bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-World Data-Derived Pharmacovigilance on Drug-Induced Cognitive Impairment Utilizing a Nationwide Spontaneous Adverse Reporting System
Authors: Sunwoo Yongjun , Eom Sae Hyun , Yun Ji Seong , Kim Yujin , Lee Jeongmin , Lee Soo Hyeon , Shin Sooyoung , Choi Yeo Jin
Published: June 2024

Background and Objectives: Despite high incidences of cognitive impairment with aging, evidence on the prevalence and the seriousness of drug-induced cognitive impairment is limited. This study aims to evaluate the prevalence and the severity of drug-induced cognitive impairment and to investigate the clinical predictors of increased hospitalization risk from serious drug-induced cognitive impairment. Materials and Methods: Adverse drug events (ADEs) regarding drug-induced cognitive impairment reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were included (KIDS KAERS DB 2212A0073). The association between the etiologic classes and the reporting serious adverse events (SAEs) was evaluated using disproportionality analysis, and the effect was estimated with reporting odds ratio (ROR). Clinical predictors associated with increased risk of hospitalization from SAEs were identified via multivariate logistic analysis, and the effect was estimated with odds ratio (OR). Results: The most etiologic medication class for drug-induced cognitive impairment ADEs was analgesics, followed by sedative-hypnotics. Anticancer (ROR 57.105, 95% CI 15.174–214.909) and anti-Parkinson agents (ROR 4.057, 95% CI 1.121–14.688) were more likely to report serious drug-induced cognitive impairments. Male sex (OR 19.540, 95% CI 2.440–156.647) and cancer diagnosis (OR 18.115, 95% CI 3.246–101.101) are the major clinical predictors for increased risk of hospitalizations due to serious drug-induced cognitive impairment. Conclusions: This study highlights the significant prevalence and severity of drug-induced cognitive impairment with cancer diagnosis and anticancer agents. However, further large-scaled studies are required because of the potential underreporting of drug-induced cognitive impairments in real practice settings, which is further contributed to by the complexity of multiple contributing factors such as comorbidities.
Stress and Quality of Life in Caregivers of Patients with Multiple Sclerosis
Authors: Kantanis Anastasios , Pelantaki Maria , Fountaki Maria Lidia , Konstantopoulos Vasilios , Paraskevas Themistoklis , Stavropoulou Evgenia , Tsiamaki Eirini , Trimmis Nikolaos , Plotas Panagiotis
Published: June 2024

Background and Objectives: Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Individuals with multiple sclerosis may require daily care and support from caregivers due to the disease’s progressive and unpredictable nature. However, the role of caregiving is not without its challenges, and caregivers themselves often face significant repercussions in terms of their quality of life, mental health, and stress levels. Our study aims to investigate the level of stress caregivers experience in their everyday life and the way stress affects their quality of life. Materials and Methods: We conducted a multicenter, cross-sectional study from 11 November 2023 to 20 March 2024 in healthcare units in Western Greece. All 96 participants were adult caregivers of patients diagnosed with multiple sclerosis (MS). We assessed caregivers’ quality of life and stress levels using the 36-item Short Form Health Survey and Kingston Caregiver Stress Scale, respectively. Non-parametric tests (Spearman’s rho test, Kruskal–Wallis and Mann–Whitney tests) were used to identify possible correlations between the aforementioned scales and between stress levels and caregiver characteristics. Results: Caregivers reported high stress, with an average KCSS score of 36.82 ± 0.851. The mean SF-36 physical component summary score (PCS) was 59.59 ± 2.77, whereas the mental component summary score (MCS) was 45.69 ± 2.32. Stress levels in the KCSS were negatively correlated with both PCS and MCS of SF-36 and female gender, education level, monthly income, limits of mobility, and patient’s level of dependence were associated with higher levels of stress. Conclusions: Stress was found to be negatively connected with caregivers’ quality of life, affecting both physical and mental health. Female caregivers, caregivers with a primary education level and a low monthly income, and caregivers of patients with serious illnesses who rely primarily on daily help were the most affected.
Mathematical Modeling of Transient Submerged Entry Nozzle Clogging and Its Effect on Flow Field, Bubble Distribution and Interface Fluctuation in Slab Continuous Casting Mold
Authors: Li Yuntong , He Wenyuan , Zhao Changliang , Liu Jianqiu , Yang Zeyu , Zhao Yuhang , Yang Jian
Published: June 2024

Submerged entry nozzle (SEN) clogging will affect the production efficiency and product quality in the continuous casting process. In this work, the transient SEN clogging model is developed by coupling the porous media model defined by the user-defined function (UDF) and the discrete phase model (DPM). The effects of the transient SEN clogging process on the flow field, the distribution of argon gas bubbles and the fluctuation of the interface between steel and slag in the concave bottom SEN in the continuous casting slab mold with a cross-section of 1500 mm × 230 mm are studied by coupling transient SEN clogging model, DPM and volume of fluid (VOF) model. The results show that the actual morphology and thicknesses of SEN clogging are in good agreement with the numerical simulation results. The measurement result of the surface velocity is consistent with the numerical simulation result. With increasing the simulation time, the degree of SEN clogging increases. The flow velocities of molten steel flowing from the outlet of the side hole increase, because the flow space is occupied with the clogging inclusions, which leads to the increased number of argon gas bubbles near the narrow wall. The steel–slag interface fluctuation near the narrow walls also increases, resulting in the increased risk of slag entrapment.
Design of Broadband High-Frequency Multi-Throw RF-MEMS Switches
Authors: Yu Jian , Zhang Maoyun , Li Jing , Si Yuheng , Zhu Zijun , Wu Qiannan , Li Mengwei
Published: June 2024

