bluuebunny/crossref_metadata_2025_split huggingface dataset:
No causal association between insomnia and bladder cancer: a bidirectional two-sample Mendelian randomization study
Authors: Du Lihuan , Wang Bohan , Wen Jiaming , Zhang Nan 
Published: June 2024

Abstract
Background
Previous observational studies have indicated a potential link between insomnia and bladder cancer, yet the underlying causal relationship remains uncertain. The current study employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate this association.

Methods
A two-sample MR analysis was conducted utilizing publicly available summary data from genome-wide association studies (GWAS) on insomnia and bladder cancer. Various regression methods including the inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode methods were employed for the MR analysis. The presence of pleiotropy and heterogeneity in the MR results was also assessed. Furthermore, additional sensitivity tests were performed to mitigate potential biases.

Results
No significant causal relationship was detected between insomnia and bladder cancer using IVW method (OR = 0.761, 95% CI 0.996–1.005; P = 0.76). Similarly, the IVW model did not reveal any causal effect of bladder cancer on the risk of insomnia (OR = 1.47, 95% CI 0.772–2.799; P = 0.24). Consistent results were obtained from the other four methods employed. There was no evidence of horizontal pleiotropy or heterogeneity in our MR analysis (P > 0.05). The sensitivity analyses further supported the reliability of the estimated causal effects.

Conclusions
This study presents no evidence for a causal relationship between insomnia and bladder cancer.
Origami manipulation by robot hand utilizing electroadhesion
Authors: Kitamori Hiroto , Dong Chenyu , Takizawa Masaru , Watanabe Shuya , Shintake Jun , Kimura Kohei , Kudoh Shunsuke 
Published: June 2024

AbstractThis study presents strategies for the three fundamental origami operations of grasping, bending, and folding using a novel robot hand and simple motions. These operations are executed using a simple geometric model and without any visual feedback or physical modeling not to restrict the motions. With a few applications in the field of paper manipulation, the electroadhesion technology is employed to perform single hand grasping. Bending is realized by a single hand utilizing the elasticity of origami and friction. Folding is performed by holding an origami with more than two points to fix it at any moment for preciseness. In addition to the design of hardware and motions, operations are demonstrated with general criteria for the crease precision evaluation.
Impact of an Ultra-Endurance Marathon on Cardiac Function in Association with Cardiovascular Biomarkers
Authors: Burger Achim Leo , Wegberger Claudia , Tscharre Maximilian , Kaufmann Christoph C. , Muthspiel Marie , Pogran Edita , Freynhofer Matthias K. , Szalay Alexander , Huber Kurt , Jäger Bernhard 
Published: June 2024

Abstract
Background
Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP).

Methods and Results
Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median.

Conclusion
A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below.
Estimation of default and pricing for invoice trading (P2B) on crowdlending platforms
Authors: Corrales Cristian Marques , González Luis Alberto Otero , Santomil Pablo Durán 
Published: June 2024

AbstractThis study developed several machine learning models to predict defaults in the invoice-trading peer-to-business (P2B) market. Using techniques such as logistic regression, conditional inference trees, random forests, support vector machines, and neural networks, the prediction of the default rate was evaluated. The results showed that these techniques can effectively improve the detection of defaults by up to 56% while maintaining levels of specificity above 70%. Unlike other studies on the same topic, this was performed using sampling techniques to address the imbalance of classes and using different time periods for the training and test datasets to ensure intertemporal validation and realistic predictions. For the first-time, default explainability in the invoice-trading market was studied by examining the impact of macroeconomic factors and invoice characteristics. The findings highlighted that gross domestic product, exports, trade type, and trade bands are significant factors that explain defaults. Furthermore, the pricing mechanisms of P2B platforms were evaluated with the observed and implicit probabilities of the default to analyze the price risk adjustment. The results showed that price reflects a significantly higher implicit probability of default than observed default, which in turn suggests that underlying factors exist besides the borrowers’ probability of default.
Mitigating the escalating threat of infectious diseases outbreaks in tropical Africa: a perspective examination of challenges and strategies for future preparedness
Authors: Hassan Hakeem Kayode , Adigun Olaniyi Abideen , Manirambona Emery , Olaleke Noah Olabode , Abioye Micheal Sunday , Lucero-Prisno III Don Eliseo , Atewologun Faith Ayobami , Okesanya Olalekan John 
Published: June 2024

Abstract
Background
The escalating threat of infectious disease outbreaks in Africa, particularly emerging and re-emerging diseases, necessitates urgent and comprehensive action. The frequency of these outbreaks demands a robust enhancement of notification and reporting systems to enable swift public health interventions.

