bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Vast Majority of Patients With Fibromyalgia Have a Straight Neck Observed on a Lateral View Radiograph of the Cervical Spine
Authors: Katz Robert S. , Leavitt Frank , Cherny Katya , Small Alexandra Katz , Small Ben J. 
Published: November 2022

Objective
A straight cervical spine is an underappreciated and often overlooked finding in fibromyalgia. The aim of this medical records review study was to evaluate the cervical curvature on radiographs of patients with fibromyalgia.

Methods
A consecutive series of 270 cervical spine radiographs of patients with neck pain from 2015 to 2018 were retrospectively analyzed for cervical curvature using the Cobb angle measurement. One hundred fifty-five patients met full American College of Rheumatology criteria for fibromyalgia, whereas 115 subjects with other rheumatic diseases who were similar in age and education served as control subjects.

Results
Mean cervical curvature in fibromyalgia was 6.4 ± 5.2 degrees and 13.8 ± 7.4 degrees in control subjects. The more than 7-degree difference was significant (p < 0.001). Curvature in the magnitude of 21 degrees is at the low end of normal. At ≤10 degrees, where the cervical spine is essentially straight, there were 129 fibromyalgia patients (83.2%) and 37 control subjects (32.2%). The 51% difference was significant (p < 0.001).

Conclusion
Most patients with fibromyalgia share an abnormality in common that is verifiable by a simple radiograph. In 83.2% of the patients, the cervical spine was essentially straight (Cobb angle ≤10 degrees). In fibromyalgia patients, the loss of cervical curvature was approximately 6.5 times greater than in control subjects (50.3% vs. 7.8%). A straight neck without other radiographic abnormalities may be a major anatomical abnormality in fibromyalgia that has gone unnoticed. It may assist in the diagnosis, as well as suggest increased muscle tension/pressure as a possible etiology.
FULL-SCALE DEEPLY SUPERVISED ATTENTION NETWORK FOR SEGMENTING COVID-19 LESIONS
Authors: Dutta Pallabi , Mitra Sushmita 
Published: November 2022

ABSTRACTAutomated delineation of COVID-19 lesions from lung CT scans aids the diagnosis and prognosis for patients. The asymmetric shapes and positioning of the infected regions make the task extremely difficult. Capturing information at multiple scales will assist in deciphering features, at global and local levels, to encompass lesions of variable size and texture. We introduce the Full-scale Deeply Supervised Attention Network (FuDSA-Net), for efficient segmentation of corona-infected lung areas in CT images. The model considers activation responses from all levels of the encoding path, encompassing multi-scalar features acquired at different levels of the network. This helps segment target regions (lesions) of varying shape, size and contrast. Incorporation of the entire gamut of multi-scalar characteristics into the novel attention mechanism helps prioritize the selection of activation responses and locations containing useful information. Determining robust and discriminatory features along the decoder path is facilitated with deep supervision. Connections in the decoder arm are remodeled to handle the issue of vanishing gradient. As observed from the experimental results, FuDSA-Net surpasses other state-of-the-art architectures; especially, when it comes to characterizing complicated geometries of the lesions.
Phase-wise Impact Analysis of the Indian National Lockdown against COVID-19 Outcomes
Authors: Mhasawade Vishwali , Zadey Siddhesh , Nair Aatmika 
Published: November 2022

AbstractIndia was one of the most vulnerable countries to the COVID-19 pandemic considering the high transmissibility of the virus, exploding population, and fragile healthcare infrastructure. As an early counter, India implemented a country-wide lockdown and we aimed to study the impact of 4 lockdowns and 2 unlock phases on 6 outcomes: case growth, death count, effective reproduction number, mobility, hospitalization, and infection growth by two methods: interrupted time series (ITR) analysis and Bayesian causal impact analysis (BCIA) for nationals and sub-national levels. We observed that the effects are heterogeneous across outcomes and phases. For example, ITR revealed the effect to be significant for all the outcomes across all phases except for case growth in phase 1. BCIA revealed that the causal effect of all four lockdown phases was positive for deaths. At the state level, Maharashtra benefited from the lockdown in comparison to Tripura. Effects of lockdown phases 3 and 4 on death count were correlated (R=0.70, p<0.05) depicting the ‘extended impact’ of phase-wise interventions. We observed the highest impact on mobility followed by hospitalization, infection growth, effective reproduction number, case growth, and death count. For optimal impact, lockdown needs to be implemented at the sub-national level considering various demographic variations between states.
Safety and Immunogenicity of a Booster SARS-Cov-2 Vaccination in Patients with Chronic Liver Disease
Authors: Qianqian Li , Jing Chen , Kai Sun , Ruixin Song , Jiayin Wang , Hongmin Lv , Yankai Yang , Jing Liang , Qing Ye , YanYing Gao , Jun Li , Ying Li , Junqing Yan , Chao Yang , Ying Liu , Tao Wang , Changen Liu , Fei Wang , Huiling Xiang 
Published: November 2022

