bluuebunny/crossref_metadata_2025_split huggingface dataset:
First step results from a phase II study of a dendritic cell vaccine in glioblastoma patients (CombiG-vax)
Authors: Ridolfi Laura , Gurrieri Lorena , Riva Nada , Bulgarelli Jenny , De Rosa Francesco , Guidoboni Massimo , Fausti Valentina , Ranallo Nicoletta , Calpona Sebastiano , Tazzari Marcella , Petrini Massimiliano , Granato Anna Maria , Pancisi Elena , Foca Flavia , Dall’Agata Monia , Bondi Isabella , Amadori Elena , Cortesi Pietro , Zani Chiara , Ancarani Valentina , Gamboni Alessandro , Polselli Antonio , Pasini Giuseppe , Bartolini Daniela , Maimone Giuseppe , Arpa Donatella , Tosatto Luigino 
Published: August 2024

BackgroundGlioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytesMethodsThis is a single-arm, monocentric, phase II trial in two steps according to Simon’s design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test).ResultsBy December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery.ConclusionsThis combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT)
Effect of glycerol on properties of chitosan/chlorhexidine membranes and antibacterial activity against Streptococcus mutans
Authors: Hachity-Ortega José Alberto , Jerezano-Domínguez Alberto V. , Pazos-Rojas Laura Abisai , Flores-Ledesma Abigailt , Pazos-Guarneros Diana del C. , Parra-Solar Karla Aimée , Reyes-Cervantes Eric , Juárez-Díaz Ismael , Medina Manuel E. , González-Martínez Mayra , Castillo-Silva Brenda Eréndida , Ávila-Curiel Beatriz Xochitl , Hernández-Juárez Jesús , Rivera-Urbalejo América , Gordillo-Guerra Paola G. , Casillas-Santana Miguel Angel 
Published: August 2024

IntroductionChitosan membranes with glycerol can function as an effective dispersing agent for different antibiotics or active ingredients that can be used in the treatment of diseases present in the oral cavity.MethodsThe effects of the addition of glycerol on the mechanical, water absorption, swelling, pH, thickness, disintegration, rugosity, and antibacterial properties of chitosan-chlorhexidine- glycerol membranes were investigated in this study.Results and discussionMechanical results indicated that chitosan membranes' rugosity, strength, flexion, and thickness differed at loading 1, 3, 5, 10, 15, and 20% of glycerol (p &lt; 0.05). The chitosan membranes' rugosity, dissolution, strength, and pH results were significantly enhanced by the presence of glycerol at 3, 5, and 10% concentrations. In this investigation, the antimicrobial activity model used was the inhibition of Streptococcus mutans CDBB-B-1455 by chitosan-chlorhexidine membranes. It was observed that there was no change in inhibition with different concentrations of glycerol. The results suggest that chitosan-glycerol-chlorhexidine membranes may be a potential candidate for topical antiseptic application in buccal-dental disorders caused by S. mutans, such as caries, periodontal diseases, and oral squamous cell carcinoma, helping to prevent the development of serious conditions that can compromise human health.
Efficacy and safety of deep brain stimulation in mesencephalic locomotor region for motor function in patients with post-stroke hemiplegia: a study protocol for a multi-center double-blind crossover randomized controlled trial
Authors: Xu Junpeng , Liu Bin , Liu Shuzhen , Feng Zhebin , Zhang Yanyang , Liu Di , Chang Qing , Yang Haonan , Chen Yuhan , Yu Xinguang , Mao Zhiqi 
Published: August 2024

