bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice
Authors: Kinoshita Shiori , Kojima Kazuaki , Ohnishi Eriko , Takayama Yuka , Kikuchi Hiroki , Takada Shuji , Nakabayashi Kazuhiko , Kawai Tomoko , Hata Kenichiro 
Published: February 2024

Background: Epigenetic disruptions have been implicated in neurodevelopmental disorders. NSD2 is associated with developmental delay/intellectual disability; however, its role in brain development and function remains unclear.Methods: We performed transcriptomic and epigenetic analyses using Nsd2 knockout mice to better understand the role of NSD2 in the brain.Results and discussion: Transcriptomic analysis revealed that the loss of NSD2 caused dysregulation of genes related to synaptic transmission and formation. By analyzing changes in H3 lysine 36 dimethylation (H3K36me2), NSD2-mediated H3K36me2 mainly marked quiescent state regions and the redistribution of H3K36me2 occurred at transcribed genes and enhancers. By integrating transcriptomic and epigenetic data, we observed that H3K36me2 changes in a subset of dysregulated genes related to synaptic transmission and formation. These results suggest that NSD2 is involved in the regulation of genes important for neural function through H3K36me2. Our findings provide insights into the role of NSD2 and improve our understanding of epigenetic regulation in the brain.
No bidirectional relationship between inflammatory bowel disease and diverticular disease: a genetic correlation and Mendelian randomization study
Authors: Aierken Ailikamu , Atabieke Falide , Aierken Munire , Li Jian , Xia Yu , Aizezi Yierzhati , Li Shui-Xue 
Published: February 2024

Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare.Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn’s disease (CD)] and DD using the Mendelian randomization (MR) analysis.Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy.Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98–1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94–1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92–1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method.Conclusion: This study’s findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.
Microplastics pollution in genetically connected populations of Holothuria forskali from south Bay of Biscay
Authors: Menéndez Daniel , Álvarez Almudena , Garcia-Vazquez Eva , Ardura Alba 
Published: February 2024

IntroductioSea cucumbers are increasingly demanded as seafood in different cultures around the world. Holothurians could be potentially exploited in southern Bay of Biscay (Iberian Cantabrian coast) where they are not fished yet. Recent studies show relatively high pollution by emerging pollutants like microplastics (MPs) in the region; perhaps the exposure of holothurians to those MPs may put them at risk.Material and methodsHere we analysed 60 samples of Holothuria forskali taken from the west and east of the Cape Peñas transition zone in different seasons. MPs were quantified from body wall tissue, and mitochondrial DNA sequences (16S and COI genes) were employed to determine population connectivity and infer replenishment capacity.ResultsMuch higher MPs content in holothurian tissue than in water and sediments confirmed bioconcentration in this species. Significant differences between sampling locations were found, holothurian pollution being consistent with the occurrence of MPs sources like rivers, fishing ports and aquaculture. Genetic connectivity and no signals of diversity reduction in the most polluted samples suggest population replenishment capacity in H. forskali in the studied region. Results for a few samples of H. mammata from the same sampling points confirmed a higher MPs pollution at the west of Cape Peñas.DiscussionAccording to these exploratory results, sea cucumbers seem to accumulate MPs especially in the western Cantabrian Sea. Further studies are recommended to understand the possible MPs threat for these holothurian species.
Case report: Treatment of Wilson’s disease by human amniotic fluid administration
Authors: Liang Libin , Xin Hong , Shen Xueyan , Xu Yanping , Zhang Lansen , Liu Dehui , Zhao Liling , Tong Xinglong 
Published: February 2024

BackgroundWilson’s disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient.Case presentationA 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19–26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8–5.5 × 104/ml was administrated by IV infusion at a rate of 50–70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson’s Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 μg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration.ConclusionAmniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively.
Efficacy of erector spine plane block in two different approaches to lumbar spinal fusion surgery: a retrospective pilot study
Authors: Birnbaums Jānis Verners , Ozoliņa Agnese , Solovjovs Leonids , Glāzniece-Kagane Zane , Nemme Jānis , Logina Ināra 
Published: February 2024

