bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network pharmacology and experimental verification: Unraveling Zhiwei Fuwei Pills’s role and mechanism in angiogenesis of precancerous lesions of gastric cancer
Authors: Dou Pengcheng , Song Ruiping , Feng Zhuangzhuang , Jiang Bing , Chen Xinyi , Luo Yuanbin , Zuo Jiaojiao , Gao Yi , Shu Jin 
Published: September 2024

Objective Precancerous lesions of gastric cancer (PLGC) are key pathological stages in the transformation of gastric “inflammation-cancer”, and timely and effective intervention at this stage is of great importance in the prevention and treatment of gastric cancer. Zhiwei Fuwei Pills (ZWFW), as a traditional Chinese medicine formulation, has been proven to have good clinical efficacy in the treatment of PLGC, but its specific mechanism of action has not been fully explained. Thus, this study validated the efficacy and explored the potential mechanisms of ZWFW in treating PLGC by integrating network pharmacology analyses and experimental verification. Methods The TCMSP database was used to obtain the active ingredients of ZWFW and their corresponding targets, and the GeneCards database was used to retrieve PLGC-related targets. The intersecting targets between ZWFW and PLGC were obtained through mapping, and protein-protein interaction (PPI) networks and “drug-active ingredient-target” networks were constructed by using Cytoscape software. The DAVID database was used for GO functional enrichment analysis and KEGG pathway enrichment analysis. AutoDockTools software was used for molecular docking of key active ingredients and key targets. In order to verify the analysis results of network pharmacology, TEM and H&E were used to observe the effects of different dosage groups of ZWFW on gastric mucosal microvasculature in PLGC rats. Subsequently, the ELISA, IF, IHC, RT-PCR and western blot were used to detected the expression levels of relevant targets in the tissues, so as to verify the potential mechanism of ZWFW in intervening PLGC. Results After the screening, 258 effective active ingredients and 325 targets were obtained, and 1294 disease-related targets were determined, resulting in 139 intersection targets through mapping. The KEGG enrichment results showed that PI3K/Akt and HIF-1 signaling pathway might play important roles in the treatment mechanism of PLGC. The molecular docking results showed that active ingredients of ZWFW all had a strong affinity and stable structure with key targets, including AKT1 and VEGF. In vivo experiments confirmed that ZWFW could improve gastric mucosal microvascular abnormalities in PLGC, effectively intervene in gastric mucosal pathological grading. Meanwhile, compared with the model group, this formulation could reduce the expression levels of PI3K, Akt, mTOR, HIF-1α, and VEGF in gastric mucosa, showing a dose-effect relationship. Conclusion ZWFW can intervene in the neovascularization and pathological evolution of PLGC, and this mechanism of action may be achieved by inhibiting abnormal activation of the PI3K/Akt/mTOR/HIF-1α/VEGF signaling pathway.
Neurological Manifestations and Complications of Neonatal Meningitis: A Systematic Review and Meta-analysis
Authors: Ong Leong Tung , Chee Nicholas Ming Zher , Loh Audrey Joe Chii , Balasubramaniam Roovam 
Published: September 2024

Background: Neonatal meningitis has significant worldwide morbidity and mortality rates. Nevertheless, the clinical manifestations of neonatal meningitis are subtle and nonspecific which can pose challenges in terms of timely diagnosis and intervention. This meta-analysis aims to the prevalence of neurological manifestations and complications associated with neonatal meningitis in term and preterm neonates. Methods: A systematic literature search was conducted in PubMed, SCOPUS, and Ovid SP to identify relevant studies. Pooled prevalence of neurological manifestations and complications with a 95% confidence interval (CI) were calculated using the random-effects generic inverse variance model. Statistical analysis was performed using Review Manager v5.4 and R programming. Results: A total of 25 studies with 2252 patients evaluated for neurological symptoms and 1822 patients evaluated for neurological complications were included in this meta-analysis. The overall prevalence of neurological manifestations in neonatal meningitis was 23% (95% CI, 20% to 26%). The overall prevalence of neurological complications in neonatal meningitis was 8% (95% CI, 6% to 9%). Conclusion: Our meta-analysis revealed a low prevalence of neurological manifestations and complications in neonatal meningitis. Although neurological complications occur less frequently, the complications are significantly associated with higher mortality and morbidity rates.
Application of the Statin-Associated Muscle Symptoms-Clinical Index to a Cohort of Patients with Type 2 Diabetes Mellitus Undergoing Phlebotomy at an Endocrinology Clinic
Authors: Tajudin Nor Humaira Mohd , Fahrni Mathumalar Loganathan , Ghani Rohana Abdul , Awang Mohd Hazriq , Chopra Hitesh , Alkhoshaiban Ali Saleh 
Published: September 2024

