatment has not been investigated.

Methods

An in vivo study was conducted using a Pliss lymphosarcoma rat model to evaluate the antitumor effects of composite cold plasma and controlled ionic therapy. Groups of rats were exposed to composite cold plasma for 3, 7, and 14 days, while the control group received no treatment. Additionally, a combination of chemotherapy with cold plasma therapy was assessed, with doxorubicin hydrochloride administered at a dosage of 5 mg/kg. PERENIO IONIC SHIELD™ emitted a controlled ionic formula during the treatment period.

Results

The in vivo study demonstrated tumor growth inhibition in groups exposed to composite cold plasma for 3, 7, and 14 days compared to the control group. Furthermore, combining chemotherapy with cold plasma therapy resulted in a threefold reduction in tumor volume. The most significant antitumor effects were observed when doxorubicin hydrochloride at a dosage of 5 mg/kg was combined with 14 days of PERENIO IONIC SHIELD™ ionic therapy.

Discussion

The use of composite cold plasma therapy, in conjunction with a controlled ionic formula emitted by PERENIO IONIC SHIELD™, in the complex treatment of lymphosarcoma in rats showed promising antitumor effects. The combination therapy, particularly when combined with doxorubicin hydrochloride, demonstrated enhanced efficacy. These findings suggest the potential for utilizing cold atmospheric plasma and controlled ions as an adjunctive treatment approach in lymphosarcoma therapy. Further research is warranted to explore the mechanisms underlying these effects and to evaluate the safety and efficacy in human clinical trials.
Molecular and genetic targets within metastatic colorectal cancer and associated novel treatment advancements
Authors: Cann Christopher G. , LaPelusa Michael B. , Cimino Sarah K. , Eng Cathy
Published: June 2023

Colorectal cancer results in the deaths of hundreds of thousands of patients worldwide each year, with incidence expected to rise over the next two decades. In the metastatic setting, cytotoxic therapy options remain limited, which is reflected in the meager improvement of patient survival rates. Therefore, focus has turned to the identification of the mutational composition inherent to colorectal cancers and development of therapeutic targeted agents. Herein, we review the most up to date systemic treatment strategies for metastatic colorectal cancer based on the actionable molecular alterations and genetic profiles of colorectal malignancies.
Using quantitative systems pharmacology modeling to optimize combination therapy of anti-PD-L1 checkpoint inhibitor and T cell engager
Authors: Anbari Samira , Wang Hanwen , Zhang Yu , Wang Jun , Pilvankar Minu , Nickaeen Masoud , Hansel Steven , Popel Aleksander S.
Published: June 2023

Although immune checkpoint blockade therapies have shown evidence of clinical effectiveness in many types of cancer, the outcome of clinical trials shows that very few patients with colorectal cancer benefit from treatments with checkpoint inhibitors. Bispecific T cell engagers (TCEs) are gaining popularity because they can improve patients’ immunological responses by promoting T cell activation. The possibility of combining TCEs with checkpoint inhibitors to increase tumor response and patient survival has been highlighted by preclinical and clinical outcomes. However, identifying predictive biomarkers and optimal dose regimens for individual patients to benefit from combination therapy remains one of the main challenges. In this article, we describe a modular quantitative systems pharmacology (QSP) platform for immuno-oncology that includes specific processes of immune-cancer cell interactions and was created based on published data on colorectal cancer. We generated a virtual patient cohort with the model to conduct in silico virtual clinical trials for combination therapy of a PD-L1 checkpoint inhibitor (atezolizumab) and a bispecific T cell engager (cibisatamab). Using the model calibrated against the clinical trials, we conducted several virtual clinical trials to compare various doses and schedules of administration for two drugs with the goal of therapy optimization. Moreover, we quantified the score of drug synergy for these two drugs to further study the role of the combination therapy.
Proliferative activity of antigen-specific CD154+ T cells against bacterial and fungal respiratory pathogens in cystic fibrosis decreases after initiation of highly effective CFTR modulator therapy
Authors: Eschenhagen Patience N. , Bacher Petra , Grehn Claudia , Mainz Jochen G. , Scheffold Alexander , Schwarz Carsten
Published: June 2023

