bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal effect of iron status on lung function: A Mendelian randomization study
Authors: Yu Zhimin , Xu Chengkai , Fang Chenggang , Zhang Fangfang 
Published: December 2022

BackgroundThe association between systemic iron status and lung function was conflicting in observational studies. We aim to explore the potential causal relationships between iron status and the levels of lung function using the two-sample Mendelian randomization (MR) design.MethodsGenetic instruments associated with iron status biomarkers were retrieved from the Genetics of Iron Status (GIS) consortium (N = 48,972). Summary statistics of these genetic instruments with lung function were extracted from a meta-analysis of UK Biobank and SpiroMeta consortium (N = 400,102). The main analyses were performed using the inverse-variance weighted method, and complemented by multiple sensitivity analyses.ResultsBased on conservative genetic instruments, MR analyses showed that genetically predicted higher iron (beta: 0.036 per 1 SD increase, 95% confidence interval (CI): 0.016 to 0.056, P = 3.51 × 10−4), log10-transformed ferritin (beta: 0.081, 95% CI: 0.047 to 0.116, P = 4.11 × 10−6), and transferrin saturation (beta: 0.027, 95% CI: 0.015 to 0.038, P = 1.09 × 10−5) were associated with increased forced expiratory volume in 1 s (FEV1), whereas higher transferrin was associated with decreased FEV1 (beta: −0.036, 95% CI: −0.064 to −0.008, P = 0.01). A significant positive association between iron status and forced vital capacity (FVC) was also observed. However, there is no causal association between iron status and FEV1-to-FVC ratio (P = 0.10). Similar results were obtained from the liberal instruments analyses and multiple sensitivity analyses.ConclusionOur study provided strong evidence to support that higher iron status is causally associated with higher levels of FEV1 and FVC, but has no impact on airway obstruction, confirming iron status as an important target for lung function management.
Socioeconomic determinants and inequalities in exclusive breastfeeding among children in Peru
Authors: Hernández-Vásquez Akram , Vargas-Fernández Rodrigo 
Published: December 2022

IntroductionAlthough Latin America and the Caribbean have one of the highest prevalences of exclusive breastfeeding (EBF), the countries in this region have socioeconomic determinants that influence the frequency of this practice and do not allow achieving the 70% target recommended by the World Health Organization. Therefore, the objective of the study was to examine the socioeconomic determinants and perform a decomposition analysis of socioeconomic inequalities in EBF in Peruvian children 6 to 59 months of age.MethodsA cross-sectional study was carried out using the 2021 Demographic and Family Health Survey. The dependent variable for the study was EBF up to 6 months of age and the wealth index variable was used to perform the inequality analysis. Poisson log generalized linear regression models were fitted to evaluate the association between EBF and the independent variables, and concentration curves and Erreygers concentration index decomposition were used to analyze inequalities in EBF.ResultsA total of 9926 surveyed participants were included. The prevalence of EBF was 70.5% (95% confidence interval: 69.2-71.8). Women who were married, self-identified as native, received EBF training, resided in the highlands and jungle, and their child was the second or older showed a higher likelihood of EBF. In the inequality analysis, EBF was concentrated among the poorest mothers and the major contributors were residing in the highlands and jungle and belonging to the middle and wealthy quintiles.DiscussionOur findings suggest that the main strategies to encourage the practice of EBF should be focused on all mothers regardless of their socioeconomic status in order to reduce the EBF gap between richer and poorer women.
Phytochemical and antioxidant screening of Moringa oleifera for its utilization in the management of hepatic injury
Authors: Younis Noor , Khan Muhammad Issa , Zahoor Tahir , Faisal Muhammad Naeem 
Published: December 2022

