bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson’s disease
Authors: Zhang Fengjiao , Chen Bin , Ren Wenhua , Yan Yayun , Zheng Xiaoqi , Jin Shuxian , Chang Ying 
Published: April 2024

IntroductionPeripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson’s disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear.MethodsIn this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients.ResultsCovariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (β = −0.27, p = 0.003) and the putamen (β = −0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: β = −0.37, p = 0.013; putamen: β = −0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011).ConclusionDopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.
Model-based closed-loop control of thalamic deep brain stimulation
Authors: Tian Yupeng , Saradhi Srikar , Bello Edward , Johnson Matthew D. , D’Eleuterio Gabriele , Popovic Milos R. , Lankarany Milad 
Published: April 2024

Introduction: Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson’s disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists’ expertise and patients’ experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients’ symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity.Methods: In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim–DBS are linked to symptomatic changes in EMG signals. By using a proportional–integral–derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim–DBS so that the power of EMG reaches a desired control target.Results and discussion: We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.
The impact of reminiscent music therapy and robot-assisted rehabilitation on older stroke patients: a protocol for a randomized controlled trial
Authors: Liu Qian , Liu Zuoyan , Cheng Hong , Xu Yang , Wang Fang , Liu Li , Hu Xiuying 
Published: April 2024

BackgroundStroke is the main disease that causes the burden of neurological disease, leading to upper limb dysfunction and affecting their self-care abilities. Robot-assisted rehabilitation therapy has been gradually used in the rehabilitation of upper limb function after stroke. However, it would be beneficial to explore auxiliary interventions such as reminiscent music therapy, a combination of music and reminiscent, to relieve negative emotions and post-stroke fatigue and improve rehabilitation outcomes. This protocol aims to evaluate the effectiveness of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients.MethodsThis trial is a single-blind, three-arm randomized controlled trial. Older stroke patients with upper limb dysfunction will be recruited. Participants will be randomly assigned to receive usual rehabilitation treatment and care, usual rehabilitation treatment and care plus robot-assisted rehabilitation and reminiscent music therapy, or usual rehabilitation treatment and care plus robot-assisted rehabilitation. Robot-assisted rehabilitation will be conducted by rehabilitation doctors five times per week for 3 weeks. In experimental group 1, a reminiscent song list will be played for patients. The primary outcome is activities of daily living. All outcomes will be evaluated at baseline and in the week immediately post-intervention.DiscussionWe are conducting the first randomized controlled trial on the effects of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients. It is expected that this study, if proven effective in improving the activities of daily living in older stroke patients with upper limb dysfunction, will provide evidence-based rehabilitation strategies for medical staff.Clinical Trial Registration: ChiCTR2200063738.
Response assessment of GBM during immunotherapy by delayed contrast treatment response assessment maps
Authors: Cuccarini Valeria , Savoldi Filippo , Mardor Yael , Last David , Pellegatta Serena , Mazzi Federica , Bruzzone Maria Grazia , Anghileri Elena , Pollo Bianca , Maddaloni Luisa , Russo Camilla , Bocchi Elisa , Pinzi Valentina , Eoli Marica , Aquino Domenico 
Published: April 2024

IntroductionAssessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting.MethodsWe recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS &gt; 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored).ResultsUsing receiver operating characteristic (ROC) curves, a threshold of −0.066 in VBlue/VCE (volume of the blue portion of tumoral area/volume of contrast enhancement) variation between values obtained in the MRI performed before PsP/TTP and at TTP/PSP allowed to discriminate TTP from PsP with a sensitivity of 71.4% and a specificity of 100%. Among HIGH-NK patients, at month 6 there was a significant reduction compared to baseline and month 2 in median “blue” volumes.DiscussionIn conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.
Higher baseline serum bilirubin levels are associated with increased risk of early neurological deterioration in women with acute ischemic stroke
Authors: Sun Meng , Weng Yingfeng , Cheng Jiwei , Li Guoyi , Xiao Qian 
Published: April 2024