This paper introduces a broadband triple-pole triple-throw (3P3T) RF MEMS switch with a frequency range from DC to 380 GHz. The switch achieves precise signal control and efficient modulation through its six-port design. It achieves an insertion loss of −0.66 dB across its frequency range, with isolation and return loss metrics of −32 dB and −15 dB, respectively. With its low actuation voltage of 6.8 V and rapid response time of 2.28 μs, the switch exemplifies power-efficient and prompt switching performance. The compact design is ideal for integration into space-conscious systems. This switch is pivotal for 6G research and has potential applications in satellite communications, military radar systems, and next-generation radio applications that require multi-antenna access.
Enhancement of Electrical Safe Operation Area of 60 V nLDMOS by Engineering of Reduced Surface Electrical Field in the Drift Region
Authors: Li Lianjie , Zhu Bao , Wu Xiaohan , Ding Shijin
Published: June 2024

To enhance the electrical safe operation area (eSOA) of laterally diffused metal oxide semiconductor (LDMOS) transistors, a novel reduced surface electric field (Resurf) structure in the n-drift region is proposed, which was fabricated by ion implantation at the surface of the LDMOS drift region and by drift region dimension optimization. Technology computer-aided design (TCAD) simulations show that the optimal value of Resurf ion implantation dose 1 × 1012 cm−2 can reduce the surface electric field in the n-drift region effectively, thereby improving the ON-state breakdown voltage of the device (BVon). In addition, the extended n-drift region length of the Ld design also improves device BVon significantly, and is aimed at reducing the current density and the electric field, and eventually suppressing the n-drift region impact ionization. The results show that the novel 60 V nLDMOS has a competitive BVon performance of 106.9 V, which is about 20% higher than that of the conventional one. Meanwhile, the OFF-state breakdown voltage of the device (BVoff) of 88.4 V and the specific ON-resistance (RON,sp) of 129.7 mΩ⋅mm2 exhibit only a slight sacrifice.
Arbuscular Mycorrhizal Fungi as Biostimulant and Biocontrol Agents: A Review
Authors: Delaeter Mathieu , Magnin-Robert Maryline , Randoux Béatrice , Lounès-Hadj Sahraoui Anissa
Published: June 2024

Arbuscular mycorrhizal fungi (AMF) are soil microorganisms living in symbiosis with most terrestrial plants. They are known to improve plant tolerance to numerous abiotic and biotic stresses through the systemic induction of resistance mechanisms. With the aim of developing more sustainable agriculture, reducing the use of chemical inputs is becoming a major concern. After providing an overview on AMF history, phylogeny, development cycle and symbiosis benefits, the current review aims to explore the potential of AMF as biostimulants and/or biocontrol agents. Nowadays, AMF inoculums are already increasingly used as biostimulants, improving mineral nutrient plant acquisition. However, their role as a promising tool in the biocontrol market, as an alternative to chemical phytosanitary products, is underexplored and underdiscussed. Thus, in the current review, we will address the mechanisms of mycorrhized plant resistance to biotic stresses induced by AMF, and highlight the various factors in favor of inoculum application, but also the challenges that remain to be overcome.
Spatiotemporal Variations in Co-Occurrence Patterns of Planktonic Prokaryotic Microorganisms along the Yangtze River
Authors: Du Wenran , Li Jiacheng , Zhang Guohua , Yu Ke , Liu Shufeng
Published: June 2024

Bacteria and archaea are foundational life forms on Earth and play crucial roles in the development of our planet’s biological hierarchy. Their interactions influence various aspects of life, including eukaryotic cell biology, molecular biology, and ecological dynamics. However, the coexistence network patterns of these microorganisms within natural river ecosystems, vital for nutrient cycling and environmental health, are not well understood. To address this knowledge gap, we systematically explored the non-random coexistence patterns of planktonic bacteria and archaea in the 6000-km stretch of the Yangtze River by using high-throughput sequencing technology. By analyzing the O/R ratio, representing the divergence between observed (O%) and random (R%) co-existence incidences, and the module composition, we found a preference of both bacteria and archaea for intradomain associations over interdomain associations. Seasons notably influenced the co-existence of bacteria and archaea, and archaea played a more crucial role in spring as evidenced by their predominant presence of interphyla co-existence and more species as keystone ones. The autumn network was characterized by a higher node or edge number, greater graph density, node degree, degree centralization, and nearest neighbor degree, indicating a more complex and interconnected structure. Landforms markedly affected microbial associations, with more complex networks and more core species found in plain and non-source areas. Distance-decay analysis suggested the importance of geographical distance in shaping bacteria and archaea co-existence patterns (more pronounced in spring). Natural, nutrient, and metal factors, including water temperature, NH4+-N, Fe, Al, and Ni were identified as crucial determinants shaping the co-occurrence patterns. Overall, these findings revealed the dynamics of prokaryotic taxa coexistence patterns in response to varying environmental conditions and further contributed to a broader understanding of microbial ecology in freshwater biogeochemical cycling.
Middle Silurian–Middle Devonian Magmatic Rocks in the Eastern Segment of the Northern Margin of the North China Craton: Implications for Regional Tectonics
Authors: Li Bin , Chen Jingsheng , Yang Fan , Liu Miao , Zang Yanqing , Zhang Chao
Published: June 2024