Main body of the abstract
Tropical diseases such as malaria, COVID-19, typhoid fever, yellow fever, arboviruses, cholera, rabies, schistosomiasis, tuberculosis, black fungus, meningitis, evolving pathogens, and antimicrobial resistance pose significant health risks globally, especially in Sub-Saharan Africa. The region faces complexities in healthcare, including weak systems, inadequate surveillance, socioeconomic disparities, and other issues. Poor health literacy, traditional practices, and distrust hinder effective disease control and contribute to disease emergence in Sub-Saharan Africa. Continuous research and global collaboration are essential to address these public health concerns, especially given Africa's unique challenges. Disease surveillance emerges as a highly effective strategy, crucial in regions vulnerable to infectious diseases. Establishing and strengthening comprehensive surveillance and reporting systems at individual, regional, national, and international levels is crucial due to the unpredictable nature of borderless outbreaks and their significant impact on morbidity, mortality, and economic stability. National surveillance relies heavily on effective control mechanisms within local community areas, necessitating the active involvement of medical personnel. Successful systems depend on functional countries using collected data for timely warnings and localized interventions. Stakeholders, including governments, health authorities, and international organizations, must collaborate urgently to implement and sustain these vital systems, mitigating the devastating consequences of infectious disease outbreaks. Additionally, a holistic approach is crucial, involving prioritized local production of vaccines, medicines, and diagnostics through initiatives like the African Vaccine Producers Initiative. This approach emphasizes the need for domestic pharmaceutical production, intensified public awareness campaigns, and the training of the next generation of global health leaders, ensuring multidimensional strategies, political and diplomatic skills, and evidence-based assessments.

Conclusion
Collaboration among governments, international organizations, and educational institutions is essential for successful policy advocacy and implementation to strengthen health security and mitigate the continuous rise of infectious diseases on the continent.
Network pharmacology, molecular docking study, and in vivo validation of the wound healing activity of the Red Sea soft coral Paralemnalia thyrsoides (Ehrenberg 1834) ethanolic extract and bioactive metabolites
Authors: el-dien Radwa Taher Mohie , Maher Sherif A. , Hisham Mohamed , Saber Entesar Ali , Khedr Amgad I. M. , Fouad Mostafa A. , Kamel Mohamed Salah , Mahmoud Basma Khalaf 
Published: June 2024

Abstract
Background
Wounds are a major health issue on a global scale, putting a great deal of financial, commercial, and social strain on healthcare organizations, patients, and individuals. So, this study aims to investigate the in vitro antioxidant activity of Paralemnalia thyrsoides soft coral total ethanolic extract. Also, bio-guided in vivo wound healing validation enhanced by the evaluation of related gene expression of Paralemnalia thyrsoides total extract, derived fractions, and three known metabolites was done. Furthermore, utilizing network pharmacology, we identified ten hub target genes associated with wound healing, including AKT1(RAC-alpha serine/threonine–protein kinase), IL6 (interleukin-6), MAPK3 (mitogen-activated protein kinase 3), MMP9 (matrix metalloproteinase 9), and APP (amyloid P protein precursor). We conducted molecular docking to assess how the three compounds interact with these hub genes and inflammatory cytokines (IL-1β (interleukin-1 beta), TGF-β (transforming growth factor-beta), TNF-α (tumor necrosis factor-alpha), and NF-KB (nuclear factor-kappa B) linked to wound healing.

