bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cross-disciplinary integration of acupuncture and modern medicine: an analysis from the perspective of subject categories
Authors: Zhang Xin , Duan Zhiguang 
Published: November 2022

AbstractThe cross-disciplinary integration of acupuncture with modern medicine is an important guarantee to maintain its advantages. Based on 13896 acupuncture articles and 404726 references in the Web of Science Core Database, this paper analyzes the cross-disciplinary integration of acupuncture and modern medicine. It was found that the trend of cross-disciplinary integration between acupuncture and modern medicine is more and more obvious. Neurosciences, Anesthesiology, Oncology, Obstetrics & Gynecology, Psychiatry, and Gastroenterology & Hepatology are the subjects with the most crossover and integration, accounting for 56% of the total disciplines. At the same time, more studies have begun to use modern medical methods to study the mechanism of acupuncture. Biochemistry & Molecular Biology, Pharmacology & Pharmacy, and Medicine, Research & Experimental have been major areas of interdisciplinary collaboration in recent years. China, the United States, and South Korea are the three countries with the largest number of publications. Among them, Chinese scholars pay more attention to the role of acupuncture in the treatment of neurological diseases, Korean scholars pay more attention to drug acupuncture, especially bee venom acupuncture, and American scholars pay more attention to the role of acupuncture in pain management. However, acupuncture has less cross-disciplinary cooperation with heart and cardiovascular system, peripheral vascular disease, and even less with non-medical disciplines. Using modern medical technology and methods to carry out research on the mechanism of acupuncture and moxibustion and strengthen the cooperation with informatics, statistics, physics and other disciplines may be an important direction for the modernization of acupuncture.关键词: 针灸; 跨学科; 学科范围
Closed-loop neurostimulation for epilepsy leads to improved outcomes when stimulation episodes are delivered during periods with less epileptiform activity
Authors: Anderson Daria Nesterovich , Charlebois Chantel M. , Smith Elliot H. , Davis Tyler S. , Peters Angela Y. , Newman Blake J. , Arain Amir M. , Wilcox Karen S. , Butson Christopher R. , Rolston John D. 
Published: November 2022

ABSTRACTIn patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. When effective, this therapy, known as closed-loop responsive neurostimulation (RNS), produces long-lasting changes in brain dynamics that correlate with clinical outcomes. Since periods with frequent epileptiform activity are less conducive to neuroplasticity, we hypothesize that stimulation timing, specifically stimulation during brain states with less epileptiform activity, is critical in driving long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk epochs—that is, stimulation during periods with a low or high risk of generating seizures and less or more epileptiform activity—in a cohort of 40 patients treated with RNS. Patients were categorized into three groups: super responders (>90% reduction, n=10), intermediate responders (≥ 50% reduction and ≤ 90% reduction), n=19, and poor responders (<50% reduction, n=11). As hypothesized, in this retrospective study, seizure reduction (median 64.6% reduction at last follow-up) was correlated with more frequent stimulation during low-risk periods compared with high-risk periods. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results suggest that stimulation during low-risk periods may more readily induce plasticity that, in turn, facilitates network changes leading to long-term seizure reduction.One Sentence SummaryIncreased stimulation during periods of reduced seizure risk corresponds with improved therapy in responsive neurostimulation for epilepsy.
A Framework for Relating Natural Movement to Length and Quality of Life in Human and Non-human Animals
Authors: Hunter Iain , Leib Raz 
Published: November 2022

