bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of atopic dermatitis with upadacitinib: adcare single center experience
Authors: Fomina Daria S. , Mukhina Olga A. , Mikhailova Valeria I. , Lebedkina Marina S. , Sedova Elizaveta L. , Bobrikova Elena N. , Elisyutina Olga G. , Fedenko Elena S. , Nurpeisov Tair T. , Karaulov Alexander V. , Lysenko Mar’yana A. , Ensina Luis Felipe C. 
Published: April 2024

IntroductionThe role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment.MethodsIn this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests.ResultsSixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.
Comparison of the fecal microbiota of adult healthy dogs fed a plant-based (vegan) or an animal-based diet
Authors: Liversidge Brooklynn D. , Gomez Diego E. , Dodd Sarah A. S. , MacNicol Jennifer L. , Adolphe Jennifer L. , Blois Shauna L. , Verbrugghe Adronie 
Published: April 2024

PurposePet guardians are increasingly seeking vegan dog foods. However, research on the impact of these diets on gastrointestinal (GI) physiology and health is limited. In humans, vegan diets modify the GI microbiota, increasing beneficial digestive microorganisms. This study aimed to examine the canine fecal microbiota in response to a vegan diet compared to an animal-based diet.MethodsSixty-one client-owned healthy adult dogs completed a randomized, double-blinded longitudinal study. Dogs were randomly assigned into two groups that were fed either a commercial extruded animal-based diet (MEAT, n = 30) or an experimental extruded vegan diet (PLANT, n = 31) for 12 weeks. Fecal collections occurred at the start of the experimental period and after 3 months of exclusively feeding either diet. Bacterial DNA was extracted from the feces, and the V4 region of the 16S rRNA gene was amplified using PCR and sequenced on Illumina MiSeq. Beta-diversity was measured using Jaccard and Bray–Curtis distances, and the PERMANOVA was used to assess for differences in fecal microbiota within and between groups. Alpha-diversity indices for richness, evenness, and diversity, as well as relative abundance, were calculated and compared between groups.ResultsBeta-diversity differences occurred between diet groups at exit time-point with differences on Bray–Curtis distances at the family and genus levels (p = 0.007 and p = 0.001, respectively), and for the Jaccard distance at the family and genus level (p = 0.006 and p = 0.011, respectively). Significant differences in alpha-diversity occurred when comparing the PLANT to the MEAT group at the exit time-point with the PLANT group having a lower evenness (p = 0.012), but no significant differences in richness (p = 0.188), or diversity (p = 0.06). At exit-timepoint, compared to the MEAT group, the relative abundance of Fusobacterium, Bacteroides, and Campylobacter was lower in the PLANT group. The relative abundance of Fusobacterium decreased over time in the PLANT group, while no change was observed in the MEAT group.ConclusionThese results indicate that vegan diets may change the canine gut microbiota. Future studies are warranted to confirm our results and determine long-term effects of vegan diets on the canine gut microbiome.
Antifungal mechanism of cell-free supernatant produced by Trichoderma virens and its efficacy for the control of pear Valsa canker
Authors: Zhang Yang , Lu Ying , Jin Zhaoyang , Li Bo , Wu Li , He Yujian 
Published: April 2024

IntroductionPear Valsa canker, caused by Valsa pyri (V. pyri), poses a major threat to pear production. We aimed to assess the effectiveness of the cell-free supernatant (CFS) produced by Trichoderma virens (T. virens) to control the development of pear Valsa canker and reveal the inhibitory mechanism against the pathogenic fungi.ResultsUsing morphological characteristics and phylogenetic analysis, the pathogen G1H was identified as V. pyri, and the biocontrol fungus WJ561 was identified as Trichoderma virens. CFS derived from WJ561 exhibited strong inhibition of mycelial growth and was capable of reducing the pathogenicity of V. pyri on pear leaves and twigs. Scanning electron microscopy (SEM) observations revealed deformations and shrinkages in the fungal hyphae treated with CFS. The CFS also destroyed the hyphal membranes leading to the leakage of cellular contents and an increase in the malondialdehyde (MDA) content. Additionally, CFS significantly inhibited the activities of catalase (CAT) and superoxide dismutase (SOD), and downregulated the expression of antioxidant defense-related genes in V. pyri, causing the accumulation of reactive oxygen species (ROS). Artesunate, identified as the main component in CFS by liquid chromatograph-mass spectrometry (LC–MS), exhibited antifungal activity against V. pyri.ConclusionOur findings demonstrate the promising potential of T. virens and its CFS in controlling pear Valsa canker. The primary inhibitory mechanism of CFS involves multiple processes, including membrane damage and negatively affecting enzymatic detoxification pathways, consequently leading to hyphal oxidative damage of V. pyri. This study lays a theoretical foundation for the utilization of T. virens to control V. pyri in practical production.
Trends in cause-specific mortality among persons with Alzheimer’s disease in South Carolina: 2014 to 2019
Authors: Brown Candace S. , Ning Xi , Money Amy , Alford Mauriah , Pan Yinghao , Miller Margaret , Lohman Matthew 
Published: April 2024