Background and objectivesEarly neurological deterioration (END) occurs in up to one-third of patients with acute ischemic stroke (AIS) and associated with poor outcome. The role of serum bilirubin in END remains controversial. This study aims to investigate the association of total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) with END.MethodsThis study was a cross-sectional retrospective study with 344 AIS patients enrolled. We retrospectively reviewed consecutive AIS patients with END through a medical record retrieval system and enrolled patients as control randomly from the AIS patients without END at the same period. The bilirubin levels were compared between the END group and No END group. The correlations of bilirubin with END were assessed according to the bilirubin tertiles on the cohort of different genders.ResultsIn women, as the bilirubin level increased, the occurrence of END showed an increasing trend. The linear association was significant based on the tertiles of all bilirubin types (TBIL p = 0.003; DBIL p = 0.025; IBIL p = 0.025), while in men no similar trend was observed. After adjustment for confounders, higher TBIL (p for trend 0.009) and DBIL (p for trend 0.033) levels were associated with increased risk of END in women. The adjusted OR for T3 relative to T1 was 5.240 (95% CI 1.496–18.347) in TBIL and 3.549 (95% CI 1.089–11.566) in DBIL. Multivariate logistic regression showed that DBIL was independently associated with END in women (OR 1.717, 95% CI 1.106–2.666). The study also found that DBIL was superior to TBIL and IBIL in prediction of END occurrence in women, with greater predictive value.DiscussionThere were gender differences in the relationship between bilirubin and END, and DBIL level was positively associated with END occurrence in women, not in men. DBIL had greater incremental predictive value for END than TBIL and IBIL.
Probiotic consumption and hepatic steatosis: results from the NHANES 2011–2016 and Mendelian randomization study
Authors: Song Yancheng , Guo Wencong , Wang Junke , Liu Shuguang , Li Zhaopeng , Li Yu 
Published: April 2024

BackgroundRecent research showed that probiotics treatment may reduce insulin resistance, regulate lipid metabolism, raise liver enzyme levels, and ameliorate inflammation in individuals with metabolic associated fatty liver disease (MAFLD). However, the possible effects of probiotic use on the progression of hepatic steatosis (HS) have not been identified. The purpose of this study was to investigate this in a large population database.MethodsThe cross-sectional research was conducted among adults with complete data on probiotic yogurt consumption and HS in the 2011–2016 National Health and Nutrition Examination Survey (NHANES). Probiotic yogurt consumption was assessed using a dietary supplement questionnaire, while HS was evaluated with HS index (HSI). To explore their relationship, weighted univariate regression analysis, subgroup analysis, and interaction analysis were conducted. To evaluate the causal association between yogurt consumption and NAFLD, mendelian randomization analysis (MR) were performed. A restricted cubic spline (RCS) was used to analyze the relationship curve between the leves of yogurt consumption and hepatic steatosis.ResultsA total of 7,891 participants were included in the study represented 146.7 million non-institutionalized residents of the United States, of whom 4,322 (54.77%) were diagnosed with HS. Multivariable logistic regression showed probiotic yogurt consumption had significantly inverse relationship for HS (OR = 0.84, 95% CI: 0.72–0.97, p = 0.02) after adjusting for all covariates. Once more, the independent relationship between probiotic yogurt consumption and HS was verified by subgroup analysis and interaction analysis. The MR analysis results indicate that there is no causal relationship between yogurt consumption and NAFLD. The RCS model demonstrated a robust J-shaped link between yogurt consumption and HS, revealing a significant decrease in risk within the lower range of yogurt consumption, which attained the lowest risk close to 0.4 cup.ConclusionAccording to the NHANES data, the consumption of probiotics and yogurt has a beneficial effect on HS, whereas the MR results indicated it was not related to NAFLD. The RCS analysis indicates a J-shaped relationship between yogurt consumption and HS, which may account for the inconsistency in the results. Based on these findings, we recommend that adults take half a cup of yogurt daily.
Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study
Authors: Lu Lihua , Luo Luting , Li Xiang , Liu Wanying , Wu Boheng , Cai Qing , Li Jiazheng , Huang Yan , Chen Yanxin , Zheng Yongzhi , Hu Jianda 
Published: April 2024