ABSTRACTThis article is aim to investigate the safety and immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine booster in patients with chronic liver disease(CLD). A total of 114 patients with CLD who received a SARS-CoV-2 vaccine booster were enrolled in this study. Serum samples were collected from enrolled patients at least 14 days after the booster dose and tested for SARS-CoV-2 neutralizing antibody (novel coronavirus neutralizing antibody, nCoV NTAb) and IgG antibody against SARS-CoV-2 spike binding domain (novel coronavirus spike receptor-binding domain antibody, nCoV S-RBD antibody) levels. The positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD were 87.72% and 91.23%, respectively, after the booster injection of coronavirus disease 2019 (COVID-19) vaccine. The booster injection resulted in the production of nCov NTAb in 66.7% of patients and nCov-SRBD antibody in 71.43% of patients with CLD who failed basic immunization. After basic SARS-CoV-2 immunization, the booster SARS-CoV2 vaccine increased the serum conversion rate and the level of nCov NTAb and nCov-SRBD antibodies in patients with CLD (including patients with cirrhosis). The severity of the liver disease is related to the immune response to COVID-19 vaccine.
Disparities in spatially variable gene calling highlight the need for benchmarking spatial transcriptomics methods
Authors: Charitakis Natalie , Salim Agus , Piers Adam T. , Watt Kevin I. , Porrello Enzo R. , Elliott David A. , Ramialison Mirana 
Published: November 2022

AbstractIdentifying spatially variable genes (SVGs) is a key step in the analysis of spatially resolved transcriptomics (SRT) data. SVGs provide biological insights by defining transcriptomic differences within tissues, which was previously unachievable using RNA-sequencing technologies. However, the increasing number of published tools designed to define SVG sets currently lack benchmarking methods to accurately assess performance. This study compares results of 6 purpose-built packages for SVG identification across 9 public and 5 simulated datasets and highlights discrepancies between results. Additional tools for generation of simulated data and development of benchmarking methods are required to improve methods for identifying SVGs.
Knowledge Discovery with Electrocardiography Using Interpretable Deep Neural Networks
Authors: Lu Lei , Zhu Tingting , H. Ribeiro Antônio , Clifton Lei , Zhao Erying , Ribeiro Antonio Luiz P. , Zhang Yuan-Ting , Clifton David A. 
Published: November 2022

AbstractDespite the potentials of artificial intelligence (AI) in healthcare, very little work focuses on the extraction of clinical information or knowledge discovery from clinical measurements. Here we propose a novel deep learning model to extract characteristics in electrocardiogram (ECG) and explore its usage in knowledge discovery. Utilising a 12-lead ECG dataset (nECGs= 2,322,513) collected from unique subjects (nSubjects= 1,558,772) in primary care, we performed three independent medical tasks with the proposed model: (i) cardiac abnormality diagnosis, (ii) gender identification, and (iii) hypertension screening. We achieved an area under the curve (AUC) score of 0.998 (95% confidence interval (CI), 0.995-0.999), 0.964 (95% CI, 0.963-0.965), and 0.839 (95% CI, 0.837-0.841) for each task, respectively; We provide interpretation of salient morphologies and further identified key ECG leads that achieve similar performance for the three tasks: (i) AVR and V1 leads (AUC=0.990 (95% CI, 0.982-0.995); (ii) V5 lead (AUC=0.900 (95% CI, 0.899-0.902)); and (iii) V1 lead (AUC=0.816 (95% CI, 0.814-0.818)). Using ECGs, our model not only has demonstrated cardiologist-level accuracy in heart diagnosis with interpretability, but also shows its potentials in facilitating clinical knowledge discovery for gender and hypertension detection which are not readily available.
Neural basis of melodic learning explains cross-cultural regularities in musical scales
Authors: Pelofi Claire , Rezaeizadeh Mohsen , Farbood Morwaread M. , Shamma Shihab 
Published: November 2022

