bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood endocan as a biomarker for breast cancer recurrence
Authors: Daiki Kentaro , Kanada Yoko , Nagata Aya , Taruno Kanae , Igarashi Katsuhide , Yamochi Toshiko , Ota Hirotaka , Sato Fumiaki , Nakamura Seigo , Kato Yoshinori 
Published: September 2024

BACKGROUND: Endocan was reported to affect breast cancer patients negatively and was able to be detected from patients’ blood. OBJECTIVE: This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. METHODS: Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). RESULTS: Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. CONCLUSIONS: Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence.
KIF18A promotes cervical squamous cell carcinoma progression by activating the PI3K/AKT pathway through upregulation of CENPE
Authors: Sun Fengyi , Zhao Tiantian 
Published: September 2024

BACKGROUND: Cervical cancer is a prevalent malignancy that significantly contributes to morbidity and mortality rates among women in developing nations. Although the association of KIF18A with various cancers has been established, its role in cervical squamous cell carcinoma (CESC) remains elusive. METHODS: The KIF18A impact on the progression of CESC and its underlying mechanism were investigated through comprehensive bioinformatics analysis utilizing publicly available datasets. The levels of KIF18A and CENPE were assessed in clinical CESC samples through western blotting and qRT-PCR. To discover the role and molecular pathways of KIF18A in CESC, a combination of experimental approaches, including wound-healing, flow cytometry, CCK-8, and Transwell assay, were employed. RESULTS: Our results demonstrate a significant KIF18A expression upregulation in CESC tissues in contrast to healthy tissues. In vitro, KIF18A upregulation was found to enhance cell growth, migration, and invasion and activate the PI3K/AKT signaling pathway while concurrently suppressing apoptosis. Conversely, downregulating KIF18A exhibited contrasting effects. Mechanistically, we observed a positive significant connection between KIF18A and CENPE in CESC cells. CONCLUSION: KIF18A promotes tumor growth in CESC by modulating the PI3K/AKT signaling pathway through regulation of CENPE, making it a potential biomarker for diagnosis and prognosis as well as a therapeutic target.
Association Between Body Mass Index Changes and All-Cause Mortality in Parkinson’s Disease
Authors: Yoon Seo Yeon , Choi Ja Young , Nam Ga Eun , Jung Jin-Hyung , Han Kyungdo , Kang Sung Hoon , Kim Chi Kyung , Kim Yong Wook , Koh Seong-Beom 
Published: September 2024

Background: Whether body weight changes are associated with Parkinson’s disease (PD) mortality remains uncertain. Objective: To investigate the association between changes in body mass index (BMI) and all-cause mortality in patients with PD. Methods: This nationwide cohort study enrolled 20,703 individuals with new-onset PD (ICD-10 code: G20 and a rare intractable disease registration code: V124) who underwent health screening program by the Korean National Health Insurance Service within two years from pre- and post-PD diagnosis. We identified nine BMI change groups based on three BMI status: underweight (BMI < 18.5 kg/m2), normal or overweight (18.5 kg/m2≤BMI < 25 kg/m2), and obese (BMI≥25 kg/m2). Results: Of 20,703 individuals, 3,789 (18.0%) died during the follow-up period. Excessive weight loss to underweight in the obese group (hazard ratio [HR] = 3.36, 95% CI:1.60–7.08), weight loss in the normal to overweight group (HR = 2.04, 95% CI:1.75–2.39), sustained underweight status (HR = 2.05, 95% CI:1.67–2.52), and weight gain from underweight to normal or overweight (HR = 1.52, 95% CI:1.15–2.02) were associated with increased mortality. Sustained obese status (HR = 0.80, 95% CI:0.74–0.87) and weight gain in the normal to overweight group (HR = 0.82, 95% CI:0.71–0.95) were associated with reduced mortality. Conclusions: We found that BMI change at diagnosis was associated with mortality in patients with PD. Specifically, being underweight either before or after diagnosis as well as experiencing weight loss, were associated with increased mortality. These findings provide valuable insights for weight management planning in PD, highlighting the importance of individualized approach that consider pre-diagnosis BMI.
Using heart rate monitoring to discover pain and discomfort in non-verbal persons with severe intellectual disability: Caregivers’ experiences
Authors: Boysen Elin Sundby , Øderud Tone , Strisland Frode , Kildal Emilie Smith-Meyer , Dahl Inger-Lise , Hassel Bjørnar , Morland Cecilie 
Published: September 2024

