bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Acute Energy Drink Consumption on Heart Rate Variability in Children and Adolescents. A Randomized Trial
Authors: Mandilaras Guido , Li Pengzhu , Dalla-Pozza Robert , Jakob André , Haas Nikolaus Alexander , Oberhoffer Felix Sebastian 
Published: January 2025

Abstract
The EDUCATE study investigated the acute impact of energy drink (ED) consumption on heart rate variability (HRV) in children and adolescents, with a focus on how these stimulant-rich beverages influence cardiac autonomic function. Given the popularity of EDs among young people, this study assessed the immediate cardiovascular response to ED intake. This randomized, double-blind, placebo-controlled crossover trial involved 26 healthy participants aged 10–18 years. Each participant consumed a weight-adjusted ED or placebo in two separate test sessions. HRV was monitored via a 24-h Holter ECG, with analysis centered on time-domain measures, such as the standard deviation of normal RR intervals (SDNN) and root-mean square of successive differences (RMSSD), along with frequency-domain metrics. Statistical analysis included a two-way repeated-measures ANOVA to examine the effects of “beverage” and “time.” The study revealed a significant increase in the SDNN in the ED group within the first hour post-consumption, with a mean difference of 17.692 ms compared with that in the placebo group (SDNN: ED = 133.346 ± 50.217 ms vs. placebo = 115.654 ± 47.583 ms, p = 0.023). However, no significant differences in the SDNN were observed in the subsequent time intervals (60–240 min). In addition, frequency-domain parameters, such as total power, RMSSD, LF, HF, and the LF/HF ratio, showed no significant changes across the four-hour observation period, indicating that sympathetic activation was transient. The findings suggest that ED consumption in children and adolescents leads to a temporary increase in autonomic activity, marked by elevated SDNN, without lasting dysregulation. While the cardiovascular effects are brief, acute sympathetic activation underscores the need for regulated ED intake among minors. Further studies are recommended to explore the long-term effects of regular ED consumption on cardiovascular health in youth.
Self-sufficient biocatalytic cascade for the continuous synthesis of danshensu in flow
Authors: Marchini Valentina , Paradisi Francesca 
Published: January 2025

Abstract
A new strategy has been developed to successfully produce the active component danshensu ex vivo. For this purpose, phenylalanine dehydrogenase from Bacillus sphaericus was combined with the novel hydroxyphenylpyruvate reductase from Mentha x piperita, thereby providing an in situ cofactor regeneration throughout the conversion process. The purified enzymes were co-immobilized and subsequently employed in batch biotransformation, resulting in 60% conversion of 10 mM L-dopa within 24 h, with a catalytic amount of NAD+ as cofactor. Furthermore, the bienzymatic system was implemented as a packed-bed reactor in continuous flow, achieving a conversion rate up to 80% with 60 min retention time. The process was further intensified by implementing a 48-h flow bioreaction. The biocatalysts demonstrated remarkable stability, retaining 62% of their initial activity at the end of the process. The final productivity of the isolated compound (96% purity) was calculated to be 1.84 g L−1 h−1 yielding a sustainable synthesis of danshensu.

Key points

• Characterization of the hydroxyphenylpyruvate reductase from Mentha x piperita

• Bi-enzymatic system in a cascade reaction to produce danshensu

• Purification and isolation
of the active compound danshensu

Graphical Abstract
Outlet type constipation in adult patients treated with type A botulinum toxin: a cohort study
Authors: Brisinda Giuseppe , Fico Valeria , Tropeano Giuseppe , Cariati Maria , Altieri Gaia , Misuriello Filomena , Pepe Gilda , Fransvea Pietro , Chiarello Maria Michela 
Published: January 2025

Abstract

Purpose
Chronic constipation is a common symptom. Constipation due to pelvic floor disorders remain a therapeutic challenge. Biofeedback therapy is considered as the first-choice treatment for pelvic floor disorders, whenever dedicated expertise is available. Type A botulinum toxin has been used to selectively weaken the external anal sphincter and puborectalis muscle in constipated patients.

Method
Eighty-two patients with chronic outlet obstruction constipation were treated with 100 units type A botulinum toxin, injected into the puborectalis muscle and the external anal sphincter.