Results
In vitro antioxidant activity of the total ethanolic extract of Paralemnalia thyrsoides revealed potent scavenging activity against H2O2 with IC50 of 178.62 μg/mL. Additionally, the bio-guided scheme of the in vivo wound healing assay leads to the most active fraction, petroleum ether, with a healing percentage of 85% ± 4. Several chromatographic procedures upon petroleum ether fraction led to the isolation of three known compounds with significant in vivo wound healing potential which are recognized as triacontan-1-ol (1), 24-methylcholesterol (2) 6α-acetyl-7α-acetate-1(10)-α-13-nornardosine [C16H24O4] (3). Noteworthy downregulation in Cox-2 (Cyclooxygenase-2), Cox-1 (Cyclooxygenase-1), IL-1β, TGF-β, TNF-α, NF-KB, and INF-ϒ (interferon-ϒ) relative genes expression and upregulation in TGF-β, and IL-10 (interleukin-10) relative genes expression proved that compounds (3), (2), and (1) were, respectively, significant. The in silico study suggests that both C16H24O4 and 24-methyl cholesterol have potential in wound healing, possibly involving the regulation of RAC-alpha serine/threonine-protein kinase (AKT1).

Conclusion
Our study highlights the antioxidant and wound-healing potential of Paralemnalia thyrsoides soft coral that can be attributed to its diverse chemical metabolites. The in vivo and in silico findings highlighted that P. thyrsoides can be an effective remedy for wound restoration with the need for extensive future detailed clinical studies to prove these results.
Prospective validation of ctHPVDNA for detection of minimal residual disease and prediction of recurrence in patients with HPV-associated head and neck cancer treated with surgery.
Authors: Hirayama Shun , Al-Inaya Yana , Aye Ling , Bryan Michael E. , Das Dipon , Mendel Julia , Naegele Saskia , Faquin William C , Sadow Peter , Fisch Adam S. , Lin Derrick , Varvares Mark A , Feng Allen , Emerick Kevin S. , Deschler Daniel G. , Lawrence Michael S. , Iafrate A. John , Chan Annie , Richmon Jeremy , Faden Daniel 
Published: June 2024

6010 Background: Prediction of minimal residual disease (MRD) following surgery, and thus the need for adjuvant therapy, is currently based on clinicopathologic risk factors which have poor individual prognostic capacity. We previously reported that MRD detection by ctHPVDNA droplet digital (dd)PCR as early as post-operative day (POD) 1 is predictive of recurrence in stage I-II HPV+HNSCC patients. Here, we applied a significantly more sensitive custom whole genome hybrid-capture-based next generation sequencing assay, termed HPV-DeepSeek, to validate the prognostic capacity of ctHPVDNA detection and explore the optimal timing of MRD testing in HPV+HNSCC patients. We tested the primary hypothesis that patients with MRD detection within 6 weeks of surgery would have inferior PFS at 2 years and the secondary hypothesis that patients with ctHPVDNA positivity detected at any point following treatment completion would have inferior PFS at 2 years. Methods: 98 patients with HPV+HNSCC were prospectively enrolled with a mean follow-up of 712 days. All patients underwent surgery as primary treatment and clinicopathologic adjusted adjuvant treatment. 10ml blood samples were collected before surgery, in the post-operative period (POD 1-42), and serially in follow-up. MRD was defined as a lack of ctHPVDNA clearance during the 6 weeks following surgery. Cell free DNA was extracted from plasma and run on HPV-DeepSeek, and on existing ddPCR assays for head to head comparisons. Results: 96/98 (98%) of patients had detectable ctHPVDNA pre-treatment. 30/98 patients (31%) were MRD positive. Patients who were MRD positive had significantly worse 2 years PFS compared to MRD negative patients (78% vs 98%, P=0.0009). Predictive performance improved by limiting time points to POD 7-42 (2 year PFS 60% vs 97%, P<0.0001) as significantly fewer patients were MRD positive >1 week after surgery, suggesting the use of an ultra-sensitive assay such as HPV-DeepSeek requires adjustment of MRD time points. Patients with detectable ctHPVDNA following completion of all treatment had significantly worse 2-year PFS compared to patients without detectable ctHPVDNA (0% vs 97%, P<0.0001). 7/98 patients had cancer recurrence during follow-up that was detected by ctHPVDNA with a mean lead time of 207 days (35-518) to clinical diagnosis. Conclusions: ctHPVDNA detection by HPV-DeepSeek is a highly specific biomarker of MRD in HPV+HNSCC, accurately predicts disease progression and detects recurrence earlier than standard care clinical.
Development and validation of an assay to quantify plasma cell-free human papillomavirus DNA for 13 high-risk types that cause 98% of HPV-positive cancers.
Authors: Wotman Michael , Xiao Weihong , Du Robyn , Jiang Bo , Liu Suyu , Gillison Maura L. 
Published: June 2024