BackgroundDeep brain stimulation (DBS) is a potential treatment for improving movement disorder. However, few large-sample studies can reveal its efficacy and safety. This study aims to initially explore the efficacy and safety of DBS in the mesencephalic locomotor region (MLR) on motor function in patients with post-stroke hemiplegia.Methods/designThis multicenter, prospective, double-blind, randomized crossover clinical trial aims to assess the safety and effectiveness of Deep Brain Stimulation (DBS) in the mesencephalic locomotor region (MLR) for patients with moderate to severe post-stroke hemiplegia. Sixty-two patients with stable disease after a year of conservative treatment will be enrolled and implanted with deep brain electrodes. Post-surgery, patients will be randomly assigned to either the DBS group or the control group, with 31 patients in each. The DBS group will receive electrical stimulation 1 month later, while the control group will undergo sham stimulation. Stimulation will be discontinued after 3 and 6 months, followed by a 2-week washout period. Subsequently, the control group will receive electrical stimulation, while the DBS group will undergo sham stimulation. Both groups will resume electrical stimulation at the 9th and 12th-month follow-ups. Post-12-month follow-up, motor-related scores will be collected for analysis, with the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) as the primary metric. Secondary outcomes include balance function, neuropsychiatric behavior, fall risk, daily living activities, and quality of life. This study aims to provide insights into the therapeutic benefits of DBS for post-stroke hemiplegia patients.Result/conclusionWe proposed this study for the first time to comprehensively explore the effectiveness and safety of DBS in improving motor function for post-stroke hemiplegia, and provide evidence for DBS in the treatment of post-stroke hemiplegia. Study limitations are related to the small sample size and short study period.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT05968248.
Neurologic manifestations of Long COVID in Colombia: a comparative analysis of post-hospitalization vs. non-hospitalized patients
Authors: Hurtado Carolina , Rojas-Gualdrón Diego Fernando , Pérez Giraldo Gina S. , Villegas Arbelaez Esteban , Mantilla Salvador Ernesto Medina , Campuzano-Sierra Mariana , Ospina-Patino Santiago , Arroyave-Bustamante Mariana , Uribe-Vizcarra Valeria , Restrepo-Arbelaez Daniel , Cardona Paul , Llano-Piedrahita Julián , Vásquez-Builes Santiago , Agudelo-Quintero Esteban , Vélez-Arroyave Juliana , Menges Sebastián , Jimenez Millenia , Miller Janet , Quique Yina M. , Koralnik Igor J. 
Published: August 2024

ObjectiveTo analyze patient-reported outcomes, cognitive function, and persistent symptoms in patients with neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in Colombia.MethodsWe recruited patients with laboratory-confirmed COVID-19 and PASC symptoms lasting more than 6 weeks at the CES University and CES Clinic (Medellín, Colombia). We included 50 post-hospitalization Neuro-PASC (PNP) and 50 non-hospitalized Neuro-PASC (NNP) patients. Long-COVID symptoms, cognitive (NIH Toolbox v2.1-Spanish for 18+), patient-reported (PROMIS) outcomes, and relevant medical history were evaluated. Statistical analyses were performed via generalized linear models.ResultsOverall, brain fog (60%), myalgia (42%), and numbness or tingling (41%) were the most common neurological symptoms, while fatigue (74%), sleep problems (46%), and anxiety (44%) were the most common non-neurological symptoms. Compared to NNP, PNP patients showed a higher frequency of abnormal neurological exam findings (64% vs. 42%, p = 0.028). Both groups had impaired quality of life (QoL) in domains of cognition, fatigue, anxiety depression and sleep disturbance, and performed worse on processing speed and attention than a normative population. In addition, NNP patients performed worse on executive function than PNP patients (T-score 42.6 vs. 48.5, p = 0.012). PASC symptoms of anxiety and depression were associated with worse QoL and cognitive outcomes. Brain fog and fatigue remained persistent symptoms across all durations of Long COVID.ConclusionOur findings highlight the high incidence and heterogeneity of the neurologic symptoms and impacts of Long COVID even more than 2 years from disease onset. Early detection, emotional support and targeted management of Neuro-PASC patients are warranted.
Factors associated with elevated SARS-CoV-2 immune response in children and adolescents
Authors: Messiah Sarah E. , Abbas Rhiana , Bergqvist Emma , Kohl Harold W. , Swartz Michael D. , Talebi Yashar , Sabharwal Rachit , Han Haoting , Valerio-Shewmaker Melissa A. , DeSantis Stacia M. , Yaseen Ashraf , Gandhi Henal A. , Amavisca Ximena Flandes , Ross Jessica A. , Padilla Lindsay N. , Gonzalez Michael O. , Wu Leqing , Silberman Mark A. , Lakey David , Shuford Jennifer A. , Pont Stephen J. , Boerwinkle Eric 
Published: August 2024