Background: Together with impaired mucociliary clearance, lung disease in cystic fibrosis (CF) is driven by dysregulation of innate and adaptive immunity caused by dysfunctional CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), leading to airway infection and hyperinflamma-tion. The highly effective CFTR modulator therapy (HEMT) elexacaftor/tezacaftor/ivacaftor (ETI) generates substantial improvements in clinical outcomes of people with CF (pwCF) by restoration of CFTR activity. Aberrant immune responses of lymphocytes due to CFTR dysfunction has been described in the past, but not the effects of CFTR restoration by HEMT on these cells. We aimed to examine the effect of ETI on the proliferative activity of antigen-specific CD154 (+) T cells against bacterial and fungal species relevant in CF and on total IgG and IgE as markers of B cell adaptive immunity.

Methods: We performed ex vivo analyses of Ki-67 expression in antigen-specific CD154 (+) T cells against Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus fumigatus, Scedosporium apiospermum and Candida albicans from 21 pwCF by cytometric assay based on antigen-reactive T cell enrichment (ARTE), and analysis of total serum IgE and IgG before and after initiation of ETI.

Results: Mean Ki-67 expression in antigen-specific CD154 (+) T cells against P. aeruginosa, A. fumigatus, S. apiospermum and C. albicans, but not S. aureus, mean total serum IgG and mean total serum IgE decreased significantly after initiation of ETI. No correlation was found to change in sputum microbiology of the examined pathogens. Mean BMI and FEV1 increased significantly.

Conclusion: HEMT is associated with decreased antigen-specific CD154 (+) T cell proliferation activity in our cohort, independent of findings in sputum microbiology of the examined pathogens. Together with the observed clinical improvement and the decrease in total IgE and IgG, this indicates effects due to CFTR restoration on CD154 (+) T cells by ETI and a reduction of B cell activation with subsequent lower immunoglobulin synthesis under HEMT therapy. These results endorse earlier evidence of CFTR dysfunction in T and B cells leading directly to aberrant immune responses with hyperinflammation.
CL-705G: a novel chemical Kir6.2-specific KATP channel opener
Authors: Gando Ivan , Becerra Flores Manuel , Chen I.-Shan , Yang Hua-Qian , Nakamura Tomoe Y. , Cardozo Timothy J. , Coetzee William A.
Published: June 2023

Background: KATP channels have diverse roles, including regulation of insulin secretion and blood flow, and protection against biological stress responses and are excellent therapeutic targets. Different subclasses of KATP channels exist in various tissue types due to the unique assemblies of specific pore-forming (Kir6.x) and accessory (SURx) subunits. The majority of pharmacological openers and blockers act by binding to SURx and are poorly selective against the various KATP channel subclasses.

Methods and Results: We used 3D models of the Kir6.2/SUR homotetramers based on existing cryo-EM structures of channels in both the open and closed states to identify a potential agonist binding pocket in a functionally critical area of the channel. Computational docking screens of this pocket with the Chembridge Core chemical library of 492,000 drug-like compounds yielded 15 top-ranked “hits”, which were tested for activity against KATP channels using patch clamping and thallium (Tl+) flux assays with a Kir6.2/SUR2A HEK-293 stable cell line. Several of the compounds increased Tl+ fluxes. One of them (CL-705G) opened Kir6.2/SUR2A channels with a similar potency as pinacidil (EC50 of 9 µM and 11 μM, respectively). Remarkably, compound CL-705G had no or minimal effects on other Kir channels, including Kir6.1/SUR2B, Kir2.1, or Kir3.1/Kir3.4 channels, or Na+ currents of TE671 medulloblastoma cells. CL-705G activated Kir6.2Δ36 in the presence of SUR2A, but not when expressed by itself. CL-705G activated Kir6.2/SUR2A channels even after PIP2 depletion. The compound has cardioprotective effects in a cellular model of pharmacological preconditioning. It also partially rescued activity of the gating-defective Kir6.2-R301C mutant that is associated with congenital hyperinsulinism.