Results
At the 2-month evaluation, a symptomatic improvement was noted in 69 patients. Seven (8.5%) patients had mild flatus incontinence. Stool frequency per week increased from 2.4 ± 0.9 to 5.1 ± 1.0 (P = 0.0001). Anorectal manometry demonstrated decreased tone during straining from 91 ± 28 mmHg to 61 ± 27 mmHg (P = 0.0001). Defecography after the treatment showed improvement in anorectal angle during straining, which increased from 96 ± 12° to 124 ± 14° (P = 0.0001).

Conclusion
Type A botulinum toxin relaxes the puborectalis muscle. Pressure values decline after the treatment. Transrectal ultrasonography to guide injections is a safe procedure. Repeated injections were needed to maintain the clinical improvement.
The dynamic interaction of pediatric ALL cells and MSCs: influencing leukemic cell survival and modulating MSC β-catenin expression
Authors: Ozdemir-Sanci Tuba , Piskin Ilkay , Köksal Yasin , Cayli Sevil , Ozbek Namik Y. , Ozguner H. Meltem 
Published: January 2025

Abstract
Bone marrow mesenchymal stromal cells (BM-MSCs) are integral components of the bone marrow microenvironment, playing a crucial role in supporting hematopoiesis. Recent studies have investigated the potential involvement of BM-MSCs in the pathophysiology of acute lymphoblastic leukemia (ALL). However, the exact contribution of BM-MSCs to leukemia progression remains unclear because of conflicting findings and limited characterization. In this study, we compared BM-MSCs derived from pediatric ALL patients with those from matched healthy donors (HDs). Our results indicate that while both ALL-MSCs and HD-MSCs meet the criteria established by the International Society for Cellular Therapy, they exhibit significant differences in proliferation and differentiation capacity. ALL-MSCs displayed markedly lower proliferation rates and reduced osteogenic/adipogenic differentiation potential compared to HD-MSCs. Furthermore, co-culture experiments revealed that MSCs enhance the survival of leukemic blasts through both soluble factors and direct cell-cell interactions, underscoring their anti-apoptotic properties. Importantly, our findings demonstrate that interactions with leukemic cells activate the Wnt/β-catenin signaling pathway in MSCs, suggesting a potential target for therapeutic intervention. Overall, this study enhances our understanding of the role of BM-MSCs in leukemia and highlights β-catenin as a promising target for future therapies.
Immunohistochemical analysis of 147 cases of low-grade endometrial stromal sarcoma: refining the immunohistochemical profile of LG-ESS on a large, molecularly confirmed series
Authors: Flídrová Miroslava , Dundr Pavel , Vránková Romana , Němejcová Kristýna , Cibula David , Poncová Renata , Michalová Květoslava , Bouda Jiří , Laco Jan , Ndukwe Munachiso , Ryś Janusz , Książek Mariusz , Berjon Alberto , Zapardiel Ignacio , Franin Ivan , Njavro Antonela , Hausnerová Jitka , Bretová Petra , Židlík Vladimír , Klát Jaroslav , Krasznai Zoard Tibor , Poka Robert , Volodko Nataliya , Yezhova Iryna , Pilka Radovan , Marek Radim , Kolnikova Georgina , Krkoška Milan , Halaška Michael , Drozenová Jana , Dolinská Dagmar , Kalist Vladimír , Bobiński Marcin , Ostrowska-Leśko Marta , Bizoń Magdalena , Sawicki Włodzimierz , Stukan Maciej , Grabowska Karolina , Jędryka Marcin , Poprawski Tymoteusz , Stolnicu Simona , Căpîlna Mihai Emil , Špůrková Zuzana , Zikán Michal , Ciccarone Francesca , Scambia Giovanni , Sharashenidze Archil , Gudadze Miranda , Piatnytska Tetiana , Varchak Ihor , Kendall Bártů Michaela 
Published: January 2025

