bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case study to investigate the effects of Chlorhexidine mouthwash on serum cytokines levels in children with Asthma
Authors: Sadr Saeed , Eslaminezhad Sahar , Mehrabi Nasab Entezar , Arora Poonam , Yavari Bahram , Khodabandehloo Hadi , Jafari Davood , Borji Mohammad , Athari Seyyed Shamsadin 
Published: June 2024

AbstractAsthma is an airways inflammatory disease and the most common chronic disease of childhood, which causes most hospital visits and placing a heavy financial burden on families and communities. Interleukins 4, 5 and 13, play a central role in the pathogenesis of asthma. Given the importance of oral hygiene in asthmatic patients and IL-4 and 5 are involved in the inflammatory process of periodontitis, the effect of chlorhexidine as mouthwash on asthma attacks in children on serum cytokines is necessary. In this study, 375 children with asthma were divided into two groups using or non-using chlorhexidine. Blood samples were taken and cytokines were measured by ELISA. From 375 patients, 17 patients were excluded. In this study, 171 males and 187 females participated and there were 180 patients in asthma group and 178 patients in asthma/Chlorhexidine group. The levels of IL-4, IL-5 and IL-13 had no significant difference (p > 0.05) between Asthma and Asthma/Chlorhexidine groups. Using chlorhexidine as mouthwash in children with asthma had no effect on the type 2 cytokines and may not trigger an asthma attack via allergo-inflammatory mechanism.
Leaching of liquation-feeding furnace dross as a first step for germanium recovery
Authors: Drzazga Michał , Ciszewski Mateusz , Kozłowicz Sylwia , Maj Izabela , Ochmański Michał , Radoń Adrian 
Published: June 2024

Abstract
Objective
Germanium, an important component of electronics, is considered by many global economies as a critical raw material. Therefore, investigating its potential new sources is crucial for prospective technology development. This paper presents the investigation results on the leaching of liquation-feeding furnace dross using sulfuric and oxalic acid solutions.

Results
The dross contained mostly zinc (68.0% wt.) but also elevated germanium concentration (0.68% wt.). The influence of temperature, time, initial acid concentration, and liquid-to-solid phase ratio (L:S) was examined. It was found that germanium availability via leaching is limited—maximum leaching yields using aqueous solutions of sulfuric and oxalic acids were 60% (80 °C, 2 h, 15% wt. H2SO4, L:S 25:1) and 57% (80 °C, 3 h, 12.5% wt. H2C2O4, L:S 10:1), respectively.
Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease
Authors: Arranz Javier , Zhu Nuole , Rubio-Guerra Sara , Rodríguez-Baz Íñigo , Ferrer Rosa , Carmona-Iragui María , Barroeta Isabel , Illán-Gala Ignacio , Santos-Santos Miguel , Fortea Juan , Lleó Alberto , Tondo Mireia , Alcolea Daniel 
Published: June 2024

Abstract
Background
Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.

Methods
We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A +) or negative (A-) according to CSF Aβ1–42/Aβ1–40 ratio. Plasma pTau217, pTau181, Aβ1–42 and Aβ1–40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman’s correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aβ1–42/Aβ1–40 ratio. We analyzed the concordance of pTau217 with CSF amyloidosis.

Results
Plasma pTau217 and pTau181 concentration were higher in A + than A- while the plasma Aβ1–42/Aβ1–40 ratio was lower in A + compared to A-. pTau181 and the Aβ1–42/Aβ1–40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92–0.97) for pTau217, and 0.88 (95% CI 0.84–0.92) for both pTau181 and Aβ1–42/Aβ1–40. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau217 had the highest fold change (× 3.2) and showed high predictive capability in discriminating A + from A-, having 4–7% misclassification rate. The global accuracy of plasma pTau217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%.