BackgroundUnderstanding the distinct immunologic responses to SARS-CoV-2 infection among pediatric populations is pivotal in navigating the COVID-19 pandemic and informing future public health strategies. This study aimed to identify factors associated with heightened antibody responses in children and adolescents to identify potential unique immune dynamics in this population.MethodsData collected between July and December 2023 from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a statewide prospective population-based antibody survey among 1-to-19-year-old participants, were analyzed. Each participant had the following data available for analysis: (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for Nucleocapsid protein antibodies (Roche N-test), (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test), and (3) self-reported antigen/PCR COVID-19 test results, vaccination, and health status. Statistical analysis identified associations between participant characteristics and spike antibody quartile group.ResultsThe analytical sample consisted of 411 participants (mean age 12.2 years, 50.6% female). Spike antibody values ranged from a low of 6.3 U/ml in the lowest quartile to a maximum of 203,132.0 U/ml in the highest quartile in the aggregate sample. Older age at test date (OR = 1.22, 95% CI: 1.12, 1.35, p &lt; .001) and vaccination status (primary series/partially vaccinated, one or multiple boosters) showed significantly higher odds of being in the highest spike antibody quartile compared to younger age and unvaccinated status. Conversely, fewer days since the last immunity challenge showed decreased odds (OR = 0.98, 95% CI: 0.96, 0.99, p = 0.002) of being in the highest spike antibody quartile vs. more days since last immunity challenge. Additionally, one out of every three COVID-19 infections were asymptomatic.ConclusionsOlder age, duration since the last immunity challenge (vaccine or infection), and vaccination status were associated with heightened spike antibody responses, highlighting the nuanced immune dynamics in the pediatric population. A significant proportion of children/adolescents continue to have asymptomatic infection, which has important public health implications.
Thonningianin A ameliorated renal interstitial fibrosis in diabetic nephropathy mice by modulating gut microbiota dysbiosis and repressing inflammation
Authors: Zhang Shujiao , Zhang Shuaixing , Bai Xuehui , Wang Yaoxian , Liu Yuning , Liu Weijing 
Published: August 2024

ObjectivesThis study was conducted to examine the potential health benefits of thonningianin A (TA) on renal injury and interstitial fibrosis in diabetic nephropathy (DN) mice.MethodsIn this study, a DN mice model was established using male C57BL/6 mice injected with streptozotocin (STZ, 50 mg/kg) intraperitoneally and treated with TA for 12 weeks. Firstly, the therapeutic and anti-fibrotic effects of TA on DN were evaluated. Secondly, the effect of TA on renal inflammation was evaluated and Western blot was used to detect the changes of NLRP3/ASC/Caspase-1 pathway-related protein expressions in kidney. Furthermore, the effect of TA on impairments in the intestinal mucosa barrier was evaluated and the changes of lipopolysaccharide (LPS) levels in feces and serum were detected by ELISA. Finally, 16S rRNA sequencing was used to detect alteration of gut microbiota diversity and abundance in mice after TA treatment.ResultsThe results showed that TA markedly mitigated blood glucose (Glu), decreased 24-h urinary total protein (24hUTP), improved renal dysfunction and kidney index (KI) in DN mice. Furthermore, TA significantly alleviated renal injury and interstitial fibrosis, repressing renal inflammation. Western blot results showed that the NLRP3/ASC/Caspase-1 signaling pathway-related proteins decreased after TA treatment. In addition, TA also ameliorated impairments in the intestinal mucosa barrier and restored the expressions of intestinal tight junction proteins (Claudin-1, Occludin and ZO-1). Subsequently, it reduced LPS levels of DN mice in fecal and serum. Furthermore, 16S rRNA high-throughput sequencing showed that TA modulated gut microbiota dysbiosis and decreased the abundance of Gram-negative bacteria (Proteobacteria and Escherichia-Shigella).ConclusionThis study suggested that TA might exert a beneficial effect on renal interstitial fibrosis in DN mice by modulating gut microbiota dysbiosis, ameliorating impairments in the intestinal mucosa barrier, reducing the production and release of LPS, inhibiting the activation of NLRP3/ASC/Caspase-1 signaling pathway, and repressing renal inflammatory.
Willingness-to-use and preferences for model-informed antenatal doses: a cross-sectional study among European healthcare practitioners and pregnant women
Authors: Koldeweij C. J. M. , Dibbets A. C. , Ceulemans M. , de Vries L. C. , Franklin B. D. , Scheepers H. C. J. , de Wildt S. N. 
Published: August 2024

