bluuebunny/crossref_metadata_2025_split huggingface dataset:
A sensory neuron-specific long non-coding RNA reduces neuropathic pain by rescuing KCNN1 expression
Authors: Wang Bing , Ma Longfei , Guo Xinying , Du Shibin , Feng Xiaozhou , Liang Yingping , Govindarajalu Gokulapriya , Wu Shaogen , Liu Tong , Li Hong , Patel Shivam , Bekker Alex , Hu Huijuan , Tao Yuan-Xiang 
Published: April 2023

Abstract
Nerve injury to peripheral somatosensory system causes refractory neuropathic pain. Maladaptive changes of gene expression in primary sensory neurons are considered molecular basis of this disorder. Long non-coding RNAs (lncRNAs) are key regulators of gene transcription; however, their significance in neuropathic pain remains largely elusive.Here, we reported a novel lncRNA, named sensory neuron-specific lncRNA (SS-lncRNA), for its expression exclusively in dorsal root ganglion (DRG) and trigeminal ganglion. SS-lncRNA was predominantly expressed in small DRG neurons and significantly downregulated due to a reduction of early B cell transcription factor 1 in injured DRG after nerve injury. Rescuing this downregulation reversed a decrease of the calcium-activated potassium channel subfamily N member 1 (KCNN1) in injured DRG and alleviated nerve injury-induced nociceptive hypersensitivity. Conversely, DRG downregulation of SS-lncRNA reduced the expression of KCNN1, decreased total potassium currents and afterhyperpolarization currents and increased excitability in DRG neurons and produced neuropathic pain symptoms.Mechanistically, downregulated SS-lncRNA resulted in the reductions of its binding to Kcnn1 promoter and heterogeneous nuclear ribonucleoprotein M (hnRNPM), consequent recruitment of less hnRNPM to the Kcnn1 promoter and silence of Kcnn1 gene transcription in injured DRG.These findings indicate that SS-lncRNA may relieve neuropathic pain through hnRNPM-mediated KCNN1 rescue in injured DRG and offer a novel therapeutic strategy specific for this disorder.
Establishing a natural history of X-linked dystonia parkinsonism
Authors: Acuna Patrick , Supnet-Wells Melanie Leigh , Spencer Neil A , de Guzman Jan Kristoper , Russo Massimiliano , Hunt Ann , Stephen Christopher , Go Criscely , Carr Samuel , Ganza Niecy Grace , Lagarde John Benedict , Begalan Shin , Multhaupt-Buell Trisha , Aldykiewicz Gabrielle , Paul Lisa , Ozelius Laurie , Bragg D Cristopher , Perry Bridget , Green Jordan R , Miller Jeffrey W , Sharma Nutan 
Published: April 2023

Abstract
X-linked dystonia parkinsonism is a neurodegenerative movement disorder that affects men whose mothers originate from the island of Panay, Philippines. Current evidence indicates that the most likely cause is an expansion in the TAF1 gene that may be amenable to treatment. To prepare for clinical trials of therapeutic candidates for X-linked dystonia parkinsonism, we focused on the identification of quantitative phenotypic measures that are most strongly associated with disease progression. Our main objective is to establish a comprehensive, quantitative assessment of movement dysfunction and bulbar motor impairments that are sensitive and specific to disease progression in persons with X-linked dystonia parkinsonism. These measures will set the stage for future treatment trials. We enrolled patients with X-linked dystonia parkinsonism and performed a comprehensive oromotor, speech and neurological assessment. Measurements included patient-reported questionnaires regarding daily living activities and both neurologist-rated movement scales and objective quantitative measures of bulbar function and nutritional status. Patients were followed for 18 months from the date of enrollment and evaluated every 6 months during that period. We analysed a total of 87 men: 29 were gene-positive and had symptoms at enrollment, seven were gene-positive and had no symptoms at enrollment and 51 were gene-negative. We identified measures that displayed a significant change over the study. We used principal variables analysis to identify a minimal battery of 21 measures that explains 67.3% of the variance over the course of the study. These measures included patient-reported, clinician-rated and objective quantitative outcomes that may serve as endpoints in future clinical trials.
Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model
Authors: Ye Sining , Theotokis Paschalis , Lee Jae Young , Kim Min Joung , Nheu Danica , Ellen Olivia , Bedford Thomas , Ramanujam Padmanabhan , Wright David K , McDonald Stuart J , Alrehaili Amani , Bakhuraysah Maha , Kang Jung Hee , Siatskas Christopher , Tremblay Cedric S , Curtis David J , Grigoriadis Nikolaos , Monif Mastura , Strittmatter Stephen M , Petratos Steven 
Published: April 2023