AbstractNatural movement is clearly related to health, however, it is also highly complex and difficult to measure. Most attempts to measure it focus on functional movements in humans, and while this a valid and popular approach, assays focussed on particular movements cannot capture the range of natural movement that occurs outside them. It is also difficult to use current techniques to compare movement across animal species. Interspecies comparison may be useful for identifying conserved biomechanical and/ or computational principles of movement that could inform human and veterinary medicine, plus several other fields of research. It is therefore important that research develops a system for quantifying movement in freely moving animals in natural environments and relating it to length and quality of life (LQOL). The present text proposes a novel theoretical framework for doing so, based on movement ability (MA).MAis comprised of three major variables – Movement Quality, Movement Complexity, and Movement Quantity – that may represent the most important components of movement as it relates to LQOL. A constrained version of the framework is validated inDrosophila, which suggests thatMAmay indeed represent a useful new paradigm for understanding the relationship between movement and length and quality of life.
Prevalence Of carbapenem resistance inAcinetobacter baumaniiandPseudomonas aeruginosain sub-Saharan Africa: a systematic review and meta-analysis
Authors: Arowolo Margaret Toluwalayo , Orababa Oluwatosin Qawiyy , Olaitan Morufat Oluwatosin , Osibeluwo Bisola Victoria , Essiet Utibeima Udo , Batholomew Olajumoke Hanah , Ogunrinde Oluwaseyi Gbotoluwa , Lagoke Oluwaseyi Aminat , Soriwei Jeffrey Difiye , Ishola Olanrewaju David , Ezeani Onyinye Maryann , Onishile Aminat Oyeronke , Olumodeji Elizabeth 
Published: November 2022

ABSTRACTBackgroundCarbapenems are drugs of last resort and resistance to them is considered a great public health threat, especially in notorious nosocomial pathogens likeAcinetobacter baumanniiandPseudomonas aeruginosa. In this study, we aimed to determine the prevalence of carbapenem resistance inA. baumanniiandP. aeruginosainfections in Sub-Saharan Africa.MethodsDatabases (PubMed, Scopus, Web of Science, and African Journal Online) were systematically searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2020 statements for articles reporting carbapenem-resistantAcinetobacter baumannii(CRAB) and carbapenem-resistantPseudomonas aeruginosa(CRPA) prevalence between 2012 and 2022. Pooled prevalence was determined with the random effect model in R.ResultsA total of 47 articles were scanned for eligibility, among which 25 (14 for carbapenem-resistantA. baumaniiand 11 for carbapenem-resistantP. aeruginosa) were included in the study after fulfilling the eligibility criteria. The pooled prevalence of CRPA in the present study was estimated at 8% (95% CI; 0.02 – 0.17; I2=98%; P <0.01). There was high heterogeneity (Q=591.71, I2=98.9%; P<0.0001). The pooled prevalence of CRAB in the present study was estimated at 20% (95% CI; 0.04 – 0.43; I2=99%; P <0.01). There was high heterogeneity (Q=1452.57, I2=99%; P<0.0001). Carbapenem-resistantA. baumanniiprevalence based on sample source gave estimates of 24% (95% CI; 6 – 49; I2=99%; P<0.01). The carbapenamse genes commonly isolated fromA. baumaniiin this study includeblaOXA23,blaOXA48,blaGES.,blaNDM,blaVIM,,blaOXA24,blaOXA58,blaOXA51,blaSIM-1,blaOXA40,blaOXA66,blaOXA69,blaOXA91, withblaOXA23andblaVIMbeing the most common. On the other hand, blaNDM,blaVIM, blaIMP,, blaOXA48, blaOXA51,blaSIM-1,blaOXA181,blaKPC,blaOXA23,blaOXA50were the commonly isolated carbapenemase genes inP. aeruginosa, among which blaVIMand blaNDMgenes were the most frequently isolated.ConclusionSurveillance of drug-resistant pathogens in sub-Saharan Africa is essential in reducing the disease burden in the region and this study has shown that the region has significantly high multi-drug resistant pathogen prevalence. This is a wake-up call for policymakers to put in place measures to reduce the spread of these critical priority pathogens.
Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits
Authors: Tang David , Freudenberg Jerome , Dahl Andy 
Published: November 2022