IntroductionInconsistencies of reports contributes to the underreporting of Alzheimer’s disease (AD) on death certificates. Whether underreporting exists within South Carolina has not been studied.MethodsWe conducted a prospective, population-based study on a cohort of persons (N = 78,534) previously diagnosed with AD and died between 2014–2019. We linked vital records with the South Carolina Alzheimer’s Disease and Related Dementias Registry to investigate their cause of death and survival rates. Descriptive analyses calculated frequencies of demographic and health-related characteristics. Turnbull’s method estimated the survival probabilities for different subgroups of patients. Hazard ratios were computed from the Cox proportional hazards model, adjusting for the following confounding variables of age at diagnosis, education level, gender, and race.ResultsThe top immediate cause of death was Alzheimer’s disease among all racial groups, except for Native American/American Indian. More females (60.3%) were affected by AD compared to males (39.7%). There is a 25% probability of survival, beyond 5 years, after AD diagnosis. Black/African American AD patients have the smallest risk of all-cause mortality across all racial/ethnic groups (HR 0.87; 95% CI, 0.85–0.89). Individuals with lower education had a lower likelihood of mortality.ConclusionAlthough AD was not underreported in the state of South Carolina further research is needed to develop protocols around classification of deaths among those diagnosed with dementia and comorbidities, including cardiovascular disease, to ensure dementia is properly reported as we move to prevent and treat Alzheimer’s disease by 2025 and beyond.
Causal role of immune cell phenotypes in idiopathic sudden sensorineural hearing loss: a bi-directional Mendelian randomization study
Authors: Li Wanqing , Zhou Qiang , Zhou Linsa , Cao Longhe , Zhu Chuansai , Dai Zhijian , Lin Sen 
Published: April 2024

BackgroundA growing body of evidence suggests that immunological processes have a significant role in developing idiopathic sudden sensorineural hearing loss (SSHL). However, few studies have examined the association between immune cell phenotype and SSHL using Mendelian Randomization (MR).MethodsThe online genome-wide association studies (GWAS) database was used to compile data from GWAS covering 731 immunophenotypes and SSHL. Inverse variance weighted (IVW) analysis was primarily used for MR study, and single nucleotide polymorphisms (SNPs) associated with immunophenotypes served as dependent variables. A sensitivity study and the false discovery rate (FDR) correction were used to examine the MR hypothesis. In addition, the possibility of reverse causality between immunophenotype and SSHL was validated by reverse MR. Reverse MR was analyzed in a manner consistent with forward MR.ResultsAfter FDR correction and sensitivity analysis, we screened 7 immunophenotypes, including IgD+ CD38dim %lymphocyte (95% CI: 1.0019, 1.0742, p = 3.87 × 10−2, FDR = 1.15 × 10−2); Unsw mem AC (95% CI: 1.004, 1.2522, p = 4.23 × 10−2, FDR = 2.25 × 10−2); CD86+ myeloid DC AC (95% CI: 1.0083, 1.1147, p = 2.24 × 10−2, FDR = 4.27 × 10−2); CD33dim HLA DR− AC (95% CI: 1.0046, 1.0583, p = 2.12 × 10−2, FDR = 4.69 × 10−2); SSC-A on CD8br (95% CI: 1.0028, 1.1461, p = 4.12 × 10−2, FDR = 4.71 × 10−2); CD45RA− CD4+ %T cell (95% CI: 1.0036, 1.0503, p = 2.32 × 10−2, FDR = 4.82 × 10−2); DP (CD4+CD8+) AC (95% CI: 1.011, 1.2091, p = 2.78 × 10−2, FDR = 4.97 × 10−2). There was a strong causal relationship with SSHL onset, and the reliability of the results was verified. Furthermore, the immunological cell profile and SSHL did not appear to be closely associated, as shown by reverse MR analysis.ConclusionOur study provides more support for the current hypothesis that immunophenotypes and the pathophysiology of SSHL are closely associated. Further validation is needed to assess the role of these immunophenotypes in SSHL.
A riboflavin transporter deficiency presenting as pure red cell aplasia: a pediatric case report
Authors: Cheng Jingying , Yao Jiafeng , Zhao Shasha , Fu Lingling , Zhang Liqiang , Jiang Jin 
Published: April 2024

IntroductionRiboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure red cell aplasia. Recognizing and understanding its clinical manifestations, diagnosis, and management is important.Case presentationA 2-year-old patient presented with pure red cell aplasia as the primary symptom of RTD. After confirming the diagnosis, rapid reversal of anemia was achieved after high-dose riboflavin treatment.ConclusionRTD often has an insidious onset, and neurological symptoms appear gradually as the disease progresses, making it prone to misdiagnosis. Genetic testing and bone marrow biopsy can confirm the diagnosis.
A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim against Streptococcus suis
Authors: Mi Kun , Sun Lei , Zhang Lan , Tang Aoran , Tian Xiaoyuan , Hou Yixuan , Sun Lingling , Huang Lingli 
Published: April 2024

Introduction: Streptococcus suis (S. suis) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against S. suis. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against S. suis and withdrawal intervals.Methods: The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages.Results: ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety.Discussion: This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs.
The nonvesicular sterol transporter Aster-C plays a minor role in whole body cholesterol balance
Authors: Banerjee Rakhee , Hohe Rachel C. , Cao Shijie , Jung Bryan M. , Horak Anthony J. , Ramachandiran Iyappan , Massey William J. , Varadharajan Venkateshwari , Zajczenko Natalie I. , Burrows Amy C. , Dutta Sumita , Goudarzi Maryam , Mahen Kala , Carter Abigail , Helsley Robert N. , Gordon Scott M. , Morton Richard E. , Strauch Christopher , Willard Belinda , Gogonea Camelia Baleanu , Gogonea Valentin , Pedrelli Matteo , Parini Paolo , Brown J. Mark 
Published: April 2024

Introduction:The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions.Method:Age-matched Gramd1c+/+ and Gramd1c−/− mice were fed either low (0.02%, wt/wt) or high (0.2%, wt/wt) dietarycholesterol and levels of sterol-derived metabolites were assessed in the feces, liver, and plasma.Results:Compared to wild type controls (Gramd1c+/+) mice, mice lackingGramd1c (Gramd1c−/−) have no significant alterations in fecal, liver, or plasma cholesterol. Given the potential role for Aster C in modulating cholesterol metabolism in diverse tissues, we quantified levels of cholesterol metabolites such as bile acids, oxysterols, and steroid hormones. Compared to Gramd1c+/+ controls, Gramd1c−/− mice had modestly reduced levels of select bile acid species and elevated cortisol levels, only under low dietary cholesterol conditions. However, the vast majority of bile acids, oxysterols, and steroid hormones were unaltered in Gramd1c−/− mice. Bulk RNA sequencing in the liver showed that Gramd1c−/− mice did not exhibit alterations in sterol-sensitive genes, but instead showed altered expression of genes in major urinary protein and cytochrome P450 (CYP) families only under low dietary cholesterol conditions.Discussion:Collectively, these data indicate nominal effects of Aster-C on whole body cholesterol transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.
Insights, beliefs, and myths surrounding tuberculosis among pulmonary patients with delayed healthcare access in a high-burden TB state in Nigeria – a qualitative inquiry
Authors: Adeoye Beatrice Damilola , Michael Turnwait Otu , Agbana Richard Dele 
Published: April 2024

IntroductionNigeria grapples with a substantial burden of tuberculosis (TB), particularly in Oyo State, designated as a high-burden State for TB. Effectively addressing this persistent health challenge necessitates more than just medical interventions; it requires a profound understanding of the diverse insights, beliefs, and myths held by TB patients.MethodsThis qualitative study explores the perspectives of pulmonary TB patients with delayed healthcare access in Oyo State, Nigeria, focusing on their beliefs, and conceptions. In-depth interviews were conducted with 25 TB patients and 20 healthcare providers.ResultsThematic analysis of patients’ responses revealed a complex interplay between cultural, spiritual, and biomedical insights. These challenges questioned the germ theory, associating TB with witchcraft and spiritual attacks. Beliefs in hereditary transmission, links between tobacco use and health outcomes, and uncertainties about infection nature underscored disparities influenced by socio-economic factors. Insights into transmission ideas, preventive measures, and treatment beliefs highlighted a blend of culturally influenced and scientifically supported strategies. Healthcare providers’ insights emphasized the necessity for targeted health education.DiscussionThese findings contribute to a nuanced understanding of TB perceptions, emphasizing the importance of culturally sensitive interventions to enhance awareness and promote timely and accurate health-seeking behaviors.
Physio-biochemical and transcriptomic analysis of Bacillus amyloliquefaciens PG-4-induced salt stress tolerance in Macrotyloma uniflorum
Authors: Wu Yanna , Guo Changlin , Xiao Yang , Li Xinyong , Yu Daogeng , Wan Qi , Liu Huizhuan , Zhang Yindong , Zhang Rui , Luo Kai 
Published: April 2024