6065 Background: Plasma cell-free HPV DNA (cfHPV) may be a valuable tool for identification of patients with local-regionally advanced HPV-positive cancers at risk for recurrence after chemoradiation. Technical validation is required for use as an integral biomarker in a prospective clinical trial. Methods: Cell-Free 13 (i.e., CF13) is a digital-droplet PCR assay for quantification of 13 high-risk HPV types and control ERV3 in plasma that considered both variant sequences into primer/probe design and a distance matrix in phylogenetic analysis in multiplex combinations. Oligonucleotides/plasmids encoding type-specific E6/E7 regions were used as positive controls. Limit of blank, detection, quantification (LoB, LoD, LoQ), linear range, inter- and intra-assay coefficients of variation (CoV), and type-specific cross-reactivity were determined as were sensitivity and specificity for an HPV-positive diagnosis in a cohort of 278 oropharyngeal/unknown primary/oral cavity cancers tested for HPV by E6/E7 mRNA qRT-PCR or p16 IHC and HPV in situ hybridization. Results: Under identical assay conditions, the LoB, LoD and linear range were <1, 5 and 5 to 200,000 virus copies without HPV type-specific cross-reactivity. Multiplexing had no effect on LoD or linearity. LoQ was 16 copies/ml plasma for all 13 HPV types. For 80 and 10,000 copies per ml, inter-assay CoV ranged from ~15-28% and ~3.2-4.6% and intra-assay CoV ranged from ~16-38% and 0.2-3.3%, respectively. cfDNA purification method (manual v automated; extraction efficiency 142% and 91% for 16 and 10,000 HPV16 copies/ml), input plasma volume (1, 2, or 4 ml), total background cfDNA (<1800ng) or genomic DNA (<700ng) did not affect quantification. For a diagnosis of HPV-positive cancer, sensitivity and specificity were 91.1% (214/235) and 97.7% (42/43), respectively. cfHPV was associated with gender, race, T stage, N stage, and primary treatment modality. When compared to below the median (≤230 copies/ml), cfHPV above the median was associated with worse progression-free survival (HR=2.26, 95% CI 1.23-4.17, p=0.009) in univariate analysis. However, this was no longer significant after adjustment for age, T stage, and M stage (HRadj=1.78, 95% CI 0.95-3.35, p=0.07). Conclusions: CF13 has high sensitivity, accuracy, precision, linearity, HPV type-specificity, and robustness, offering a rigorously validated assay applicable to ~98% of patients with HPV-positive cancer. CF13 had excellent clinical sensitivity and specificity for a diagnosis of HPV-positive OPC.
Survival outcomes of concurrent radiotherapy and toripalimab versus radiotherapy alone for elderly patients with postoperative head and neck squamous cell carcinoma unfit for cisplatin.
Authors: Dou Shengjin , Jiang Wen , Ye Lulu , Li Rongrong , Zhu Guopei 
Published: June 2024