SummarySeeking exposure to unfamiliar experiences constitutes an essential aspect of the human condition, and the brain must adapt to the constantly changing environment by learning the evolving statistical patterns emerging from it. Cultures are shaped by norms and conventions and therefore novel exposure to an unfamiliar culture induces a type of learning that is often described as implicit: when exposed to a set of stimuli constrained by unspoken rules, cognitive systems must rapidly build a mental representation of the underlying grammar. Music offers a unique opportunity to investigate this implicit statistical learning, as sequences of tones forming melodies exhibit structural properties learned by listeners during short- and long-term exposure. Understanding which specific structural properties of music enhance learning in naturalistic learning conditions reveals hard-wired properties of cognitive systems while elucidating the prevalence of these features across cultural variations. Here we provide behavioral and neural evidence that the prevalence of non-uniform musical scales may be explained by their facilitating effects on melodic learning. In this study, melodies were generated using an artificial grammar with either a uniform (rare) or non-uniform (prevalent) scale. After a short exposure phase, listeners had to detect ungrammatical new melodies while their EEG responses were recorded. Listeners’ performance on the task suggested that the extent of statistical learning during music listening depended on the musical scale context: non-uniform scales yielded better syntactic learning. This behavioral effect was mirrored by enhanced encoding of musical syntax in the context of non-uniform scales, which further suggests that their prevalence stems from fundamental properties of learning.
Differential effects of multiplex and uniplex affiliative relationships on biomarkers of inflammation
Authors: Vandeleest Jessica , Wooddell Lauren J. , Nathman Amy C. , Beisner Brianne A. , McCowan Brenda 
Published: November 2022

AbstractSocial relationships profoundly impact health in social species. Much of what we know regarding the impact of affiliative social relationships on health in nonhuman primates (NHPs) has focused on the structure of connections or the quality of relationships. These relationships are often quantified by comparing different types of affiliative behaviors (e.g., contact sitting, grooming, alliances, proximity) or pooling affiliative behaviors into an overall measure of affiliation. The influence of the breadth of affiliative behaviors (e.g., how many different types or which ones) a dyad engages in on health and fitness outcomes remains unknown. Here we employed a social network approach to explicitly explore whether the integration of different affiliative behaviors within a relationship can point to the potential function of those relationships and their impact on health-related biomarkers (i.e., pro-inflammatory cytokines) in a commonly studied non-human primate model system, the rhesus macaque (Macaca mulatta). Being well connected in multiplex grooming networks (networks where individuals both contact sat and groomed), which were more modular and kin biased, was associated with lower inflammation (IL-6, TNF-alpha). In contrast, being well connected in uniplex grooming networks (dyad engaged only in grooming and not in contact sitting), which were more strongly linked with social status, was associated with greater inflammation. Results suggest that multiplex relationships may function as supportive relationships that promote health. In contrast, the function of uniplex grooming relationships may be more transactional and may incur physiological costs. This complexity is important to consider for understanding the mechanisms underlying the association of social relationships on human and animal health.
Small Molecule Inducers of Neuroprotective miR-132 Identified by HTS-HTS in Human iPSC-derived Neurons
Authors: Nguyen Lien D. , Wei Zhiyun , Silva M. Catarina , Barberán-Soler Sergio , Rabinovsky Rosalia , Muratore Christina R. , Stricker Jonathan M. S. , Hortman Colin , Young-Pearse Tracy L. , Haggarty Stephen J. , Krichevsky Anna M. 
Published: November 2022