BackgroundErector spine plane block (ESPB) has been widely used in spinal surgery, although there are variable data about its efficacy.ObjectivesThis study aimed to evaluate the efficacy of ESPB in elective lumbar spinal fusion surgery patients with two different surgical approaches.Materials and methodsRetrospectively, 45 elective lumbar transpedicular fusion (TPF) surgery patients undergoing open surgery with different approaches [posterior transforaminal fusion approach (TLIF) or combined posterior and anterior approach (TLIF+ALIF)] were divided into 2 groups: general anesthesia (GA, n = 24) and general anesthesia combined with ESPB (GA + ESPB, n = 21). The primary outcome was to analyze the efficacy of ESPB in two different surgical approaches in terms of pain intensity in the first 48 h. Secondary: Fentanyl-free patients and opioid consumption in the first 24 h postoperatively. Comparative analysis was performed (SPSS® v. 28.0) (p &lt; 0.05).ResultsOut of 45 patients (27 female), 21 received GA + ESPB and 24 received GA. The average age was 60.3 ± 14.3 years. Chronic back pain before the operation was registered in 56% of patients. ESPB was performed in 17 TLIF and in 4 TLIF+ALIF patients. ESPB significantly reduced pain intensity at rest in both surgical approaches 48 h after surgery (p &lt; 0.05). The need for postoperative fentanyl infusion was significantly lower in the group treated with GA + ESPB in both surgical approaches than in those who only received GA (29% vs. 77% in TLIF and 0% vs. 80% in TLIF+ALIF); p = 0.01 and p = 0.004. Additionally, we observed that ESPB provides a good analgesic effect for up to 6.8 ± 3.2 h in the TLIF and 8.9 ± 7.6 h in the TLIF+ALIF approaches. Consequently, ESPB reduced the initiation of the fentanyl compared to GA alone, with a mean difference of 3.2 ± 4.2 h in the TLIF subgroup (p = 0.045) and 6.7 ± 5.3 h in TLIF +ALIF (p = 0.028). Only in the TLIF+ALIF approach, ESPB reduced the total fentanyl consumption compared to those with GA (1.43 ± 0.45 mg/24 h vs. 0.93 ± 0.68 mg/24 h; p = 0.015).ConclusionESPB significantly reduced pain at rest after surgery, the number of patients requiring immediate postoperative fentanyl analgesia, and total fentanyl consumption in both surgical approaches, particularly in TLIF+ALIF. However, the application of ESPB does not always provide completely sufficient analgesia.
A new score for airway assessment using clinical and ultrasound parameters
Authors: De Luis-Cabezón Nekari , Ly-Liu Diana , Renedo-Corcostegui Pablo , Santaolalla-Montoya Francisco , Zabala-Lopez de Maturana Aitor , Herrero-Herrero Jose Carlos , Martínez-Hurtado Eugenio , De Frutos-Parra Raúl , Bilbao-Gonzalez Amaia , Fernandez-Vaquero Miguel Angel 
Published: February 2024

BackgroundOver the last few years, ultrasonography has been introduced as the fifth pillar to patient’s bedside physical examination. Clinical assessments aim to screen and look for airway difficulties to predict difficult intubations, but none have demonstrated a significant predictive capacity. Recent systematic reviews have established a correlation between ultrasound imaging and difficult direct laryngoscopy. The primary objective of this study was to determine whether the utilization of ultrasonography to examine the upper airway could accurately predict difficult direct laryngoscopy.MethodsThis is a prospective observational study including 102 adult patients that required general anesthesia for elective surgery. Preoperatively, clinical airway assessments were performed. Data such as Mallampati-Samsoon grade (MS), upper lip bite test (ULBT), thyromental (TMD) and sternomental distance (SMD), cervical circumference (CC) and the Arné risk index were collected. Ultrasound evaluation was taken at five different levels in two planes, parasagittal and transverse. Therefore, the following measurements were registered: distance from skin to hyoid bone (DSHB), distance from skin to thyrohyoid membrane (DSTHM), distance from skin to epiglottis (DSE), distance from skin to thyroid cartilage (DSTC) and distance from hyoid bone and thyroid cartilage (DHBTC). Patients were divided into two groups based on the difficulty to perform direct laryngoscopy, according to Cormack-Lehane (C-L) classification. Grades I and II were classified as easy laryngoscopy and grades III or IV as difficult. Logistic regression models and the Receiver Operating Characteristic (ROC) curve was employed to determine the diagnostic precision of ultrasound measurements to distinguish difficult laryngoscopy (DL).ResultsThe following risk score for DL was obtained, DSTHM ≥ 1.60 cm (2 points), DSTC ≥ 0.78 cm (3 points) and gender (2 points for males). The score can range from 0 to 7 points, and showed and AUC (95% CI) of 0.84 (0.74–0.95). A score of 5 points or higher indicates a 34-fold increase in the risk of finding DL (p = 0.0010), sensitivity of 91.67, specificity of 75.56, positive predictive value of 33.33, and negative predictive value of 98.55.ConclusionThe use of ultrasonography combined with classic clinical screening tests are useful tools to predict difficult direct laryngoscopy.
Protocol for a randomized, placebo-controlled, double-blind phase IIa study of the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with Parkinson’s disease (ROCK-PD)
Authors: Wolff Andreas W. , Bidner Helen , Remane Yvonne , Zimmer Janine , Aarsland Dag , Rascol Olivier , Wyse Richard K. , Hapfelmeier Alexander , Lingor Paul 
Published: February 2024