Conclusion: CL-705G is a new Kir6.2 opener with little cross-reactivity with other channels tested, including the structurally similar Kir6.1. This, to our knowledge, is the first Kir-specific channel opener.
Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation
Authors: Yuen Jason , Goyal Abhinav , Rusheen Aaron E. , Kouzani Abbas Z. , Berk Michael , Kim Jee Hyun , Tye Susannah J. , Abulseoud Osama A. , Oesterle Tyler S. , Blaha Charles D. , Bennet Kevin E. , Lee Kendall H. , Oh Yoonbae , Shin Hojin
Published: June 2023

Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone.

Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.).

Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min−1 vs. 67.9 ± 8.3 min−1; pre- vs. post-oxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min−1 vs. 105.2 ± 4.1 min−1; pre- vs. post-oxycodone; p = 0.072).

Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction.
Deciphering the role of NETosis-related signatures in the prognosis and immunotherapy of soft-tissue sarcoma using machine learning
Authors: Qi Lin , Chen Fangyue , Wang Lu , Yang Zhimin , Zhang Wenchao , Li Zhihong
Published: June 2023

Background: Soft-tissue sarcomas (STSs) are a rare type of cancer, accounting for about 1% of all adult cancers. Treatments for STSs can be difficult to implement because of their diverse histological and molecular features, which lead to variations in tumor behavior and response to therapy. Despite the growing importance of NETosis in cancer diagnosis and treatment, researches on its role in STSs remain limited compared to other cancer types.

Methods: The study thoroughly investigated NETosis-related genes (NRGs) in STSs using large cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine Recursive Feature Elimination (SVM-RFE) were employed for screening NRGs. Utilizing single-cell RNA-seq (scRNA-seq) dataset, we elucidated the expression profiles of NRGs within distinct cellular subpopulations. Several NRGs were validated by quantitative PCR (qPCR) and our proprietary sequencing data. To ascertain the impact of NRGs on the sarcoma phenotype, we conducted a series of in vitro experimental investigations. Employing unsupervised consensus clustering analysis, we established the NETosis clusters and respective NETosis subtypes. By analyzing DEGs between NETosis clusters, an NETosis scoring system was developed.

Results: By comparing the outcomes obtained from LASSO regression analysis and SVM-RFE, 17 common NRGs were identified. The expression levels of the majority of NRGs exhibited notable dissimilarities between STS and normal tissues. The correlation with immune cell infiltration were demonstrated by the network comprising 17 NRGs. Patients within various NETosis clusters and subtypes exhibited different clinical and biological features. The prognostic and immune cell infiltration predictive capabilities of the scoring system were deemed efficient. Furthermore, the scoring system demonstrated potential for predicting immunotherapy response.

Conclusion: The current study presents a systematic analysis of NETosis-related gene patterns in STS. The results of our study highlight the critical role NRGs play in tumor biology and the potential for personalized therapeutic approaches through the application of the NETosis score model in STS patients.
Relationship between hyperlipidemia and the risk of death in aneurysm: a cohort study on patients of different ages, genders, and aneurysm locations
Authors: Ding Dianzhu , Yang Yongbin , Jiang Guangwei , Peng Yanhui
Published: June 2023

Aims: The study aimed to assess the association of hyperlipidemia and the risk of death in the aneurysm population, focusing on age, gender, and aneurysm location differences.

Methods: All patients’ data on this retrospective cohort study were obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database, and the baseline characteristics and laboratory parameters of all patients were collected. The COX regression model was established to explore the association of hyperlipidemia and the risk of death for patients with aneurysms. More importantly, subgroup analyses based on the age, gender, and aneurysm location differences were performed.