Background Statin-associated muscle symptoms (SAMS), the commonest statin-induced adverse effects, could hinder patient adherence and possibly lead to discontinuation of therapy, which then increases patients’ risks for developing cardiovascular events. Although statins are the most frequently prescribed lipid-lowering medication, the occurrence and severity of SAMS among the Malaysian population are less known. Objectives To examine the likelihood and types of muscle symptoms attributable to statins, and the risk factors for developing the symptoms among statins users. Materials and Methods This was a cross-sectional study conducted with convenience sampling of patients with type 2 diabetes mellitus undergoing phlebotomy at an endocrinology clinic of a secondary hospital in a suburban city. Demographic and clinical data for the evidence of SAMS were retrieved from the hospital information system. A total of 214 patients were screened, and 50 subjects were recruited for interviews based on the study’s inclusion and exclusion criteria. Muscle symptoms that were evident through clinician notes, and self-reported signs and symptoms by patients during the interview were assessed to determine whether they were SAMS or not. This was done using a pre-structured published questionnaire via patient interview, and the likelihood was then determined using the SAMS-clinical index (SAMS-CI) tool. Results In this cohort, the probability of having had a statin-associated muscle adverse event was 0.48, i.e., 48% “probable” and “possible” likelihood of SAMS having occurred for a patient who consumed a statin. The mean SAMS-CI score was 6.32 ± 0.470 (±7.4%) [CI: 5.85–6.79], which fell under an “unlikely” category. The most frequent type of muscle symptom was myalgia, which was experienced as muscle aches, stiffness, cramps, symptoms worsening after exercise, muscle tenderness, and trouble moving knees or arm joints. These symptoms were proximal and symmetrical in nature and commonly involved large muscle groups such as the thighs, buttocks, calves, and back muscles. An elevation in creatinine kinase was not commonly observed. Conclusion A minority (6%) of the patients that we sampled experienced SAMS, which were probably attributable to statins. Nevertheless, caution must be exercised for female patients with a familial history of heart disease being prescribed with the lipophilic statins, atorvastatin, and simvastatin, and those who report aches in the large muscle groups.
No Effects of Auditory and Visual White Noise on Oculomotor Control in Children with ADHD
Authors: Jostrup Erica , Claesdotter-Knutsson Emma , Tallberg Pia , Söderlund Göran , Gustafsson Peik , Nyström Marcus 
Published: September 2024

Background: White noise stimulation has demonstrated efficacy in enhancing working memory in children with ADHD. However, its impact on other executive functions commonly affected by ADHD, such as inhibitory control, remains largely unexplored. This research aims to explore the effects of two types of white noise stimulation on oculomotor inhibitory control in children with ADHD. Method: Memory guided saccade (MGS) and prolonged fixation (PF) performance was compared between children with ADHD ( N = 52) and typically developing controls (TDC, N = 45), during auditory and visual white noise stimulation as well as in a no noise condition. Results: Neither the auditory nor the visual white noise had any beneficial effects on performance for either group. Conclusions: White noise stimulation does not appear to be beneficial for children with ADHD in tasks that target oculomotor inhibitory control. Potential explanations for this lack of noise benefit will be discussed.
Trends in patient characteristics and mortality among Medicare patients diagnosed with peripheral artery disease
Authors: Fowler Xavier , Mehta Kunal , Eid Mark , Gladders Barbara , Kearing Stephen , Moore Kayla O , Creager Mark A , Austin Andrea M , Feinberg Mark W , Bonaca Marc P , Greenland Philip , McDermott Mary M , Goodney Philip P 
Published: September 2024