BackgroundThe Rho-kinase (ROCK) inhibitor Fasudil has shown symptomatic and disease-modifying effects in Parkinson’s disease (PD) models in vitro and in vivo. In Japan, Fasudil has been approved for the treatment of subarachnoid haemorrhage since 1995 and shows a favourable safety profile.Objectives/designTo investigate the safety, tolerability, and symptomatic efficacy of ROCK-inhibitor Fasudil in comparison to placebo in a randomized, national, multicenter, double-blind phase IIa study in patients with PD.Methods/analysisWe plan to include 75 patients with at least ‘probable’ PD (MDS criteria), Hoehn and Yahr stages 1–3, and age 30–80 years in 13 German study sites. Patients must be non-fluctuating and their response to PD medication must have been stable for 6 weeks. Patients will be randomly allocated to treatment with the oral investigational medicinal product (IMP) containing either Fasudil in two dosages, or placebo, for a total of 22 days. As primary analysis, non-inferiority of low/high dose of Fasudil on the combined endpoint consisting of occurrence of intolerance and/or treatment-related serious adverse events (SAEs) over 22 days will be assessed in a sequential order, starting with the lower dose. Secondary endpoints will include tolerability alone over 22 days and occurrence of treatment-related SAEs (SARs) over 22 and 50 days and will be compared on group level. Additional secondary endpoints include efficacy on motor and non-motor symptoms, measured on established scales, and will be assessed at several timepoints. Biomaterial will be collected to determine pharmacokinetics of Fasudil and its active metabolite, and to evaluate biomarkers of neurodegeneration.Ethics/registration/discussionAfter positive evaluation by the competent authority and the ethics committee, patient recruitment started in the 3rd quarter of 2023. ROCK-PD is registered with Eudra-CT (2021-003879-34) and clinicaltrials.gov (NCT05931575). Results of this trial can pave way for conducting extended-duration studies assessing both symptomatic efficacy and disease-modifying properties of Fasudil.
Design and assessment of a reconfigurable behavioral assistive robot: a pilot study
Authors: Shi Enming , Zhi Wenzhuo , Chen Wanxin , Han Yuhang , Zhang Bi , Zhao Xingang 
Published: February 2024

IntroductionFor patients with functional motor disorders of the lower limbs due to brain damage or accidental injury, restoring the ability to stand and walk plays an important role in clinical rehabilitation. Lower limb exoskeleton robots generally require patients to convert themselves to a standing position for use, while being a wearable device with limited movement distance.MethodsThis paper proposes a reconfigurable behavioral assistive robot that integrates the functions of an exoskeleton robot and an assistive standing wheelchair through a novel mechanism. The new mechanism is based on a four-bar linkage, and through simple and stable conformal transformations, the robot can switch between exoskeleton state, sit-to-stand support state, and wheelchair state. This enables the robot to achieve the functions of assisted walking, assisted standing up, supported standing and wheelchair mobility, respectively, thereby meeting the daily activity needs of sit-to-stand transitions and gait training. The configuration transformation module controls seamless switching between different configurations through an industrial computer. Experimental protocols have been developed for wearable testing of robotic prototypes not only for healthy subjects but also for simulated hemiplegic patients.ResultsThe experimental results indicate that the gait tracking effect during robot-assisted walking is satisfactory, and there are no sudden speed changes during the assisted standing up process, providing smooth support to the wearer. Meanwhile, the activation of the main force-generating muscles of the legs and the plantar pressure decreases significantly in healthy subjects and simulated hemiplegic patients wearing the robot for assisted walking and assisted standing-up compared to the situation when the robot is not worn.DiscussionThese experimental findings demonstrate that the reconfigurable behavioral assistive robot prototype of this study is effective, reducing the muscular burden on the wearer during walking and standing up, and provide effective support for the subject's body. The experimental results objectively and comprehensively showcase the effectiveness and potential of the reconfigurable behavioral assistive robot in the realms of behavioral assistance and rehabilitation training.
Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition
Authors: Beltran-Casanueva Rasiel , Hernández-García Aracelis , de Amo García Paula , Blanco-Reina Encarnación , Serrano-Castro Pedro , García-Casares Natalia , Fuxe Kjell , Borroto-Escuela Dasiel O. , Narváez Manuel 
Published: February 2024