Results: A total of 1,645 eligible patients were enrolled in this study. These patients were divided into the survival group (n = 1,098) and the death group (n = 547), with a total mortality rate of approximately 33.25%. The result displayed that hyperlipidemia was associated with a decreased death risk in aneurysm patients. In addition, we also found that hyperlipidemia was associated with a lower death risk of abdominal aortic aneurysm and thoracic aortic arch aneurysm among aneurysm patients aged ≥60 years; hyperlipidemia was only a protective factor for the death risk of male patients diagnosed with abdominal aortic aneurysm. For female patients diagnosed with abdominal aortic aneurysm and thoracic aortic arch aneurysm, hyperlipidemia was associated with a decreased death risk.

Conclusion: The relationship of hyperlipidemia, hypercholesterolemia, and the risk of death for patients diagnosed with aneurysms was significantly associated with age, gender, and aneurysm location.
The eNAMPT/TLR4 inflammatory cascade drives the severity of intra-amniotic inflammation in pregnancy and predicts infant outcomes
Authors: Ahmed Mohamed , Casanova Nancy G. , Zaghloul Nahla , Gupta Akash , Rodriguez Marisela , Robbins Ian R. , Kempf Carrie L. , Sun Xiaoguang , Song Jin H. , Hernon Vivian Reyes , Sammani Saad , Camp Sara M. , Moreira Alvaro , Hsu Chaur-Dong , Garcia Joe G. N.
Published: June 2023

Introduction: Intra-amniotic inflammation (IAI) or chorioamnionitis is a common complication of pregnancy producing significant maternal morbidity/mortality, premature birth and neonatal risk of chronic lung diseases such as bronchopulmonary dysplasia (BPD). We examined eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a critical inflammatory DAMP and TLR4 ligand, as a potential therapeutic target to reduce IAI severity and improve adverse fetal/neonatal outcomes.

Methods: Blood/tissue samples were examined in: 1) women with histologically-proven chorioamnionitis, 2) very low birth weight (VLBW) neonates, and 3) a preclinical murine pregnancy model of IAI. Groups of pregnant IAI-exposed mice and pups were treated with an eNAMPT-neutralizing mAb.

Results: Human placentas from women with histologically-proven chorioamnionitis exhibited dramatic NAMPT expression compared to placentas without chorioamnionitis. Increased NAMPT expression in whole blood from VLBW neonates (day 5) significantly predicted BPD development. Compared to untreated LPS-challenged murine dams (gestational day 15), pups born to eNAMPT mAb-treated dams (gestational days 15/16) exhibited a > 3-fold improved survival, reduced neonate lung eNAMPT/cytokine levels, and reduced development and severity of BPD and pulmonary hypertension (PH) following postnatal exposure to 100% hyperoxia days 1–14. Genome-wide gene expression studies of maternal uterine and neonatal cardiac tissues corroborated eNAMPT mAb-induced reductions in inflammatory pathway genes.

Discussion: The eNAMPT/TLR4 inflammatory pathway is a highly druggable contributor to IAI pathobiology during pregnancy with the eNAMPT-neutralizing mAb a novel therapeutic strategy to decrease premature delivery and improve short- and long-term neonatal outcomes. eNAMPT blood expression is a potential biomarker for early prediction of chronic lung disease among premature neonates.
Nitrogen sources differentially affect respiration, growth, and carbon allocation in Andean and Lowland ecotypes of Chenopodium quinoa Willd
Authors: Jerez María Paz , Ortiz José , Castro Catalina , Escobar Elizabeth , Sanhueza Carolina , Del-Saz Néstor Fernández , Ribas-Carbo Miquel , Coba de la Peña Teodoro , Ostria-Gallardo Enrique , Fischer Susana , Castro Patricio Alejandro , Bascunan-Godoy Luisa
Published: June 2023