IntroductionAn increasing number of cohort studies have shown a correlation between serum bilirubin and tumors, but no definitive causal relationship has been established between serum bilirubin and hematological malignancies.Therefore, the aim of the present study was to assess the causal relationship of serum bilirubin, including total bilirubin (TBIL) and direct bilirubin (DBIL), with hematological malignancies, including leukemia, lymphoma, and myeloma.MethodsWe used a genome-wide association study (GWAS) collection of TBIL, DBIL, and hematological malignancies data. Using two-sample Mendelian randomization(MR), we assessed the impact of TBIL and DBIL on hematological malignancies. For this study, the inverse variance weighting method (IVW) was the primary method of MR analysis. In the sensitivity analysis, the weighted median method, MR Egger regression, and MR-PRESSO test were used. To understand the mechanisms behind TBIL and DBIL, we used three different approaches based on screening single nucleotide polymorphisms (SNPs) and their associated genes, followed by bioinformatics analysis.ResultsThe IVW test results showed evidence of effects of TBIL (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.58-12.62) and DBIL (OR: 3.31, 95% CI: 1.08-10.18) on the risk of acute myeloid leukemia (AML).The findings from bioinformatics indicated that TBIL could potentially undergo xenobiotic metabolism through cytochrome P450 and contribute to chemical carcinogenesis.DiscussionIn this study, two-sample MR analysis revealed a causal relationship between TBIL, DBIL, and AML.
Primary catastrophic antiphospholipid syndrome in children with midbrain infarction: a case report
Authors: Dong Qinghua , Yin Jianyun , Su Hang , Ni Qian 
Published: April 2024

BackgroundCatastrophic antiphospholipid syndrome (CAPS) is a multi-system autoimmune disease characterized by extensive thrombosis. Pediatric CAPS is extremely rare and associated with a high mortality rate, especially when midbrain infarction is involved. Hence, early diagnosis and prompt initiation of appropriate treatment for CAPS complicated by midbrain infarction are of utmost importance in achieving favorable outcomes.Case presentationIn this report, we present the case of a 14-year-old girl who presented with neurological symptoms and digestive system infection and was initially diagnosed with an “intracranial infection”. After a series of rigorous diagnostic procedures, the patient was ultimately diagnosed with primary CAPS and was immediately transferred to the intensive care unit where she was treated with anticoagulation, glucocorticoids, intravenous immunoglobulin (IVIG) therapy, and multiple plasma infusions. Twenty-seven days after admission, the patient's condition improved with standardized treatment, and she was discharged and followed up regularly.ConclusionThis case report provides a description of the clinical features observed in a pediatric patient with CAPS and concurrent midbrain infarction, highlighting the crucial role of early diagnosis and timely treatment in influencing patient prognosis.
Early stress during NICU stay and parent-reported health-related quality of life after extremely preterm birth: an exploratory study with possible targets for early intervention
Authors: van Dokkum Nienke H. , Bos Arend F. , Kraft Karianne E. , Bouma Helene A. , Reijneveld Sijmen A. , Krabbe Paul F. M. , de Kroon Marlou L. A. 
Published: April 2024