Conclusion
The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.
Generalized kinetic theory of coarse-grained systems. I. Partial equilibrium and Markov approximations
Authors: Gaveau Bernard , Moreau Michel 
Published: June 2024

AbstractThe general kinetic theory of coarse-grained systems is presented in the abstract formalism of communication theory developed by Shannon and Weaver, Khinchin and Kolmogorov. The martingale theory shows that, under reasonable, general hypotheses, coarse-grained systems can be approximated by generalized Markov systems. For mixing systems, the Kolmogorov entropy production can be defined for nonstationary processes as Kolmogorov defined it for stationary processes.
Improving Clinical Registry Data Quality via Linkage With Survival Data From State-Based Population Registries
Authors: Smith Samuel , Drummond Kate , Dowling Anthony , Bennett Iwan , Campbell David , Freilich Ronnie , Phillips Claire , Ahern Elizabeth , Reeves Simone , Campbell Robert , Collins Ian M. , Johns Julie , Dumas Megan , Hong Wei , Gibbs Peter , Gately Lucy 
Published: June 2024

PURPOSE Real-world data (RWD) collected on patients treated as part of routine clinical care form the basis of cancer clinical registries. Capturing accurate death data can be challenging, with inaccurate survival data potentially compromising the integrity of registry-based research. Here, we explore the utility of data linkage (DL) to state-based registries to enhance the capture of survival outcomes. METHODS We identified consecutive adult patients with brain tumors treated in the state of Victoria from the Brain Tumour Registry Australia: Innovation and Translation (BRAIN) database, who had no recorded date of death and no follow-up within the last 6 months. Full name and date of birth were used to match patients in the BRAIN registry with those in the Victorian Births, Deaths and Marriages (BDM) registry. Overall survival (OS) outcomes were compared pre- and post-DL. RESULTS Of the 7,346 clinical registry patients, 5,462 (74%) had no date of death and no follow-up recorded within the last 6 months. Of the 5,462 patients, 1,588 (29%) were matched with a date of death in BDM. Factors associated with an increased number of matches were poor prognosis tumors, older age, and social disadvantage. OS was significantly overestimated pre-DL compared with post-DL for the entire cohort (pre- v post-DL: hazard ratio, 1.43; P < .001; median, 29.9 months v 16.7 months) and for most individual tumor types. This finding was present independent of the tumor prognosis. CONCLUSION As revealed by linkage with BDM, a high proportion of patients in a brain cancer clinical registry had missing death data, contributed to by informative censoring, inflating OS calculations. DL to pertinent registries on an ongoing basis should be considered to ensure accurate reporting of survival data and interpretation of RWD outcomes.
Cardiovascular complications associated with asciminib use: A retrospective analysis.
Authors: Savani Saloni , Pawa Arpita , Mahadevia Himil , Master Samip R. 
Published: June 2024

6563 Background: Asciminib, a newly developed drug, has shown promising results in the treatment of several diseases. It is a cellular tyrosine kinase inhibitor (TKI) that specifically targets ABL myristoyl pocket (STAMP) inhibitor, responsible for the malignant growth and proliferation of leukemia cells in chronic myeloid leukemia (CML) patients, assuring a positive treatment of CML. However, as with all medications, there are possible side effects that must be carefully monitored. In comparison to Ponatinib (tyrosine kinase inhibitor) which is extensively used to treat CML and exhibits a cardiovascular risk profile, cardiovascular side effects with the use of Asciminib are rarely reported in literature, prompting its use in patients at a higher risk of these events. Through this study, we aim to highlight the cardiovascular complications associated with the use of Asciminib by integrating patient experience and clinical research. Methods: A publicly available FDA Adverse Events Reporting System (FAERS) database was utilized to review cardiovascular events associated with the use of Asciminib in patients with Chronic Myeloid leukemia (CML) between 2018-2023. Cardiovascular events such as coronary artery disease (CAD), peripheral arterial disease (PAD), and cerebrovascular accidents (CVA) were reviewed. The study focused only on adverse events reported by healthcare providers and observed in adults (above 18 years old). Results: We identified a total of 563 adverse events pertaining to the use of Asciminib in patients with CML. Of which, 63 were cardiovascular events, contributing to 11.2% of the total adverse events. Out of the reported cardiovascular side effects, 29 (46%) were due to CAD, 6 (9.5%) were due to PAD, and 28 (44.45%) were due to CVA. The mortality rate amongst patients who experienced cardiovascular side effects was 11%. Moreover, cardiovascular events contributed to 7% of all mortality associated with the use of Asciminib, with CAD contributing to most of the deaths. Conclusions: It is imperative to consider the potential of cardiovascular events in patients initiated on Asciminib. This study emphasizes the importance of using patient records and medical research to obtain complete information. Patients with underlying risk factors for the development of cardiovascular diseases should be thoroughly evaluated before drug initiation. The minimum threshold for drug discontinuation should be considered in patients with suspected heart disease.
DeLLphi-301: Tarlatamab phase 2 trial in small cell lung cancer (SCLC)—Efficacy and safety analyzed by presence of brain metastasis.
Authors: Dingemans Anne-Marie C. , Ahn Myung-Ju , Blackhall Fiona Helen , Reck Martin , Hummel Horst-Dieter , Ramalingam Suresh S. , Johnson Melissa L. , Akamatsu Hiroaki , Wolf Juergen , Sands Jacob , Owonikoko Taofeek K. , Borghaei Hossein , Mukherjee Sujoy , Huang Shuang , Martinez Pablo , Paz-Ares Luis G. 
Published: June 2024