AbstractEpistasis is central in many domains of biology, but it has not yet proven useful for complex traits. This is partly because complex trait epistasis involves polygenic interactions that are poorly captured in current models. To address this gap, we develop a new model called Epistasis Factor Analysis (EFA). EFA assumes that polygenic epistasis can be factorized into interactions between a few Epistasis Factors (EFs), which represent latent polygenic components of the observed complex trait. The statistical goals of EFA are to improve polygenic prediction and to increase power to detect epistasis, while the biological goal is to unravel genetic effects into more-homogeneous units. We mathematically characterize EFA and use simulations to show that EFA outperforms current epistasis models when its assumptions approximately hold. Applied to predicting yeast growth rates, EFA outperforms the additive model for several traits with large epistasis heritability and uniformly outperforms the standard epistasis model. We replicate these prediction improvements in a second dataset. We then apply EFA to four previously-characterized traits in the UK Biobank and find statistically significant epistasis in all four, including two that are robust to scale transformation. Moreover, we find that the inferred EFs partly recover pre-defined biological pathways for two of the traits. Our results demonstrate that more realistic models can identify biologically and statistically meaningful epistasis in complex traits, indicating that epistasis has potential for precision medicine and characterizing the biology underlying GWAS results.
The RNA binding proteins hnRNP H and F regulate splicing of a MYC dependent HRAS exon in Prostate Cancer Cells
Authors: Chen Xinyuan , Yang Harry Taegyun , Zhang Beatrice , Phillips John W. , Cheng Donghui , Rigo Frank , Witte Owen N. , Xing Yi , Black Douglas L. 
Published: November 2022

ABSTRACTThe Myc proto-oncogene contributes to the pathogenesis of more than half of human cancers. Malignant transformation by Myc transcriptionally upregulates the core pre-mRNA splicing machinery and causes mis-regulation of alternative splicing. However, our understanding of how splicing changes are directed by Myc is limited. We performed a signaling pathway-guided splicing analysis to identify Myc dependent splicing events. These included an HRAS cassette exon repressed by Myc across multiple tumor types. To molecularly dissect the regulation of this HRAS exon, we used antisense oligonucleotide tiling to identify splicing enhancers and silencers in its flanking introns. RNA binding motif prediction indicated multiple binding sites for hnRNP H and hnRNP F within these cis-regulatory elements. Using siRNA knockdown and cDNA expression, we found that both hnRNP H and F activate the HRAS cassette exon.Mutagenesis and targeted RNA immunoprecipitation implicate two downstream G-rich elements in this splicing activation. Analyses of ENCODE RNA-seq datasets confirmed hnRNP H regulation of HRAS splicing. Analyses of RNA-seq datasets across multiple cancers showed a negative correlation of hnRNP H gene expression with Myc hallmark enrichment, consistent with the effect of hnRNP H on HRAS splicing. Interestingly, hnRNP F expression showed a positive correlation with Myc hallmarks and thus was not consistent with the observed effects of hnRNP F. Loss of hnRNP H/F altered cell cycle progression and induced apoptosis in the PC3 prostate cancer cell line. Collectively, our results reveal new mechanisms for Myc-dependent regulation of splicing, and point to new possible therapeutic targets in prostate cancers.SIGNIFICANCE STATMENTMyc Transformation by the proto-oncogene c-Myc causes dysregulation of the pre-mRNA splicing reaction in cancer, but it is not known how mRNA isoform changes are directed by Myc. Here, we use bioinformatics to identify a splicing event in another proto-oncogene, HRAS, that is regulated by Myc across multiple tumor types. We identify new splicing regulators, hnRNP’s H and F, that control this HRAS exon by binding to enhancer elements within its downstream intron. Additional pan-cancer bioinformatic analyses show hnRNP H expression to be anti- correlated with Myc hallmarks, consistent with the reduced splicing of the HRAS exon in Myc driven cancer. These findings uncover new mechanisms by which Myc can alter splicing in cancer cells and provide new molecular targets for potential therapeutics.
Acute effect of antiseizure drugs on background oscillations inScn1aA1783VDravet syndrome mouse model
Authors: Quinn Shir , Brusel Marina , Ovadia Mor , Rubinstein Moran 
Published: November 2022

AbstractObjectiveDravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. First-line treatment for DS patients includes valproic acid (VA) or clobazam with or without stiripentol (CLB+STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. As patients are rarely seizure-free, drug therapy focuses on reducing the seizure burden, as reported by caregivers. In addition to their effect on epileptic phenotypes, antiseizure medications (ASMs) were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alternations in Dravet.MethodsUtilizing Dravet mice (DS,Scn1aA1783V/WT), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes.ResultsCompared to wild-type mice, background ECoG activity in DS had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, including VA or a combination of CLB+STP, caused, in most mice, a reduction of frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands.SignificanceThese data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations and highlight a possible correlation between their effect on epilepsy and background activity. Thus, examining these properties, following an acute administration, may be used as an additional tool for rapid evaluation of the therapeutic potential of ASMs.Key PointsReduced background power and phase coherence in Dravet miceDS-recommended medicines (VA, CLB+STP) increase the relative beta powerDS-contraindicated drugs (CBZ, LTG) do not cause spectral changesCorrelation between reduction in background power and interictal spike frequencyCorrelation between theta to beta bands ratio and interictal spike frequency
Investigations into an overlooked early component of painful nociceptive withdrawal reflex responses in humans
Authors: Thorell Oumie , Ydrefors Johannes , Svantesson Mats , Gerdle Björn , Olausson Håkan , Mahns David A. , Nagi Saad S. 
Published: November 2022

AbstractIntroductionThe role of pain as a warning system necessitates a rapid transmission of information from the periphery for the execution of appropriate motor responses. The nociceptive withdrawal reflex (NWR) is a physiological response to protect the limb from a painful stimulus and is often considered an objective measure of spinal nociceptive excitability. The NWR is commonly defined by its latency in the presumed Ad-fiber range consistent with the canonical view that “fast pain” is signaled by Ad nociceptors. We recently demonstrated that human skin is equipped with ultrafast (Aβ range) nociceptors. Here, we investigated the short-latency component of the reflex and explored the relationship between reflex latency and pain perception.MethodsWe revisited our earlier work on NWR measurements in which, following convention, only those reflex responses were selected that were in the presumed Ad range (taken to be latencies ≥90 ms in that study). In our current analysis, we expanded the time window to search for shorter latency responses and compared those with pain ratings.ResultsIn both cohorts, we found an abundance of recordings with short-latency reflex responses. In nearly 90% of successful recordings, only single reflex responses (not dual) were seen which allowed us to compare pain ratings to reflex latencies. We found that shorter latency reflexes were just as painful as those in the conventional latency range.DiscussionWe found a preponderance of short-latency painful reflex responses. Based on this finding, we suggest that short-latency responses must be considered in future studies. We predict these might be signaled by the ultrafast nociceptors, warranting further investigation.
Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2
Authors: Gil Dácil Alonso , Cuadrado Ana , Giménez-Llorente Daniel , Rodríguez-Corsino Miriam , Losada Ana 
Published: November 2022

AbstractCohesin organizes the genome through the formation of chromatin loops. NIPBL activates cohesin’s ATPase and is essential for loop extrusion, but its requirement for cohesin loading is currently unclear. Here we have examined the effect of reducing NIPBL levels on the behavior of the two cohesin variants carrying STAG1 or STAG2 by combining a flow cytometry assay to measure chromatin-bound cohesin with analyses of its genome-wide distribution and genome contacts. We show that NIPBL depletion results in increased cohesin-STAG1 on chromatin that further accumulates at CTCF positions while cohesin-STAG2 diminishes genome-wide. Our data support a model in which NIPBL is not required for initial association of cohesin with chromatin but it is for loop extrusion, which in turn facilitates stabilization of cohesin-STAG2 at CTCF positions after being loaded elsewhere. In contrast, cohesin-STAG1 is loaded and stabilized at CTCF sites even under low NIPBL levels, but genome folding is severely impaired.
Rapid Phenotypic Detection of Carbapenem-ResistantE. coliwith Fluorogenic Culture Media
Authors: Makharashvili Nodar , McNamara James O. 
Published: November 2022