BACKGROUND Non-verbal persons with intellectual disabilities (ID) may suffer from pain or discomfort, but caregivers may not notice this because of the communication difficulties. Previously, we conducted a study in which professional caregivers used heart rate (HR) monitoring to identify situations that cause acute pain or distress in the everyday life of non-verbal persons with ID. OBJECTIVE To explore professional caregivers’ experience with using HR monitors to better understand non-verbal persons with ID. METHODS Fifteen professional caregivers and 30 final-year students of social education were recruited as informants based on their experience with HR monitoring in non-verbal persons. The informants were interviewed, and they responded to a questionnaire with open-ended questions. The qualitative data were analysed thematically. RESULTS Caregivers reported that HR monitoring provided information about acute pain, acute or prolonged distress, occurrence of epileptic seizures, and the non-verbal persons’ preferences and dislikes. HR data had to be interpreted contextually to be meaningful. Some informants found HR monitoring time-consuming or the interpretation of HR data challenging due to multiple possible causes of increased HR. CONCLUSIONS Caregivers experience HR monitoring as a potentially important source of information that may help them better understand non-verbal persons with ID.
Morphine-Sparing Effect of Intermittent Versus Continuous Intravenous Infusion of Nefopam in Patients After Total Knee Arthroplasty: A Randomized Trial
Authors: Kachacheewa Woratanat , Wattanavijitkul Thitima , Wongsak Siwadol , Chalacheewa Theerawat 
Published: September 2024

Background: Nefopam, a nonopioid analgesic, is recommended to improve pain control and minimize opioid-related side effects following total knee arthroplasty (TKA).
Objective: To compare cumulative morphine consumption between intermittent infusion (II) and continuous infusion (CI) of nefopam, combined with other multimodal analgesics, in TKA patients.
Methods: Fifty-eight patients were randomly assigned to receive either intermittent nefopam infusion (II group) (20 mg IV every 6 hours) or continuous infusion (CI group) (80 mg/day). The primary outcome was cumulative morphine consumption via patient-controlled analgesia, with secondary outcomes including pain scores every 4 hours and adverse drug reactions (ADRs).
Results: No significant difference was found in cumulative morphine consumption (median [range], 4 [0 -12] mg in II and 6 [0 - 18] mg in CI; P = .579) and the ADRs over 48 hours between groups. At 4 hours, the II group had significantly lower pain scores compared to the CI group (median [range], 0 [0 - 4] and 0 [0 - 8]; P = .008). However, by 24 and 36 hours, the CI group reported significantly lower pain scores compared to the II group; median (range), 0 (0 - 5) vs 2 (0 - 9) at 24 hours (P = .020) and 0 (0 - 4) vs 2 (0 - 8) at 36 hours (P = .014).
Conclusions: Both intermittent and continuous nefopam infusion in primary TKA showed no significant difference in morphine-sparing or occurrence of ADRs within the 48-hour follow-up period. These findings suggest that both infusion methods are comparable in managing post-operative pain in TKA patients.
Release kinetics of growth factors loaded into β-TCP ceramics in an in vitro model
Authors: Waldmann Marco , Bohner Marc , Baghnavi Anna , Riedel Bianca , Seidenstuecker Michael 
Published: September 2024

Introductionβ-TCP ceramics are bone replacement materials that have recently been tested as a drug delivery system that can potentially be applied to endogenous substances like growth factors found in blood platelets to facilitate positive attributes.MethodsIn this work, we used flow chamber loading to load β-TCP dowels with blood suspensions of platelet-rich plasma (PRP), platelet-poor plasma (PPP), or buffy coat (BC) character. PRP and BC platelet counts were adjusted to the same level by dilution. Concentrations of TGF-β1, PDGF-AB, and IGF-1 from dowel-surrounding culture medium were subsequently determined using ELISA over 5 days. The influence of alginate was additionally tested to modify the release.ResultsConcentrations of TGF-β1 and PDGF-AB increased and conclusively showed a release from platelets in PRP and BC compared to PPP. The alginate coating reduced the PDGF-AB release but did not reduce TGF-β1 and instead even increased TGF-β1 in the BC samples. IGF-1 concentrations were highest in PPP, suggesting circulating levels rather than platelet release as the driving factor. Alginate samples tended to have lower IGF-1 concentrations, but the difference was not shown to be significant.DiscussionThe release of growth factors from different blood suspensions was successfully demonstrated for β-TCP as a drug delivery system with release patterns that correspond to PRP activation after Ca2+-triggered activation. The release pattern was partially modified by alginate coating.
Association of monocyte-lymphocyte ratio and myocardial infarction in the U.S. population with diabetes
Authors: Wu Yue , Xiang Hong-Ju , Yuan Min 
Published: September 2024