IntroductionMacrotyloma uniflorum is an important legume fodder crop and green fertilizer. Salinity impedes plant growth and productivity of legume crops by disrupting the ionic and osmotic balance and hormonal regulation. Plant growth-promoting rhizobacteria (PGPR) are rhizosphere bacteria that contribute to the improvement of plant growth through diverse physiological mechanisms.MethodsIn this study, the growth promoting characteristics of the isolated strain Bacillus amyloliquefaciens PG-4 were analyzed, and to further investigated the possible mechanism of PG-4 in mitigating the damage caused by salt stress in M. uniflorum plants through pot experiments.ResultsIn presence of different salt levels, PG-4 showed a high potentiality to produce several plant growth promoting metabolites such as NH3, siderophore, 1-aminocyclopropane-1-carboxylic acid deaminase (ACC-deaminase), and hydrolytic enzymes. Inoculation of the PG-4 significantly enhanced plant tolerance to salt stress, as demonstrated by promotion of plant growth (shoot and root biomass) under salt stress condition. Furthermore, PG-4 improved salt tolerance of Macrotyloma uniflorum seedlings by affecting the antioxidant enzymes including peroxidase (POD) and superoxide dismutase (SOD), by increasing the levels of proline, soluble sugars and chlorophyll. Treatment with PG-4 increased the K+ content while decreased the Na+ concentration level under salt stress. Transcriptomic analysis revealed 5525 genes were differentially expressed (PG-4-inoculated versus non-inoculated samples) at 0 mM NaCl, of which 3277 were upregulated and 2248 downregulated, while 1298 genes were differentially expressed at 100 mM NaCl, of which 819 were upregulated and 479 were downregulated. GO and KEGG enrichment analyses showed that these DEGs were significantly enriched in several terms and pathways mainly involved in the regulation of the cellular redox state, cell wall modification, metabolic adjustments, hemoglobin, biosynthesis of secondary metabolites and plant hormone signal transduction.DiscussionThese data showed that Bacillus amyloliquefaciens PG-4 significantly enhance salt stress tolerance in Macrotyloma uniflorum plants during salt stress conditions. Therefore, the results may be useful for explaining the mechanism by which PGPR inoculation regulates the salt tolerance of crops.
Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study
Authors: Giral Magali , Grimbert Philippe , Morin Baptiste , Bouvier Nicolas , Buchler Matthias , Dantal Jacques , Garrigue Valérie , Bertrand Dominique , Kamar Nassim , Malvezzi Paolo , Moreau Karine , Athea Yoni , Le Meur Yannick 
Published: April 2024

Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients. The primary endpoint was change in The Essential Tremor Rating Assessment Scale (TETRAS) score; secondary endpoints included 12-item Short Form Survey (SF-12) scores, tacrolimus trough concentrations, neurologic symptoms, and safety assessments. Subgroup analyses were conducted to assess change in TETRAS score and tacrolimus trough concentration/dose (C0/D) ratio by prior tacrolimus formulation and tacrolimus metabolizer status. Among 221 patients, the mean decrease of TETRAS score after switch to LCPT was statistically significant (p &lt; 0.0001 vs. baseline). There was no statistically significant difference in change in TETRAS score after switch to LCPT between patients who had received IR-TAC and those who had received PR-TAC before switch, or between fast and slow metabolizers of tacrolimus. The overall increase of C0/D ratio post-switch to LCPT was statistically significant (p &lt; 0.0001) and from baseline to either M1 or M3 (both p &lt; 0.0001) in the mITT population and in all subgroups. In the fast metabolizers group, the C0/D ratio crossed over the threshold of 1.05 ng/mL/mg after the switch to LCPT. Other neurologic symptoms tended to improve, and the SF-12 mental component summary score improved significantly. No new safety concerns were evident. In this observational study, all patients had a significant improvement of tremor, QoL and C0/D ratio post-switch to LCPT irrespective of the previous tacrolimus formulation administered (IR-TAC or PR-TAC) and irrespective from their metabolism status (fast or slow metabolizers).