bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French Pharmacovigilance Database
Authors: Yavordios Sophie , Beltramo Guillaume , Freppel Romane , Beau Salinas Frédérique , Le Beller Christine , Bihan Kevin , Mouillot Pierre , Georges Marjolaine , Grandvuillemin Aurélie , Bonniaud Philippe 
Published: November 2024

BackgroundDrug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung disease (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through adverse drug reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs.MethodsThis retrospective study included cases registered in the FPVD from 1 January 1985 to 1 April 2022 which had ADRs coded in MedDRA with a High-Level Group Term “Lower respiratory tract disorders (excluding obstruction and infection)” involving patients aged ≥18 years.ResultsWe analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and death ensued in 13.3%. Males accounted for 54.4% of the cases. Median (range) age was 69 (18–103) years. The most prevalent ADRs were “Interstitial lung disease” (51.0%), “Pulmonary oedema” (acute/non-acute) (15.6%) and “Pulmonary fibrosis” (10.5%). Anti-cancer drugs (31.2%) and cardiovascular drugs (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%).ConclusionThis study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify the diseases properly and discontinue the culprit drug urgently.
Pirfenidone and risk of lung cancer development in idiopathic pulmonary fibrosis: a nationwide population-based study
Authors: Yoon Hee-Young , Kim Hoseob , Bae Yoonjong , Song Jin Woo 
Published: November 2024

BackgroundIdiopathic pulmonary fibrosis (IPF) carries a high risk of lung cancer, but the effect of pirfenidone on lung cancer development remains uncertain. We investigated the association between pirfenidone use and lung cancer development in patients with IPF.MethodsWe included 9938 patients with IPF from the Korean national claims database. Propensity score analysis with inverse probability of treatment weighting (IPTW) and landmark analyses were employed to evaluate lung cancer occurrence according to pirfenidone use. The association was evaluated using Cox regression models adjusted for clinical and socioeconomic variables. A single-centre IPF clinical cohort (n=941) was used for validating the findings.ResultsThe mean patient age was 69.4 years, 73.7% were men and 32.1% received pirfenidone. Lung cancer developed in 766 patients with IPF (7.7%; 21.9 cases per 1000 person-years) during a median follow-up of 3.0 years. After IPTW, the pirfenidone group showed lower incidence (10.4versus27.9 cases per 1000 person-years) than the no pirfenidone group. Landmark analysis at 6 months after IPF diagnosis also showed lower incidence of lung cancer in the pirfenidone group than in the no pirfenidone group. Pirfenidone use was independently associated with a reduced lung cancer risk (weighted adjusted hazard ratio (HR) 0.347, 95% CI 0.258–0.466). A clinical cohort showed similar association (weighted adjusted HR 0.716, 95% CI 0.517–0.991). The association persisted across subgroups defined by age or sex.ConclusionPirfenidone use may be associated with a reduced lung cancer risk in patients with IPF.
Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity
Authors: Lenz Maximilian , Turko Paul , Kruse Pia , Eichler Amelie , Chen Zhuo Angel , Rappsilber Juri , Vida Imre , Vlachos Andreas 
Published: November 2024

AbstractUnderstanding the mechanisms of synaptic plasticity is crucial for elucidating how the brain adapts to internal and external stimuli. A key objective of plasticity is maintaining physiological activity states during perturbations by adjusting synaptic transmission through negative feedback mechanisms. However, identifying and characterizing novel molecular targets orchestrating synaptic plasticity remains a significant challenge. This study investigated the effects of tetrodotoxin (TTX)-induced synaptic plasticity within organotypic entorhino-hippocampal tissue cultures, offering insights into the functional, transcriptomic, and proteomic changes associated with network inhibition via voltage-gated sodium channel blockade. Our experiments demonstrate that TTX treatment induces substantial functional plasticity of excitatory synapses, as evidenced by increased miniature excitatory postsynaptic current (mEPSC) amplitudes and frequencies in both dentate granule cells and CA1 pyramidal neurons. Correlating transcriptomic and proteomic data, we identified novel targets for future research into homeostatic plasticity, including cytoglobin, SLIT-ROBO Rho GTPase Activating Protein 3, Transferrin receptor, and 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. These data provide a valuable resource for future studies aiming to understand the orchestration of homeostatic plasticity by metabolic pathways in distinct cell types of the central nervous system.
Influence of physico-chemical properties of hydroxypropyl methylcellulose on quetiapine fumarate release from sustained release matrix tablets
Authors: Ellakwa Takwa E. , Abu-Khadra Ahmad S. , Ellakwa Doha El-Sayed 
Published: November 2024