Background and objectiveThe monocyte-to-lymphocyte ratio (MLR) has emerged as a novel inflammatory biomarker; however, its relationship with myocardial infarction (MI) in diabetic populations remains unclear. This study aimed to elucidate the association between MLR and MI prevalence in this unique population.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES), 2015-2018. MLR was utilized as both a continuous and categorical factor to examine its correlation with MI in individuals diagnosed with DM. Subgroup and sensitivity analyses were also performed.ResultsIn this study, 1,295 individuals with DM were enrolled, among whom 148 (11.4%) were diagnosed with MI. Patients with MI showed a greater MLR. Using a smoothed curve-fitting analysis, a linear relationship was observed between MLR and MI (pfor non−linearity = 0.27). Multivariate logistic regression analysis showed that MLR * 10 was positively correlated with the risk of MI (OR = 1.14, 95% CI 1.01∼1.29, p = 0.041). Compared with the lowest quartile, the OR for Q2, Q3, and Q4 were 2.13 (95% CI: 1.01∼4.47), 2.95 (95% CI: 1.45∼6.00), and 2.74 (95% CI: 1.32∼5.69), respectively. Subgroup analyses showed no significant interaction for MLR in any subgroup (all P &gt; 0.05). The receiver operating characteristic (ROC) curve indicated that the area under the curve (AUCs) of MLR for predicting MI was 0.661 (95% CI: 0.617–0.706; P &lt; 0.05).ConclusionsOur study demonstrated that MLR is significantly correlated with MI in patients with DM.
Clinical outcomes of three follitropin alfa preparations for ovarian stimulation using an oral micronized progesterone-primed protocol in an oocyte donation program
Authors: Cruz María , Howles Colin M. 
Published: September 2024

IntroductionThis large multicenter study aimed to evaluate clinical outcomes using three follitropin alfa preparations within a progestin-primed ovarian stimulation (PPOS) protocol, while identifying contributing factors to cycle success.MethodsA retrospective, anonymized cohort analysis was conducted on donor-recipient cycles from 12 clinics during 2019 to 2021. 7389 oocyte donors underwent ovarian stimulation (OS) with three follitropin alfa preparations (Ovaleap® [n=3231], Bemfola® [n=3542], Gonal-F® [n=616]) were included. Stimulation began on cycle days 2 or 3 with daily administration of 150-225 IU follitropin alfa. 10 mg medroxyprogesterone acetate (MPA) was administered daily until GnRH agonist trigger using a single dose of 0.2mg GnRH agonist for final follicular maturation. Statistical analysis included ANOVA, Chi-squared, and logistic regression.ResultsWhilst there were some differences in patient and stimulation characteristics, including donor age and number of retrieved oocytes, clinical variables did not significantly differ among the three study groups. Linear regression revealed donor age [0.986 (0.974-0.999)] and number of mature oocytes [1.027 (1.007-1.047)] significantly impacted ongoing pregnancy rates, while the type of follitropin alfa [1.048 (0.956-1.149)] used did not. No significant differences were observed in the cumulative live birth rate (CLBR) among oocytes obtained from stimulation with Bemfola (64.9%), Gonal-F (64.1%) and Ovaleap (66.1%), p= 0.385.DiscussionThis study demonstrated comparable clinical outcomes and CLBR between biosimilars and the reference product of follitropin alfa within PPOS protocols, hence they are interchangeable in a real-world patient setting.
Accelerated calciprotein crystallization time (T50) is correlated with impaired lung diffusion capacity in systemic sclerosis
Authors: Geroldinger-Simic Marija , Sohail Azmat , Razazian Mehdi , Krennmayr Beatrice , Pernsteiner Victoria , Putz Thomas , Lackner Helmut K. , Pasch Andreas , Sepp Norbert , Alesutan Ioana , Voelkl Jakob 
Published: September 2024

