bluuebunny/crossref_metadata_2025_split huggingface dataset:
New design of interdental rubber picks - does the archimedean screw design bring an improvement for experimental cleaning efficacy and force?
Authors: Härdter Ann-Kristin , Nordloh Anna , Cyris Miriam , Straßburger Martin , Rinder Thomas , Dörfer Christof E. , Sälzer Sonja , Graetz Christian 
Published: March 2024

Abstract
Background
Up to date, interdental brushes (IDB) are the first choice for interdental cleaning because of their cleaning efficacy. Cylindrical ones must be selected individually according to the size/morphology of the interdental area (IDR), whereas conical ones cover a larger variability of IDR. However, there is a trend on the part of patients towards interdental rubber picks (IRP) which are in general conically shaped, and which seem to be linked with lower cleaning efficacy. A new IRP with an Archimedes´ screw design was developed to overcome this limitation. Therefore, the in vitro study aimed to measure the experimental cleaning efficacy (ECE) and force (ECF) during interdental use of IDBs versus the new IRP type.

Methods
Three IRPs with different tapers (PHB angled: 0.039, PHB straight S: 0.027, Vitis straight M: 0.045; all Flexipicks, Dentaid, Cerdanyola del Vallès, Spain) were compared to one IDB (Interprox micro PHD 0.9, Dentaid, Cerdanyola del Vallès, Spain). IDR were reproduced by a 3D-printer (Form2, Formlabs Sommerville, MA, USA) according to human teeth and matched to equivalent pairs (isosceles triangle, concave, convex) in three different diameters (1.0 mm,1.1 mm,1.3 mm). Covered with simulated biofilm, pre-/ post-brushing situations of IDR (standardized, computer-aided ten cycles) were photographed and quantified by digital image subtraction to calculate ECE [%]. ECF were registered with a load cell [N]. Statistically significant differences were detected using the Mann-Whitney-U-test and the Kruskal-Wallis-test with Bonferroni correction for multiple testing.

Results
Overall, the ECE (mean ± SD) was higher for IDB micro 0.9 (45.95 ± 11.34%, p < 0.001) compared to all IRPs (PHB angled: 25.37 ± 15.29%; PHB straight: 22.28 ± 16.75%; Vitis straight: 25.24 ± 12.21%; p ≤ 0.001), whereat best ECE was achieved in isosceles triangle IDR of 1.0–1.1 mm (IDB micro 0.9: 70.7 ± 7.7%; PHB angled S: 57.30 ± 4.43%; p < 0.001). The highest ECF occurred for Vitis straight M with 2.11 ± 0.46 N, while IDB micro 0.9 showed lowest ECF values (0.64 ± 0.14 N; p < 0.001).

Conclusions
IRP with an Archimedes´ screw design and a higher taper were associated with advanced ECE but also higher ECF, nevertheless, ECE didn’t reach the cleaning efficacy of conventional IDBs.
Outcomes of neoadjuvant chemotherapy and radical hysterectomy for locally advanced cervical cancer at Kigali University Teaching Hospital, Rwanda: a retrospective descriptive study
Authors: Ngabonziza Eugene , Ghebre Rahel , DeBoer Rebecca J. , Ntasumbumuyange Diomede , Magriples Urania , George Jessica , Grover Surbhi , Bazzett-Matabele Lisa 
Published: March 2024

Abstract
Background
Half of countries in Africa lack access to radiation (RT), which is essential for standard treatment of locally advanced cervical cancers. We evaluated outcomes for patients treated with neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in settings where no RT is available.

Methods
We performed a retrospective descriptive study of all patients with FIGO stage IB2-IIA2 and some exceptional stage IIB cases who received NACT and surgery at Kigali University Teaching Hospital in Rwanda. Patients were treated with NACT consisting of carboplatin and paclitaxel once every 3 weeks for 3–4 cycles before radical hysterectomy. We calculated recurrence rates and overall survival (OS) rate was determined by Kaplan-Meier estimates.

Results
Between May 2016 and October 2018, 57 patients underwent NACT and 43 (75.4%) were candidates for radical hysterectomy after clinical response assessment. Among the 43 patients who received NACT and surgery, the median age was 56 years, 14% were HIV positive, and FIGO stage distribution was: IB2 (32.6%), IIA1 (7.0%), IIA2 (51.2%) and IIB (9.3%). Thirty-nine (96%) patients received 3 cycles and 4 (4%) received 4 cycles of NACT. Thirty-eight (88.4%) patients underwent radical hysterectomy as planned and 5 (11.6%) had surgery aborted due to grossly metastatic disease. Two patients were lost to follow up after surgery and excluded from survival analysis. For the remaining 41 patients with median follow-up time of 34.4 months, 32 (78%) were alive with no evidence of recurrence, and 8 (20%) were alive with recurrence. One patient died of an unrelated cancer. The 3-year OS rate for the 41 patients who underwent NACT and surgery was 80.8% with a recurrence rate of 20%.

