bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic profiling of CSF and blood serum elucidates general and sex-specific patterns for mild cognitive impairment and Alzheimer’s disease patients
Authors: Berezhnoy Georgy , Laske Christoph , Trautwein Christoph 
Published: August 2023

BackgroundBeta-amyloid (Abeta) and tau protein in cerebrospinal fluid (CSF) are established diagnostic biomarkers for Alzheimer’s disease (AD). However, these biomarkers may not the only ones existing parameters that reflect Alzheimer’s disease neuropathological change. The use of quantitative metabolomics approach could provide novel insights into dementia progression and identify key metabolic alterations in CSF and serum.MethodsIn the present study, we quantified a set of 45 metabolites in CSF (71 patients) and 27 in serum (76 patients) in patients with mild cognitive impairment (MCI), AD, and controls using nuclear magnetic resonance (NMR)-based metabolomics.ResultsWe found significantly reduced CSF (1.32-fold, p = 0.0195) and serum (1.47-fold, p = 0.0484) levels of the ketone body acetoacetate in AD and MCI patients. Additionally, we found decreased levels (1.20-fold, p = 0.0438) of the branched-chain amino acid (BCAA) valine in the CSF of AD patients with increased valine degradation pathway metabolites (such as 3-hydroxyisobutyrate and α-ketoisovalerate). Moreover, we discovered that CSF 2-hydroxybutyrate is dramatically reduced in the MCI patient group (1.23-fold, p = 0.039). On the other hand, vitamin C (ascorbate) was significantly raised in CSF of these patients (p = 0.008). We also identified altered CSF protein content, 1,5-anhydrosorbitol and fructose as further metabolic shifts distinguishing AD from MCI. Significantly decreased serum levels of the amino acid ornithine were seen in the AD dementia group when compared to healthy controls (1.36-fold, p = 0.011). When investigating the effect of sex, we found for AD males the sign of decreased 2-hydroxybutyrate and acetoacetate in CSF while for AD females increased serum creatinine was identified.ConclusionQuantitative NMR metabolomics of CSF and serum was able to efficiently identify metabolic changes associated with dementia groups of MCI and AD patients. Further, we showed strong correlations between these changes and well-established metabolomic and clinical indicators like Abeta.
Long-term survival of LGR5 expressing supporting cells after severe ototoxic trauma in the adult mouse cochlea
Authors: Smith-Cortinez Natalia , Hendriksen Ferry G. J. , Ramekers Dyan , Stokroos Robert J. , Versnel Huib , Straatman Louise V. 
Published: August 2023

IntroductionThe leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is a tissue resident stem cell marker, which it is expressed in supporting cells (SCs) in the organ of Corti in the mammalian inner ear. These LGR5+ SCs can be used as an endogenous source of progenitor cells for regeneration of hair cells (HCs) to treat hearing loss and deafness. We have recently reported that LGR5+ SCs survive 1 week after ototoxic trauma. Here, we evaluated Lgr5 expression in the adult cochlea and long-term survival of LGR5+ SCs following severe hearing loss.MethodsLgr5GFP transgenic mice and wild type mice aged postnatal day 30 (P30) and P200 were used. P30 animals were deafened with a single dose of furosemide and kanamycin. Seven and 28 days after deafening, auditory brainstem responses (ABRs) were recorded. Cochleas were harvested to characterize mature HCs and LGR5+ SCs by immunofluorescence microscopy and quantitative reverse transcription PCR (q-RT-PCR).ResultsThere were no significant age-related changes in Lgr5 expression when comparing normal-hearing (NH) mice aged P200 with P30. Seven and 28 days after ototoxic trauma, there was severe outer HC loss and LGR5 was expressed in the third row of Deiters’ cells and in inner pillar cells. Seven days after induction of ototoxic trauma there was an up-regulation of the mRNA expression of Lgr5 compared to the NH condition; 28 days after ototoxic trauma Lgr5 expression was similar to NH levels.DiscussionThe presence of LGR5+ SCs in the adult mouse cochlea, which persists after severe HC loss, suggests potential regenerative capacity of endogenous cochlear progenitor cells in adulthood. To our knowledge, this is the first study showing not only long-term survival of LGR5+ SCs in the normal and ototoxically damaged cochlea, but also increased Lgr5 expression in the adult mouse cochlea after deafening, suggesting long-term availability of potential target cells for future regenerative therapies.
Effective utilization of attentional resources in postural control in athletes of skill-oriented sports: an event-related potential study
Authors: Chen Jiacheng , Kwok Alex Pak Ki , Li Yanan 
Published: August 2023