Introduction: Peripheral artery disease (PAD) is a well-described risk factor for mortality, but few studies have examined secular trends in mortality over time for patients with PAD. We characterized trends in mortality in patients with PAD in recent years among Medicare patients. Methods: We used Medicare claims to identify patients with a new diagnosis code for PAD between January 1, 2006 and December 31, 2018 using International Classification of Diseases (ICD) diagnosis codes. The primary outcome of interest was the 1-year all-cause age-adjusted mortality rate. Our secondary outcome was the 5-year all-cause mortality rate. Multivariable regression was used to identify factors which predict mortality at 1 year. Results: We identified 4,373,644 patients with a new diagnosis code for PAD during the study period. Between 2006 and 2018, 1-year all-cause age-adjusted mortality declined from 12.6% to 9.9% ( p < 0.001). One-year crude all-cause mortality also declined from 14.6% to 9.5% ( p < 0.001). Similar results were observed for 5-year age-adjusted mortality rates (40.9% to 35.2%, p < 0.001). Factors associated with increased risk of death at 1 year included age ⩾ 85 years (hazard ratio [HR] 3.030; 95% CI 3.008–3.053) and congestive heart failure (HR 1.86; 95% CI 1.85–1.88). Patients who were regularly dispensed statins, ace-inhibitors, beta-blockers, antithrombotic agents, and anticoagulants all had lower mortality (range OR 0.36; CI 0.35–0.37 for statins to OR 0.60; CI 0.59–0.61 for anticoagulants; all p < 0.001). Conclusion: Among US Medicare patients diagnosed with PAD between 2006 and 2019, 1-year age-adjusted mortality declined by 2.7%. This decline in mortality among patients with PAD occurred in the context of a younger mean age of diagnosis of PAD and improved cardiovascular prevention therapy.
Inventory Management Performance for Tracer Medicines in Public Health Facilities of Southwest Shewa Zone Oromia Region, Ethiopia: A mixed study
Authors: Gutesa Alemayehu , Jebena Tariku , Kebede Oliyad 
Published: September 2024

Introduction: Tracer medicines are medicines that must be available in sufficient quantities at all times to satisfy the priority health care needs of the population. Inventory mismanagement of these medicines poses significant challenges to public health systems, especially in countries like Ethiopia, where access to healthcare services is already limited. Objective: This study aims to assess inventory management performance for tracer medicines at public health facilities of the southwest Shewa zone, Oromia region, Ethiopia. Method: Concurrent triangulation mixed-method study was conducted from 1 to 30 June 2022. The quantitative data were collected using interviewer-administered semistructured questionnaires and observational checklists. The qualitative data were gathered through in-depth interviews with key informants. The quantitative data were analyzed using the SPSS version 26 and Excel spreadsheet version 16. We calculated the stock-out rate, inventory accuracy rate, percentage of facilities that fulfill appropriate storage conditions, percentage of facilities that submitted reports on time, and received the exact quantity of drugs they ordered. Qualitative data were analyzed manually using the thematic content analysis technique. Results: The inventory accuracy rate for tracer medicines was 76% for hospitals and 72.5% for health centers. The overall mean stock-out rate was 24.99%. Bin card updating practice was 93.3%, and only 25% health facilities met the acceptable storage conditions criteria. Among submitted reports, 88.8% were timely reported, 72.2% were accurate, and 75% were complete. Inventory management challenges include a shortage of supplies from the supplier and in the market, price inflation, inadequate training, lack of supportive supervision, insufficient IT and storage infrastructures, lack of communication, and budget constraints. Conclusion: From this finding, we concluded that facilities’ report quality, inventory record accuracy, storage conditions, and logistics management information system needs improvements. Therefore, Ministry of Health, assessed facilities and Ethiopian pharmaceuticals Supply Services should take measures to improve them.
A regression predictive model for QuantiFERON-TB Gold Plus® indeterminate results in immunosuppressed patients
Authors: Bellagha Rahma , Dhaouadi Tarak , Riahi Awatef , Ben Rehouma Wahiba , Jedidi Hajer , Mouelhi Leila , Abdelmoula Leila , Ben Abdallah Taïeb , Gorgi Yousr , Sfar Imen 
Published: September 2024

