bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal associations of fatigue and functional outcome after ischemic stroke: a mediation Mendelian randomization study
Authors: Jiang Ping , Gao Ying , Zhang Leyi , Jiang Li , Li Chuanpeng 
Published: July 2024

Background and objectivesFatigue has been associated with adverse effects on recovery from ischemic stroke based on previous observational research. The purpose of our study was to explore the potential causal association of fatigue with poor functional outcome after ischemic stroke by employing Mendelian randomization (MR).MethodsA set of instrumental variables, comprising 36 single-nucleotide polymorphisms (SNPs) that are only related to fatigue, were derived from a genome-wide association study (GWAS) that included 449,019 general individuals. The functional outcomes after ischemic stroke were derived from a GWAS (Genetics of Ischemic Stroke Functional Outcome Network) involving 6,021 survivors. Two-sample MR methods were used to assess the causal effect, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. In bidirectional MR analysis, the reverse causal association was analyzed using the Wald ratio method. The mediation effects of lipid metabolites were analyzed using two-step MR analysis.ResultsGenetic liability to fatigue was causally associated with the poor functional outcome (modified Rankin Scale ≥3 at 3 months) after ischemic stroke (OR = 4.20, 95%CI [1.11–15.99], p &lt; 0.05). However, genetic predicted poor functional outcome after ischemic stroke was not associated with fatigue (OR = 1.00, 95%CI [0.99–1.02], p &gt; 0.05). The results of the two-step MR showed that cholesteryl esters to total lipids ratio in large very low-density lipoprotein (VLDL) (ME = −0.13, p &lt; 0.05); concentration of very large VLDL particles (ME = −0.13, p &lt; 0.05); free cholesterol in large VLDL (ME = −0.13, p &lt; 0.05); free cholesterol to total lipids ratio in very large VLDL (ME = −0.22, p &lt; 0.05); phospholipids in large VLDL (ME = −0.15, p &lt; 0.05); phospholipids in very large VLDL (ME = −0.13, p &lt; 0.05); phospholipids to total lipids ratio in large high-density lipoprotein (HDL) (ME = −0.17, p &lt; 0.05); total lipids in very large VLDL (ME = −0.14, p &lt; 0.05); triglycerides in small VLDL (ME = −0.11, p &lt; 0.05); and triglycerides to total lipids ratio in large HDL (ME = −0.10, p &lt; 0.05) assumed a pivotal role in mediating the association between fatigue and poor functional outcome after ischemic stroke.ConclusionOur study provides evidence supporting the causal association between fatigue and the poor functional outcome after ischemic stroke, which emphasizes the importance of implementing interventions aimed at addressing fatigue. This could offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context. One potential mechanism by which fatigue affects functional outcomes after ischemic stroke is through the action of lipid metabolites.
Intrauterine transfusion under fetal analgesia: the evaluation of perinatal outcomes
Authors: Lanna Mariano , Casati Daniela , Bianchi Chiara , Faiola Stefano , Laoreti Arianna , Cavigioli Francesco , Savasi Valeria , Lista Gianluca 
Published: July 2024