Background: Physiological changes in pregnancy may affect drug safety and efficacy, sometimes requiring dose adjustments. Pregnancy-adjusted doses, however, are missing for most medications. Increasingly, pharmacokinetic models can be used for antenatal dose finding. Given the novelty of this technique and questions regarding dose credibility, the acceptability of model-informed antenatal doses should be explored.Objective: We aimed to assess the willingness-to-use and preferred features for model-informed antenatal doses among healthcare practitioners (HCPs) and pregnant women in European countries.Methods: A cross-sectional, web-based study drawing on two open surveys was performed between 8 September and 30 November 2022. Each survey comprised statements drawn from prior focus groups, associated with Likert-scales. Themes included respondents’ information needs, search behaviours along with their willingness-to-use and preferred features for model-informed antenatal doses. The surveys were disseminated through professional societies, pregnancy websites and social media. A descriptive analysis was performed.Results: In total, 608 HCPs from different specialties and 794 pregnant women across 15 countries participated, with 81% of respondents across both groups in the Netherlands or Belgium. Among pregnant women, 31% were medical professionals and 85% used medication during pregnancy. Eighty-three percent of HCPs found current antenatal pharmacotherapy suboptimal and 97% believed that model-informed antenatal doses would enhance the quality of antenatal care. Most HCPs (93%) and pregnant women (75%) would be willing to follow model-informed antenatal doses. Most HCPs desired access to the evidence (88%), including from pharmacokinetic modelling (62%). Most pregnant women (96%) wanted to understand antenatal dosing rationales and to be involved in dosing decisions (97%).Conclusion: The willingness-to-use model-informed antenatal doses is high among HCPs and pregnant women provided that certain information needs are met.
Efficacy and safety of Cordyceps sinensis (Hirsutella sinensis, Cs-C-Q80) in chronic bronchitis
Authors: Shu Xinyang , Xu Dongfeng , Qu Yumin , Shang Xiaofeng , Qiao Kehong , Feng Cuiling , Cui Hongsheng , Zhao Xianping , Li Yuxin , Peng Yu , Li Demin , Zhang Hongchun 
Published: August 2024

Background:Cordyceps sinensis is a traditional Chinese medicine that has shown promise for the management of chronic bronchitis (CB). We aim to assess the efficacy and safety of a preparation of C sinensis named Bailing capsule (Hirsutella sinensis, Cs-C-Q80) compared with a placebo in patients with CB.Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial (Chinese Clinical Trial Registry; registration number: ChiCTR1900025707) recruited patients with CB from eight hospitals in China between May 2019 and December 2020. Patients were randomized 2:1 to receive Bailing capsule or a placebo orally for 48 weeks (2.0 g, three times a day).Results: Among 240 patients who were randomized, 238 (Bailing capsule: 159, placebo: 79) were included in the primary analysis. Bailing capsule significantly reduced the frequency of acute exacerbation of CB (AECB) compared with the placebo during treatment (0.43 ± 0.82 vs. 1.56 ± 1.34; P &lt; 0.001) and follow-up (0.21 ± 0.64 vs. 0.45 ± 0.93; P = 0.026). Bailing capsule improved the severity of expectoration (P = 0.046) and wheezing (P = 0.010) in AECB during follow-up. The severity of CB after treatment was significantly improved in the Bailing capsule group compared with the placebo group (P = 0.035), particularly in terms of expectoration (P = 0.012) and wheezing (P = 0.003). The risk of adverse events, mainly including infectious and invasive diseases and gastrointestinal symptoms, did not significantly differ between the two groups (29.6% vs. 30.4%).Conclusion: In patients with CB, Bailing capsule significantly reduces the frequency of AECB and ameliorates the severity of AECB and CB symptoms.Clinical Trail Registration:https://www.chictr.org.cn, identifer ChiCTR1900025707.
Chemico-pharmacological evaluations of the dwarf elephant ear (Colocasia affinis Schott) plant metabolites and extracts: health benefits from vegetable source
Authors: Alam Safaet , Richi Fahmida Tasnim , Hasnat Hasin , Ahmed Firoj , Emon Nazim Uddin , Uddin Md. Jasim , Rana G. M. Masud , Wang Shuanghu , Yeasmin Mst. Sarmina , Ahmed Nazim Uddin , Khan Md. Salim , Al Mamun Abdullah 
Published: August 2024