This paper presents a detailed study including LA-ICP-MS zircon U-Pb dating, geochemical, zircon Hf isotope, and whole rock Sr-Nd isotope analysis of magmatic rocks from the Yitong County, Jilin Province, NE China. These data are used to better constrain the Middle Silurian–Middle Devonian tectonic evolution in the eastern segment of the northern margin of the North China Craton (NCC). Zircon U-Pb dating results show that the Ximangzhang tonalite formed in the Late Silurian (425 ± 6 Ma); the basalt, andesite, and metamorphic olivine-bearing basalt in the Fangniugou volcanic rocks formed in the Middle Silurian (428 ± 6.6 Ma) and Middle Devonian (388.4 ± 3.9 Ma, and 384.1 ± 4.9 Ma). The Late Silurian tonalites are characterized by high SiO2 and Na2O and low K2O, MgO, FeOT, and TiO2, with an A/CNK ratio of 0.91–1.00, characteristic of calc-alkaline I-type granite. They are enriched in Rb, Ba, Th, U, and K, and depleted in Nb, Sr, P, and Ti, with positive εNd(t) (+0.35) and εHf(t) (+0.44 to +6.31) values, suggesting that they mainly originated from the partial melting of Meso–Neoproterozoic accretionary lower crustal material (basalt). The Middle Silurian basalts are characterized by low SiO2, P2O5, TiO2, and Na2O and high Al2O3, FeOT, and K2O, enriched in Rb, Ba, Th, U, and K and depleted in Nb, Ta, Sr, P, and Ti, indicative of shoshonitic basalt. The Late Silurian tonalites have positive εNd(t) (+4.91 to +6.18) values and primarily originated from depleted mantle magmas metasomatized by subduction fluids, supplemented by a small amount of subducted sediments and crustal materials. The Middle Devonian volcanic rocks exhibit low SiO2, TiO2, and Na2O and high K2O, and MgO, enriched in Rb, K, and LREEs and depleted in Nb, Ta, Sr, and HREEs, characteristic of shoshonitic volcanic rocks. Their εNd(t) (+2.11 to +3.77) and εHf(t) (+5.90 to +11.73) values are positive. These characteristics indicate that the Middle Devonian volcanic rocks primarily originated from depleted mantle magmas metasomatized by subduction fluids, with the addition of crustal materials or subducted sediments during their formation. Based on regional geological data, it is believed that the study area underwent the following evolutionary stages during the Silurian–Devonian period: (1) active continental margin stage of southward subduction of the Paleo–Asian Ocean (PAO) (443–419 Ma); (2) arc-continent collision stage (419–405 Ma); (3) post-collision extension stage (404–375 Ma); (4) active continental margin stage, with the PAO plate subducting southward once again (375–360 Ma).
Enhancement of Photodetector Characteristics by Zn-Porphyrin-Passivated MAPbBr3 Single Crystals
Authors: Soopy Abdul Kareem Kalathil , Liu Shengzhong (Frank) , Najar Adel
Published: June 2024

Perovskite single crystals have garnered significant interest in photodetector applications due to their exceptional optoelectronic properties. The outstanding crystalline quality of these materials further enhances their potential for efficient charge transport, making them promising candidates for next-generation photodetector devices. This article reports the synthesis of methyl ammonium lead bromide (MAPbBr3) perovskite single crystal (SC) via the inverse-temperature crystallization method. To further improve the performance of the photodetector, Zn-porphyrin (Zn-PP) was used as a passivating agent during the growth of SC. The optical characterization confirmed the enhancement of optical properties with Zn-PP passivation. On single-crystal surfaces, integrated photodetectors are fabricated, and their photodetection performances are evaluated. The results show that the single-crystalline photodetector passivated with 0.05% Zn-PP enhanced photodetection properties and rapid response speed. The photoelectric performance of the device, including its responsivity (R), external quantum efficiency (EQE), detective nature (D), and noise-equivalent power (NEP), showed an enhancement of the un-passivated devices. This development introduces a new potential to employ high-quality perovskite single-crystal-based devices for more advanced optoelectronics.
P-Type ZnO Films Made by Atomic Layer Deposition and Ion Implantation
Authors: Zhang Guoxiu , Rebohle Lars , Ganss Fabian , Dawidowski Wojciech , Guziewicz Elzbieta , Koh Jung-Hyuk , Helm Manfred , Zhou Shengqiang , Liu Yufei , Prucnal Slawomir
Published: June 2024