IntroductionIntrauterine transfusion is the treatment for fetal anemia resulting from maternal alloimmunization, infections (parvovirus B19 and cytomegalovirus), single demise of a monochorionic twin, chorioangioma, and other rare conditions. Fetal analgesia is mandatory to reduce movement and pain perception during the procedure. This study aims to evaluate perinatal outcomes for such procedures, following the routine use of fetal analgesia in our clinical practice.Materials and methodsRetrospective analysis of cases from 2009 to 2022, including all confirmed fetal anemia with fetal blood sampling. After fetal analgesia, Rh-negative concentrated red blood cells were transfused, with ultrasonographic follow-up 24 h and 1 week later. In case of suspected brain lesion, magnetic resonance imaging was performed. Elective delivery was considered in case of persistent anemia after 34 weeks. Post-natal follow-up and comprehensive obstetric and perinatal outcomes data were collected.ResultsAltogether 59 anemic fetuses were included, with 34 (57.6%) being hydropic. The causes of anemia were maternal alloimmunization (22, 37.3%), infections (13, 22%), monochorionicity (10, 16.9%), rare conditions (9, 15.3%), and two chorioangiomas (3.4%). The median gestational age at the procedure was 25.2 weeks (18–32 weeks), with no related preterm premature rupture of membranes (&lt;48 h), or side effects from fetal analgesia. Gestational age at delivery was 33 weeks (26–41 weeks), with survival rate of 90%. There were four fetal demises, two termination of pregnancies, and eight neonatal deaths due to persistent severe anemia after preterm delivery. The main contributors to adverse outcome were the type of anemia, and the management with a preterm delivery.ConclusionIntrauterine transfusion of red blood cells under analgesia is safe, with low incidence of obstetric complication.
Use of Streptococcus Salivarius K12 in a cohort of PFAPA patients
Authors: Spagnolo Alessandra , Mileto Vincenzo , Civino Adele , Maggio Maria Cristina , Risso Paolo , Sestito Simona , Gallizzi Romina 
Published: July 2024

BackgroundPeriodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA) is the most common cause of periodic fever in childhood. Although PFAPA is generally a self-limited condition, it can have negative impact on child's and parents’ quality of life and family functioning. Our primary aim was to assess the potential effectiveness of Streptococcus Salivarius K12 (SSK12) in preventing febrile attacks in PFAPA patients. Secondary objectives included evaluating the effectiveness of SSK12 in mitigating the severity of febrile episodes seen as a statistically significant reduction in the episode duration, highest fever temperature reached during fever, in the frequency of each associated symptom, calculated in the six months before and after the start of therapy.ResultsA total of 117 patients with PFAPA were evaluated using Marshall's criteria, modified by Thomas et al. and according to Eurofever/PRINTO classification criteria, aged 6 months to 9 years, with a median age at the onset of the disease of 2 years, treated with SSK12, since January 2021 to January 2023. Data were collected retrospectively. Before using SS K12, febrile episodes recurred on average every 26.1 ± 11.5 days, with a febrile episode duration of 4.1 ± 1.4 days. The highest fever temperature during the episode was 39.8 ± 0.7 °C. After six months of SS K12, febrile episodes recurred on average every 70 ± 53,1 days (p value &lt;0.01), the mean lenght of febrile episodes was 3.3 ± 1.6 (p value &lt;0.01) and the highest fever temperature reached during the febrile episode was 39.1 ± 1.1 °C (p value &lt;0.01). We also documented a reduction in the frequency of exudative pharyngotonsillitis present in 72 vs. 103 patients (p value &lt;0.01), oral aphthosis present in 47 vs. 80 patients (p value &lt;0.01), lateral cervical lymphadenopathy in 45 vs. 83 (p value &lt;0.01). Erythematous pharyngotonsillitis decreased in frequency but it was not statistically significant.ConclusionsThe results of our study indicate that the use of SS K12 could be beneficial in decreasing febrile episodes related to PFAPA syndrome and its associated symptoms, potentially improving the quality of life in pediatric patients and decreasing the need for additional pharmacological therapies.
When to consider intra-target microdosing: physiologically based pharmacokinetic modeling approach to quantitatively identify key factors for observing target engagement
Authors: Aoki Yasunori , Rowland Malcom , Sugiyama Yuichi 
Published: July 2024