Introduction:Colocasia affinis Schott (Family: Araceae), found in the Asian region, is a traditional root vegetable consumed by the locals and well-known as Dwarf Elephant Ear.Methods: For the pharmacological exploration of this root vegetable, four kupchan fractions (i.e. HSF, DCMSF, EASF, and AQSF) from ethanolic extract of C. affinis were employed to in vitro i.e. antioxidant, cytotoxicity, and antimicrobial and in vivo i.e. antidiarrheal and analgesic assays, followed by phytochemical screening and GC-MS protocol.Result and Discussion: In the antioxidant assay, the AQSF showed promising potential with an IC50 value of 29.4 μg/mL and additionally, it exhibited the greatest overall phenolic content, measuring 57.23 mg GAE/gm. of extract among other fractions. The AQSF also revealed promising cytotoxic activity in brine shrimp lethality assay with an LC50 value of 1.36 μg/mL. Both AQSF and EASF exhibited substantial antimicrobial efficacy against both gram-positive and gram-negative bacteria as well as various fungus species with a remarkable zone of inhibitions compared to standards. Whereas, during both the castor oil-induced antidiarrheal and acetic acid-induced writhing assay, the DCMSF at 400 mg/kg dose exhibited the highest 51.16% reduction of diarrhea and 52.33% reduction of writhing. Phytochemical screening revealed several chemical groups while GC-MS study of different fractions of dwarf elephant ear ethanolic extract revealed 48 different bioactive phytochemicals in total. Several targets such as KAS, DHFR for anti-microbial activities, GLR, URO for antioxidant activities, EGFR, BCL-2 for cytotoxicity, KOR, DOR for antidiarrheal activities and COX-2, TNF-α for analgesic activities are considered for molecular docking against identified phytocompounds and standards along with ADME/T studies to ascertain their safety, efficacy and drug likeliness profiles.Conclusion: To recapitulate, our study revealed that vegetables such as dwarf elephant ear can be considered as a prospective source of therapeutics and drug development besides their nutritive food values.
Assessing the real-world safety of tralokinumab for atopic dermatitis: insights from a comprehensive analysis of FAERS data
Authors: Zhao Kaidi , Zhao Yang , Xiao Shengxiang , Tu Chen 
Published: August 2024

BackgroundTralokinumab, a humanized monoclonal antibody targeting interleukin-13, has been primarily used for the treatment of moderate-to-severe atopic dermatitis. Given its extensive use in clinical practice, understanding its safety profile in the real-world setting is crucial.MethodsThis study utilized disproportionality analysis to evaluate the safety of tralokinumab in clinical practice by analyzing all adverse event reports since 2021 in the FDA Adverse Event Reporting System database that identified tralokinumab as the primary suspected drug. Reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network were used for disproportionality analyses of adverse events related to tralokinumab. Additionally, the Weibull distribution was employed to model the risk of adverse events over time.ResultsAdverse reactions documented on the drug label, such as injection site reactions, conjunctivitis, and upper respiratory infections, displayed positive signals. Additionally, potential adverse reactions not mentioned on the label were also identified, including dizziness, headache, nausea, vomiting, hair loss, and acne. The importance of adverse event monitoring, particularly in the first month after treatment initiation, was emphasized.ConclusionThis study has provided preliminary safety data on the real-world application of tralokinumab, confirming some known adverse reactions and revealing additional potential risks. The findings offer critical safety information for clinicians prescribing tralokinumab to treat atopic dermatitis.