Conclusions
Neoadjuvant chemotherapy with radical hysterectomy is a feasible treatment option for locally advanced cervical cancer in settings with limited access to RT. With an increase in gynecologic oncologists skilled at radical surgery, this approach may be a more widely available alternative treatment option in countries without radiation facilities.
Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study
Authors: Kim Taeyun , Shin Sun Hye , Kim Hyunsoo , Im Yunjoo , Cho Juhee , Kang Danbee , Park Hye Yun 
Published: March 2024

Abstract
Background
The association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated.

Methods
This retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed.

Results
BMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively.

Conclusions
A decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.
Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study
Authors: Choi JungMin , Lee So‑Ryoung , Choi Eue-Keun , Lee Kyung-Yeon , Ahn Hyo-Jeong , Kwon Soonil , Han Kyung‑Do , Oh Seil , Lip Gregory Y. H. 
Published: March 2024

Abstract
Background
Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration.

Methods
Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015–2016 were grouped by DM duration: new onset and < 5, 5–9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500–999, 1,000–1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF.

Results
The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5–9 years and 1,000–1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5–9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002).

Conclusions
Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.
Evidence that tirzepatide protects against diabetes-related cardiac damages
Authors: Taktaz Fatemeh , Scisciola Lucia , Fontanella Rosaria Anna , Pesapane Ada , Ghosh Puja , Franzese Martina , Tortorella Giovanni , Puocci Armando , Sommella Eduardo , Signoriello Giuseppe , Olivieri Fabiola , Barbieri Michelangela , Paolisso Giuseppe 
Published: March 2024

Abstract
Background
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist.

Methods
A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT.

Results
Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure.

Conclusion
Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.

Graphical Abstract
Associations of triglyceride-glucose (TyG) index with chest pain incidence and mortality among the U.S. population
Authors: Zhao Yao , Gu Yu , Zhang Bili 
Published: March 2024

Abstract
Background
The triglyceride and glucose (TyG) index, a simple surrogate marker of insulin resistance, is related to cardiovascular disease. However, there is a lack of evidence for the relationship between the TyG index and chest pain. This study aimed to investigate the association of the TyG index with chest pain and to evaluate the relationship between the TyG index and all-cause mortality in participants with or without chest pain.

Methods
The present study utilized data from the 2001–2012 National Health and Nutrition Examination Survey (NHANES), employing a combination of cross-sectional and cohort study designs. The association between the TyG index and chest pain was investigated using weighted logistic regression models. Weighted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality. Restricted cubic spline analysis was used to explore linear or nonlinear relationships between the TyG index and chest pain or all-cause mortality.

Results
The findings revealed a positive correlation between the TyG index and chest pain, even after adjusting for potential confounding factors (quartile 4 versus quartile 1, odds ratio [OR] 1.42, 95% confidence interval [CI] 1.14–1.77, P = 0.002). During a mean follow-up time of 139 months, a total of 2286 individuals (27.43%) experienced mortality. Weighted multivariate Cox regression models indicated that for each one-unit increase in the TyG index, the adjusted hazard ratio (HR) for mortality was 1.14 (95% CI = 0.94–1.37) for participants with chest pain and 1.25 (95% CI = 1.09–1.43) for those without chest pain. Furthermore, restricted cubic spline analysis revealed a linear relationship between the TyG index and chest pain (P for nonlinearity = 0.902), whereas a nonlinear relationship was shown between the TyG index and all-cause mortality among populations regardless of chest pain (all P for nonlinearity < 0.01).

Conclusion
The TyG index was positively linked to a higher incidence of chest pain. Moreover, the TyG index was associated with all-cause mortality not only in participants with chest pain but also in those without chest pain.
β-hydroxybutyrate inhibits malignant phenotypes of prostate cancer cells through β-hydroxybutyrylation of indoleacetamide-N-methyltransferase
Authors: Zhang Yifan , Li Yunlong 
Published: March 2024

Abstract
Background
Prostate cancer (PCa) is one of the most prevalent cancers in men and is associated with high mortality and disability rates. β-hydroxybutyrate (BHB), a ketone body, has received increasing attention for its role in cancer. However, its role in PCa remains unclear. This study aimed to explore the mechanism and feasibility of BHB as a treatment alternative for PCa.

Methods
Colony formation assay, flow cytometry, western blot assay, and transwell assays were performed to determine the effect of BHB on the proliferation and metastasis of PCa cells. Tumor sphere formation and aldehyde dehydrogenase assays were used to identify the impact of BHB or indoleacetamide-N-methyltransferase (INMT) on the stemness of PCa cells. N6-methyladenosine (m6A)–meRIP real-time reverse transcription polymerase chain reaction and dual luciferase assays were conducted to confirm INMT upregulation via the METTL3–m6A pathway. Co-IP assay was used to detect the epigenetic modification of INMT by BHB-mediated β-hydroxybutyrylation (kbhb) and screen enzymes that regulate INMT kbhb. Mouse xenograft experiments demonstrated the antitumor effects of BHB in vivo.

Results
BHB can inhibit the proliferation, migration, and invasion of PCa cells by suppressing their stemness. Mechanistically, INMT, whose expression is upregulated by the METTL3–m6A pathway, was demonstrated to be an oncogenic gene that promotes the stem-like characteristics of PCa cells. BHB can suppress the malignant phenotypes of PCa by kbhb of INMT, which in turn inhibits INMT expression.