Background: Screening for latent tuberculosis infection using Interferon-Gamma Release Assays is a routine procedure prior to the initiation of anti-tumor necrosis factor (TNF) biotherapy or immunosuppressive therapy. However, indeterminate results are relatively frequent and are an obstacle to treatment initiation. Aim: The aim of this cross-sectional study was to estimate the frequency of indeterminate QuantiFERON-TB Gold Plus® test results in Tunisian patients, and to analyze the potential clinico-biological risk factors associated with these indeterminate results. Methods: Whole blood samples from 712 patients being monitored for autoimmune diseases and candidates for anti-TNF biotherapy or switch of immunosuppressive therapy were used to screen for latent tuberculosis infection using the QuantiFERON-TB Gold Plus® test. Based on literature background, the following variables were tested for the association with indeterminate results: gender, age, diabetes, immunosuppressive drugs, lymphocyte count, Neutrophil-to-lymphocyte ratio, serum albumin, and estimated glomerular filtration rate. Results: The QuantiFERON-TB Gold Plus® test was negative in 572 (80.3%) patients, positive in 106 (14.9%), and indeterminate in 34 (4.8%) cases. Positive results were significantly associated with a family history of confirmed and treated tuberculosis, OR (95% CI) = 52 (20.2–134.3). The use of immunosuppressive drugs and duration of treatment were significantly associated with the occurrence of indeterminate results: OR (95% CI) = 24.5 (5.8–103) and OR (95% CI) = 1.004 (1.002–1.007), respectively. Biologically, lymphopenia, hypoalbuminemia, and decreased estimated glomerular filtration rate were significant risk factors for indeterminate results: p = 5 E-6, p = 4.3 E-4, and p = 0.002, respectively. Thus, a multiple logistic regression model based on these three biological parameters enabled us to develop a predictive score for indeterminate results with a sensitivity of 91.2% and a specificity of 99.9%, AUC = 0.9964 (0.9917–1), p = 2.8 E-52. Conclusion: Immunosuppressive therapy, lymphopenia, hypoalbuminemia, and kidney failure appeared to be risk factors for indeterminate QuantiFERON-TB Gold Plus® results.
Disparities between objectively measured hearing loss and subjectively perceived aided hearing loss: A scoping review
Authors: Hindhede Anette Lykke , Soendergaard Natascha Sofie , Toldam Eva Juul , Hansen Niels-Henrik Møller 
Published: September 2024

Objectives: This scoping review aims to summarize and synthesize research findings on the disparities between audiometrically diagnosed and aided hearing loss versus the individual’s own experience of hearing loss. Methods: A systematic search strategy was employed across multiple databases to identify studies published between 1990 and October 2023 focusing on the experiences of hearing problems among individuals with aided hearing loss. The selected studies underwent screening based on predetermined inclusion and exclusion criteria. These criteria revolved around including papers featuring a population of adult (+18) individuals with audiometrically measured hearing loss who had undergone technological rehabilitation. Data charting was employed to provide an overview of the studies and was additionally utilized to identify key themes. Narrative analysis was used to identify subthemes within the data set. Results: A total of 11 articles met the inclusion criteria. The analysis identified five themes: “disability experience and discrepancy between measured and self-perceived hearing loss”; “listening effort”; “mental burden/psychological consequences”; “factors that alleviate the consequences of HL”; and “sociodemographic factors.” Conclusions: The scoping review shows that, despite the proliferation of technological options, there is a pressing need for a more concentrated effort to identify and scrutinize the supplementary facets of hearing loss that remain inadequately addressed by current hearing technology. This includes subjective experiences associated with hearing loss that may not be effectively treated solely with hearing aids.
In vivo silencing of intestinal DMT1 mitigates iron loading in β-thalassemia intermedia (Hbbth3/+) mice
Authors: Yu Yang , Woloshun Regina R. , Lee Jennifer K. , Ebea-Ugwuanyi Pearl O. , Shine Jacob S. , Zhu Sean , He Yue , Collins James F. 
Published: September 2024