Zinc oxide (ZnO) is a wide bandgap semiconductor that holds significant potential for various applications. However, most of the native point defects in ZnO like Zn interstitials typically cause an n-type conductivity. Consequently, achieving p-type doping in ZnO is challenging but crucial for comprehensive applications in the field of optoelectronics. In this work, we investigated the electrical and optical properties of ex situ doped p-type ZnO films. The p-type conductivity has been realized by ion implantation of group V elements followed by rapid thermal annealing (RTA) for 60 s or flash lamp annealing (FLA) on the millisecond time scale in nitrogen or oxygen ambience. The phosphorus (P)-doped ZnO films exhibit stable p-type doping with a hole concentration in the range of 1014 to 1018 cm−3, while antimony (Sb) implantation produces only n-type layers independently of the annealing procedure. Microstructural studies of Sb-doped ZnO show the formation of metallic clusters after ms range annealing and SbZn-oxides after RTA.
A 28-Day Repeated Oral Administration Study of Mechanically Fibrillated Cellulose Nanofibers According to OECD TG407
Authors: Yamashita Yoshihiro , Tokunaga Akinori , Aoki Koji , Ishizuka Tamotsu , Fujita Satoshi , Tanoue Shuichi
Published: June 2024

The impact of oral administration of mechanically fibrillated cellulose nanofibers (fib-CNF), a commonly used nanofiber, on toxicity and health remains unclear, despite reports of the safety and beneficial effects of chitin-based nanofibers. Thus, evaluating the oral toxicity of fib-CNF in accordance with OECD Test Guideline 407 (TG407) is essential. This study aimed to assess the safety of orally administered fib-CNF through an acute toxicity study in rats, following the OECD TG407 guidelines for 4 weeks. CNF “BiNFi-s” FMa-10005, derived from mechanically fibrillated pulp cellulose, was administered via gavage to male and female Crl:CD(SD) rats at doses of 50, 150, 500, and 1000 mg/kg/day for 28 days, with a control group receiving water for injection. The study evaluated the toxic effects of repeated administration, and the rats were monitored for an additional 14 days post-administration to assess recovery from any toxic effects. The results showed no mortality in either sex during the administration period, and no toxicological effects related to the test substance were observed in various assessments, including general condition and behavioral function observations, urinalysis, hematological examination, blood biochemical examination, necropsy findings, organ weights, and histopathological examination. Notably, only female rats treated with 1000 mg/kg/day of CNF exhibited a consistent reduction in body weight during the 14-day recovery period after the end of treatment. They also showed a slight decrease in pituitary and liver weights. However, hematological and blood biochemical tests did not reveal significant differences, suggesting a potential weight-suppressive effect of CNF ingestion.
Changes in Ammonium-to-Nitrate Ratio along Faidherbia albida Tree Age Gradients in Arenosols
Authors: Amare Solomon , Haile Mitiku , Birhane Emiru
Published: June 2024

Faidherbia albida can enhance the bio-physicochemical fertility of inherently infertile Arenosols. Changes in the soil ammonium (NH4+)-to-nitrate (NO3−) ratio have agricultural, environmental, and ecological implications. Thus, the present study mainly examined the changes in Arenosol NH4+/NO3− ratios, as influenced by varying Faidherbia albida tree age classes. We collected 40 composite soil samples (4 tree age classes×2 soil depths×5 replications) from 0 to 15 and 15 to 30 cm soil depths following core and auger sampling techniques. Analyses of variance have shown that the highest NH4+/NO3− ratios for soil under the old tree canopies are followed by the medium age. In contrast, the significantly lowest NH4+/NO3− ratios were recorded for soil out-of-canopy. Pearson correlation analysis revealed that the NH4+/NO3− ratio was strongly and positively correlated with clay content, total nematode abundance, the fungi/bacterial biomass ratio, cation exchange capacity, microbial biomass carbon, total nitrogen, and soil organic carbon but negative for sand content, bulk density, and pH. The increment in the plant-available forms of nitrogen might be attributed to the accumulation of biologically fixed nitrogen by the Faidherbia albida tree–Rhizobium bacteria symbiosis. The NH4+/NO3− ratio approached one in soil under the old Faidherbia albida trees. The findings suggest that (1) the ability of soil to retain NH4+ increased and (2) the rate of nitrification might be decreased due to inhibition of nitrification by direct and indirect effects of the tree on the nitrifying group of bacteria. The increment in the NH4+/NO3− ratio could also be due to the lowering of the soil’s pH in the older Faidherbia albida trees because lower pH is known to inhibit the activities of nitrifying bacteria. Moreover, maintaining older Faidherbia albida trees in farmlands could contribute to retaining nitrogen and trigger below- and above-ground communities’ successions and ultimately surpass the productivity of arid and semi-arid Arenosols.
Post Natal Microbial and Metabolite Transmission: The Path from Mother to Infant
Authors: Vélez-Ixta Juan Manuel , Juárez-Castelán Carmen Josefina , Ramírez-Sánchez Daniela , Lázaro-Pérez Noemí del Socorro , Castro-Arellano José Javier , Romero-Maldonado Silvia , Rico-Arzate Enrique , Hoyo-Vadillo Carlos , Salgado-Mancilla Marisol , Gómez-Cruz Carlos Yamel , Krishnakumar Aparna , Piña-Escobedo Alberto , Benitez-Guerrero Tizziani , Pizano-Zárate María Luisa , Cruz-Narváez Yair , García-Mena Jaime
Published: June 2024