6099 Background: For elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the role of postoperative concurrent chemotherapy was controversial since the intolerable toxicities and increased acute mortality, thus, radiotherapy alone was recommended. We aimed to assess if addition of toripalimab (anti-PD-1) to radiotherapy could improve treatment outcomes for this patient population. Methods: This trial was an, open-label, phase 2, randomized study.We randomly assigned (1:1) patients aged>65 years, with ECOG Performance Status(PS) of 0–2, and with postoperative Stage III-IV (AJCC 8th Staging system) HNSCC unfit for cisplatin to concurrent radiotherapy (60-66Gy) and toripalimab (240mg on D0, D21 and D42)(RT+PD-1 group) or radiotherapy alone(RT group). The primary endpoint was 2-year disease free survival (DFS). It is hypothesized to detect a difference between arms of 45%-65% in 2-year DFS. Results: Between September 2020 and May 2023, 87 patients were randomly assigned (43 in RT+PD-1 group and 44 in RT group). The median age were 71.0 years (range 66-81) for the RT+PD-1 group and 72.5 years (range 67-80 years) for RT group. In the RT+PD-1 group, 35 (81.4%) patients received at least one dose of toripalimab; 38 (88.3%) patients in the RT+PD-1 group and 36 (81.8%) patients in the RT group complete the planed radiation dose. Median follow-up was 24 months in both arms. The 2-year DFS was 55.3% with RT+PD-1 and 51.2% with RT alone (p=0.866), and the 2-year OS was 63.3% with RT+PD-1 and 78.4% with RT alone(p=0.557). In RT+PD-1 group, 18(41.8%) patients were CPS≥20%; 2-year DFS was 72.2% in patients with CPS≥20%, which was 53.8% in patients with CPS<20 (p=0.412). Conclusions: The primary objective of prolonging DFS with concurrent radiotherapy and toripalimab in elderly patients unfit for cisplatin with locally advanced HNSCC was not met. For patients with CPS≥20, further study still warranted to evaluate the benefit of toripalimab in this patient setting. Biomarker analysis is still ongoing. Clinical trial information: NCT04523883 .
CODOX-M/IVAC-R versus DA-EPOCH-R in double/triple-hit large B cell lymphoma in patients ≤ 60 years.
Authors: Atallah-Yunes Suheil Albert , Rees Matthew J. , Witzig Thomas E. , Habermann Thomas Matthew , McPhail Ellen D , Munoz Javier , Iqbal Madiha , Nowakowski Grzegorz S. 
Published: June 2024

7067 Background: High intensity induction with regimens such asDA-EPOCH-R, CODOX-M/IVAC-R and HyperCVAD are often used for young patients with DHL/THL despite no overall survival (OS) benefit compared to R-CHOP. Reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate it. We aimed to investigate outcomes difference between CODOX-M/IVAC-R and DA-EPOCH-R in patients ≤ 60 years with DHL/THL diagnosed via FISH. Methods: Retrospective review of DHL/THL patients from the Mayo Clinic diagnosed between July15th 2010-October19th 2023 treated with CODOX-M/IVAC-R or DA-EPOCH-R at age of up to 60 years. Event free survival (EFS) was defined as time from diagnosis to progression, relapse, next line of treatment or death from any cause. Results: 113 patients were included; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). Patient and disease characteristics are in table. 80% (N=39) achieved CR on end of treatment (EOT) PET CT with CODOX-M/IVAC-R compared to only 58% (N=37) with DA-EPOCH-R. CODOX-M/IVAC-R was associated with superior EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL2 vs BCL6 translocation and receipt of consolidation ASCT (aHR=0.53, 95%CI=0.29-0.95), however, there was no significant influence on OS (aHR=0.97, 95%CI=0.50-1.91). At a median follow-up of 5.3 years and 3.3 years for the CODOX-M-IVAC and DA-R-EPOCH group respectively; EFS was superior in the CODOX-M/IVAC-R group having 1, 2 and 5 years EFS of 68.3%, 64.1 and 61.5% respectively compared to 52.4%, 48.9% and 39.5% respectively in the DA-EPOCH-R group (p=0.035). 33%(16/49) of the CODOX-M/IVAC-R patients had R/R disease (No CR on EOT PET CT or relapsed) with a median OS of 10.3 months compared to 33.7 months in the R/R DA EPOCH-R group (54%, 35/64). Number of patients who were able to receive salvage ASCT, CAR T and Allo-SCT were 5, 17 and 4 respectively in the DA EPOCH-R group compared to 1, 6 and 3 patients respectively in the CODOX-M/IVAC-R group. None died of regimen toxicity in both groups. 19% underwent ASCT consolidation after CR with initial induction (11 patients in each group); no OS was noticed however consolidation with ASCT was associated with increased EFS regardless of the induction regimen with best outcomes being in the CODOX-M/IVAC-R group (P=0.0072). Conclusions: Our study showed that young patients with DHL/THL who received CODOX-M/IVAC-R had superior EFS compared to DA-EPOCH-R with no OS benefit. CODOX-M/IVAC-R can spare patients receiving more subsequent therapies. Patients who have R/R disease following CODOX-M/IVAC-R have poor outcomes. [Table: see text]