Abstract
Nogo receptor 1 is the high affinity receptor for the potent myelin-associated inhibitory factors that make up part of the inflammatory extracellular milieu during experimental autoimmune encephalomyelitis. Signalling through the Nogo receptor 1 complex has been shown to be associated with axonal degeneration in an animal model of multiple sclerosis, and neuronal deletion of this receptor homologue, in a disease specific manner, is associated with preserving axons even in the context of neuroinflammation. The local delivery of Nogo receptor(1-310)-Fc, a therapeutic fusion protein, has been successfully applied as a treatment in animal models of spinal cord injury and glaucoma. As multiple sclerosis and experimental autoimmune encephalomyelitis exhibit large numbers of inflammatory cell infiltrates within the CNS lesions, we utilized transplantable haematopoietic stem cells as a cellular delivery method of the Nogo receptor(1-310)-Fc fusion protein. We identified CNS-infiltrating macrophages as the predominant immune-positive cell type that overexpressed myc-tagged Nogo receptor(1-310)-Fc fusion protein at the peak stage of experimental autoimmune encephalomyelitis. These differentiated phagocytes were predominant during the extensive demyelination and axonal damage, which are associated with the engulfment of the protein complex of Nogo receptor(1-310)-Fc binding to myelin ligands. Importantly, mice transplanted with haematopoietic stem cells transduced with the lentiviral vector carrying Nogo receptor(1-310)-Fc and recovered from the peak of neurological decline during experimental autoimmune encephalomyelitis, exhibiting axonal regeneration and eventual remyelination in the white matter tracts. There were no immunomodulatory effects of the transplanted, genetically modified haematopoietic stem cells on immune cell lineages of recipient female mice induced with experimental autoimmune encephalomyelitis. We propose that cellular delivery of Nogo receptor(1-310)-Fc fusion protein through genetically modified haematopoietic stem cells can modulate multifocal experimental autoimmune encephalomyelitis lesions and potentiate neurological recovery.
Multi-omic integration via similarity network fusion to detect molecular subtypes of ageing
Authors: Yang Mu , Matan-Lithwick Stuart , Wang Yanling , De Jager Philip L , Bennett David A , Felsky Daniel 
Published: April 2023

AbstractMolecular subtyping of brain tissue provides insights into the heterogeneity of common neurodegenerative conditions, such as Alzheimer’s disease. However, existing subtyping studies have mostly focused on single data modalities and only those individuals with severe cognitive impairment. To address these gaps, we applied similarity network fusion, a method capable of integrating multiple high-dimensional multi-omic data modalities simultaneously, to an elderly sample spanning the full spectrum of cognitive ageing trajectories. We analyzed human frontal cortex brain samples characterized by five omic modalities: bulk RNA sequencing (18 629 genes), DNA methylation (53 932 CpG sites), histone acetylation (26 384 peaks), proteomics (7737 proteins) and metabolomics (654 metabolites). Similarity network fusion followed by spectral clustering was used for subtype detection, and subtype numbers were determined by Eigen-gap and rotation cost statistics. Normalized mutual information determined the relative contribution of each modality to the fused network. Subtypes were characterized by associations with 13 age-related neuropathologies and cognitive decline. Fusion of all five data modalities (n = 111) yielded two subtypes (nS1 = 53, nS2 = 58), which were nominally associated with diffuse amyloid plaques; however, this effect was not significant after correction for multiple testing. Histone acetylation (normalized mutual information = 0.38), DNA methylation (normalized mutual information = 0.18) and RNA abundance (normalized mutual information = 0.15) contributed most strongly to this network. Secondary analysis integrating only these three modalities in a larger subsample (n = 513) indicated support for both three- and five-subtype solutions, which had significant overlap, but showed varying degrees of internal stability and external validity. One subtype showed marked cognitive decline, which remained significant even after correcting for tests across both three- and five-subtype solutions (pBonf = 5.9 × 10−3). Comparison to single-modality subtypes demonstrated that the three-modal subtypes were able to uniquely capture cognitive variability. Comprehensive sensitivity analyses explored influences of sample size and cluster number parameters. We identified highly integrative molecular subtypes of ageing derived from multiple high dimensional, multi-omic data modalities simultaneously. Fusing RNA abundance, DNA methylation, and histone acetylation measures generated subtypes that were associated with cognitive decline. This work highlights the potential value and challenges of multi-omic integration in unsupervised subtyping of post-mortem brain.
Fibroscan–Aspartate Aminotransferase Score Predicts Liver-Related Outcomes, but Not Extrahepatic Events, in a Multicenter Cohort of People With Human Immunodeficiency Virus
Authors: Sebastiani Giada , Milic Jovana , Kablawi Dana , Gioè Claudia , Al Hinai Al Shaima , Lebouché Bertrand , Tsochatzis Emmanuel , Finkel Jemima , Ballesteros Luz Ramos , Ramanakumar Agnihotram V , Bhagani Sanjay , Benmassaoud Amine , Mazzola Giovanni , Cascio Antonio , Guaraldi Giovanni 
Published: April 2023