Abstract

Low-grade endometrial stromal sarcoma (LG-ESS) can present diagnostic challenges, due to its overlapping morphological features with other uterine mesenchymal tumors. Misdiagnosis rates remain significant, and immunohistochemical data for LG-ESS are limited to small series and inconsistent antibody panels. This study aimed to refine the IHC profile of LG-ESS by analyzing a large, molecularly confirmed series of 147 cases using a panel of 24 antibodies, including newer markers like transgelin and smoothelin. CD10 and IFITM1, key endometrial stromal markers, were expressed in 86% (92% of those extensively) and 69% (60% of those extensively) of cases, with fusion-positive tumors showing significantly higher expression. Smooth muscle markers (α-SMA, desmin, h-caldesmon, calponin, transgelin) were variably expressed, predominantly in focal or low-intensity patterns, with α-SMA reaching the highest frequency of expression (44%). However, the intensity of smooth muscle marker expression was usually very low. Smoothelin was rarely expressed. Hormone receptors were frequently positive, with PR showing a higher frequency (92% vs. 83%) and intensity than ER. Markers like S-100, HMB45, and CD117 were largely negative; all tumors were p53 wild-type, with preserved SMARCB1/SMARCA4 expression and ALK and ROS1 negativity. This work represents the largest molecularly validated IHC study on LG-ESS, providing a robust diagnostic profile for routine pathology. By addressing key diagnostic limitations and examining newer markers, our study supports a more standardized approach to diagnosing LG-ESS and underscores the value of immunohistochemical panels, particularly in fusion-negative tumors where diagnosis relies on morphological and immunohistochemical interpretation. These findings contribute critical data for improving diagnostic accuracy.
Diagnosing alkaptonuria-related nephropathy with urine albumin analysis
Authors: Gülbahçe Aliye , Muderrisoglu Ahmet 
Published: January 2025

Abstract
Homogentisic acid (HGA) accumulation in alkaptonuria (AKU) causes injuries in various organs including the kidney. We present a case of a 9-year-old girl initially diagnosed with AKU-related nephropathy due to proteinuria found in her urine analyses. Despite 1 month of ramipril treatment, the patient’s proteinuria progressed, and as a result, kidney biopsy and nitisinone treatment were planned. In addition, we controlled her proteinuria with urine albumin measurement. After finding a normal urine albumin level in the 24-h urine sample, we realized that the patient was misdiagnosed with proteinuria because of HGA interference with urine protein level measurement using benzethonium. The patient’s treatment for kidney injury was canceled. Urine albumin level was measured as normal 2 months later, confirming proteinuria was a false-positive test result. AKU-related nephropathy should be evaluated with urine albumin measurement instead of protein. In this way, the complication risk of unnecessary interventions and pharmacotherapies can be avoided.
Optimizing navigational graph queries
Authors: Mulder Thomas , Fletcher George , Yakovets Nikolay 
Published: January 2025

Abstract
We study the optimization of navigational graph queries in the form of the Regular Queries, i.e., queries which combine recursive and pattern-matching fragments. Current approaches to their evaluation are not effective in practice. Towards addressing this, we present a number of novel powerful optimization techniques which aim to constrain the intermediate results during query evaluation. We show how these techniques can be planned effectively and executed efficiently towards the first practical evaluation solution for complex navigational queries on real-world workloads. Indeed, our experimental results show several orders of magnitude improvement in query evaluation performance over state-of-the-art techniques on a wide range of queries on diverse datasets.
Combined Effects of Nitrogen Deposition and Climate on Root-to-Shoot Ratios and Root Morphology in Temperate Tree Regeneration
Authors: Dietrich Viktoria , Niederberger Jörg , Patriarca Nico Espadilha , Becker Meike E. , Müller Stefan , Lorösch Hannah , Boll Sophie , Hoque Naima , Jüngling Helena , Beck Nico , Dierks Adrian , Ebert Pauline , Troidl Emma , Hauck Markus 
Published: January 2025