Abstract
β-thalassemia is an iron-loading anemia caused by homozygous mutation of the hemoglobin subunit β (HBB) gene. In β-thalassemia intermedia (βTI), a non–transfusion-dependent form of the disease, iron overload is caused by excessive absorption of dietary iron due to inappropriately low production of the iron-regulatory hormone hepcidin. Low hepcidin stabilizes the iron exporter ferroportin (FPN) on the basolateral membrane of enterocytes. High FPN activity may deplete intracellular iron and enhance expression of the predominant iron importer divalent metal-ion transporter 1 (DMT1). In mice, DMT1 mediates normal iron absorption under physiological conditions and excessive iron absorption in pathological iron overload (eg, hereditary hemochromatosis). Here, we hypothesized that DMT1 drives elevated iron absorption in βTI. Accordingly, we crossed Hbbth3/+ mice, a preclinical model of βTI, with intestine-specific DMT1-knockout mice. Ablation of intestinal DMT1 in Hbbth3/+ mice caused a pathophysiological shift from iron overload to an iron-deficiency phenotype with exacerbated anemia. DMT1 is thus required for iron absorption and iron loading in Hbbth3/+ mice. Based upon these outcomes, we further logically postulated that in vivo knockdown of intestinal DMT1 would mitigate iron loading in Hbbth3/+ mice. Ginger-derived, lipid nanoparticles carrying DMT1-specific (or control) small interfering RNAs (siRNAs) were administered by oral, intragastric gavage to 4-week-old Hbbth3/+ mice daily for 16 days. siRNA treatment reduced DMT1 expression by &gt;80% and blunted iron loading, as indicated by significant reductions in liver iron and serum ferritin (which reflect body iron stores). These notable experimental outcomes establish intestinal DMT1 as a plausible therapeutic target to mitigate iron overload in βTI.
MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study
Authors: Humbert Marc , Hassoun Paul M. , Chin Kelly M. , Bortman Guillermo , Patel Mahesh J. , La Rosa Carmen , Fu Wei , Loureiro Maria José , Hoeper Marius M. 
Published: September 2024

BackgroundMK-5475 is an investigational inhaled soluble guanylate cyclase stimulator hypothesised to avoid most side-effects of systemic vasodilation.MethodsThe phase 2 INSIGNIA-PAH (NCT04732221) trial randomised adults with pulmonary arterial hypertension (PAH) on stable background therapy 1:1:1:1 to once-daily dosing with placebo, MK-5475 32 µg, 100 µg or 380 µgviadry powder inhalation for 12 weeks.ObjectivesThe objectives were to evaluate pulmonary vascular resistance (PVR; primary), 6-min walk distance (6MWD; secondary), additional selected haemodynamic parameters, and safety and tolerability in participants with PAH.Results168 participants were randomised to placebo (n=41), MK-5475 32 µg (n=42), 100 µg (n=44), and 380 µg (n=41). Median age was 51 years. Most participants were female (73.8%), diagnosed with idiopathic PAH (63.7%), receiving concomitant phosphodiesterase type 5 inhibitors (PDE5i; 93.5%), and treated with double or triple combination therapy (85.1%). At week 12, the placebo-corrected changes in PVR by least-squares means were −9.2% (95% CI −21.3%, 2.9%; p=0.068) with 32 µg, −22.0% (95% CI −33.7%, −10.3%; p<0.001) with 100 µg, and −19.9% (95% CI −33.4%, −6.4%; p=0.002) with 380 µg MK-5475. No treatment differencesversusplacebo were observed in 6MWD. Treatment-related adverse events and serious adverse events were similar across treatment groups. Three participants died: two on placebo and one on MK-5475 100 µg. One participant had symptomatic hypotension and one had haemoptysis (both on MK-5475 100 µg).ConclusionsIn participants with PAH on stable background therapy, including PDE5i, inhaled MK-5475 reduced PVR and was well tolerated, without evidence of systemic side-effects such as hypotension, suggesting a pulmonary selective pharmacodynamic effect.