BackgroundSystemic sclerosis (SSc) is a complex auto-immune disease characterized by vascular damage, inflammation, fibrosis and calcinosis, where pulmonary involvement is the leading cause of mortality. Calciprotein particles (CPPs) are increasingly formed upon disbalance of the physiological mineral buffering system and induce pro-inflammatory effects. This exploratory study investigated whether functional indicators of the endogenous mineral buffering system are dysregulated in SSc and linked to disease activity.MethodsT50 (calciprotein crystallization test or serum calcification propensity) and hydrodynamic radius of secondary CPPs (CPP2) were determined in serum samples from 78 SSc patients and 44 controls without SSc, and were associated with disease activity markers of SSc.ResultsT50 was reduced and CPP2 radius was increased in SSc patients as compared to controls, indicating a deranged mineral buffering system. This was accompanied by slightly higher serum phosphate and PTH levels in SSc patients, while iFGF23 was not significantly modified. Longitudinally, all parameters remained unchanged over time in SSc patients, only iFGF23 increased. While the modified Rodnan skin score showed some inconsistent correlations with mineral buffering indicators, their association was not independent of other factors. However, lower T50 was significantly correlated to reduced lung diffusion capacity and this association remained significant in a multivariate linear regression model.ConclusionThis study provides indications for a disturbed mineral buffering system in SSc. Increased serum calcification propensity (lower T50) is correlated with impaired lung diffusion capacity, suggesting a possible role of deranged mineral buffering in disease progression. Further studies are required to confirm these observations in larger cohorts and to investigate a putative functional relevance.
Association of outdoor artificial light at night with myopia among Chinese adolescents: a representative cross-sectional study
Authors: Liu Ting , Tan Weixing , Fu Youjuan , Cheng Beijing , Tian Hua , Liu Can , Wang Zhixiang , Zhang Yanting , Guan Suzhen , Liu Zhihong 
Published: September 2024

BackgroundThe association between the rapid increase in myopia among adolescents and the amount of outdoor artificial light at night (ALAN) remains unclear. The aim of this study was to investigate the association between outdoor ALAN and myopia in adolescents.MethodsStratified cluster random sampling was used to obtain a sample of 33,160 students (age range: 9–18 years; mean: 13.51 years) with complete data from 120 primary and secondary schools across the Ningxia region in China in 2021. Myopia was defined as a spherical equivalent (SE) ≤−0.5 diopters (D) in at least one eye, determined by automated refractometers without cycloplegia. Outdoor ALAN data were obtained from satellite data and the two-year average outdoor ALAN exposure for each participant was determined by matching it to their school address (home addresses were not available). The association between ALAN and myopia was assessed using multiple logistic regression models and restricted cubic spline (RCS) regression. Stratified analyses were performed by age, sex, residence, school level, and outdoor exercise time.ResultsThe myopia group had higher outdoor ALAN levels than the non-myopia group [median (interquartile spacing): 14.44 (3.88–26.56) vs. 6.95 (1.21–21.74) nanoWatts/cm2/sr]. After adjusting for covariates identified through stepwise regression, it was observed that the prevalence of myopia increased by 4% for every 10-unit change [95% confidence interval (CI): 1.02–1.07]. Compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratio (OR) of myopia was 1.20 (95% CI: 1.08–1.34) in the fourth quantile. RCS further showed a positive nonlinear relationship between outdoor ALAN exposure and myopia (p for nonlinear &lt;0.001). Stronger effects were not found in subgroup analyses.ConclusionOutdoor ALAN exposure is positively and nonlinearly associated with the prevalence of myopia in adolescents. Controlling outdoor light pollution may constitute a potential strategy to reduce the incidence of myopia in adolescents.
Multimodal functional imaging and clinical correlates of pain regions in chronic low-back pain patients treated with spinal cord stimulation: a pilot study
Authors: Shamli Oghli Yazan , Ashok Arjun , Glener Steven , Ailes Isaiah , Syed Mashaal , Kang Ki Chang , Naghizadehkashani Sara , Fayed Islam , Mohamed Feroze B. , Talekar Kiran , Krisa Laura , Wu Chengyuan , Matias Caio , Alizadeh Mahdi 
Published: September 2024

ObjectiveSpinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions.MethodsMulti-delay 3D GRASE pseudo-continuous ASL and rs-fMRI data were acquired from five patients post-SCS with cLBP and five healthy controls. Three ASL measures and four rs-fMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from a pain atlas were extracted and compared between patients and controls. Clinical pain scores assessing intensity, sensitization, and catastrophizing, as well as others assessing global pain effects (sleep quality, disability, anxiety, and depression), were obtained in patients and correlated with pain regions using linear regression analysis.ResultsArterial transit time derived from ASL and several rs-fMRI measures were significantly different in patients in regions involved with sensation (primary somatosensory cortex and ventral posterolateral thalamus [VPL]), pain input (posterior short gyrus of the insula [PS]), cognition (dorsolateral prefrontal cortex [DLPC] and posterior cingulate cortex [PCC]), and fear/stress response (hippocampus and hypothalamus). Unidimensional pain rating and sensitization scores were linearly associated with PS, VPL, DLPC, PCC, and/or amygdala activity in cLBP patients.ConclusionThe present results provide evidence that ASL and rs-fMRI can contrast functional activation in pain regions of cLBP patients receiving SCS and healthy subjects, and they can be associated with clinical pain evaluations as quantitative assessment tools.
BRAF/MEK inhibitors use for pediatric gliomas; real world experience from a resource-limited country
Authors: Abu Laban Dima , Alsharif Abeer , Al-Hussaini Maysa , Obeidat Mouness , Maraqa Bayan , Alzoubi Qasem , Musharbash Awni , Jaddoua Saad , Ramlawi Raed , Khaleifeh Kawther , Ibrahimi Ahmad Kh. , Sarhan Nasim , Bouffet Eric , Amayiri Nisreen 
Published: September 2024

IntroductionMost pediatric low-grade-gliomas (LGG) and some high-grade-gliomas (HGG) have alterations in the RAS/MAPK pathway. Promising high tumor response rates were achieved using BRAF/MEK inhibitors, however data on their use in low-middle-income-countries (LMICs) are limited.MethodsWe retrospectively reviewed our Jordanian experience of using compassionate BRAF/MEK inhibitors in treating children with gliomas. We reviewed patients’ clinical characteristics, tumor response, and side effects.ResultsTwenty patients (13 males, 7 females) were identified. Median age at diagnosis was 8.3 years (0.3-18.9years). There were fifteen LGGs, three HGGs and two grade-2 pleomorphic xanthoastrocytoma (PXA-2). Fifteen tumors were supratentorial, three posterior fossa/brainstem, one diffuse-glioneuronal tumor (DLGNT) and one spinal. Five tumors were metastatic. Except for one patient with neurofibromatosis, ten patients underwent partial resection and nine had biopsy. All patients, except three, received BRAF/MEK inhibitors after initial standard chemo/radiotherapy. Seven LGGs had BRAF-mutation, six had BRAF-fusion, and two were empirically treated (one neurofibromatosis and one DLGNT). Fourteen LGGs were treated with 1-4 chemotherapy regimens before BRAF/MEK inhibitors’ use; all had partial/stable response on targeted therapy at a median of 1.9 years (0.5-5.4years). Two patients with BRAFv600E-mutated/CDKN2A deleted PXA-2, had progression following resection, and experienced stable/partial response at 9 months of dabrafenib use. Two patients with HGGs had BRAFv600E-mutation, and one had an FGFR-mutation. All three patients with HGG had temporary stable/partial response, two with significant clinical improvement. At a median of 2.7 years (1.3-3.2years), all patients experienced tumor progression, and two died. Eight patients (40%) developed acneiform rash, three (15%) paronychia, and one had significant panniculitis and fatigue. Six patients (30%) needed dose-reduction. Nine patients had temporary drug interruptions [due to side effects (5) and drug shortage (4)]. Two patients who stopped trametinib due to side effects (significant acneiform rash/paronychia and intracranial bleeding) did not experience progression.ConclusionsOur experience with BRAF/MEK inhibitors’ use was positive achieving response in all LGGs and provided sustained response with good quality of life for patients with HGG. Cost effectiveness analyses and patients’ satisfaction comparisons with chemotherapy are needed to evaluate the routine use of these drugs in LMICs.