ObjectivePostural control plays a key role in skill-oriented sports. Athletes of skill-oriented sports (hereinafter referred to as “skilled athletes”) usually showed better control ability compared with non-athletes. However, research focused on the single postural task, rarely considering the actual situation in skill-oriented sports in which other processes, such as cognitive control, frequently accompany postural control. This study aims to explore how skilled athletes control their posture under the dual-task situation and use limited attentional resources.MethodA total of 26 skilled athletes and 26 non-athletes were required to perform the postural control and N-back tasks simultaneously. Center of pressure (COP) trajectory, reaction times (RTs), and discriminability (d′) of N-back tasks were recorded and evaluated, along with event-related potentials, including N1 (Oz, PO7, and PO8), P2 (Fz, FCz, Cz, and Pz) components, and the spectral power of alpha band.ResultsSkilled athletes demonstrated more postural control stability and a higher d′ than non-athletes in all dual tasks. Besides, they showed enhanced N1, P2 amplitudes and reduced alpha band power during dual-tasking. Notably, in skilled athletes, a significant negative correlation between N1 amplitude and d′ was observed, while significant positive correlations between alpha band power and postural control performance were also identified.ConclusionThis study investigates the potential advantages of skilled athletes in postural control from the view of neuroscience. Compared to non-athletes, skilled athletes could decrease the consumption of attentional resources in postural control and recruit more attentional resources in stimulus discrimination and evaluation in cognitive tasks. Since the allocation of attentional resources plays a crucial part in postural control in skilled athletes, optimizing the postural control training program and the selection of skilled athletes from a dual-task perspective is important.
Machine learning-based classification of chronic traumatic brain injury using hybrid diffusion imaging
Authors: Muller Jennifer J. , Wang Ruixuan , Milddleton Devon , Alizadeh Mahdi , Kang Ki Chang , Hryczyk Ryan , Zabrecky George , Hriso Chloe , Navarreto Emily , Wintering Nancy , Bazzan Anthony J. , Wu Chengyuan , Monti Daniel A. , Jiao Xun , Wu Qianhong , Newberg Andrew B. , Mohamed Feroze B. 
Published: August 2023

Background and purposeTraumatic brain injury (TBI) can cause progressive neuropathology that leads to chronic impairments, creating a need for biomarkers to detect and monitor this condition to improve outcomes. This study aimed to analyze the ability of data-driven analysis of diffusion tensor imaging (DTI) and neurite orientation dispersion imaging (NODDI) to develop biomarkers to infer symptom severity and determine whether they outperform conventional T1-weighted imaging.Materials and methodsA machine learning-based model was developed using a dataset of hybrid diffusion imaging of patients with chronic traumatic brain injury. We first extracted the useful features from the hybrid diffusion imaging (HYDI) data and then used supervised learning algorithms to classify the outcome of TBI. We developed three models based on DTI, NODDI, and T1-weighted imaging, and we compared the accuracy results across different models.ResultsCompared with the conventional T1-weighted imaging-based classification with an accuracy of 51.7–56.8%, our machine learning-based models achieved significantly better results with DTI-based models at 58.7–73.0% accuracy and NODDI with an accuracy of 64.0–72.3%.ConclusionThe machine learning-based feature selection and classification algorithm based on hybrid diffusion features significantly outperform conventional T1-weighted imaging. The results suggest that advanced algorithms can be developed for inferring symptoms of chronic brain injury using feature selection and diffusion-weighted imaging.
Global burden of non-communicable chronic diseases associated with a diet low in fruits from 1990 to 2019
Authors: Pan Shijie , Lin Zhihan , Yao Teng , Guo Xiaoli , Xu Tongtong , Sheng Xinyan , Song Xi , Chen Zuhai , Wei Wanting , Yan Yizhong , Hu Yunhua 
Published: August 2023