SUMMARYMicroRNAs (miRNAs) are short RNAs that regulate fundamental biological processes. miR-132, a key miRNA with established functions in Tau homeostasis and neuroprotection, is consistently downregulated in Alzheimer’s disease (AD) and other tauopathies. miR-132 overexpression rescues neurodegenerative phenotypes in several AD models. To complement research on miRNA-mimicking oligonucleotides targeting the central nervous system, we developed a high-throughput-screen coupled high-throughput-sequencing (HTS-HTS) in human induced pluripotent stem cell (iPSC)-derived neurons to identify small molecule inducers of miR-132. We discovered that cardiac glycosides, which are canonical sodium-potassium ATPase inhibitors, selectively upregulated miR-132 in the sub-μM range. Coordinately, cardiac glycoside treatment downregulated total and phosphorylated Tau in rodent and human neurons and protected against toxicity by glutamate, N-methyl-D-aspartate, rotenone, and Aβ oligomers. In conclusion, we identified small-molecule drugs that upregulated the neuroprotective miR-132 and ameliorated neurodegenerative phenotypes. Our dataset also represents a comprehensive resource for discovering small molecules that modulate specific miRNAs for therapeutic purposes.
Making waves: Comparative analysis of gene drive spread characteristics in a continuous space model
Authors: Pan Mingzuyu , Champer Jackson 
Published: November 2022

AbstractWith their ability to rapidly increase in frequency, gene drives can be used to modify or suppress target populations after an initial release of drive-containing individuals. Recent advances in this field have revealed many possibilities for different types of drives, and several of these have been realized in experimental demonstrations. These drives all have unique advantages and disadvantages related to their ease of construction, confinement, and capacity to act as a modification or suppression system. While many properties of these drives have been explored in modelling studies, assessment of these drives in continuous space environments has been limited, often focusing on outcomes rather than fundamental properties. Here, we conduct a comparative analysis of many different gene drive types that have the capacity to form a wave of advance against wild-type alleles in one-dimensional continuous space. We evaluate the drive wave speed as a function of drive performance and ecological parameters, which reveals substantial differences between drive performance in panmictic versus spatial environments. In particular, we find that suppression drive waves are uniquely vulnerable to fitness costs and undesired CRISPR cleavage activity that can form resistance alleles in embryos by maternal deposition. Some drives, though, retain robust characteristics even with widely varying performance characteristics. To gain a better understanding of drive waves, we compare panmictic performance of drives across the full range of drive frequencies. We find that rates of wild-type allele removal in panmictic setting is correlated with drive wave speed, though this is also affected by a range of other factors. Overall, our results provide a useful resource for understanding the performance of drives in continuous spatial environments, which may be most representative of potential drive deployment in many relevant scenarios.
Retinitis pigmentosa associated mutations in mouse Prpf8 cause misexpression of circRNAs and degeneration of cerebellar granule neurons
Authors: Krausová Michaela , Kreplová Michaela , Banik Poulami , Kubovčiak Jan , Modrák Martin , Zudová Dagmar , Lindovský Jiří , Kubik-Zahorodna Agnieszka , Pálková Marcela , Kolář Michal , Prochazka Jan , Sedlacek Radislav , Staněk David 
Published: November 2022

AbstractA subset of patients suffering from a familial retinitis pigmentosa (RP) carry mutations in several spliceosomal components including PRPF8 protein. Here, we established two novel alleles of murinePrpf8that genocopy or mimic aberrant PRPF8 found in RP patients - the substitution p.Tyr2334Asn and an extended protein variant p.Glu2331ValfsX15. Homozygous mice expressing either of the aberrant Prpf8 variants developed within first 2 months progressive atrophy of the cerebellum due to extensive granule neuron loss. Comparison of transcriptome from pre-degenerative and degenerative tissues revealed a subset of circRNAs that were deregulated in all tissues and both Prpf8-RP mouse strains. To identify potential risk factors that sensitize cerebellum for Prpf8 mutations we monitored expression of several splicing proteins during first eight weeks. We observed downregulation of all selected splicing proteins in wild-type cerebellum, which coincided with neurodegeneration onset. The decrease in splicing protein expression was further pronounced in mouse strains expressing mutated Prpf8. Collectively, we propose a model where physiological reduction of spliceosomal components during postnatal tissue maturation sensitizes cells to expression of aberrant Prpf8 and the subsequent deregulation of circRNAs triggers neuron death.
Association of intrinsic functional connectivity between the locus coeruleus and salience network with attentional ability
Authors: Neal Joshua , Song Inuk , Katz Benjamin , Lee Tae-Ho 
Published: November 2022