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan–aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH.

Methods
Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST &gt;0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis.

Results
Of the 1472 PWH included, 8% had FAST &gt;0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14–1.29]), hypertension (aOR, 2.24 [95% CI, 1.16–4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20–2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02–4.85]) were associated with FAST &gt;0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5–4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST &gt;0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2–77.7] vs 5.0 [95% CI, 2.9–8.6] per 1000 person-years). FAST &gt;0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97–12.51]). Conversely, FAST did not predict extrahepatic events.

Conclusions
A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population.
Stratification of lymph node metastasis improves diagnostic efficiency in thoracic esophageal squamous cell carcinoma
Authors: Li Zhenxuan , Li Yin , Liu Xianben , Zheng Yan , Sun Haibo , Liang Guanghui , Wang Zongfei , Xing Wenqun 
Published: April 2023

Abstract

Introduction
Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore.

Methods
The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology.

Results
A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively.

Conclusion
Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.
Using information criteria to select averages in CCE
Authors: Margaritella Luca , Westerlund Joakim 
Published: April 2023

Summary
In the interactive effects panel data literature information criteria are commonly used to consistently determine which of the estimated principal components factors to include. The present paper shows that the same approach can be applied to factors estimated by taking the cross-sectional averages of the observables, as prescribed by the popular common correlated effects (CCE) approach. This should be useful to practitioners because at the moment there is no other theory that justifies the use of information criteria in CCE.
Leap or lag: left atrial appendage closure and guidelines
Authors: Camm A John 
Published: April 2023

Abstract
Atrial fibrillation (AF) is associated with life-threatening thromboembolism. Most emboli stem from thrombosis in the left atrial appendage (LAA). The current treatment of choice is oral anticoagulants (OACs), but a small proportion of patients cannot take OACs predominantly because of the so-called unacceptable bleeding risks. However, many who initially accept OACs subsequently stop therapy or reduce the OAC treatment to a potentially non-effective dose leaving them exposed to thromboembolic risk.
A relatively simple alternative therapy involves the catheter-based insertion of a LAA closure (LAAC) device to prevent thromboembolism from the LAA. There is a considerable evidence base for this therapy consisting of clinical trials and observational data which suggests comparable therapeutic efficacy with a possible small excess of ischaemic strokes.
Although LAAC has been very closely examined by regulators and approved for market release, guidelines from most professional societies give only weak recommendations for use of this device which may be the only known effective therapy available to some at-risk AF patients. Guidance materials from the same societies more enthusiastically endorse LAAC.
Clinical practice is running well ahead of the guidelines because equipoise has been lost by physicians faced with patients for whom they have no other effective therapy. Guideline writers are correct in providing recommendations which are less strong for LAAC than for OACs, for those who are able and willing to take OAC treatment, but for those who are not, a stronger recommendation is needed. But, should the guidelines lag behind or leap ahead of the available evidence?
In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study
Authors: Platzbecker Katharina , Müller-Fielitz Helge , Foraita Ronja , Koepp Matthias J , Voss Annemarie , Pflock René , Linder Roland , Pigeot Iris , Schink Tania , Schwaninger Markus 
Published: April 2023

Abstract

Aims
Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).