The entero–mammary pathway is a specialized route that selectively translocates bacteria to the newborn’s gut, playing a crucial role in neonatal development. Previous studies report shared bacterial and archaeal taxa between human milk and neonatal intestine. However, the functional implications for neonatal development are not fully understood due to limited evidence. This study aimed to identify and characterize the microbiota and metabolome of human milk, mother, and infant stool samples using high-throughput DNA sequencing and FT-ICR MS methodology at delivery and 4 months post-partum. Twenty-one mothers and twenty-five infants were included in this study. Our results on bacterial composition suggest vertical transmission of bacteria through breastfeeding, with major changes occurring during the first 4 months of life. Metabolite chemical characterization sheds light on the growing complexity of the metabolites. Further data integration and network analysis disclosed the interactions between different bacteria and metabolites in the biological system as well as possible unknown pathways. Our findings suggest a shared bacteriome in breastfed mother–neonate pairs, influenced by maternal lifestyle and delivery conditions, serving as probiotic agents in infants for their healthy development. Also, the presence of food biomarkers in infants suggests their origin from breast milk, implying selective vertical transmission of these features.
More Adult Women than Men at High Cardiometabolic Risk Reported Worse Lifestyles and Self-Reported Health Status in the COVID-19 Lockdown
Authors: Oncina-Cánovas Alejandro , Compañ-Gabucio Laura , Vioque Jesús , Ruiz-Canela Miguel , Corella Dolores , Salas-Salvadó Jordi , Fitó Montserrat , Martínez Alfredo , Alonso-Gómez Ángel M. , Wärnberg Julia , Romaguera Dora , López-Miranda José , Estruch Ramón , Tinahones Francisco J. , Lapetra José , Álvarez-Pérez Jacqueline , Bueno-Cavanillas Aurora , Tur Josep A. , Martín-Sánchez Vicente , Esteve-Luque Virginia , Delgado-Rodríguez Miguel , Ortiz-Ramos María , Vidal Josep , Vázquez Clotilde , Daimiel Lidia , Ros Emilio , Razquin Cristina , Paz-Graniel Indira , Sorlí Jose V. , Castañer Olga , García-Rios Antonio , Torres-Collado Laura , Fernández-Barceló Olga , Zulet María Angeles , Rayó-Gago Elena , Casas Rosa , Cano-Ibáñez Naomi , Tojal-Sierra Lucas , Simón-Frapolli Víctor J. , Carlos Silvia , Shyam Sangeetha , Fernández-Carrión Rebeca , Goday Albert , Torres-Peña Jose David , González-Palacios Sandra , Eguaras Sonia , Babio Nancy , Zomeño María Dolores , García-de-la-Hera Manuela
Published: June 2024

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.
Regulations of Citrus Pectin Oligosaccharide on Cholesterol Metabolism: Insights from Integrative Analysis of Gut Microbiota and Metabolites
Authors: Hu Haijuan , Zhang Peipei , Liu Fengxia , Pan Siyi
Published: June 2024

(1) Background: Recently, academic studies are demonstrating that the cholesterol-lowering effects of pectin oligosaccharides (POSs) are correlated to intestinal flora. However, the mechanisms of POS on cholesterol metabolisms are limited, and the observations of intestinal flora are lacking integrative analyses. (2) Aim and methods: To reveal the regulatory mechanisms of POS on cholesterol metabolism via an integrative analysis of the gut microbiota, the changes in gut microbiota structure and metabolite composition after POS addition were investigated using Illumina MiSeq sequencing and non-targeted metabolomics through in vitro gut microbiota fermentation. (3) Results: The composition of fecal gut flora was adjusted positively by POS. POS increased the abundances of the cholesterol-related bacterial groups Bacteroidetes, Bifidobacterium and Lactobacillus, while it decreased conditional pathogenic Escherichia coli and Enterococcus, showing good prebiotic activities. POS changed the composition of gut microbiota fermentation metabolites (P24), causing significant changes in 221 species of fermentation metabolites in a non-targeted metabolomics analysis and promoting the production of short-chain fatty acids. The abundances of four types of cholesterol metabolism-related metabolites (adenosine monophosphate, cyclic adenosine monophosphate, guanosine and butyrate) were significantly higher in the P24 group than those in the control group without POS addition. (4) Conclusion: The abovementioned results may explain the hypocholesterolemic effects of POS and promotion effects on cholesterol efflux of P24. These findings indicated that the potential regulatory mechanisms of citrus POS on cholesterol metabolism are modulated by cholesterol-related gut microbiota and specific metabolites.
The Impact of Vitamin D and L-Cysteine Co-Supplementation on Upregulating Glutathione and Vitamin D-Metabolizing Genes and in the Treatment of Circulating 25-Hydroxy Vitamin D Deficiency
Authors: Jain Sushil K. , Justin Margret Jeffrey , Abrams Steven A. , Levine Steven N. , Bhusal Kamal
Published: June 2024

Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.
Forward & Far-Forward Heavy Hadrons with Jethad: A High-Energy Viewpoint
Authors: Celiberto Francesco Giovanni
Published: June 2024

Inspired by recent findings that semi-inclusive detections of heavy hadrons exhibit fair stabilization patterns in high-energy resummed distributions against (missing) higher-order corrections, we review and extend our studies on the hadroproduction of light and heavy hadrons tagged in forward and far-forward rapidity ranges. We analyze the NLL/NLO+ behavior of rapidity rates and angular multiplicities via the Jethad method, where the resummation of next-to-leading energy logarithms and beyond is consistently embodied in the collinear picture. We explore kinematic regions that are within LHC typical acceptances, as well as novel sectors accessible thanks the combined tagging of a far-forward light or heavy hadron at future Forward Physics Facilities and a of central particle at LHC experiments via a precise timing-coincidence setup.
Hepatitis C Virus and Molecular Mimicry
Authors: Goh Lynette , Kerkar Nanda
Published: June 2024

This review delves into the interactions between hepatitis C virus (HCV) and the host immune system, shedding light on how by using the mechanism of molecular mimicry, the virus strategically evades the immune system, resulting in a cascade of diverse complications. HCV, notorious for its ability to persistently infect hepatocytes, employs molecular mimicry to resemble host proteins, thereby avoiding immune detection and mounting an effective defense. This mimicry also triggers systemic autoimmune responses that lead to various sequelae. The objective of this review is to comprehensively explore the role of HCV-induced molecular mimicry, which not only facilitates viral survival but is also instrumental in developing autoimmune and inflammatory disorders. By mimicking host proteins, HCV triggers an immune response that inadvertently attacks the host, fostering the development of autoimmune and other inflammatory disorders. Understanding the nuanced mechanisms of HCV-mediated molecular mimicry provides crucial insights into the multifaceted sequelae of viral infections on host immune responses. Unravelling these complexities is paramount for advancing therapeutic strategies that not only target the virus directly but also mitigate the secondary autoimmune and inflammatory complications induced by HCV.
Predicting Drugs Suspected of Causing Adverse Drug Reactions Using Graph Features and Attention Mechanisms
Authors: Yang Jinxiang , Hu Zuhai , Zhang Liyuan , Peng Bin
Published: June 2024

Background: Adverse drug reactions (ADRs) refer to an unintended harmful reaction that occurs after the administration of a medication for therapeutic purposes, which is unrelated to the intended pharmacological action of the drug. In the United States, ADRs account for 6% of all hospital admissions annually. The cost of ADR-related illnesses in 2016 was estimated at USD 528.4 billion. Increasing the awareness of ADRs is an effective measure to prevent them. Assessing suspected drugs in adverse events helps to enhance the awareness of ADRs. Methods: In this study, a suspect drug assisted judgment model (SDAJM) is designed to identify suspected drugs in adverse events. This framework utilizes the graph isomorphism network (GIN) and an attention mechanism to extract features based on patients’ demographic information, drug information, and ADR information. Results: By comparing it with other models, the results of various tests show that this model performs well in predicting the suspected drugs in adverse reaction events. ADR signal detection was conducted on a group of cardiovascular system drugs, and case analyses were performed on two classic drugs, Mexiletine and Captopril, as well as on two classic antithyroid drugs. The results indicate that the model can accomplish the task of predicting drug ADRs. Validation using benchmark datasets from ten drug discovery domains shows that the model is applicable to classification tasks on the Tox21 and SIDER datasets. Conclusions: This study applies deep learning methods to construct the SDAJM model for three purposes: (1) identifying drugs suspected to cause adverse drug events (ADEs), (2) predicting the ADRs of drugs, and (3) other drug discovery tasks. The results indicate that this method can offer new directions for research in the field of ADRs.
Sexual Dysfunction Induced by Antidepressants—A Pharmacovigilance Study Using Data from VigiBaseTM
Authors: Zeiss Rene , Malejko Kathrin , Connemann Bernhard , Gahr Maximilian , Durner Verena , Graf Heiko
Published: June 2024