Chenopodium quinoa Willd. is a native species that originated in the High Andes plateau (Altiplano) and its cultivation spread out to the south of Chile. Because of the different edaphoclimatic characteristics of both regions, soils from Altiplano accumulated higher levels of nitrate (NO3−) than in the south of Chile, where soils favor ammonium (NH4+) accumulation. To elucidate whether C. quinoa ecotypes differ in several physiological and biochemical parameters related to their capacity to assimilate NO3− and NH4+, juvenile plants of Socaire (from Altiplano) and Faro (from Lowland/South of Chile) were grown under different sources of N (NO3− or NH4+). Measurements of photosynthesis and foliar oxygen-isotope fractionation were carried out, together with biochemical analyses, as proxies for the analysis of plant performance or sensitivity to NH4+. Overall, while NH4+ reduced the growth of Socaire, it induced higher biomass productivity and increased protein synthesis, oxygen consumption, and cytochrome oxidase activity in Faro. We discussed that ATP yield from respiration in Faro could promote protein production from assimilated NH4+ to benefit its growth. The characterization of this differential sensitivity of both quinoa ecotypes for NH4+ contributes to a better understanding of nutritional aspects driving plant primary productivity.
Variation in supplemental lighting quality influences key aroma volatiles in hydroponically grown ‘Italian Large Leaf’ basil
Authors: Hammock Hunter A. , Sams Carl E.
Published: June 2023

The spectral quality of supplemental greenhouse lighting can directly influence aroma volatiles and secondary metabolic resource allocation (i.e., specific compounds and classes of compounds). Research is needed to determine species-specific secondary metabolic responses to supplemental lighting (SL) sources with an emphasis on variations in spectral quality. The primary objective of this experiment was to determine the impact of supplemental narrowband blue (B) and red (R) LED lighting ratios and discrete wavelengths on flavor volatiles in hydroponic basil (Ocimum basilicum var. Italian Large Leaf). A natural light (NL) control and different broadband lighting sources were also evaluated to establish the impact of adding discrete and broadband supplements to the ambient solar spectrum. Each SL treatment provided 8.64 mol.m-2.d-1 (100 µmol.m-2.s-1, 24 h.d-1) photon flux. The daily light integral (DLI) of the NL control averaged 11.75 mol.m-2.d-1 during the growth period (ranging from 4 to 20 mol.m-2.d-1). Basil plants were harvested 45 d after seeding. Using GC-MS, we explored, identified, and quantified several important volatile organic compounds (VOCs) with known influence on sensory perception and/or plant physiological processes of sweet basil. We found that the spectral quality from SL sources, in addition to changes in the spectra and DLI of ambient sunlight across growing seasons, directly influence basil aroma volatile concentrations. Further, we found that specific ratios of narrowband B/R wavelengths, combinations of discrete narrowband wavelengths, and broadband wavelengths directly and differentially influence the overall aroma profile as well as specific compounds. Based on the results of this study, we recommend supplemental 450 and 660 nm (± 20 nm) wavelengths at a ratio of approximately 10B/90R at 100-200 µmol.m-2.s-1, 12-24 h.d-1 for sweet basil grown under standard greenhouse conditions, with direct consideration of the natural solar spectrum and DLI provided for any given location and growing season. This experiment demonstrates the ability to use discrete narrowband wavelengths to augment the natural solar spectrum to provide an optimal light environment across variable growing seasons. Future experiments should investigate SL spectral quality for the optimization of sensory compounds in other high-value specialty crops.
Metabolomics and transcriptomics analyses provide new insights into the nutritional quality during the endosperm development of different ploidy rice
Authors: Xian Lin , Tian Jiaqi , Long Yanxi , Ma Huijin , Tian Min , Liu Xiangdong , Yin Guoying , Wang Lan
Published: June 2023