Methods and results
We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011–17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)].

Conclusion
In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.
Association between anaemia and vitamin D insufficiency among 6- to 12-month-old infants: implications for clinical practice
Authors: Boonrusmee Sasivara , Kasemsripitak Staporn , Navykarn Thitiporn , Jaruratanasirikul Somchit 
Published: April 2023

Abstract

Background
Anaemia and vitamin D insufficiency (VDI) are among the most common nutritional problems. Anaemia screening is routinely performed; however, screening for VDI is not usually recommended.

Objectives
To study the association between anaemia and VDI and identify the risk factors for VDI.

Methods
We conducted a cross-sectional study of 120 infants aged 6–12 months attending a well-child clinic at Songklanagarind Hospital between December 2020 and November 2021. Sociodemographic data and 24-h food records were also collected. Blood samples were obtained for complete blood count and 25-hydroxyvitamin D [25(OH)D] levels. Logistic regression analysis was used to determine risk factors for VDI.

Results
The mean 25(OH)D level was 22.2 ± 8.9 ng/mL in anaemic infants and 27.2 ± 9.6 ng/mL in non-anaemic infants (P value 0.01). The median (IQR) Hb level was 11.1 g/dL (10.3, 11.4) in the VDI group and 11.4 g/dL (11, 12.1) in the non-VDI group (P value 0.002). The proportion of breastfed infants was higher in infants with anaemia (80%) (P &lt; 0.001) and VDI (85.3%) (P &lt; 0.001). Sunlight exposure &lt;15 min/day (odds ratio [OR] 3.84; 95% confidence interval [CI]: 1.23–12.00; P = 0.020) was a risk factor, and vitamin D intake (OR 0.37; 95% CI: 0.20–0.74; P = 0.004) was a protective factor for VDI.

Conclusion
Infants with anaemia, short duration of sunlight exposure, breastfeeding, low vitamin D intake, and low iron intake were more likely to be vitamin D insufficient. However, after adjustment in the multivariate analyses, only sunlight exposure and vitamin D intake were significantly associated with vitamin D insufficiency.
Recruiting general practitioners and older patients with multimorbidity to randomized trials
Authors: McCarthy Caroline , Pericin Ivana , Smith Susan M , Moriarty Frank , Clyne Barbara 
Published: April 2023

Abstract

Background
Older patients with multimorbidity are under-represented in experimental research.

Objective
To explore the barriers and facilitators to general practitioner (GP) and older patient recruitment and retention in a cluster randomized controlled trial (RCT).

Method
This descriptive study uses qualitative and quantitative data from a cluster RCT, designed to evaluate the effectiveness of a medicines optimization intervention. The SPPiRE cluster RCT enrolled 51 general practices and 404 patients aged ≥65 years and prescribed ≥15 medicines. Quantitative data were collected from all recruited practices and 32 additional practices who were enrolled, but unable to recruit sufficient participants. Qualitative data were collected from purposive samples of intervention GPs (18/26), patients (27/208), and researcher logs and analysed thematically using inductive coding.

Results
Enrolment rates for practices and patients were 37% and 25%, respectively. Barriers to GP recruitment were lack of resources and to patient recruitment were difficulty understanding trial material and concern about medicines being taken away. GPs’ primary motivation was perceived importance of the research question, whereas patients’ primary motivation was trust in their GP. All general practices were retained. Thirty-five patients (8.6%) were lost to follow-up for primary outcomes, mainly because they had died and 45% did not return patient-reported outcome measures (PROMs).

Conclusion
Patient retention for the primary outcome was high, as it was collected directly from patient records. Patient completion of PROM data was poor, reflecting difficulty in understanding trial material. Recruiting older patients with multimorbidity to clinical trials is possible but requires significant resource and planning.

Trial registration
ISRCTN Registry ISRCTN12752680.