BackgroundThe aim of this study was to assess the global burden of disease from non-communicable chronic diseases (NCD) due to diet low in fruits from 1990 to 2019.MethodsBased on data from the Global Burden of Disease (GBD) 2019, the global burden of disease due to diet low in fruits was analyzed for each country or region, disaggregated by disease type, age, sex, and year. The number of deaths and disability-adjusted life years (DALYs), population attributable fraction (PAF), age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were calculated, and the average annual percentage change (AAPC) was calculated to describe trends in ASMR and ASDR from 1990 to 2019.ResultsFrom 1990 to 2019, the number of deaths and DALYs due to diet low in fruits increased by 31.5 and 27.4%, respectively. Among the tertiary diseases, ischemic heart disease, stroke, and diabetes and kidney disease were the top three contributors to the global increase in deaths and DALYs. However, both ASMR and ASDR showed a decreasing trend. The fastest decline in ASMR and ASDR was in stroke, with AAPC of −2.13 (95% CI: −2.22, −2.05, p &lt; 0.05) and −0.56 (95% CI: −0.62, −0.51, p &lt; 0.05), respectively. For GBD regions, high PAF occurred mainly in South Asia, Oceania, and sub-Saharan Africa. Age-specific PAF for stroke and ischemic heart disease death attributable to diet low in fruits was significantly negatively associated with age. Diet low in fruits related ASMR and ASDR showed an M-shaped relationship with the socio-demographic index (SDI), but with an overall decreasing trend.ConclusionThe number of deaths and DALYs due to diet low in fruits continues to increase. Therefore, early nutritional interventions should be implemented by the relevant authorities to reduce the burden of diseases caused by diet low in fruits.
The effects of Ascophyllum nodosum, Camellia sinensis-leaf extract, and their joint interventions on glycolipid and energy metabolism in obese mice
Authors: Xu Yuhan , Jia Xiuzhen , Zhang Wei , Xie Qiaoling , Zhu Meizhen , Zhao Zifu , Hao Jingyu , Li Haoqiu , Du Jinrui , Liu Yan , Feng Haotian , He Jian , Li Hongwei 
Published: August 2023

ObjectivesObesity is often associated with glucolipid and/or energy metabolism disorders. Ascophyllum nodosum extract (seaweed extract, SE) and Camellia sinensis-leaf extract (tea extract, TE) have been reported to promote positive metabolic effects through different mechanisms. We investigated the effects of SE and TE on metabolic homeostasis in diet-induced obese mice and discussed their functional characteristics.MethodsMale C57BL/6J mice fed with high-fat diets for 8 weeks were established as obese models and subsequently divided into different intervention groups, followed by SE, TE, and their joint interventions for 10 weeks. Body weight and food intake were monitored. Fasting glucose and oral glucose tolerance tests were interspersed during the experiment. After the intervention, the effects on obesity control were assessed based on body composition, liver pathology section, blood lipids and glucose, respiratory exchange ratio (RER), energy expenditure (EE1, EE2, and EE3), inflammatory factors, lipid anabolism enzymes, and gut flora of the obese mice.ResultsAfter continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower ~4.93 g, vs. HFD 38.02 g), peri-testicular fat masses (lower ~0.61 g, vs. HFD 1.92 g), and perirenal fat masses (lower ~0.21 g, vs. HFD mice 0.70 g). All interventions prevented diet-induced increases in plasma levels of glucose, adiponectin, leptin, and the inflammatory factors IL-1β and TNF-α. The RER was modified by the interventions, while the rhythm of the RER was not. Blood lipids (total cholesterol, triglycerides, and LDL) decreased and were associated with lower lipid anabolism enzymes. In addition, the SE and TE interventions altered the structure and abundance of specific flora. Different interventions inhibited the growth of different genera positively associated with obesity (Escherichia–Shigella, Helicobacter, etc.) and promoted the growth of Akkermansia and Bacteroides, thus affecting the chronic inflammatory state.ConclusionSE and TE both have synergistic effects on weight control and glucolipid metabolism regulation by improving insulin sensitivity and reducing lipid synthesis-related enzyme expression, whereas the combination of SE and TE (3:1) has a better effect on regulating energy metabolism and inhibiting chronic inflammation.
Case Report: Brain tumor’s pitfalls: two cases of high-grade brain tumors mimicking autoimmune encephalitis with positive onconeuronal antibodies
Authors: Consoli Stefano , Dono Fedele , Evangelista Giacomo , Corniello Clarissa , Onofrj Marco , Thomas Astrid , Sensi Stefano L. 
Published: August 2023