IntroductionThe association between neonatal intensive care unit (NICU) related stress in preterm infants and their health-related quality of life (HRQoL) in the first year following preterm birth remains unexplored. Understanding this association is crucial for enhancing preventive and supportive measures for infants and parents within and beyond the NICU.MethodsFrom a single center observational cohort study, we included infants with gestational ages below 30 weeks and/or birth weights under 1,000 grams. HRQoL was quantified using the Infant Quality of Life Instrument (IQI) at 3-, 6-, 9- and 12-months corrected age, covering seven domains. NICU stress was quantified using the Neonatal Infant Stressor Scale (NISS) for the first week of life. We performed Spearman's correlation analyses to test this association.ResultsOf the 45 included infants, the IQI was completed for 27 (60%) at 3, 15 (33%) at 6, 14 (31%) at 9 and 15 (33%) at 12 months. The HRQoL sum scores were related to neonatal stress at 9 and 12 months (ρ = 0.643 and 0.591, p = 0.013 and p = 0.019, respectively) but not at 3 and 6 months (ρ = −0.001 and −0.077 respectively, p &gt; 0.05). Higher NICU stress tended to be associated with more respiratory and mood problems throughout the first year.DiscussionFrom a parental perspective on infant HRQoL, extremely preterm infants with higher stress exposure show more problems in the second half-year of life, mainly breathing and possibly mood-related problems. This knowledge may help improve our neonatal care, both during NICU stay and in follow-up clinics, by implementing targeted interventions.
Effect of P. corylifolia on the pharmacokinetic profile of tofacitinib and the underlying mechanism
Authors: Wang Yu , Zhou Quan , Wang Huihui , Song Wei , Wang Jianfeng , Mamun Abdullah Al , Geng Peiwu , Zhou Yunfang , Wang Shuanghu 
Published: April 2024

This work aimed to explore the mechanisms underlying the interaction of the active furanocoumarins in P. corylifolia on tofacitinib both in vivo and in vitro. The concentration of tofacitinib and its metabolite M8 was determined using UPLC-MS/MS. The peak area ratio of M8 to tofacitinib was calculated to compare the inhibitory ability of furanocoumarin contained in the traditional Chinese medicine P. corylifolia in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4 (rCYP3A4). We found that bergapten and isopsoralen exhibited more significant inhibitory activity in RLMs than other furanocoumarins. Bergapten and isopsoralen were selected to investigate tofacitinib drug interactions in vitro and in vivo. Thirty rats were randomly allocated into 5 groups (n = 6): control (0.5% CMC-Na), low-dose bergapten (20 mg/kg), high-dose bergapten (50 mg/kg), low-dose isopsoralen (20 mg/kg) and ketoconazole. 10 mg/kg of tofacitinib was orally intervented to each rat and the concentration level of tofacitinib in the rats were determined by UPLC-MS/MS. More imporrantly, the results showed that bergapten and isopsoralen significantly inhibited the metabolism of tofacitinib metabolism. The AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and Cmax of tofacitinib increased in varying degrees compared with the control group (all p &lt; 0.05), but CLz/F decreased in varying degrees (p &lt; 0.05) in the different dose bergapten group and isopsoralen group. Bergapten, isopsoralen and tofacitinib exhibit similar binding capacities with CYP3A4 by AutoDock 4.2 software, confirming that they compete for tofacitinib metabolism. P. corylifolia may considerably impact the metabolism of tofacitinib, which can provide essential information for the accurate therapeutic application of tofacitinib.
Effects of the menstrual cycle on the performance of female football players. A systematic review
Authors: Hamed-Hamed Dina , González-Muñoz Ana , Cuevas-Cervera Maria , Perez-Montilla Jose Javier , Aguilar-Nuñez Daniel , Aguilar-García María , Pruimboom Leo , Navarro-Ledesma Santiago 
Published: April 2024

Background:Women’s football has been booming for a few years now, which has led to an increase in the expectation of the players’ performance, leading to a more detailed study of women’s physiology in the field of sports.Objectives:To analyze the scientific evidence on the influence of menstruation on the performance of female footballers, as well as to analyze the methodological quality of the studies included in this review.Materials and methods:The possible hormonal effects of the menstrual cycle phases on the performance of female footballers were analyzed. The databases used to conduct the searches were Pubmed, Scopus, Virtual Health Library, Web of Science, EBSCO and the Cochrane Library. All included studies met the inclusion criteria. The Cochrane risk of bias tool was used. This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023390652).Results:A total of nine clinical trials were included in this review. A low quality of evidence was observed in the studies. Not all the results support the idea that the menstrual cycle phases can alter the performance of female footballers.Conclusion:This systematic review shows that there is a great deal of controversy about the influence of the menstrual cycle phases on the performance of female footballers. Studies are focused on solely biological factors and gender is normally no part of those studies. Further research with larger samples, and taking not only biological but also sociological factors, are necessary to determine the effects of menstruation on the performance of female footballers.