AbstractQuetiapine fumarateis a typical antipsychotic with a short half-life of 6 h and is administered multiple times daily. In this study, a copolymer for controlled delivery of quetiapine fumarate will be developed. In order to prevent side effects and improve patient compliance, hydroxypropyl methylcellulose K15M (HPMC K15M) was included in the formulation of the quetiapine fumarate oral sustained-release tablets at a concentration of 10–30%. A series of analytical methods were used to determine the characteristics of the prepared hydrogels, including Fourier transform-infrared spectroscopy, Differential scanning calorimetry, X-ray diffraction, and Scanning electron microscope. At two different pH values (1.2 and 6.8), swelling and release studies were conducted. A variety of release kinetic models was used to study drug release mechanisms. A non-Fickian diffusion mechanism released hydrogels prepared from quetiapine fumarate. It was found that swelling was increased by increasing the amount of HPMC K15M. Compared to the other batches (10–20%), the produced tablets with 30% HPMC K15M content had a better release profile after 20 h of dissolution. Because of the effective matrix complex’s limited solubility in water, the drug diffuses through the gel layer at a steady rate rather than dissolving quickly.
Carry-over effects of Bacillus thuringiensis on tolerant Aedes albopictus mosquitoes
Authors: Bahrami Romina , Quaranta Stefano , Perdomo Hugo D. , Bonizzoni Mariangela , Khorramnejad Ayda 
Published: November 2024

AbstractBackgroundThe biological larvicideBacillus thuringiensissubsp.israelensis(Bti) represents a safe and effective alternative to chemical insecticides for mosquito control. Efficient control of mosquitoes implicates continuous and extensive application of Bti. This massive use of Bti imposes strong selective pressure, but the complex mode of action of the numerous synergistic Bti endotoxins lower the risk of the emergence of resistance. Although resistance to Bti has not been identified at the population level in nature, some larvae can survive Bti exposure, suggesting tolerance mechanisms. Here we investigated whether Bti-tolerantAedes albopictuslarvae experience any fitness costs. We also studied how this tolerance affects different aspects of the phenotype of the emerging adults that could be relevant for arboviral transmission.MethodsWe exposedAe. albopictuslarvae to lethal concentration of Bti and studied the fitness and gut microbiota of tolerant larvae and their adult counterparts. We further compared the transcript abundance of nine key immunity genes in the gut of Bti-tolerant larvae and their emerging adults versus those not exposed to Bti.ResultsOur results showed that Bti exposure has multifaceted impacts onAe. albopictusmosquitoes during both larval and adult stages. The carry-over effect of Bti exposure on tolerant larvae manifested in reduced adult emergence rate, shorter lifespan, and decreased fecundity. Bti also alters the gut microbiota of both larvae and adults. We observed higher microbial diversity in Bti-tolerant larvae and changes in the richness of core microbiota. Bti infection and the altered microbiota triggered immune responses in the larval and adult guts.ConclusionsThe observed reduction in mosquito fitness and changes in the composition of the microbiota of adults emerging from tolerant larvae could negatively influence mosquito vectorial capacity. Understanding these impacts is crucial for evaluating the broader implications of Bti-based insecticides in mosquito control programs.Graphical Abstract
Protective efficacy of a recombinant adenovirus expressing novel dual F and HN proteins of bovine parainfluenza virus type 3
Authors: Zhang Jiaqi , Wu Jinbo , Zhu Qing , Huang Xiangyue , Zhang Zhaohui , Zhu Chenxi , Deng Gunan , Ake Ajia , Ma Yuanzhen , He Chunsai , Guo Rui , Yue Hua , Lan Lan , Zhang Bin 
Published: November 2024

AbstractBovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3+/CD8+T lymphocytes and IL-4+ cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection.
Prolonged alkali water irrigation: impacts of treatment strategies on soil health and microbial dynamics
Authors: Yadav Kirti , Singh Awtar , Aggarwal Neeraj K. , Yadav Gajender , Basak Nirmalendu , Bhardwaj Ajay Kumar , Yadav Rajender Kumar 
Published: November 2024

Abstract
Background
The extent of natural salt-laden groundwaters used for irrigation is increasing worldwide, which is a fast-emerging threat to agroecosystems and global food security. The salt buildup in the soil is linked to deteriorated soil chemical, physical, and biological health and decreased land productivity. Alkali waters with high residual sodium carbonate (RSC) is one of the severe poor-quality waters that deteriorate soil. We evaluated soil microbial dynamics and soil health at critical growth stages of rice crop receiving two-decade-long irrigation with three levels of alkali water and two reclamation strategies. These included good-quality water (GQW), alkali water (ALKW) with an RSC concentration of 5 me L⁻1 (ALKW1), ALKW with an RSC concentration of 10 me L⁻1 (ALKW2), ALKW2 treated to neutralize RSC to 5 me L⁻1 using gypsum (CaSO4·2H2O; ALKW2 + GYP), and ALKW2 treated with sulfuric acid (H2SO4; ALKW2 + SA). Eleven microbial parameters were used to develop a soil microbial activity index (SMAI), and eight soil health indicators were correlated with changes in SMAI and crop productivity.