IntroductionPhytochemicals present in Moringa oleifera (M. oleifera) leaves have performed several physiological functions in human system such as anticarcinogenic, antidiabetic, antioxidant, immunomodulatory, hepatoprotective and antiatherogenic functions.MethodsPhytochemical and antioxidant potential of M. oleifera leaves extracts were measured. Histopathology, biochemical analysis, and gene expression tests were performed on serum, blood, and liver in animal model.Results and discussionsThe toxic dose of N-acetyl-para-aminophenol (APAP) induced severe structural and functional changes in liver. Pre-treatment with M. oleifera ameliorated organ injury by normalizing the level of liver biomarkers and serum proteins. A low expression level of MAPK-8, TRAF-4, and TRAF-6 genes was observed in the M. oleifera treated group in comparison to positive control (hepatotoxic rats). M. oleifera leaves pretreatment amended APAP induced apoptosis and replenished hepatic cells. M. oleifera leaves extract as low-cost and sustainable treatment could be used in pharmaceutical industry for reducing hepatic degenerative changes in non-communicable diseases.
Investigation of M2 macrophage-related gene affecting patients prognosis and drug sensitivity in non-small cell lung cancer: Evidence from bioinformatic and experiments
Authors: Zeng Zhen , Yu Jiachen , Yang Zhuo , Du Kangming , Chen Yuewei , Zhou Lei 
Published: December 2022

BackgroundThe progression process of lung cancer can be accelerated by M2 macrophages. However, genes that affect M2 macrophage polarization remain unidentified.MethodsThe Cancer Genome Atlas, Gene Expression Omnibus, and Arrayexpress databases were used to obtain open-access data. The analysis of public data was mostly performed with R studio. The RNA levels of specific genes were detected using quantitative real-time PCR. The proliferation ability of the cells was assessed by CCK8, colony formation, and EdU assays.ResultsBased on the multiple datasets, we noticed a poor prognosis in patients with high M2 macrophage infiltration. There were 114 genes differentially expressed between high and low M2 macrophages infiltrated samples, regarded as M2 macrophage-related genes. Subsequently, a prognosis prediction signature consisting of ABHD5, HS3ST2, TM6SF1, CAPZA2, LEPROT, HNMT, and MRO was identified and presented a satisfactory performance. The pathway enrichment results revealed a positive correlation between riskscore and enrichment scores for most immunotherapy-related positive terms. Also, there might be an increase in genomic instability among patients at high risk. Interestingly, low risk patients are most likely to benefit from PD-1 therapy, while high risk patients may benefit from CTLA-4 therapy. Meanwhile, the estimated IC50 of seven drugs differs significantly between two risk groups, including Cisplatin, Docetaxel, Doxorubicin, Gefitinib, Paclitaxel, Sunitinib and Vinorelbine. Moreover, further experiments indicated that HNMT was overexpressed and can enhance the proliferation ability in lung cancer cells.ConclusionsIn summary, our study identified the molecules significantly affecting M2 macrophage infiltration and identified a prognosis signature that robustly indicated patients prognosis. Moreover, we validated the cancer-promoting effect of HNMT using in vitro experiments.
Effect of clinical decision support systems on emergency medicine physicians' decision-making: A pilot scenario-based simulation study
Authors: Assadi Azadeh , Laussen Peter C. , Freire Gabrielle , Ghassemi Marzyeh , Trbovich Patricia C. 
Published: December 2022