Autotetraploid rice is developed from diploid rice by doubling the chromosomes, leading to higher nutritional quality. Nevertheless, there is little information about the abundances of different metabolites and their changes during endosperm development in autotetraploid rice. In this research, two different kinds of rice, autotetraploid rice (AJNT-4x) and diploid rice (AJNT-2x), were subjected to experiments at various time points during endosperm development. A total of 422 differential metabolites, were identified by applying a widely used metabolomics technique based on LC-MS/MS. KEGG classification and enrichment analysis showed the differences in metabolites were primarily related to biosynthesis of secondary metabolites, microbial metabolism in diverse environments, biosynthesis of cofactors, and so on. Twenty common differential metabolites were found at three developmental stages of 10, 15 and 20 DAFs, which were considered the key metabolites. To identify the regulatory genes of metabolites, the experimental material was subjected to transcriptome sequencing. The DEGs were mainly enriched in starch and sucrose metabolism at 10 DAF, and in ribosome and biosynthesis of amino acids at 15 DAF, and in biosynthesis of secondary metabolites at 20 DAF. The numbers of enriched pathways and the DEGs gradually increased with endosperm development of rice. The related metabolic pathways of rice nutritional quality are cysteine and methionine metabolism, tryptophan metabolism, lysine biosynthesis and histidine metabolism, and so on. The expression level of the genes regulating lysine content was higher in AJNT-4x than in AJNT-2x. By applying CRISPR/Cas9 gene-editing technology, we identified two novel genes, OsLC4 and OsLC3, negatively regulated lysine content. These findings offer novel insight into dynamic metabolites and genes expression variations during endosperm development of different ploidy rice, which will aid in the creation of rice varieties with better grain nutritional quality.
Students managing work and study role boundaries: a person-centred approach
Authors: Creed Peter A. , Hood Michelle , Bialocerkowski Andrea , Machin M. Anthony , Brough Paula , Kim Sujin , Winterbotham Sonya , Eastgate Lindsay
Published: June 2023

To cope with demands of working while studying, students must structure the boundaries between these roles (e.g., integrate or segment them) to suit their preferences and circumstances. However, students differ on how well they do this, and we do not yet understand the factors that contribute to managing work and study well. We sought to determine if different student groups existed and if the groups reported different work, study, and wellbeing outcomes. Using latent profile analysis and assessing work-study boundary congruence and flexibility (N = 808; 76% female; MAge 19.6 years), we identified four groups of (a) “balanced” (65.4%; with moderate boundary congruence and flexibility); (b) “high work congruence and flexibility” (17.5%; working arrangements supportive of study role); (c) “low work congruence and flexibility” (9.7%; unsupportive workplace arrangements); and (d) “low study congruence” (7.3%; study arrangements unsupportive of work role). These groups reported different work/study demands, role conflict, study burnout, and perceived employability, with “balanced” and “high work congruence and flexibility” groups scoring more positively and “low work congruence and flexibility” and “low study congruence” groups scoring more negatively. Results supported that different student groups existed, and these will need different supports to manage their multiple role responsibilities.
Computing within-study covariances, data visualization, and missing data solutions for multivariate meta-analysis with metavcov
Authors: Lu Min
Published: June 2023

Multivariate meta-analysis (MMA) is a powerful statistical technique that can provide more reliable and informative results than traditional univariate meta-analysis, which allows for comparisons across outcomes with increased statistical power. However, implementing appropriate statistical methods for MMA can be challenging due to the requirement of various specific tasks in data preparation. The metavcov package aims for model preparation, data visualization, and missing data solutions to provide tools for different methods that cannot be found in accessible software. It provides sufficient constructs for estimating coefficients from other well-established packages. For model preparation, users can compute both effect sizes of various types and their variance-covariance matrices, including correlation coefficients, standardized mean difference, mean difference, log odds ratio, log risk ratio, and risk difference. The package provides a tool to plot the confidence intervals for the primary studies and the overall estimates. When specific effect sizes are missing, single imputation is available in the model preparation stage; a multiple imputation method is also available for pooling the results in a statistically principled manner from models of users' choice. The package is demonstrated in two real data applications and a simulation study to assess methods for handling missing data.
Analysis of the influences of social isolation on cognition and the therapeutic potential of deep brain stimulation in a mouse model
Authors: Hu Yun-Yun , Ding Xuan-Si , Yang Gang , Liang Xue-Song , Feng Lei , Sun Yan-Yun , Chen Rui , Ma Quan-Hong
Published: June 2023

Background

Social interaction is a fundamental human need. Social isolation (SI) can have negative effects on both emotional and cognitive function. However, it is currently unclear how age and the duration of SI affect emotion and recognition function. In addition, there is no specific treatment for the effects of SI.