Results
The SMAI peaked under good-quality water (GQW) conditions (0.84–0.89), while the lowest values were recorded under ALKW2 (0.06–0.18). Neutralized alkali waters, ALKW2 + SA and ALKW2 + GYP, significantly improved SMAI with corresponding values of 0.25–0.35 and 0.13–0.32, respectively. SMAI across all stages correlated positively (R2 = 0.91–0.98) with rice yield. Microbial activity varied with the crop growth stage, peaking at tillering. Gypsum application alone, aimed at neutralizing alkalinity from an RSC of 10 to 5 me L⁻1, proved insufficient in bringing the SMAI up to the ALKW1 (RSC level of 5 me L⁻1).

Conclusions
The application of dilute sulfuric acid demonstrated better results in restoring the soil microbial activity index than gypsum amendment; however, sulfuric acid treatment depends on native calcium carbonate (CaCO3) dissolution for its effectiveness. It may not suffice for soil stability improvement in the long term, especially when native CaCO3 is low. Therefore, integrating gypsum and dilute sulfuric acid for RSC neutralization is worthwhile; however, further assessment is needed to confirm their combined impact on soil biochemical and physical properties.
Experimental study on the effect of surface-projected conditions on the mechanical behavior of pile embedded in sand
Authors: Park Suhyuk , Kim Gi-Yun , Chang Ilhan 
Published: November 2024

AbstractSurface-projected piles, such as helical and under-reamed piles, are widely utilized in geotechnical engineering to enhance the load-carrying capacities of pile structures with surface projection part. Despite the use of a wide variety of surface-projected conditions, detailed investigations considering various dimensions and angles of surface-projected piles remain limited in the current literature. This study aims to assess the effects of surface-projected widths wp (10 mm, 20 mm, 40 mm) and angles θ (18°, 27°, 45°, 90°) on pile penetration resistance using a two-dimensional model and PIV analysis. Wider projections increased resistance, with a maximum of 1.84 kN—57% higher than conventional piles in the model ground. Penetration resistance was proportional to width at 90°; for wp = 20 mm, penetration resistance decreased with increasing θ, while for wp = 40 mm, it increased. Theoretical ultimate bearing capacity calculations emphasize differences from experimental results due to neglected shaft friction. Residual penetration resistance and particle displacement were observed for wp of 20 mm and 40 mm after failure. This study provides insights into optimizing surface-projected pile design and understanding ground failure mechanisms.
Assessing agricultural practices and insecticides resistance for effective malaria vector control in northwestern Iran
Authors: Abbasi Madineh , Yousefi Saideh , Nikpour Fatemeh 
Published: November 2024

Abstract
Background
After three years with no local transmission of malaria, an outbreak occurred in Iran in 2022. Key malaria control methods in Iran are including indoor residual spraying (IRS), long-lasting insecticide-treated nets (LLINs), and prompt diagnosis and treatment of malaria cases. Anopheles sacharovi is one of the main malaria vectors in Iran. This study aimed to determine the insecticides resistance status of An. sacharovi in northwestern Iran, to inform effective vector control programs in this region.

Methods
Larval stages of An. sacharovi were collected from various larval habitats located in the villages along the Aras River. Adult susceptibility tests were performed on An. sacharovi using diagnostic doses of insecticides accordance to World Health Organization (WHO) guidelines. The study also evaluated agricultural insecticide and fertilizer usage alongside the presence of natural mosquito predators in breeding sites in the study area.

Results
Alongside various chemicals such as silica, humic acid, superphosphate, sulfur, urea, and solupotasse at different dose levels, organophosphorus and pyrethroid insecticides are commonly used in rice fields and orchards. Anopheles sacharovi displayed diverse reactions to insecticides, demonstrating resistance to DDT but sensitivity to malathion, and showing similar reactions to carbamate and pyrethroid insecticides.