ABSTRACTThe LC is a brainstem region associated with broad physiological and neural arousal as part of the release of norepinephrine, but it has increasingly been associated with multiple specific cognitive processes. These include sustained attention, deficits in which are associated with a variety of neuropsychological disorders. Neural models of attention deficits to date have focused on interrupted dynamics between the salience network (SAL) with the fronto-parietal network (FPN), which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings based on these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggest the LC may play this role. In this study, resting-state functional connectivity (FC) and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to the LC activity in the bilateral insula, anterior cingulate cortex (ACC), and bilateral ventral striatum, all regions associated with the SAL. Given previous findings that attention deficits may be caused by dysfunctions in network switching by the SAL, our findings here further suggest that dysfunction in LC signaling to the SAL may interfere with attention.
Preservation of prehearing spontaneous activity enables early auditory system development in deaf mice
Authors: Kersbergen Calvin J. , Babola Travis A. , Kanold Patrick O. , Bergles Dwight E. 
Published: November 2022

ABSTRACTIntrinsically generated neural activity propagates through the developing auditory system to promote maturation and refinement of sound processing circuits prior to hearing onset. This early patterned activity is induced by non-sensory supporting cells in the organ of Corti, which are highly interconnected through gap junctions containing connexin 26 (Gjb2). Although loss of function mutations inGjb2impair cochlear development and are the most common cause of congenital deafness, it is not known if these mutations disrupt spontaneous activity and the developmental trajectory of sound processing circuits in the brain. Here, we show in a new mouse model ofGjb2-mediated congenital deafness that cochlear supporting cells unexpectedly retained intercellular coupling and the capacity to generate spontaneous activity, exhibiting only modest deficits prior to hearing onset. This coordinated activation of IHCs led to coincident bursts of activity in central auditory neurons that will later process similar frequencies of sound. Despite alterations in the structure of the sensory epithelium, hair cells within the cochlea ofGjb2deficient mice were intact and central auditory neurons could be activated within appropriate tonotopic domains by loud sounds at hearing onset, indicating that early maturation and refinement of auditory circuits was preserved. Only after cessation of spontaneous activity following hearing onset did progressive hair cell degeneration and enhanced auditory neuron excitability manifest. This preservation of cochlear spontaneous activity in the absence of connexin 26 may increase the effectiveness of early therapeutic interventions to restore hearing.
PARK15/FBXO7 is dispensable for PINK1/Parkin mitophagy in iNeurons and HeLa cell systems
Authors: Kraus Felix , Goodall Ellen A. , Smith Ian R. , Jiang Yizhi , Paoli Julia C. , Adolf Frank , Zhang Jiuchun , Paulo Joao A. , Schulman Brenda A. , Harper J. Wade 
Published: November 2022

AbstractThe protein kinase PINK1 and ubiquitin ligase Parkin promote removal of damaged mitochondria via a feed-forward mechanism involving ubiquitin (Ub) phosphorylation (pUb), Parkin activation, and ubiquitylation of mitochondrial outer membrane proteins to support recruitment of mitophagy receptors. The ubiquitin ligase substrate receptor FBXO7/PARK15 is mutated in an early-onset parkinsonian-pyramidal syndrome. Previous studies have proposed a role for FBXO7 in promoting Parkin-dependent mitophagy. Here, we systematically examine the involvement of FBXO7 in depolarization andmtUPR-dependent mitophagy in the well-established HeLa and induced-neurons cell systems. We find that FBXO7-/-cells have no demonstrable defect in: 1) kinetics of pUb accumulation, 2) pUb puncta on mitochondria by super-resolution imaging, 3) recruitment of Parkin and autophagy machinery to damaged mitochondria, 4) mitophagic flux, and 5) mitochondrial clearance as quantified by global proteomics. Moreover, global proteomics of neurogenesis in the absence of FBXO7 reveals no obvious alterations in mitochondria or other organelles. These results argue against a general role for FBXO7 in Parkin-dependent mitophagy and point to the need for additional studies to define how FBXO7 mutations promote parkinsonian-pyramidal syndrome.