BackgroundGlioblastoma (GBM) is the most common primary brain tumor in adulthood. Initial diagnosis is generally based on clinical and MRI findings, which may be misinterpreted as other neurological pictures, including autoimmune encephalitis (AE). AE is a heterogeneous group of neuroinflammatory diseases due to the presence of auto-antibodies targeting antigens on neuronal synaptic or cell surface. In the present report, we describe two peculiar cases of GBM initially misdiagnosed as AE, focusing on the diagnostic pitfalls and the treatment strategies.MethodsWe report the case of two patients with high-grade brain tumors, initially misdiagnosed and treated for AE. Clinical, laboratory, and neuroradiological data are discussed in terms of differential diagnosis between AE and GBM.ResultsThe presence of atypical brain MRI findings and the unresponsiveness to immunosuppressive treatment are major red flags in the differential diagnosis between AE and GBM. In these cases, a brain biopsy is necessary to confirm the diagnosis.ConclusionsAtypical brain tumor presentation causes a diagnostic and therapeutic delay. A positive onconeural autoantibodies result should always be interpreted cautiously, considering the possibility of a false-positive test. A brain biopsy is mandatory for a definite diagnosis.
Point-of-care ultrasound for monitoring catheter tip location during umbilical vein catheterization in neonates: a prospective study
Authors: Xie Hao-Qiang , Xie Cai-Xuan , Liao Jin-Feng , Xu Feng-Dan , Du Bang , Zhong Bai-Mao , He Xiao-Guang , Li Ning 
Published: August 2023

BackgroundPoint-of-care ultrasound (POCUS) can guide umbilical vein catheter placement in real time and monitor catheter tip position, allowing avoidance of severe complications due to catheter malposition. This study aims to explore the effectiveness of POCUS in guiding venous catheter insertion and monitoring complications.MethodsSixty-eight neonates with ultrasound-guided venous catheter insertion at the Neonatal Department of Dongguan Children's Hospital between December 2020 and February 2022 were included. POCUS was applied to monitor catheter tip location daily until catheter removal. A displacement range exceeding the intersection of the inferior vena cava and right atrium by ±0.5 cm was considered misalignment.ResultsSixty-four neonates had a displaced catheter tip (94.1%, 64/68), with a median displacement distance of 0.4 cm (minimum −0.2 cm, maximum 1.2 cm). Ten neonates had a misalignment (14.7%, 10/68) caused by displacement. Displacement usually occurs within 2–4 days after placement, with displacement rates of 94.1% (64/68), 90.6% (58/64), and 98.3% (59/60) on days 2, 3, and 4, respectively, and could still occur on day 9 post-placement. In addition, misalignment mainly occurs on the second day after placement. During the monitoring process, 58 neonates had catheter tip displacement ≥2 times, resulting in 252 displacement and 22 misalignment incidents. Among them, the catheter tip migrated outward from the inferior vena cava seven times, all of which were removed in time. Ultrasound was used for positioning 486 times, and x-ray was indirectly avoided 486 times.ConclusionThe catheter tip is prone to displacement and misalignment after umbilical vein catheterization, which most commonly occurs on days 2–4. POCUS is recommended for daily monitoring of the tip location during umbilical vein catheterization until catheter removal.
Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness
Authors: Tu Sheng , Qiu Yunqing 
Published: August 2023

Background: Transcription factors in Foxo signaling pathway influence hepatocellular carcinoma metastasis through epithelial mesenchymal transition-related pathways. Prognostic factors in the Foxo signaling pathway are feasible for HCC prognosis and therapeutic management.Methods: Based on the differentially expressed genes and Foxo signaling pathway genes in HCC, the ConsensusClusterPlus package was conducted to identify Foxo signaling pathway-related molecular subtypes in HCC. Based on the DEGs in the FMSs, the optimal prognostic factors in HCC were screened by cox and least absolute shrinkage and selection operator (LASSO) cox analysis to form the Foxo prognosis score (FPS). The prognostic predictive effectiveness of FPS was assessed by Kaplan Meier (K-M) analysis and Receiver Operating Characteristic (ROC) analysis. Additionally, tumor microenvironment (TME) score, tumor mutation burden (TMB) and treatment sensitivity differences in FMSs and FPS groups were also evaluated.Results: There were low, medium and high Foxo signaling pathway activity molecular subtypes in HCC named FMS 1, FMS 2 and FMS 3, respectively. FMS 1 with lowest Foxo signaling pathway activity presented an excellent survival advantage, while FMS 3 with highest Foxo signaling pathway activity exhibited an inhibitory TME status. According to FPS grouping, low FPS exhibited favorable survival, low TMB and anti-tumor activity. Patients in the low FPS group were mostly in the early stage of cancer. Moreover, we found that patients with high and low FPS exhibited different sensitivity to chemotherapy, and patients with low FPS were more sensitive to immunotherapy.Conclusion: We revealed a novel molecular subtype and prognostic tool based on Foxo signaling pathway signature, which could potentially provide a direction for accurate and effective assessment of potential personalized treatment options and prognostic management for HCC patients.
Combining single-cell and transcriptomic analysis revealed the immunomodulatory effect of GOT2 on a glutamine-dependent manner in cutaneous melanoma
Authors: Song Lebin , Wei Xiyi , Zhang Xi , Lu Yan 
Published: August 2023

