bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topographic gradients define the projection patterns of the claustrum core and shell in mice
Authors: Marriott Brian A. , Do Alison D. , Zahacy Ryan , Jackson Jesse 
Published: September 2020

ABSTRACTThe claustrum is densely connected to the cortex and participates in brain functions such as attention and sleep. Although some studies have reported the widely divergent organization of claustrum projections, others describe parallel claustrocortical connections to different cortical regions. Therefore, the details underlying how claustrum neurons broadcast information to cortical networks remain incompletely understood. Using multicolor retrograde tracing we determined the density, topography, and co-projection pattern of fourteen claustrocortical pathways, in mice. We spatially registered these pathways to a common coordinate space and found that the claustrocortical system is topographically organized as a series of overlapping spatial modules, continuously distributed across the dorsoventral claustrum axis. The claustrum core projects predominantly to frontal-midline cortical regions, whereas the dorsal and ventral shell project to the cortical motor system and temporal lobe, respectively. Anatomically connected cortical regions receive common input from a subset of claustrum neurons shared by neighboring modules, whereas spatially separated regions of cortex are innervated by different claustrum modules. Therefore, each output module exhibits a unique position within the claustrum and overlaps substantially with other modules projecting to functionally related cortical regions. Claustrum inhibitory cells containing parvalbumin, somatostatin, and neuropeptide Y also show unique topographical distributions, suggesting different output modules are controlled by distinct inhibitory circuit motifs. The topographic organization of excitatory and inhibitory cell types may enable parallel claustrum outputs to independently coordinate distinct cortical networks.
Behavioral Time Scale Plasticity of Place Fields: Mathematical Analysis
Authors: Shouval Harel Z. , Cone Ian 
Published: September 2020

AbstractTraditional synaptic plasticity experiments and models depend on tight temporal correlations between pre- and postsynaptic activity. These tight temporal correlations, on the order of tens of milliseconds, are incompatible with significantly longer behavioral time scales, and as such might not be able to account for plasticity induced by behavior. Indeed, recent findings in hippocampus suggest that rapid, bidirectional synaptic plasticity which modifies place fields in CA1 operates at behavioral time scales. These experimental results suggest that presynaptic activity generates synaptic eligibility traces both for potentiation and depression, which last on the order of seconds. These traces can be converted to changes in synaptic efficacies by the activation of an instructive signal that depends on naturally occurring or experimentally induced plateau potentials. We have developed a simple mathematical model that is consistent with these observations. This model can be fully analyzed to find the fixed points of induced place fields, the convergence to these fixed points, and how these fixed points depend on system parameters such as the size and shape of presynaptic place fields, the animal’s velocity, and the parameters of the plasticity rule.
Selection of AVP-shortage patients as candidates for low-dose oral desmopressin administration
Authors: Takeuchi Takumi , Maki Kazuki , Okuno Yumiko , Hattori-Kato Mami , Mikami Koji 
Published: September 2020

AbstractIntroductionDiabetes insipidus (DI) is characterized by the excretion of large volumes of hypotonic urine and thirst due to an impaired ability to concentrate urine, leading to uncontrolled diuresis, which may cause life-threatening dehydration and electrolyte imbalances. Central DI is caused by the deficient secretion of the posterior pituitary antidiuretic hormone arginine vasopressin (AVP). Desmopressin (Deamino-8-D-AVP, the synthetic analogue of AVP, Minirinmelt®) is generally used to treat central DI. Desmopressin orally disintegrating tablets are recently administered to male patients with nocturia. We herein attempted to select male patients with an elevated nocturnal urinary frequency possibly due to a shortage of AVP. These patients may be good candidates for low-dose oral desmopressin administration.Patients and methodsSerum and spot urine osmolality, electrolytes, serum creatinine, casual blood glucose, plasma brain natriuretic polypeptide (BNP), and plasma AVP were measured at the same time in 97 elderly male patients with urinary symptoms under free water drinking. The International Prostate Symptom Score, Overactive Bladder Symptom Score, and frequency-volume charts at least twice were also evaluated.ResultsA binary plot of plasma AVP and serum osmolality indicated a region at which patients had relatively lower AVP considering higher serum osmolality. It was tentatively named the Desmopressin region. Twenty out of 97 (20.6 %) patients were in the Desmopressin region.No significant differences were observed in the frequency of administered urinary drugs or existing co-morbidities between patients in the Desmopressin and non-Desmopressin regions. Daily urine output did not exceed 3 L in any patient. Plasma AVP was lower, while serum osmolality and serum sodium were higher in patients in the Desmopressin region than in those in non-Desmopressin region. Furthermore, urine osmolality was slightly lower in patients in the Desmopressin region. No significant differences were observed in urine volume, urinary frequency, or urination questionnaire scores between both groups.ConclusionAVP-shortage patients may be selected for treatment with oral desmopressin based on measurements of serum osmolality and plasma AVP. After the exclusion of patients with marked hyperglycemia, decreased cardiac, or renal function, low-dose oral desmopressin may be administered to patients with an increased urine output, nocturia, elevated plasma osmolality, and relatively low plasma AVP.
Tonsillectomy Outcomes for Coblation versus Bipolar Diathermy Techniques in Adult Patients: A Systematic Review and Meta-Analysis
Authors: Alsaif Abdulmalik , Alazemi Mohammad , Kahlar Narvair , Karam Mohammad , Abul Ahmad , AlNaseem Abdulrahman , Almuhanna Abdulredha , Aldrees Turki 
Published: September 2020