Conclusions
Our findings indicate a role of BHB in PCa metabolic therapy, thereby suggesting an epigenetic therapeutic strategy to target INMT in aggressive PCa.

Trial registration
Not applicable.
The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up
Authors: Jiang Wen-Mei , Tian Jia-Yuan , Guo Yi-Han , Qiu Li-Hong , Luo Xing-Yu , Huang Yang-Yu , Long Hao , Zhang Lan-Jun , Lin Peng , Xu Xin-Xin , Wu Lei-Lei , Ma Guo-Wei 
Published: March 2024

Abstract
Objective
This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up.

Methods
The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS).

Results
A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients’ prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001).

Conclusions
Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.
Receipt of seasonal malaria chemoprevention by age-ineligible children and associated factors in nine implementation states in Nigeria
Authors: Ibinaiye Taiwo , Rotimi Kunle , Balogun Ayodeji , Aidenagbon Adaeze , Oguoma Chibuzo , Rassi Christian , Baker Kevin , Oresanya Olusola , Nnaji Chuks 
Published: March 2024

Abstract
Background
As part of implementation quality standards, community distributors are expected to ensure that only age-eligible children (aged 3–59 months) receive seasonal malaria chemoprevention (SMC) medicines during monthly campaigns. There is uncertainty about the extent to which SMC medicines are administered to ineligible children. This study aimed to assess the magnitude of this occurrence, while exploring the factors associated with it across nine states where SMC was delivered in Nigeria during the 2022 round.

Methods
This analysis was based on data from representative end-of-round SMC household surveys conducted in nine SMC-implementing states in Nigeria. Data of 3299 age-ineligible children aged > 5 years and their caregivers were extracted from the survey dataset. Prevalence of receipt of SMC medicines by ineligible children was described by child-, caregiver- and SMC-related factors. Mixed-effects multivariable logistic regression models were fitted to explore the factors associated with ineligible receipt of SMC medicines.

Results
30.30% (95% CI 27.80–32.90) of ineligible children sampled received at least one dose of SMC medicines in 2022, the majority (60.60%) of whom were aged 5–6 years while the rest were aged 7–10 years. There were lower odds of an age-ineligible child receiving SMC medicines among caregivers who were knowledgeable of SMC age eligibility (OR: 0.53, 95% CI 0.37–0.77, p < 0.001), compared with those who were not knowledgeable of age eligibility. Higher odds of receipt of SMC were found among age-ineligible children whose caregivers had higher confidence in the protective effect of SMC against malaria (OR: 2.01, 95% CI 1.07–3.72, p = 0.030), compared with those whose caregivers were less confident. Compared with ineligible children of younger caregivers (aged < 20 years), those whose caregivers were older had lower odds of receiving SMC than those whose caregivers were younger; with lower odds among children of caregivers aged 20–39 years (OR: 0.50, 95% CI 0.30–0.82, p = 0.006).

Conclusions
This study contributes important evidence on the magnitude of the receipt of SMC medicines by age-ineligible children, while identifying individual and contextual factors associated with it. The findings provide potentially useful insights that can help inform and guide context-specific SMC implementation quality improvement efforts.
Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii
Authors: Lan Xing , Qin Shugang , Liu Huan , Guo Mengran , Zhang Yupei , Jin Xinyang , Duan Xing , Sun Min , Liu Zhenjun , Wang Wenyan , Zheng Qian , Liao Xuelian , Chen Jinpeng , Kang Yan , Xie Yongmei , Song Xiangrong 
Published: March 2024

AbstractMultidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood–brain barrier (BBB). In this study, we prepared a novel core–shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.
Graphical abstract
An integrated framework for prognosis prediction and drug response modeling in colorectal liver metastasis drug discovery
Authors: Zhou Xiuman , Qian Yuzhen , Ling Chen , He Zhuoying , Shi Peishang , Gao Yanfeng , Sui Xinghua 
Published: March 2024

Abstract
Background
Colorectal cancer (CRC) is the third most prevalent cancer globally, and liver metastasis (CRLM) is the primary cause of death. Hence, it is essential to discover novel prognostic biomarkers and therapeutic drugs for CRLM.

Methods
This study developed two liver metastasis-associated prognostic signatures based on differentially expressed genes (DEGs) in CRLM. Additionally, we employed an interpretable deep learning model utilizing drug sensitivity databases to identify potential therapeutic drugs for high-risk CRLM patients. Subsequently, in vitro and in vivo experiments were performed to verify the efficacy of these compounds.

Results
These two prognostic models exhibited superior performance compared to previously reported ones. Obatoclax, a BCL-2 inhibitor, showed significant differential responses between high and low risk groups classified by prognostic models, and demonstrated remarkable effectiveness in both Transwell assay and CT26 colorectal liver metastasis mouse model.

Conclusions
This study highlights the significance of developing specialized prognostication approaches and investigating effective therapeutic drugs for patients with CRLM. The application of a deep learning drug response model provides a new drug discovery strategy for translational medicine in precision oncology.