Background: Reprogramming in glutamine metabolism is a hallmark of cancers, while its role in cutaneous melanoma has not been studied at great length.Methods: Here, we constructed a glutamine metabolism-related prognostic signature in cutaneous melanoma with a variety of bioinformatics methods according to the glutamine metabolism regulatory molecules. Moreover, experimental verification was carried out for the key gene.Results: We have identified two subgroups of cutaneous melanoma patients, each with different prognoses, immune characteristics, and genetic mutations. GOT2 was the most concerned key gene among the model genes. We verified its role in promoting tumor cell proliferation by CCK-8 and clone formation assays.Conclusion: Our study cast new light on the prognosis of cutaneous melanoma, and the internal mechanism regulating glutamine metabolism of GOT2 may provide a new avenue for treating the cutaneous melanoma disease precisely.
Analysis of changes in bacterial diversity in healthy and bacterial wilt mulberry samples using metagenomic sequencing and culture-dependent approaches
Authors: Yuan Ting , Qazi Izhar Hyder , Li Jinhao , Yang Peijia , Yang Hongyu , Zhang Xueyin , Liu Weili , Liu Jiping 
Published: August 2023

IntroductionMulberry bacterial wilt is a serious destructive soil-borne disease caused by a complex and diverse group of pathogenic bacteria. Given that the bacterial wilt has been reported to cause a serious damage to the yield and quality of mulberry, therefore, elucidation of its main pathogenic groups is essential in improving our understanding of this disease and for the development of its potential control measures.MethodsIn this study, combined metagenomic sequencing and culture-dependent approaches were used to investigate the microbiome of healthy and bacterial wilt mulberry samples.ResultsThe results showed that the healthy samples had higher bacterial diversity compared to the diseased samples. Meanwhile, the proportion of opportunistic pathogenic and drug-resistant bacterial flora represented by Acinetobacter in the diseased samples was increased, while the proportion of beneficial bacterial flora represented by Proteobacteria was decreased. Ralstonia solanacearum species complex (RSSC), Enterobacter cloacae complex (ECC), Klebsiella pneumoniae, K. quasipneumoniae, K. michiganensis, K. oxytoca, and P. ananatis emerged as the main pathogens of the mulberry bacterial wilt.DiscussionIn conclusion, this study provides a valuable reference for further focused research on the bacterial wilt of mulberry and other plants.
Bicarbonate rather than high pH in growth medium induced Fe-deficiency chlorosis in dwarfing rootstock quince A (Cydonia oblonga Mill.) but did not impair Fe nutrition of vigorous rootstock Pyrus betulifolia
Authors: Zhao Yanyan , Chen Yinglong , Liu Songzhong , Li Fei , Sun Mingde , Liang Zhenxu , Sun Zhi , Yu Futong , Rengel Zed , Li Haigang 
Published: August 2023

IntroductionQuince A (Cydonia oblonga Mill.), a typical dwarfing rootstock in pear cultivation, is susceptible to iron (Fe) deficiency in calcareous soils. The aim of this study was to compare the strategies in Fe uptake and utilization in dwarfing rootstock quince A (low Fe efficiency) versus a typical vigorous rootstock Pyrus betulifolia (PB) with high Fe efficiency.MethodsQuince A and PB were grown in nutrient solution (pH 6.3) for 4 weeks followed by three pH treatments: pH6.3, pH8.3a (adjusted with hydroxide) and pH8.3b (adjusted with bicarbonate). The Fe uptake and utilization indicators of the rootstocks were assessed at the onset of chlorosis symptoms (after 58 days of treatments).Results and discussionIn contrast to PB, quince A exhibited Fe deficiency chlorosis under bicarbonate (pH8.3b). Bicarbonate stimulated the root proton secretion, inhibited root growth and ferric chelate reductase (FCR) activity in both PB and quince A, whereas high pH without bicarbonate (pH8.3a) stimulated only root proton release. Both species accumulated more Fe in roots under high pH treatments than under pH6.3, resulting in Fe sufficiency in leaves. Both high pH treatments increased the activity of leaf FCR in PB and quince A. However, extractable Fe(II) concentration in leaves was increased by high pH treatments in PB only. This study demonstrated that depressed Fe(III) reduction in leaves caused by bicarbonate rather than high pH explained Fe deficiency in quince A grown in bicarbonate-containing medium.