AbstractIntroductionThere is no consensus on the most superior tonsillectomy technique in adult patients. Recent trials involving coblation technique have shown promising results.AimThe study aims to compare the outcomes of coblation versus bipolar diathermy in adult patients undergoing tonsillectomy.MethodsA systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a search of electronic information was conducted to identify all Randomised Controlled Trials (RCTs) as well as non-randomised studies comparing the outcomes of coblation versus bipolar diathermy in adult patients undergoing tonsillectomy. Reactionary haemorrhage, delayed haemorrhage and postoperative pain were primary outcome measures. Secondary outcome measures included a return to theatre, administration of analgesia, intraoperative bleeding, diet, the effect on tonsils (degree of healing of tonsillar fossae) and operation time. Fixed effects modelling was used for the analysis.ResultsFour RCTs and two non-randomised studies were identified enrolling a total of 1824 patients. There were no significant differences between the coblation and bipolar groups in terms of reactionary haemorrhage (Odds Ratio [OR] = 1.81, P = 0.51), delayed haemorrhage (OR = 0.72, P = 0.20) or postoperative pain by day 7 (standardised Mean Difference [MD] = -0.15, P = 0.45). For secondary outcomes, there were no differences noted in terms of intraoperative blood loss, diet and the number of cases returned to theatre. Administration of analgesia was reported to be either insignificant between the two groups or higher in the coblation group Also, the coblation group had longer operation time and greater healing effect on tonsillar tissue.ConclusionsCoblation is neither a superior or inferior option when compared to bipolar diathermy used in the current clinical practice for adult patients undergoing tonsillectomy as both techniques have similar haemorrhage rates and post-operative pain whilst also lengthening the operative time in coblation.Highlights-Coblation is neither inferior or superior compared to bipolar diathermy in adult tonsillectomy-Administration of analgesia either has insignificant difference or higher in the coblation group.-Coblation has a longer operative time than bipolar diathermy.
ATPase SRCAP is a new player in cell division, uncovering molecular aspects of Floating-Harbor syndrome
Authors: Messina Giovanni , Prozzillo Yuri , Delle Monache Francesca , Santopietro Maria Virginia , Atterrato Maria Teresa , Dimitri Patrizio 
Published: September 2020

AbstractFloating-Harbor syndrome (FHS) is a rare genetic disease affecting human development caused by heterozygous truncating mutations in theSrcapgene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. Using a combined approach, we studied the involvement of SRCAP protein in cell cycle progression in HeLa cells. In addition to the canonical localization in interphase nuclei, both SRCAP and itsDrosophilaorthologue DOMINO-A localized to the mitotic apparatus after nuclear envelope breakdown. Moreover, SRCAP and DOMINO-A depletion impaired mitosis and cytokinesis in human and Drosophila cells, respectively. Importantly, SRCAP interacted with several cytokinesis regulators at telophase, strongly supporting a direct role in cytokinesis, independent of its chromatin remodeling functions. Our results provide clues about previously undetected, evolutionarily conserved roles of SRCAP in ensuring proper mitosis and cytokinesis. We propose that perturbations in cell division contribute to the onset of developmental defects characteristic of FHS.SummarySignificance statementSrcapis the causative gene of the rare Floating Harbor syndrome (FHS). It encodes the ATPase SRCAP, the core catalytic subunit of the homonymous multiprotein chromatin-remodeling complex in humans, which promotes the exchange of canonical histone H2A with the H2A.Z variant. According to the current view on SRCAP protein functions, FHS is caused by chromatin remodeling defects. Our findings suggest that, in addition to the established function as epigenetic regulator, SRCAP plays previously undetected and evolutionarily conserved roles in cell division. Hence, we propose that perturbations in cell division produced by SRCAP mutations are important causative factors co-occurring at the onset of FHS.
GR chaperone cycle mechanism revealed by cryo-EM: reactivation of GR by the GR:Hsp90:p23 client-maturation complex
Authors: Noddings Chari M. , Wang Ray Yu-Ruei , Agard David A. 
Published: September 2020