Abstract
Nitrogen (N) availability is known to interact with the drought tolerance in plants, but its effects on the morphological acclimation of forest trees to low precipitation have rarely been investigated. Based on a Germany-wide field-study design covering different combinations of climatic conditions and atmospheric N deposition, we harvested young trees up to 70 cm in height of Fagus sylvatica, Quercus petraea, Pseudotsuga menziesii, and Abies alba. We tested the hypothesis that high N deposition decreases the root/shoot ratio, alters fine root morphology (for example, by reducing specific root length of absorptive roots) and reduces mycorrhizal colonization rate, which are factors that would reduce the capacity for water uptake under drought. European beech showed reduced root/shoot ratios at high N deposition and reduced specific root length and mycorrhizal colonization of absorptive roots at sites with both high N deposition and low precipitation. These observations were consistent with the optimal portioning theory, as less investment in belowground biomass was required to meet the N demand at high N deposition. Sessile oak showed no effect of N deposition or mean annual precipitation on the parameters studied, indicating that the gradients studied were not large enough to cause changes. Douglas-fir and silver fir expanded their root systems with increasing N deposition, with higher specific root length in Douglas-fir and a trend towards higher root tip abundance in silver fir. Thus, in contrast to European beech, we found no indication that the tree's ability to cope with drought was reduced by high N deposition in sessile oak, Douglas-fir, and silver fir. The combined negative effect of drought and high N deposition on the root system in European beech as Central Europe’s most dominant tree species in the natural vegetation emphasizes the need for curtailing N emissions, especially from agriculture.
Exploring the influence of medical staffing and birth volume on observed-to-expected cesarean deliveries: a panel data analysis of integrated obstetric and gynecological departments in Germany
Authors: Stöcker Arno , Pfaff Holger , Scholten Nadine , Kuntz Ludwig 
Published: January 2025

Abstract

Introduction
Cesarean deliveries account for approximately one-third of all births in Germany, prompting ongoing discussions on cesarean section rates and their connection to medical staffing and birth volume. In Germany, the majority of departments integrate obstetric and gynecological care within a single department.

Methods
The analysis utilized quality reports from German hospitals spanning 2015 to 2019. The outcome variable was the annual risk-adjusted cesarean section ratio—a metric comparing expected to observed cesarean sections. Explanatory variables included annual counts of physicians, midwives, and births. To account for case number-related staffing variations, full-time equivalent midwife and physician staff positions were normalized by the number of deliveries. Uni- and multivariate panel models were applied, complemented by multiple instrument variable analyses, including two-stage least square and generalized method of moments models.

Results
Incorporating data from 509 integrated obstetric departments and 2089 observations, representing 2,335,839 deliveries with 720,795 cesarean sections (over 60% of all inpatient births in Germany), multivariate model with fixed effects revealed a statistically significant positive association between the number of physicians per birth and the risk-adjusted cesarean section ratio (0.004, p = 0.004). Two-stage least square instrument variable analysis (0.020, p < 0.001) and a system GMM estimator models (0.004, p < 0.001) validated these results, providing compelling evidence for a causal relationship.

Conclusion
The study established a robust connection between the number of physicians per birth and the risk-adjusted cesarean section ratio in integrated obstetric and gynecological departments in Germany. While the cause of the effect remains unclear, one possible explanation is a lack of specialization within these departments due to the combined provision of both obstetric and gynecological care.
Response rate of submerged macrophyte chlorophyll content under changing light conditions
Authors: Estlander Satu , Rajala Salla , Pippingsköld Ella , Nurminen Leena , Horppila Jukka 
Published: January 2025

Abstract
Lake browning, i.e., a gradual and long-term increase in the water colour, is a recognized and topical water quality problem that has received much less attention in water protection than eutrophication. Thus, new bioindicators that respond to environmental stress are needed to monitor lake browning. Recent study suggests that the chlorophyll content of macrophytes is a promising indicator for assessing lake browning, yet little is known about how quickly the changes in the total chlorophyll content of aquatic plants occur. For instance, it is not known whether the plants adjust their chlorophyll content to the daily changes in light availability or to the longer-term light environment in the lake. Therefore, the response time of macrophytes to changes in light availability needs to be clarified to assess their suitability for detecting changes in water quality. The objectives of this experimental study were to investigate the chlorophyll content of Egeria densa and their response time to changes in light availability. No significant change in total chlorophyll content was observed in E.densa, but our study showed a change in macrophyte chlorophyll a:b ratio within 5–7 days of light intensity alternation, suggesting the chlorophyll ratio can be a more promising indicator for the light conditions varying on the daily scale than the snapshot weather monitoring. Thus, our study corroborates the idea of using macrophytes as bioindicators of browning.
A parametric insurance policy for beekeepers and honey production: random forest regressions and real-world pricing
Authors: Colivicchi Ilaria , Dell’Acqua Silvia , Russo Vincenzo 
Published: January 2025