Methods

The adolescence or adult mice were individually housed in cages for 1, 6 or 12 months and for 2 months to estabolish SI mouse model. We investigated the effects of SI on behavior in mice at different ages and under distinct durations of SI, and we explored the possible underlying mechanisms. Then we performed deep brain stimulation (DBS) to evaluate its influences on SI induced behavioral abnormalities.

Results

We found that social recognition was affected in the short term, while social preference was damaged by extremely long periods of SI. In addition to affecting social memory, SI also affects emotion, short-term spatial ability and learning willingness in mice. Myelin was decreased significantly in the medial prefrontal cortex (mPFC) and dorsal hippocampus of socially isolated mice. Cellular activity in response to social stimulation in both areas was impaired by social isolation. By stimulating the mPFC using DBS, we found that DBS alleviated cellular activation disorders in the mPFC after long-term SI and improved social preference in mice.

Conclusion

Our results suggest that the therapeutic potential of stimulating the mPFC with DBS in individuals with social preference deficits caused by long-term social isolation, as well as the effects of DBS on the cellular activity and density of OPCs.
Associations of the perceived benefits and harms of COVID-19 with confidence in coping with the pandemic and mental health symptoms: a population-based survey in Hong Kong
Authors: Yao Ying , Gong Wei Jie , Lai Agnes Yuen Kwan , Wu Yongda Socrates , Sit Shirley Man Man , Wang Man Ping , Ho Sai Yin , Lam Tai Hing
Published: June 2023

Introduction

Both perceived benefits and harms of COVID-19 have been reported, but whether they affect confidence in coping with the pandemic and mental health remains uncertain.

Objective

To examine the association of perceived benefits and harms of COVID-19 with confidence in coping with the pandemic and mental health symptoms.

Methods

A population-based survey was conducted on 7,535 Hong Kong adults from 22 February to 23 March 2021, when the 4th wave of COVID-19 was under control. Information on sociodemographic characteristics, perceived benefits (10 options) and harms (12 options) of COVID-19, confidence in coping with the pandemic (range 0–10), loneliness (range 0–4), anxiety (General Anxiety Disorders-2, range 0–6) and depression (Patient Health Questionnaire-2, range 0–6) was collected. Latent profile analysis was used to identify the combined patterns of perceived benefits and harms of COVID-19. The associations of combined patterns with confidence in coping with COVID-19, loneliness, anxiety, and depression were examined using linear regression (β coefficient) adjusting for sociodemographic characteristics.

Results

The combined patterns of perceived benefits and harms were classified into benefit (n = 4,338, 59.3%), harm (n = 995, 14.0%), and ambivalent (n = 2,202, 26.7%) groups. Compared with the ambivalent group, the benefit group had a significantly higher level of confidence (adjusted β 0.46, 95% CI 0.33 to 0.58), and lower levels of loneliness (−0.35, −0.40 to-0.29), anxiety (−0.67, 0.76 to-0.59), and depression (−0.65, −0.73 to-0.57). The harm group had a significantly lower level of confidence (−0.35, −0.53 to-0.16), and higher levels of loneliness (0.38, 0.30 to 0.45), anxiety (0.84, 0.73 to 0.96), and depression (0.95, 0.84 to 1.07).