Intra-Target Microdosing (ITM), integral to Phase 0 clinical studies, offers a novel approach in drug development, effectively bridging the gap between preclinical and clinical phases. This methodology is especially relevant in streamlining early drug development stages. Our research utilized a Physiologically Based Pharmacokinetic (PBPK) model and Monte Carlo simulations to examine factors influencing the effectiveness of ITM in achieving target engagement. The study revealed that ITM is capable of engaging targets at levels akin to systemically administered therapeutic doses for specific compounds. However, we also observed a notable decrease in the probability of success when the predicted therapeutic dose exceeds 10 mg. Additionally, our findings identified several critical factors affecting the success of ITM. These encompass both lower dissociation constants, higher systemic clearance and an optimum abundance of receptors in the target organ. Target tissues characterized by relatively low blood flow rates and high drug clearance capacities were deemed more conducive to successful ITM. These insights emphasize the necessity of taking into account each drug’s unique pharmacokinetic and pharmacodynamic properties, along with the physiological characteristics of the target tissue, in determining the suitability of ITM.
Case report: A pregnant woman accidental treated with spironolactone in mid-gestation
Authors: Deng Nianying , Zhong Jiayi , Deng Zhengjun , Chen Minling , Yan Liangqi , Li Haiting , Han Jiawei , Tao Enfu 
Published: July 2024

Spironolactone, a potassium-sparing diuretic, is used to treat hypertension, heart failure, and certain hyperandrogenic disorders. Its use during pregnancy is not recommended due to the risk of feminizing male fetuses, primarily because of its antiandrogenic activity. However, human data remain scarce and largely inconclusive. Here, we present the first case of a 25-year-old pregnant woman, at 16 weeks of gestation, who was inadvertently exposed to spironolactone (240 mg/day) for 1 week due to a pharmacy dispensing error. The patient subsequently delivered a healthy male infant with normal genitalia at 38 weeks of gestation following vaginal delivery. Current follow-up shows that the infant is healthy and developing normally. This article summarizes the potential causes of spironolactone-induced anomalous genital development and explores the safety of new-generation mineralocorticoid receptor antagonists (MRAs) during pregnancy. The mechanisms behind spironolactone-induced anomalous genital development in male fetuses have not been fully elucidated. Spironolactone competes with dihydrotestosterone for binding to androgen receptors and inhibits enzymes involved in androgen biosynthesis, which may partly explain its antiandrogenic effects. Recent advancements in MRAs have led to the development of compounds with higher selectivity for the mineralocorticoid receptor, thereby reducing the incidence of antiandrogen side effects. These new-generation MRAs may be effective alternatives during pregnancy, but more data are needed to establish their safety in pregnant women. This case contributes to the limited but growing body of literature on the safety profile of spironolactone in pregnancy, providing insights into its effects during a critical period of fetal development.
A novel methodology for emotion recognition through 62-lead EEG signals: multilevel heterogeneous recurrence analysis
Authors: Wang Yujie , Chen Cheng-Bang , Imamura Toshihiro , Tapia Ignacio E. , Somers Virend K. , Zee Phyllis C. , Lim Diane C. 
Published: July 2024

ObjectiveRecognizing emotions from electroencephalography (EEG) signals is a challenging task due to the complex, nonlinear, and nonstationary characteristics of brain activity. Traditional methods often fail to capture these subtle dynamics, while deep learning approaches lack explainability. In this research, we introduce a novel three-phase methodology integrating manifold embedding, multilevel heterogeneous recurrence analysis (MHRA), and ensemble learning to address these limitations in EEG-based emotion recognition.ApproachThe proposed methodology was evaluated using the SJTU-SEED IV database. We first applied uniform manifold approximation and projection (UMAP) for manifold embedding of the 62-lead EEG signals into a lower-dimensional space. We then developed MHRA to characterize the complex recurrence dynamics of brain activity across multiple transition levels. Finally, we employed tree-based ensemble learning methods to classify four emotions (neutral, sad, fear, happy) based on the extracted MHRA features.Main resultsOur approach achieved high performance, with an accuracy of 0.7885 and an AUC of 0.7552, outperforming existing methods on the same dataset. Additionally, our methodology provided the most consistent recognition performance across different emotions. Sensitivity analysis revealed specific MHRA metrics that were strongly associated with each emotion, offering valuable insights into the underlying neural dynamics.SignificanceThis study presents a novel framework for EEG-based emotion recognition that effectively captures the complex nonlinear and nonstationary dynamics of brain activity while maintaining explainability. The proposed methodology offers significant potential for advancing our understanding of emotional processing and developing more reliable emotion recognition systems with broad applications in healthcare and beyond.
Increasing cotton lint yield and water use efficiency for subsurface drip irrigation without mulching
Authors: Li Nan-nan , Li Jun-hong , Shi Xiao-juan , Shi Feng , Tian Yu , Wang Jun , Hao Xian-zhe , Luo Hong-hai , Wang Zhan-biao 
Published: July 2024