Conclusions
These results provide significant insights into agricultural practices and the presence of mosquito larvae in the study area. The extensive use of a specific herbicide illustrates its popularity among farmers for weed control, while other agricultural products focus on enhancing soil fertility and productivity. The absence of mosquito larvae in habitats with predators indicates the usefulness of these predators in controlling the population of mosquitoes. The resistance of mosquitoes to certain insecticides highlights the need for careful selection and intermittent use of insecticides in vector control programs. These findings can inform the development of targeted strategies to reduce malaria transmission risks. Further research is essential for assessing the effectiveness of these interventions.
Burden and impact of substance abuse among epileptic patients attending epilepsy outpatient clinic
Authors: Abdou Ashraf Moustafa , Karim Ahmed Mohamed Abdel , Abozaid Reham Mahmoud , Gaber Dina El Sayed 
Published: November 2024

Abstract
Background
To date, the burden and impact of substance use among epileptic patients were studied in a small number of studies and showed inconsistent findings, which may be attributed to the variation in age, test batteries, epilepsy subtypes, and substance use characteristics across research. The aim of the study was to determine the burden and impact of substance abuse among a sample of epileptic patients attending Alexandria University outpatient clinics. This study was conducted on 200 epileptic patients (100 male and 100 female patients). The diagnosis of epilepsy in those patients was confirmed by expert neurologists. Using the international league against epilepsy 2017 classification, they underwent a complete physical examination. EEG was done for all patients. Every patient was assessed using a semi-structured interview and a self-designed questionnaire to collect data concerning history of epilepsy, seizure type, EEG findings, as well as questions derived from the Addiction Severity Index (ASI). The Timeline between epilepsy and substance abuse, as well as the Effect of substance intake on epileptic seizures, were assessed.

Results
A total of 27 epileptic patients had a history of substance abuse; hence, the percentage of substance use among epileptic patients was 13.5%. Mean age in the male age group was (29.74 ± 11.52) years and (27.34 ± 9.35) years in females; mean seizure frequency per month was higher among males than females and this was statistically significant (P = 0.037*). More male (24%) than females (3%) had history of substance use and this was statistically significant (P < 0.001*). Regarding the Effect of substance intake on epileptic seizures, the male group (91.7%) had Seizure worsening, while in the female group, all three patients (100%) had seizures worsening with substance use. The mean Frequency of seizures was 4.48 ± 5.08 attacks per month for substance users and 2.49 ± 3.84 attacks per month for non-users; this was statistically significant. (t = 2.392) (P = 0.018*). Non-substance use patients had better compliance to treatment (79%) in comparison to 44.4%) of Substance use patients and this was statistically significant (P < 0.001*).

Conclusion
Drug abuse can have a negative impact on epilepsy in both sexes regarding seizure severity frequency, and even compliance with medication.
SLC2A1 variants cause late-onset epilepsy and the genetic-dependent stage feature
Authors: Zhang Dongming , Guo Jing , Lin Zisheng , Yan Hongjun , Peng Kai , Fei Linxia , Zhai Qiongxiang , Zou Dongfang , Zhong Jiayi , Ding Yan , Ye Hong , Wang Pengyu , Wang Jie , Luo Sheng , Li Bingmei , Li Bin , Liao Weiping 
Published: November 2024

Abstract
Background
The SLC2A1 gene plays a vital role in brain energy metabolism. SLC2A1 variants have been reported to be associated with early-onset refractory seizures. This study aims to explore the association between the SLC2A1 gene and late-onset epilepsy.

Methods
Trios-based whole-exome sequencing was performed on patients with epilepsy without acquired etiologies. The pathogenicity of the variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.

Results
A total of 14 heterozygous SLC2A1 variants were identified in 16 unrelated families. The variants were evaluated as “pathogenic” or “likely pathogenic” according to the ACMG guidelines. Ten cases (62.5%) presented with infantile onset seizures and developmental delay/intellectual disability and were diagnosed with developmental and epileptic encephalopathy (DEE). The other six cases (37.5%) exhibited late-onset seizures and normal development. They were diagnosed with idiopathic partial epilepsy (n = 2) or idiopathic generalized epilepsy (n = 4). Further analysis showed that DEE-associated variants tended to cluster in the transmembrane region, whereas the mild epilepsy-associated variants tended to locate in regions outside the transmembrane region, suggesting a potential molecular sub-regional effect. A total of 15 cases had delayed diagnosis, with the longest delay being 22 years. The SLC2A1 expression stage, which is expressed at relatively high level throughout the whole life span, from the embryonic to adult stages with two peaks at approximately four and 14 years, is generally consistent with the seizure onset age. In addition, patients with early-onset age had variants that were potentially associated with severe damage, suggesting a potential correlation between the age of disease onset and the damaging effects of the variants.

Conclusions
SLC2A1 variants are associated with late-onset epilepsy, which is consistent with the genetic-dependent stage feature of SLC2A1. Early genetic diagnosis is important for treatment of patients with SLC2A1 variants.