Background and objectivesChildren with congenital heart disease (CHD) are predisposed to rapid deterioration in the face of common childhood illnesses. When they present to their local emergency departments (ED) with acute illness, rapid and accurate diagnosis and treatment is crucial to recovery and survival. Previous studies have shown that ED physicians are uncomfortable caring for patients with CHD and there is a lack of actionable guidance to aid in their decision making. To support ED physicians' key decision components (sensemaking, anticipation, and managing complexity) when managing CHD patients, a Clinical Decision Support System (CDSS) was previously designed. This pilot study evaluates the effect of this CDSS on ED physicians' decision making compared to usual care without clinical decision support.MethodsIn a pilot scenario-based simulation study with repeated measures, ED physicians managed mock CHD patients with and without the CDSS. We compared ED physicians' CHD-specific and general decision-making processes (e.g., recognizing sepsis, starting antibiotics, and managing symptoms) with and without the use of CDSS. The frequency of participants' utterances related to each key decision components of sensemaking, anticipation, and managing complexity were coded and statistically analyzed for significance.ResultsAcross all decision-making components, the CDSS significantly increased ED physicians' frequency of “CHD specific utterances” (Mean = 5.43, 95%CI: 3.7–7.2) compared to the without CDSS condition (Mean = 2.05, 95%CI: 0.3–3.8) whereas there was no significant difference in frequencies of “general utterances” when using CDSS (Mean = 4.62, 95%CI: 3.1–6.1) compared to without CDSS (Mean = 5.14 95%CI: 4.4–5.9).ConclusionA CDSS that integrates key decision-making components (sensemaking, anticipation, and managing complexity) can trigger and enrich communication between clinicians and enhance the clinical management of CHD patients. For patients with complex and subspecialized diseases such as CHD, a well-designed CDSS can become part of a multifaceted solution that includes knowledge translation, broader communication around interpretation of information, and access to additional expertise to support CHD specific decision-making.
Hydrogen sulfide alleviates uremic cardiomyopathy by regulating PI3K/PKB/mTOR-mediated overactive autophagy in 5/6 nephrectomy mice
Authors: Feng Jianan , Li Han , Wang Shixiang 
Published: December 2022

The gasotransmitter hydrogen sulfide (H2S) plays important physiological and pathological roles in the cardiovascular system. However, the involvement of H2S in recovery from uremic cardiomyopathy (UCM) remains unclear. This study aimed to determine the therapeutic efficacy and elucidate the underlying mechanisms of H2S in UCM. A UCM model was established by 5/6 nephrectomy in 10-week-old C57BL/6 mice. Mice were treated with sodium hydrosulfide (NaHS, H2S donor), L-cysteine [L-Cys, cystathionine gamma-lyase (CSE) substrate], and propargylglycine (PPG, CSE inhibitor). Treatment of H9C2 cardiomyocytes utilized different concentrations of uremic serum, NaHS, PPG, and PI3K inhibitors (LY294002). Mouse heart function was assessed by echocardiography. Pathological changes in mouse myocardial tissue were identified using hematoxylin and eosin and Masson’s trichrome staining. Cell viability was assessed using the Cell Counting Kit-8. The protein expressions of CSE, p-PI3K, PI3K, p-PKB, PKB, p-mTOR, mTOR, and autophagy-related markers (Beclin-1, P62, and LC3) were detected using Western blotting. We found that NaHS and L-Cys treatment attenuated myocardial disarray, fibrosis, and left ventricular dysfunction in UCM mice. These abnormalities were further aggravated by PPG supplementation. Enhanced autophagy and decreased phosphorylation of PI3K, PKB, and mTOR protein expression by UCM were altered by NaHS and L-Cys treatment. In vitro, uremic serum increased overactive autophagy and decreased the phosphorylation levels of PI3K, PKB, and mTOR in cardiomyocytes, which was substantially exacerbated by endogenous H2S deficiency and attenuated by pre-treatment with 100 µm NaHS. However, the protective effects of NaHS were completely inhibited by LY294002. These findings support a protective effect of H2S exerted against UCM by reducing overactive autophagy through activation of the PI3K/PKB/mTOR pathway.
The effect of a long-term treatment with cannabidiol-rich hemp extract oil on the adenosinergic system of the zucker diabetic fatty (ZDF) rat atrium
Authors: Viczjan Gabor , Szilagyi Anna , Takacs Barbara , Ovari Ignac , Szekeres Reka , Tarjanyi Vera , Erdei Tamas , Teleki Vanda , Zsuga Judit , Szilvassy Zoltan , Juhasz Bela , Varga Balazs , Gesztelyi Rudolf 
Published: December 2022

Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle via gavage for 4 weeks. We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one. In contrast, adenosine, a quickly metabolized and transported adenosine receptor agonist, evoked a significantly stronger response in the CBD-treated group than in the vehicle-treated counterpart (excepting its highest concentrations). These results can be explained only with the adenosine transport inhibitory property of CBD (and not with its adenosine receptor agonist activity). If all the effects of CBD are attributed to the interstitial adenosine accumulation caused by CBD in the myocardium, then a significantly increased adenosinergic activation can be assumed during the long-term oral CBD treatment, suggesting a considerably enhanced adenosinergic protection in the heart. Considering that our results may have been influenced by A1 adenosine receptor downregulation due to the chronic interstitial adenosine accumulation, an adenosinergic activation smaller than it seemed cannot be excluded, but it was above the CBD-naïve level in every case. Additionally, this is the first study offering functional evidence about the adenosine transport inhibitory action of CBD in the myocardium.
Naringin attenuates fructose-induced NAFLD progression in rats through reducing endogenous triglyceride synthesis and activating the Nrf2/HO-1 pathway
Authors: Pengnet Sirinat , Sumarithum Phinsuda , Phongnu Nuttaphong , Prommaouan Sakdina , Kantip Napapas , Phoungpetchara Ittipon , Malakul Wachirawadee 
Published: December 2022

Background: Excessive fructose consumption causes hepatic lipid accumulation via increased triglyceride (TG) synthesis, leading to the development and progression of non-alcoholic fatty liver disease (NALFD). Naringin, a flavanone glycoside found in citrus fruit, has antioxidant and hypolipidemic properties. Therefore, the aim of this study was to investigate the effect of naringin on fructose-induced NAFLD in rats and the possible underlying mechanism.Methods: Male Sprague Dawley rats were given 10% (w/v) fructose in drinking water for 12 weeks. Naringin (100 mg/kg/day) was administered orally to rats for the last 4 weeks of fructose overload. After 12 weeks of treatment, the hepatic lipid content was determined. In addition, the expression of proteins involved in de novo lipogenesis (DNL) and TG synthesis as well as antioxidant and inflammatory mediators in the liver were examined by western blot analysis.Results: Treatment of fructose-fed rats with naringin significantly decreased the hepatic TG and cholesterol content as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Naringin treatment also decreased the hepatic expression of carbohydrate response element binding protein (ChREBP), sterol regulatory element-binding protein-1c (SREBP-1c) and nuclear SREBP-1c (nSREBP-1c) as well as enzymes involved in DNL (acetyl CoA carboxylase [ACC] and fatty acid synthase [FAS]) and an enzyme involved in TG synthesis (glycerol-3-phosphate acyltransferase 1 [GPAT-1] and diacylglycerol acyltransferase2 [DGAT2]) in fructose-fed rats. In addition, naringin induced a significant decrease in the hepatic expression of nuclear factor kappa B (NF-κB) and tumor necrosis factor α (TNF-α). Furthermore, naringin administration restored the expression of the antioxidant mediators nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in the liver of fructose-fed rats.Conclusion: These results demonstrate that oral administration of naringin protects against fructose-induced hepatic steatosis by decreasing DNL and TG synthesis. In addition, naringin could prevent NAFLD progression via targeting the Nrf2/HO-1 and the NF-κB/TNF-α pathways.
TJ-M2010-5, a novel CNS drug candidate, attenuates acute cerebral ischemia-reperfusion injury through the MyD88/NF-κB and ERK pathway
Authors: Li Zeyang , Zhao Minghui , Zhang Xiaoqian , Lu Yiran , Yang Yang , Xie Yalong , Zou Zhimiao , Zhou Liang , Shang Runshi , Zhang Limin , Jiang Fengchao , Du Dunfeng , Zhou Ping 
Published: December 2022