IntroductionPlanting without mulching can eliminate the residual film pollution caused by the long-term use of plastic film covers, but it will increase soil moisture evaporation and heat loss and severely reduce water use efficiency and cotton productivity in cotton (Gossypium hirsutum L.) fields in arid regions. It is unclear whether the advantages of subsurface drip irrigation and nighttime irrigation can be leveraged to reduce the amount of irrigation applied in fields, improve the soil and leaf hydrothermal environments, and increase the synchronicity of yield and water use efficiency (WUE).MethodsTherefore, in a two-year field experiment (2019-2020), cotton was grown under different irrigation treatments (I5, 3753 m3 ha-1; I4, 3477 m3 ha-1; I3, 3201 m3 ha-1; I2, 2925 m3 ha-1; and I1, 2649 m3 ha-1). The soil volumetric moisture content, soil temperature, leaf relative water content (RWC), daily changes in gas exchange parameters, lint yield, and WUE were evaluated.Results and discussionThe results showed that reducing irrigation can reduce the soil volumetric moisture content (0-40 cm soil layer), increase the soil temperature and soil temperature conductivity, and increase the leaf temperature, intercellular carbon dioxide concentration (Ci), and WUE; however, reducing irrigation is not conducive to increasing the leaf RWC, net photosynthetic rate (Pn), stomatal conductance (Gs), or transpiration rate (Tr). There was no significant difference in WUE between the I3 and I4 treatments from 8:00 to 20:00, but the lint yield in these treatments increased by 2.8-12.2% compared to that in the I5 treatment, with no significant difference between the I3 and I4 treatments. In addition, a related analysis revealed that the positive effects of the leaf hydrothermal environment on the Pn and soil temperature on the WUE occurs during the same period (10:00-16:00). Overall, an irrigation amount of 3201-3477 m3 ha-1 applied with a subsurface nighttime irrigation system without mulching can enhance the soil moisture content and soil temperature, maintain a high photosynthetic capacity, and increase the lint yield and WUE. These results revealed that the negative impacts of plastic film contamination in arid areas can be alleviated.
Prevalence of demoralization and depressive symptoms in a sample of patients with supraventricular tachyarrhythmias: preliminary results
Authors: Accinni Tommaso , Maraone Annalisa , Bonucci Alessio , D’Amato Andrea , Lavalle Carlo , Bersani Francesco Saverio , Severino Paolo , Pasquini Massimo 
Published: July 2024

IntroductionSupraventricular tachyarrhythmias (ST) are the most common cardiac arrhythmias. Little is known about the potential impact of demoralization, which is considered as partially distinct from depression, on the course of ST. A correct assessment of both depressive symptoms and demoralization appears relevant for the treatment of these cardiac diseases, potentially influencing their course.MethodsThe sample consisted of 110 subjects affected by different ST, such as atrial fibrillation (AF), atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). They all underwent a psychiatric evaluation; the Italian version of 9-item Patient Health Questionnaire (PHQ-9) and the Italian version of Demoralization Scale (DS) were administered. Descriptive statistics, pairwise comparisons, and correlational analysis have been implemented.Results26 individuals (23.6%) presented high levels of demoralization. Of these, 20 (76.9%) had a diagnosis of AF and six patients (23.1%) received a diagnosis of other ST. No differences in demoralization levels resulted in regard of sex, cardiac diagnoses and anticoagulant therapies. Amongst people with high levels of demoralization, 13 (50%) received no formal psychiatric diagnosis, and 12 (46.2%) showed moderate/severe depressive symptoms. Demoralization levels and PHQ-9 scores showed a significant positive correlation in the whole sample (r=0.550, p&lt;0.001).DiscussionThe present study found that in a sample of patients suffering from ST, high levels of demoralization were more frequent than clinically relevant depressive symptoms. We propose that demoralization and depression show partially distinguished psychopathological features, potentially associated with different therapeutic trajectories.
A cross-sectional study of non-suicidal self-injury in adolescent depression: association with demographic characteristics and physiological indicators
Authors: He Yangliuqing , Wei Yuhan , Wang Yiming , Liang Fenrong , Ma Tianpei 
Published: July 2024