8015 Background: Brain metastases affect 40%–70% of patients with SCLC. Tarlatamab, a BiTE (bispecific T-cell engager) immunotherapy targeting delta-like ligand 3, demonstrated durable responses and promising survival outcomes in patients with previously treated SCLC (10 mg Q2W) (DeLLphi-301; NCT05060016; Ahn M-J, N Engl J Med 2023). Here, tarlatamab efficacy and safety in patients with baseline brain metastases from DeLLphi-301 are reported. Methods: The DeLLphi-301 study design has been published. Patients with treated, stable, asymptomatic brain metastases were included. Subgroup analyses for efficacy (blinded independent central review [BICR] assessments) and safety by presence or absence of baseline brain metastases were performed. Intracranial activity was assessed. Post enrollment, brain imaging was performed if clinically indicated. Results: As of 27 June 2023, 186 patients had received tarlatamab (ECOG PS: 0–1; median prior lines of therapy: 2; median follow-up: 13.6 months). 29% of patients (54/186) had treated and stable brain metastases at baseline. Most patients (91%) with brain metastases had received prior local radiotherapy; 6% each had received surgery only or both radiotherapy and surgery. Overall systemic objective response rate (ORR; RECIST 1.1) was 45.3% in patients with brain metastases and 32.6% in patients without brain metastases (Table). Any grade immune effector cell associated neurotoxicity syndrome and associated neurological events occurred in 24.1% of patients with brain metastases and in 13.6% of patients without brain metastases; grade ≥ 3 events occurred in the 100 mg group only: 9.4% and 1.8%, respectively, and did not lead to tarlatamab discontinuation in any patient with brain metastases. Analysis of intracranial activity will be presented. Conclusions: Tarlatamab showed promising efficacy and a favorable benefit-risk profile in patients with previously treated SCLC and stable brain metastases. Clinical trial information: NCT05060016 . [Table: see text]
A randomized phase II study of toripalimab consolidation or observation after concurrent chemoradiotherapy in limited-stage small cell lung cancer.
Authors: Zhang PengXin , Liu FangJie , Wang DaQuan , Zheng ShiYang , Guo JinYu , Zou YingYi , Liang Ying , Zhao Yuanyuan , Qiu Bo , Liu Hui 
Published: June 2024

8098 Background: In recent years, the use of immune checkpoint inhibitors has led to significant progress in the treatment of extensive-stage small cell lung cancer. However, there is limited data on the efficacy of immunotherapy in patients with limited-stage disease (LS-SCLC). Therefore, we conducted a phase II randomized study to verify the efficacy and safety of Toripalimab consolidation following definitive concurrent chemoradiotherapy (CCRT) in patients with LS-SCLC (ClinicalTrials.gov ID: NCT04418648). Methods: Patients with LS-SCLC who had achieved complete or partial response after definitive CCRT (including four to six cycles of etoposide and cisplatin , and curative-intent thoracic radiotherapy) were randomly assigned (1:1) to receive Toripalimab consolidation (240mg intravenously, every 3 weeks for 6 months) or observation. Prophylactic cranial irradiation (PCI) was recommended but not mandatory. The primary endpoint was progression-free survival (PFS) calculated from randomization, and secondary endpoints included overall survival (OS) and toxicity. Results: As of data cutoff (November 30, 2023), a total of 64 eligible patients (intent-to-treat population) were randomly assigned to the Toripalimab group (n = 31) or the observation group (n = 33), respectively. With the median follow-up of 25 months, PFS was significantly improved with Toripalimab (hazard ratio [95% CI]: 0.47 [0.22-1.02]; P = 0.04). The median PFS in observation group was 12.3 months (95% CI, 0.04-24.50), while the median PFS in the Toripalimab group has not been reached. The 24-month PFS rate was 61.6% (95% CI, 43.0%-88.3%) in the Toripalimab group and 34.8% (95% CI, 21.5%-56.3%) in the observation group. The 24-month OS was 82.7% (95% CI, 65.2%-100%; P = 0.23) in the Toripalimab group and 59.1%(95% CI, 44.2%-79.1%) in the observation group. There were 5(16.1%) and 3 (9.1%) patients in the Toripalimab group and observation group experiencing G2+ pneumonitis respectively. No G4+ toxic events occurred in either group. Conclusions: Our preliminary results suggested Toripalimab consolidation following definitive CCRT was effective and tolerable in LS-SCLC. Clinical trial information: NCT04418648 . [Table: see text]
Exploring gut microbiome markers in predicting efficacy of immunotherapy against lung cancer.
Authors: Han Wenjie , Xu Junnan , Sun Tao , Zhou Yuhang , Feng Yun , Han Li , Liu Xiaolin 
Published: June 2024