Conclusion

Perceived greater benefit from COVID-19 was associated with better mental health and stronger confidence in coping with the pandemic.
The implementation of community-based programs in Vietnam is promising in promoting health
Authors: Pardoel Zinzi E. , Reijneveld Sijmen A. , Lensink Robert , Postma Maarten , Thuy Tran B. , Viet Nga C. , Phuong Lien N. T. , Koot Jaap A. R. , Landsman Jeanet J. A.
Published: June 2023

Background

Low-and middle-income countries mostly have ageing populations with many unmet economic, social, or health-related needs, Vietnam being an example. Community-based support in Vietnam, organized as Intergenerational Self-Help Clubs (ISHCs) based on the Older People Associations (OPA) model, can help to meet these needs by the provision of services for various aspects of life. This study aims to assess the implementation of the ISHCs and whether successful implementation is associated with more member-reported positive health.

Methods

We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to evaluate the implementation using multiple data sources: ISHC board surveys (n = 97), ISHC member surveys (n = 5,080 in 2019 and n = 5,555 in 2020), focus group discussions (6; n = 44), and interviews with members and board leaders (n = 4).

Results

Reach ranged between 46 and 83% of ISHCs reaching target groups, with a majority of women and older people participating. Regarding Effectiveness, members indicated high satisfaction with the ISHCs. Adoption scores were high, with 74%–99% for healthcare and community support activities, and in 2019, higher adoption scores were associated with more members reporting good positive health. In 2020, reported positive health slightly decreased, probably due to the influence of the COVID-19 pandemic. A total of 61 ISHCs had consistent or improving Implementation from 2019 to 2020, and confidence in Maintenance was high.

Conclusion

The implementation of the OPA model in Vietnam is promising regarding its promotion of health and may help to tackle the needs of an ageing population. This study further shows that the RE-AIM framework helps to assess community health promotion approaches.
Trends in antimicrobial susceptibility patterns of bacterial isolates in Lahore, Pakistan
Authors: Khalid Nauman , Akbar Zunaira , Mustafa Nosheen , Akbar Jamshaid , Saeed Shanawar , Saleem Zikria
Published: June 2023

Background

Antimicrobial resistance (AMR) has provoked a global health issue. Antimicrobial stewardship programs should be implemented to overcome this issue. The aim of this study was to determine the sensitivity patterns of the WHO Access, Watch, Reserve (AWaRe) group of antibiotics that assists in the selection of appropriate empiric antibiotic therapies.

Method

A descriptive, cross-sectional study was conducted for 6 months, in which 422 culture sensitivity sample reports from the Ghurki Trust Teaching Hospital’s laboratory were obtained through a convenience sampling technique, and the sensitivity patterns of nine offending bacteria to the WHO AWaRe group antibiotics were determined. Descriptive statistics and differences in frequency distribution among the categorical variables were obtained using the Statistical Package for Social Sciences (SPSS) software, version 21.

Results

Among 422 culture sensitivity sample reports,Escherichia coli(16.1%) was the most common Gram-negative pathogen.Acinetobacter, E. coli, Klebsiella, andPseudomonasshowed 100% sensitivity to polymyxin-b and colistin.Proteusshowed the highest sensitivity to meropenem (90%),Staphylococcus aureusshowed a 98% sensitivity to linezolid,Staphylococcus epidermidiswas 100% sensitive to vancomycin and linezolid, andStreptococcusshowed the highest sensitivity to penicillin (100%) and vancomycin (94.7%). Polymyxin b and colistin were found to be the most effective antibiotics against Gram-negative bacteria (100%). Gram-positive bacteria were highly sensitive to linezolid (99.4%), vancomycin (98.2%), chloramphenicol (89.5%), and tigecycline (82.6%).

Conclusion

Culture sensitivity reports help to rationalize the empirical use of antibiotics in clinical practice in addressing the challenge of antimicrobial resistance. This study showed that polymyxin-b and colistin were the most effective antibiotics against Gram-negative isolates and that Gram-positive bacteria were highly susceptible to linezolid. Updated antibiograms should be used by clinicians to evaluate bacterial susceptibility patterns and rationalize antibiotic empiric therapy.