Sexual dysfunction is a common side effect of antidepressants, significantly impacting patients’ quality of life and treatment adherence. This study investigates the relationship between sexual dysfunction and antidepressants by analyzing data from VigiBase™, the World Health Organization’s global database of individual case safety reports. In this study, we examined, for the first time, reports related to sexual response—desire, arousal, and orgasm—by grouping appropriate side effect terms and calculated the reporting odds ratios (RORs) for various antidepressants. The findings of this study highlight a high disproportional reporting of sexual dysfunction, particularly with selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors. In contrast, agents such as agomelatine, bupropion, and mirtazapine showed a lower association. Furthermore, we investigated the correlation between reporting odds ratios and the binding affinities of antidepressants to specific neurotransmitter receptors and transporters, unveiling significant relationships that provide insights into the pharmacodynamic pathways underlying these adverse effects. For instance, a positive correlation was observed between the serotonin transporter and side effects in the category desire: r (19) = 0.67, p = 0.001 These insights underscore the necessity for clinicians to consider sexual side effects when prescribing antidepressants and to monitor and address these issues to improve patient outcomes.
Polymeric Microneedles Enhance Transdermal Delivery of Therapeutics
Authors: Nguyen Hiep X. , Kipping Thomas , Banga Ajay K.
Published: June 2024

This research presents the efficacy of polymeric microneedles in improving the transdermal permeation of methotrexate across human skin. These microneedles were fabricated from PLGA Expansorb® 50-2A and 50-8A and subjected to comprehensive characterization via scanning electron microscopy, Fourier-transform infrared spectroscopy, and mechanical analysis. We developed and assessed a methotrexate hydrogel for physicochemical and rheological properties. Dye binding, histological examinations, and assessments of skin integrity demonstrated the effective microporation of the skin by PLGA microneedles. We measured the dimensions of microchannels in the skin using scanning electron microscopy, pore uniformity analysis, and confocal microscopy. The skin permeation and disposition of methotrexate were researched in vitro. PLGA 50-8A microneedles appeared significantly longer, sharper, and more mechanically uniform than PLGA 50-2A needles. PLGA 50-8A needles generated substantially more microchannels, as well as deeper, larger, and more uniform channels in the skin than PLGA 50-2A needles. Microneedle insertion substantially reduced skin electrical resistance, accompanied by an elevation in transepidermal water loss values. PLGA 50-8A microneedle treatment provided a significantly higher cumulative delivery, flux, diffusion coefficient, permeability coefficient, and predicted steady-state plasma concentration; however, there was a shorter lag time than for PLGA 50-2A needles, base-treated, and untreated groups (p < 0.05). Conclusively, skin microporation using polymeric microneedles significantly improved the transdermal delivery of methotrexate.
Investigation of the Electrokinetic Potential of Granules and Optimization of the Pelletization Method Using the Quality by Design Approach
Authors: Mahmoud Azza A. K. , Hassan Alharith A. A. , Dobó Dorina Gabriella , Ludasi Krisztina , Janovák László , Regdon Géza , Csóka Ildikó , Kristó Katalin
Published: June 2024

The preparation of pellets using a high-shear granulator in a rapid single-step is considered a good economic alternative to the extrusion spheronization process. As process parameters and material attributes greatly affect pellet qualities, successful process optimization plays a vital role in producing pellet dosage forms with the required critical quality attributes. This study was aimed at the development and optimization of the pelletization technique with the Pro-CepT granulator. According to the quality by design (QbD) and screening design results, chopper speed, the volume of the granulating liquid, binder amount, and impeller speed were selected as the highest risk variables for a two-level full factorial design and central composite design, which were applied to the formula of microcrystalline cellulose, mannitol, and with a binding aqueous polyvinylpyrrolidone solution. The design space was estimated based on physical response results, including the total yield of the required size, hardness, and aspect ratio. The optimized point was tested with two different types of active ingredients. Amlodipine and hydrochlorothiazide were selected as model drugs and were loaded into an optimized formulation. The kinetics of the release of the active agent was examined and found that the results show a correlation with the electrokinetic potential because amlodipine besylate can be adsorbed on the surface of the MCC, while hydrochlorothiazide less so; therefore, in this case, the release of the active agent increases. The research results revealed no significant differences between plain and model drug pellets, except for hydrochlorothiazide yield percent, in addition to acceptable content uniformity and dissolution enhancement.
Development of an Educational Brochure about Treatment Options for Pregnant Women with Opioid Use Disorders
Authors: Jeminiwa Ruth , Park Sohyeon , Popielaski Caroline , Gannon Meghan , Myers Ronald , Abatemarco Diane J.
Published: June 2024

The goal of this study was to describe the development of an educational brochure for pregnant women with opioid use disorders (OUDs) about treatment options. Based on findings from a preliminary review of the literature, we drafted a brochure that addressed the following questions: (1) What are your options (Medication-Assisted Treatment (MAT) versus no treatment)? (2) What are the benefits of MAT? (3) What are the risks of MAT? (4) Can I take buprenorphine or methadone while breastfeeding? (5) Which medication should I choose? Clinicians and doulas (n = 19) who provide care to pregnant women with OUDs were recruited. Semi-structured interviews elicited participants’ feedback on brochure content and their perceptions about brochure use for patient education. Thematic data analyses were performed. Three emergent themes were identified (suggested uses and settings of use, content revisions, and perceptions about the brochure) and used to refine the final brochure. This study provides valuable insights into the desired content of an educational brochure describing treatment options for pregnant women with OUDs from the provider’s standpoint. Research is needed to assess the use of the brochure in shared decision-making conversations with providers about treatment.
Microwave Photonic Frequency Multiplier with Low Phase Noise Based on an Optoelectronic Oscillator
Authors: Luo Hao , Yu Jinlong , Wang Ju , Ma Chuang , Han Xu , Su Xuemin , Gao Ye , Jia Shi
Published: June 2024