IntroductionThis study may unveil novel insights into the interactions between neuropeptide Y receptor 1 (NPY1R) and galanin receptor 2 (GALR2), in the dentate gyrus of the dorsal hippocampus, shedding light on their role in neurogenesis and cognitive functions. Existing literature highlights the potential of these interactions in enhancing learning and memory, yet detailed mechanisms remain underexplored.MethodsUtilizing intracerebroventricular injections of GALR2 and NPY1R agonists in Sprague-Dawley male rats, we examined neurogenesis via markers PCNA and DCX, and memory consolidation through the object-in-place task over a three-week period.ResultsSignificant increases in NPY1R-GALR2 co-localization and neuroblast proliferation were observed, alongside enhanced memory consolidation. These findings suggest a synergistic effect of NPY1R and GALR2 activation on cognitive functions.DiscussionOur findings may foster the development of novel heterobivalent or multitargeting drugs, affecting NPY1R-GALR2 interaction, and suggest a future pharmacogical strategy for improving learning and memory found in many brain diseases. Further research is encouraged to explore these mechanisms in pathological models.
Loss of Ezh2 in the medial ganglionic eminence alters interneuron fate, cell morphology and gene expression profiles
Authors: Rhodes Christopher T. , Asokumar Dhanya , Sohn Mira , Naskar Shovan , Elisha Lielle , Stevenson Parker , Lee Dongjin R. , Zhang Yajun , Rocha Pedro P. , Dale Ryan K. , Lee Soohyun , Petros Timothy J. 
Published: February 2024

IntroductionEnhancer of zeste homolog 2 (Ezh2) is responsible for trimethylation of histone 3 at lysine 27 (H3K27me3), resulting in repression of gene expression. Here, we explore the role of Ezh2 in forebrain GABAergic interneuron development.MethodsWe removedEzh2in the MGE by generatingNkx2-1Cre;Ezh2conditional knockout mice. We then characterized changes in MGE-derived interneuron fate and electrophysiological properties in juvenile mice, as well as alterations in gene expression, chromatin accessibility and histone modifications in the MGE.ResultsLoss ofEzh2increases somatostatin-expressing (SST+) and decreases parvalbumin-expressing (PV+) interneurons in the forebrain. We observe fewer MGE-derived interneurons in the first postnatal week, indicating reduced interneuron production. Intrinsic electrophysiological properties in SST+ and PV+ interneurons are normal, but PV+ interneurons display increased axonal complexity inEzh2mutant mice. Single nuclei multiome analysis revealed differential gene expression patterns in the embryonic MGE that are predictive of these cell fate changes. Lastly, CUT&amp;Tag analysis revealed that some genomic loci are particularly resistant or susceptible to shifts in H3K27me3 levels in the absence ofEzh2, indicating differential selectivity to epigenetic perturbation.DiscussionThus, loss of Ezh2 in the MGE alters interneuron fate, morphology, and gene expression and regulation. These findings have important implications for both normal development and potentially in disease etiologies.
Fine tuned personalized machine learning models to detect insomnia risk based on data from a smart bed platform
Authors: Winger Trevor , Chellamuthu Vidhya , Guzenko Dmytro , Aloia Mark , Barr Shawn , DeFranco Susan , Gorski Brandon , Mushtaq Faisal , Garcia-Molina Gary 
Published: February 2024

IntroductionInsomnia causes serious adverse health effects and is estimated to affect 10–30% of the worldwide population. This study leverages personalized fine-tuned machine learning algorithms to detect insomnia risk based on questionnaire and longitudinal objective sleep data collected by a smart bed platform.MethodsUsers of the Sleep Number smart bed were invited to participate in an IRB approved study which required them to respond to four questionnaires (which included the Insomnia Severity Index; ISI) administered 6 weeks apart from each other in the period from November 2021 to March 2022. For 1,489 participants who completed at least 3 questionnaires, objective data (which includes sleep/wake and cardio-respiratory metrics) collected by the platform were queried for analysis. An incremental, passive-aggressive machine learning model was used to detect insomnia risk which was defined by the ISI exceeding a given threshold. Three ISI thresholds (8, 10, and 15) were considered. The incremental model is advantageous because it allows personalized fine-tuning by adding individual training data to a generic model.ResultsThe generic model, without personalizing, resulted in an area under the receiving-operating curve (AUC) of about 0.5 for each ISI threshold. The personalized fine-tuning with the data of just five sleep sessions from the individual for whom the model is being personalized resulted in AUCs exceeding 0.8 for all ISI thresholds. Interestingly, no further AUC enhancements resulted by adding personalized data exceeding ten sessions.DiscussionThese are encouraging results motivating further investigation into the application of personalized fine tuning machine learning to detect insomnia risk based on longitudinal sleep data and the extension of this paradigm to sleep medicine.