Abstract
In the past years, climate change has affected honey production more and more and the reduction has become a significant risk for beekeepers. In this paper, we discuss the pricing of a parametric insurance policy drafted to cover the potential losses in terms of honey production due to unfavorable weather conditions: the payment of the insurance benefit is triggered by the breaching of predefined thresholds of a weather index, measured over specific relevant periods. The effectiveness of the coverage is verified by the means of random forests, where the honey production is forecast under different real-world weather scenarios and the beekeepers’ loss is compared with the insurance benefit reimbursed (or not) by the policy. The random forest technique is put along with more common ones, such as ordinary least squares regression and mixed linear models. A practical example is given for the Italian market, where the pricing is derived and assessed for three different zones: North, Centre, and South.
On vanishing diffusivity selection for the advection equation
Authors: Mescolini Giulia , Pitcho Jules , Sorella Massimo 
Published: January 2025

Abstract
We study the advection equation along vector fields singular at the initial time. More precisely, we prove that for divergence-free vector fields in

$$L^1_{loc}((0,T];BV(\mathbb {T}^d;\mathbb {R}^d))\cap L^2((0,T) \times \mathbb {T}^d;\mathbb {R}^d))$$

L

loc

1

(

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0
,
T
]

;
B
V

(

T

d

;

R

d

)

)

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L
2

(

(
0
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T
)

×

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d

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, there exists a unique vanishing diffusivity solution. This class includes the vector field constructed by Depauw in [13], for which there are infinitely many distinct bounded solutions to the advection equation.
Evaluation of the anti-inflammatory, antioxidant and wound healing effects of pterostilbene in human gingival fibroblasts in vitro
Authors: Yerebakan Mukaddes , Tuter Gulay , Bagriacik Emin Umit , Oruklu Nihan , Guldurur Tugce 
Published: January 2025

Abstract
We aimed to investigate the wound-healing, antioxidant, and anti-inflammatory effects of pterostilbene (PTS) on human gingival fibroblasts (GF). Different concentrations of PTS were applied to GFs and cell viability was evaluated by MTT assay. GFs were stimulated by lipopolysaccharide (LPS) and the study groups were determined as LPS, LPS + 1 μM PTS, LPS + 10 μM PTS, and control. The most effective PTS concentrations were applied in a wound-healing model, with cell counts in the wound area assessed at 0, 24, 48, and 72 h. The effect of PTS on the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), basic fibroblast growth factor (bFGF), and collagen type I (COL I) was assessed at 24 and 48 h by ELISA. The data was statistically analyzed. Our results showed that PTS had a dose-dependently negative effect on wound healing and cell proliferation at 10 μM concentration, but not at low concentration (1 μM). PTS exhibited a potent anti-inflammatory effect by reducing IL-6 and TNF-α levels, while also enhancing antioxidant activity, as evidenced by increased GSH-Px levels in the LPS + 1 μM PTS group (P < 0.05). According to our results, PTS could be a potential and promising substance with anti-inflammatory and antioxidant effects on LPS-stimulated GF. Therefore our results have merit in terms of providing pioneering data for future studies.
Boosting nutritional value: the role of iron fortification in meat and meat products
Authors: Hamad Ahmed , Singh Pallavi 
Published: January 2025

Abstract
Iron deficiency is a widespread nutritional problem affecting millions of people globally, leading to various health issues including anemia. Iron fortification of meat and meat products has emerged as an effective strategy to combat this issue. This review explores the process and benefits of iron fortification, focusing on the types of iron compounds suitable for fortification, such as ferrous sulfate and ferric pyrophosphate, their bioavailability, and their impact on the sensory and nutritional qualities of meat products. Technological challenges and solutions, including encapsulation, chelation, and microencapsulation techniques, have been examined to minimize their negative impacts on sensory qualities. This review also discusses the regulatory framework governing iron fortification and consumer acceptance. Analytical methods for determining iron content, such as spectrophotometric and colorimetric detection, are discussed. Although iron-fortified meat products offer health benefits, sensory aspects and consumer acceptance are important considerations. This review provides a comprehensive understanding of the role and significance of iron fortification in meat products as a public health intervention to address iron deficiency.