A microwave photonic frequency multiplier with low phase noise based on an optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. In this scheme, a dual-parallel Mach–Zehnder modulator (DPMZM) is employed to generate the third-harmonic frequency of the input radio frequency (RF) signal, while the oscillation frequency of the OEO is also three times the RF signal frequency. By adjusting the bias voltages of different arms in the DPMZM, a triple-frequency signal with a high side-mode suppression ratio of 64.8 dB can be obtained. The experimental results indicate that the output of the frequency-multiplier has a better single-sideband phase noise value, for instance, −126 dBc/Hz@10 kHz at 20.019 GHz. It has improvements of 34 dB and 43.5 dB compared with the input RF signal and the simulated electrical frequency tripler module, respectively.
New Cultivars of Galanthus nivalis in Slovenia
Authors: Bavcon Jože , Ravnjak Blanka
Published: June 2024

In Slovenia there is only one species of common snowdrop (Galanthus nivalis L.) that occurs in all four of its phytogeographical regions. Slovenia is located in the center of the distribution of this species. At some sites the subpopulations of snowdrop are common and abundant, but at other sites they may consist of only a few individuals within small populations. Galanthus nivalis occurs in a diversity of habitats and individual plants within stands are extremely variable in many of their characteristics. The purpose of this research is to determine the diversity within the species and to identify new stable variants that are interesting for horticultural purposes and use. We examined plants in populations that were the most diverse and isolated individual characteristics from them, which we then cultivated for several years and determined their stability. We found two new varieties that have a very distinctive smell, and one of the new varieties retains its outer perigone leaves completely closed at the end of flowering. The new varieties belong to three different groups: the Skirt group, the Imperial group and the Green group.
First Gynogenesis of Vanilla planifolia for Haploid Production and Ploidy Verification Protocol
Authors: Gastelbondo Manuel , Nicholls Ursula , Chen Sisi , Chambers Alan , Wu Xingbo
Published: June 2024

Vanilla orchids are members of the Vanilloideae orchid subfamily, and they hold significant economic value as a spice crop in tropical regions. Despite the presence of 180 known species within this subfamily, commercial production focuses on only three species (Vanilla planifolia, V. odorata, and V. pompona) and one hybrid (V. × tahitensis), prized for their aromatic qualities and bioactive compounds. Limited modern breeding initiatives have been undertaken with vanilla orchids, although recent advancements in genomic research are shedding light on this crop’s potential. The protracted breeding cycle of vanilla, coupled with increasing demand for germplasm, underscores the importance of research and breeding efforts in vanilla. This paper outlines a protocol for haploid production in V. planifolia using unfertilized ovaries in tissue culture conditions. Additionally, we present a methodology to confirm the haploid nature of putative haploid lines through stomatal size comparison, chromosome counting, and flow cytometry analysis, proving the successful development of haploid vanilla plants. These findings contribute to the advancement of breeding programs and genetic improvement strategies for the vanilla industry.
Biochar Effectively Promoted Growth of Ardisia crenata by Affecting the Soil Physicochemical Properties
Authors: Niu Muqi , Chen Xiuming , Pan Yun , Wang Shunshun , Xue Luyu , Duan Yanru , Ahmad Sagheer , Zhou Yuzhen , Zhao Kai , Peng Donghui
Published: June 2024

Biochar is regarded as a soil improvement material possessing superior physical and chemical properties that can effectively enhance plant growth. However, there exists a paucity of research examining the efficacy of biochar in supplanting traditional materials and its subsequent impact on the growth of Ardisia crenata, which is currently domesticated as fruit ornamentals. In this study, the mechanism of biochar’s effect on Ardisia crenata was analyzed by controlled experiments. For 180 days, their growth and development were meticulously assessed under different treatments through the measurement of various indices. Compared with the references, the addition of biochar led to an average increase in soil nutrient content, including a 14.1% rise in total nitrogen, a 564.1% increase in total phosphorus, and a 63.2% boost in total potassium. Furthermore, it improved the physical and chemical properties of the soil by reducing soil bulk density by 6.2%, increasing total porosity by 6.33%, and enhancing pore water by 7.35%, while decreasing aeration porosity by 1.11%. The growth and development of Ardisia crenata were better when the appending ratio of biochar was in the range of 30% to 50%, with the root parameters, such as root length, root surface area, and root volume, 48.90%, 62.00%, and 24.04% higher to reference. At the same time, the biomass accumulation of roots in the best group with adding biochar also increased significantly (55.80%). The addition of biochar resulted in a significant improvement in the content of chlorophyll a and chlorophyll b (1.947 mg g−1) and the net photosynthetic rate (5.6003 µmol m−2 s−1). This study’s findings underpinned the addition of biochar in soil improvement and plant response. Therefore, biochar can favor the cultivation and industrial application of Ardisia crenata in the future, leading to an efficient and environmentally friendly industrial development.