Background: Cerebral ischemia-reperfusion injury (CIRI) inevitably occurs after vascular recanalization treatment for ischemic stroke. The accompanying inflammatory cascades have a major impact on outcome and regeneration after ischemic stroke. Evidences have demonstrated that TLR/MyD88/NF-κB signaling contributes to CIRI. This study aimed to investigate the druggability of MyD88 in the central nervous system (CNS) and the neuroprotective and anti-neuroinflammatory effects of the MyD88 inhibitor TJ-M2010-5 on CIRI.Methods: A middle cerebral artery occlusion (MCAO) model was used to simulate CIRI in mice. BV-2 cells were stimulated with oxygen glucose deprivation/reoxygenation (OGD/R) or lipopolysaccharide, and SH-SY5Y cells were induced by OGD/R in vitro. Neurological deficit scores and cerebral infarction volumes were evaluated. Immunofluorescence staining was performed to measure neuronal damage and apoptosis in the brain. The anti-neuroinflammatory effect of TJ-M2010-5 was evaluated by analyzing the expression of inflammatory cytokines, activation of microglia, and infiltration of peripheral myeloid cells. The expression of proteins of the MyD88/NF-κB and ERK pathway was detected by Simple Western. The concentrations of TJ-M2010-5 in the blood and brain were analyzed by liquid chromatography-mass spectrometry.Results: The cerebral infarction volume decreased in mice treated with TJ-M2010-5, with the most prominent decrease being approximately 80% of the original infarction volume. Neuronal loss and apoptosis were reduced following TJ-M2010-5 treatment. TJ-M2010-5 inhibited the infiltration of peripheral myeloid cells and the activation of microglia. TJ-M2010-5 also downregulated the expression of inflammatory cytokines and inhibited the MyD88/NF-κB and ERK pathway. Furthermore, TJ-M2010-5 showed good blood-brain barrier permeability and no neurotoxicity.Conclusion: TJ-M2010-5 has an excellent therapeutic effect on CIRI as a novel CNS drug candidate by inhibiting excessive neuroinflammatory responses.
Perceptions of healthcare professionals and patients on the role of the pharmacist in TB management in Pakistan: A qualitative study
Authors: Atif Muhammad , Munir Kiran , Malik Iram , Al-Worafi Yaser Mohammed , Mushtaq Irem , Ahmad Nafees 
Published: December 2022

Background: Globally, tuberculosis (TB) is the second major cause of death from infectious diseases, particularly in developing countries. A multidisciplinary approach to the management of TB may help to curb the disease burden.Objective: The objective of this study was to outline the perceptions of healthcare professionals and patients regarding the potential role of pharmacists in TB management in Pakistan.Method: This was a large-scale qualitative study conducted at the Chest Disease Unit (CDU) of the Bahawal Victoria Hospital (BVH), Punjab, Pakistan. Data were collected through semi-structured interviews with physicians, pharmacists, and patients recruited using a mix of convenient and snowball sampling. The sample size was decided through standard saturation point criteria. All interviews were audio recorded and transcribed verbatim. The data were analyzed to draw conclusions using a thematic analysis approach.Results: Analysis of the data yielded 19 categories and seven themes. Physicians considered pharmacists qualified healthcare professionals, whereas patients considered them merely dispensers. Inventory management and dispensing of medicines were considered as major responsibilities of pharmacists. Physicians were extremely overburdened and wanted to delegate certain duties to pharmacists, subject to their prior extensive trainings. However, most of the physicians were unaware of the legal scope of pharmacy practice in Pakistan. With regard to the potential duties of pharmacists, physicians, pharmacists, and patients (patients—upon explaining the potential roles during the interview) endorsed monitoring, counseling, medicine brand selection, dose adjustment, inventory management, dispensing, and polypharmacy assessment as their potential roles. In view of all stakeholders, the rationale for integrating pharmacists in TB management included overburdened physicians, sub-standard patient care, medication safety issues, and patient dissatisfaction. The healthcare professionals highlighted that the major barriers to integrating pharmacists within the TB management system were limited interest of regulatory authorities and policy makers, followed by inadequate training and experience-driven questionable competency of pharmacists.Conclusion: The study participants acknowledged the potential role of pharmacists in TB management. However, it was emphasized that healthcare policy makers should devise strategies to overcome the underlying barriers before assigning medicine-related clinical roles to pharmacists.