AbstractFaster, and simpler methods that determine the susceptibility of bacterial pathogens to antibiotics are needed to enable more effective treatment of bacterial infections and reduce the overuse of antibiotics. Here, we demonstrate a simple method for rapidly detecting bacteria and simultaneously determining their antibiotic susceptibility status. We demonstrate the method withE. coli, a high-impact pathogen, and meropenem, a member of the carbapenem class of antibiotics which is usually reserved for multi-drug resistant infections. Inclusion of a fluorogenic oligonucleotide substrate for endonuclease I, a well-conserved nuclease of the Enterobacteriaceae family, in a tryptic soy agar-based media enabled fluorescence-based detection ofE. coligrowth within 9 hours. Plating established carbapenem-resistant and -susceptibleE. colistrains on this media with and without inclusion of meropenem, followed by fluorescent imaging yielded a clear phenotypic measure of the antibiotic susceptibility status of the strains in 9 hours. In addition to its simplicity and fast turnaround time, advantages of this approach include its ability to provide a measure of the bacterial load of the tested samples, and its easy integration into current microbiology laboratory workflows.
Exploring the conformational changes of the Munc18-1/syntaxin 1a complex
Authors: Stefani Ioanna , Iwaszkiewicz Justyna , Fasshauer Dirk 
Published: November 2022

AbstractNeurotransmitters are released from synaptic vesicles, the membrane of which fuses with the plasma membrane upon calcium influx. This membrane fusion reaction is driven by the formation of a tight complex comprising the plasma membrane SNARE proteins syntaxin-1a and SNAP-25 with the vesicle SNARE protein synaptobrevin. The neuronal protein Munc18-1 forms a stable complex with syntaxin-1a. Biochemically, syntaxin-1a cannot escape the tight grip of Munc18-1, so formation of the SNARE complex is inhibited. However, Munc18-1 is essential for the release of neurotransmittersin vivo. It has therefore been assumed that Munc18-1 makes the bound syntaxin-1a available for SNARE complex formation. Exactly how this occurs is still unclear, but it is assumed that structural rearrangements occur. Here, we used a series of mutations to specifically weaken the complex at different critical positions in order to induce these rearrangements biochemically. Our approach was guided through sequence and structural analysis and supported by molecular dynamics simulations. Subsequently, we created a homology model showing the complex in an altered conformation. This conformation presumably represents a more open arrangement of syntaxin-1a that permits the formation of SNARE complex to be initiated while still bound to Munc18-1. In the future, research should investigate how this central reaction for neuronal communication is controlled by other proteins.
NaWRKY3 is a master transcriptional regulator of defense network againstAlternaria alternatainNicotiana attenuata
Authors: Xu Zhen , Zhang Shuting , Wu Jinsong 
Published: November 2022

AbstractWRKY transcription factors are involved in plant defense responses against pathogens. However, no WRKYs have been reported yet in resistance ofNicotianaspecies toAlternaria alternata, a necrotrophic fungal pathogen causing brown spot disease. Here, we found that silencingNaWRKY3lead to wild tobaccoNicotiana attenuatahighly susceptible toA. alternata. Combination of transcriptome, electrophoretic mobility shift, ChIP-qPCR and dual-LUC analyses, we uncovered that NaWRKY3 bound to many defense genes’ promoter and activated their expression. Target genes included: 1)lipoxygenases 3,ACC synthase 1andACC oxidase 1, three key enzyme genes for JA and ethylene biosynthesis which were critical forA. alternataresistance; 2)feruloyl-CoA 6’-hydroxylase 1(NaF6’H1), the key enzyme gene for phytoalexins againstA. alternata, scopoletin and scopolin; and 3) threeA. alternataresistance genes, long non-coding RNA (LncRNA L2),NADPH oxidase(NaRboh D) andberberine bridge-like(NaBBL28). SilencingLncRNA L2reducedA. alternata-induced levels of JA andNaF6’H1expression.NaRboh D-silenced plants were strongly impaired in ROS production and stomata closure responses.NaBBL28was the firstA. alternataresistance BBLs identified and was involved in HGL-DTGs hydroxylation. Finally, NaWRKY3 could bind to its own promoter but acted as a transcriptional repressor. Thus we demonstrated that NaWRKY3 is a fine-tuned master regulator of defense network againstA. alternatainN. attenuataby regulating different signaling pathways and defense metabolites. For the first time, such an important WRKY was identified inNicotianaspecies, providing new insight into defense mechanism ofNicotianaplants toA. alternata.