IntroductionNon-suicidal self-injury (NSSI) is a prevalent concern among adolescents with depression, yet its relationship with demographic characteristics and physiological indicators remains underexplored. This study aimed to investigate these relationships among inpatient adolescents aged 13 to 18 at a hospital affiliated with Guizhou Medical University.MethodsA cross-sectional study was conducted involving 222 adolescent inpatients diagnosed with depression. Data on NSSI occurrence, demographic variables (gender, only-child status, age), and physiological indicators (ALT, TSH, FT4, PLR, TG, HDLC, LDLC, FT3, NLR, MLR) were collected and analyzed. Statistical analyses, including correlations and group comparisons, were performed to assess the associations between NSSI and these factors.ResultsThe prevalence of NSSI among the participants was 40.5%. Significant correlations were found between NSSI and several demographic and physiological factors. Specifically, NSSI was significantly associated with female gender, non-only-child status, younger age, lower ALT levels, higher TSH levels, lower FT4 levels, and higher PLR values. However, no significant differences were observed in TG, HDLC, LDLC, FT3, NLR, or MLR between the NSSI and non-NSSI groups.DiscussionThe findings highlight distinct demographic and physiological profiles associated with NSSI among adolescents with depression. The prevalence rate of NSSI underscores its significance as a behavioral manifestation in this population. Further research should explore the underlying mechanisms linking these factors to better inform targeted interventions and treatment strategies for adolescents experiencing NSSI in the context of depression.
Daily life participation in PTSD: pilot study on patterns and correlators
Authors: Shapira Ruth , Baris Ginat Yisca Jessica , Lipskaya-Velikovsky Lena 
Published: July 2024

IntroductionParticipation in daily life activities with both the personal and community meaning is an important component of health and well-being. Even though there are mounting reports on the challenges in various aspects of daily-life functioning among individuals with post-traumatic stress disorder (PTSD), to date little research has been conducted on their comprehensive patterns of participation. The study aimed to describe objective and subjective participation dimensions in PTSD compared to healthy controls and investigate the association between personal and environmental factors and participation.MethodsSixty-one individuals were enrolled in two groups: PTSD (N=31; age: M=34.3; women:77.4%) and healthy controls matched by age and gender. The PTSD group completed standard assessments for symptom severity, general cognition, executive function (EF), sensory processing, self-efficacy, functional capacity, and environmental properties. Both groups completed a participation questionnaire.ResultsIndividuals with PTSD participated with low intensity and diversity, more occupations were abandoned (-4.73&lt;t&lt;5.73, p&lt;0.05), and less meaning was found in the included occupations. Participation objective dimensions were associated with self-reported EF (-0.47&lt;r&lt;-0.42, p&lt;0.05), sensory modulation profile (2.51&lt;t&lt;2.81, p&lt;0.05), and environmental properties (-0.44&lt;r&lt;0.5, p&lt;0.05), but not with PTSD symptom severity, and objective measures of cognition and functional capacity. No correlators were identified for subjective participation dimensions.DiscussionThe study demonstrates profound restrictions in participation in PTSD raising serious concerns. There are unique patterns of association between objective participation dimensions, subjective cognitive indices, sensory modulation, and environmental factors, suggesting a need for PTSD feature-specific intervention approaches to advance the participation of those with PTSD as a means of promoting health and well-being.