8525 Background: Immunotherapy has profoundly changed the treatment landscape for lung cancer (LC) due to its tolerable safety profile and longer sustained therapeutic response. However, only about 20% of patients with locally advanced and metastatic disease can derive long-term clinical benefit from ICIs. Previous studies have suggested that the microbiome is involved in the development of LC in some way. We aimed to use the gut microbiome (GM) to model the benefit of immunotherapy and to mine the biomarkers with a global impact on immune response. Methods: We performed human gut metagenomic analysis on the responder patients and non-responder patients with immunotherapy. A total of 296 fecal samples, including baseline samples (71 responders, 98 non-responders and 72 healthy controls), and 55 samples during treatment were enrolled in our study, the taxonomic and functional features of these samples also were excavated. A machine-learning model was developed to identify responders and non-responders. At the same time, we also explored the influence of antibiotic use on the above results. Results: Specific species, Bacteroides caccae and Bacteroides uniformis, were positively correlated with responders. In non-responders, Prevotella copri was the main enrichment species. The α diversity of microbiota in responding patients was significantly higher than that in non-responding groups, and antibiotic use increased this trend. There was no significant difference in β diversity between the two groups, but LEFSE analysis also could obtain biomarkers of biological significance between the two groups. We used the biomarkers from the above analysis to construct a random forest model, and the area under the receiver operating characteristic curve (AUC) (species level: 82.10%; genus level: 79.4%). In addition, our studies suggested that metabolism such as amino acid metabolism, valine, leucine might be important in regulating the immunotherapy response that warrants further investigation. Conclusions: Overall, our study explored the relationship between microbial composition and immunotherapy efficacy in LC patients and mined relevant markers, and further research is needed to investigate the mechanisms of action of these key strains in influencing immunotherapy in the future.
Germline NQO1c.559C>T as a biomarker of genetic susceptibility to immune checkpoint blockade resistance.
Authors: Benitez Jose Carlos , Oliver Javier , Onieva Juan Luis , Cobo Manuel , Mesas Andres , Rios-Muñoz Alberto , Perez Ruiz Elisabeth , Garrido-Barros Maria , Vazquez Rojas Paula , Martinez Beatriz , Cantero-Gonzalez Alexandra , Gonzalez Andrea , Zafra Martín Juan , Barragán Isabel , Rueda Dominguez Antonio 
Published: June 2024

8537 Background: Tobacco is the main risk factor for developing lung cancer. Yet, some heavy smokers do not develop cancer while others do at young ages. The study of cancer immunology has led to the surge of immune checkpoint blockade (ICB), which transformed the treatment landscape of cancer pts. NQO1 has been associated with extreme phenotypes of high risk for the development of tobacco-induced NSCLC and with poor survival outcomes for xerographs. Development of biomarkers for ICB has been mainly focused on tumor-related factors while genetic susceptibility of the host has been poorly explored to date and some evidence suggests that genetic dysregulation may enables immune escape. Methods: From June 2016 to January 2023, 326 NSCLC pts from two main University Hospitals of Malaga (Spain) receiving ICB were prospectively enrolled, blood samples were gathered. We selected a representative set of 60 consecutive pts for exome sequencing to characterize the germline contribution to resistance (progression within the first 6 months of treatment). PBMC DNA was extracted and prepared for exome sequencing. Raw sequencing data was processed and aligned to a reference genome using BWA. Base recalibration, germline variant calling and variant filtering was performed through GATK. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. We explored the lung cancer related genes among our results. Results: Median age at diagnosis of 64 (54-85). 76,6% were men. 44/60 (73,3%) were adenocarcinoma (ADC), PD-L1≥1% in 55% of patients, 22% shown PD-L≥50%. 78% had advanced disease at diagnosis. 65% received ICB in combination with chemotherapy. We found NQO1c.559C>T in 46,6% of pts (28/60). The variation was not associated with survival outcomes in the multivariant analysis (p>0.05) but with poor OS for non-ADC histology (19.7m vs 6m for mutated and WT, respectively; p<0.01). In addition, we found 26 germline variants associated with OS and PFS, and 52 variants with response to ICB. The variants were missense or involved a stop gain/loss. Conclusions: Exome sequencing analysis of germline variants could be a suitable methodology to identify subrogated biomarkers of immune resistance in NSCLC patients. NQO1c.559C>T might help to identify poor prognosis non-ADC pts in the ICB setting.
Five-year outcomes with first-line (1L) nivolumab + ipilimumab + chemotherapy (N + I + C) vs C in patients (pts) with metastatic NSCLC (mNSCLC) in CheckMate 9LA.
Authors: Reck Martin , Ciuleanu Tudor-Eliade , Schenker Michael , Bordenave Stephanie , Cobo Manuel , Juan-Vidal Oscar , Reinmuth Niels , Richardet Eduardo , Felip Enriqueta , Menezes Juliana , Cheng Ying , Mizutani Hideaki , Carbone David Paul , Lu Shun , John Tom , Aoyama Takekazu , Mahmood Javed , Hu Nan , Eccles Laura , Paz-Ares Luis G. 
Published: June 2024

8560 Background: InCheckMate 9LA (NCT03215706), 1L N + I + C demonstrated long-term, durable survival benefit vs C alone in pts with mNSCLC, regardless of tumor PD-L1 expression or histology. Here, we report updated efficacy and safety data with a 5-y follow up (f/u) and outcomes in 5-y survivors. Methods: Adults with stage IV or recurrent NSCLC, ECOG PS ≤ 1, and EGFR/ALK wild-type were randomized 1:1 to N 360 mg Q3W + I 1 mg/kg Q6W + C Q3W (2 cycles; n = 361) or C alone Q3W (4 cycles; n = 358). Maintenance pemetrexed was allowed for pts with non-squamous (NSQ) NSCLC (C arm only). Assessments were OS, PFS, ORR, DOR, treatment (tx)-free interval (TFI; time from last study tx dose to start of subsequent systemic tx or death), and safety. Exploratory analyses included quantifying the number of ipilimumab doses received by 5-y survivors, as well as PFS and TFI in these pts. Results: With a median f/u of 64.5 mo (database lock, 15 Dec 2023), clinical benefit continued to be seen with N + I + C vs C in all randomized pts (Table); 5-y OS rates were 18% vs 11%, respectively. Of pts treated with N + I + C, 11% were tx-free at 5 y. Clinical outcomes favored N + I + C vs C across tumor PD-L1 expression and histology subgroups (Table). In pts with tumor PD-L1 < 1%, 5-y OS and PFS rates with N + I + C were both ~3-fold higher than with C, and 5-y DOR rates were 25% vs 0% in the respective tx arms. Among pts who discontinued N + I + C due to tx-related adverse events (TRAEs; n = 61), 37% were alive at 5 y, and the TFI rate was 22%. In analyses of 5-y survivors, PFS favored N + I + C (n = 48) vs C (n = 30; HR, 0.52 [95% CI, 0.26–1.02]), and 5-y TFI rates were 72% vs 35%, respectively. Of 5-y survivors in the N + I + C arm, 21/48 (44%) received ≥ 17 doses of ipilimumab; of those who received < 17 doses, most had discontinued ipilimumab due to TRAEs. The extended f/u revealed no new safety signals. Conclusions: 1L N + I + C maintained long-term, durable survival benefit vs C in pts with mNSCLC at this 5-y f/u, particularly in pts with tumor PD-L1 expression < 1% or squamous (SQ) histology. N + I + C increased 5-y survivorship, with improved PFS and TFI in 5-y survivors over C. These data further underscore 1L N + I + C as an efficacious tx option for pts with mNSCLC. Clinical trial information: NCT03215706 . [Table: see text]