AbstractHsp90 is a conserved and essential molecular chaperone responsible for the folding and activation of hundreds of ‘client’ proteins1,2. The glucocorticoid receptor (GR) is a model client that constantly depends on Hsp90 for activity3. Previously, we revealed GR ligand binding is inhibited by Hsp70 and restored by Hsp90, aided by the cochaperone p234. However, a molecular understanding of the chaperone-induced transformations that occur between the inactive Hsp70:Hsp90 ‘client-loading complex’ and an activated Hsp90:p23 ‘client-maturation complex’ is lacking for GR, or for any client. Here, we present a 2.56Å cryo-EM structure of the GR-maturation complex (GR:Hsp90:p23), revealing that the GR ligand binding domain is, surprisingly, restored to a folded, ligand-bound conformation, while simultaneously threaded through the Hsp90 lumen. Also, unexpectedly, p23 directly stabilizes native GR using a previously uncharacterized C-terminal helix, resulting in enhanced ligand-binding. This is the highest resolution Hsp90 structure to date and the first atomic resolution structure of a client bound to Hsp90 in a native conformation, sharply contrasting with the unfolded kinase:Hsp90 structure5. Thus, aided by direct cochaperone:client interactions, Hsp90 dictates client-specific folding outcomes. Together with the GR-loading complex structure (Wang et al. 2020), we present the molecular mechanism of chaperone-mediated GR remodeling, establishing the first complete chaperone cycle for any client.
Self-collected Saline Gargle Samples as an Alternative to Healthcare Worker Collected Nasopharyngeal Swabs for COVID-19 Diagnosis in Outpatients
Authors: Goldfarb David M. , Tilley Peter , Al-Rawahi Ghada N. , Srigley Jocelyn A. , Ford Geoffrey , Pedersen Heather , Pabbi Abhilasha , Hannam-Clark Stephanie , Charles Marthe , Dittrick Michelle , Gadkar Vijay J. , Pernica Jeffrey M. , Hoang Linda M. N. 
Published: September 2020

AbstractBackgroundWe assessed the performance, stability, and user acceptability of swab-independent self-collected saliva and saline mouth rinse/gargle sample types for the molecular detection of SARS-CoV-2 in adults and school-aged children.MethodsOutpatients who had recently been diagnosed with COVID-19 or were presenting with suspected COVID-19 were asked to have a nasopharyngeal swab collected and provide at least one self-collected sample type. A portion of participants were also asked about sample acceptability. Samples underwent molecular testing using multiple assays. Saline mouth rinse/gargle and saliva samples were tested daily at time zero, day one, and day 2 to assess nucleic acid stability at room temperature.Results50 participants (aged 4 to 71 years) were included; of these, 40 had at least one positive sample and were included in the primary sample yield analysis. Saline mouth rinse/gargle samples had a sensitivity of 98% (39/40) while saliva samples had a sensitivity of 79% (26/33). Both saline mouth rinse/gargle and saliva samples showed stable viral RNA detection after 2 days of room temperature storage. Mouth rinse/gargle samples had the highest (mean 4.9) and HCW-collected NP swabs had the lowest acceptability scores (mean 3.1).ConclusionSaline mouth rinse/gargle samples demonstrated the highest combined user acceptability ratings and analytical performance when compared with saliva and HCW collected NP swabs. This sample type is a promising swab-independent option, particularly for outpatient self-collection in adults and school aged children.
Coblation versus Bipolar Diathermy Hemostasis in Pediatric Tonsillectomy Patients: Systematic Review and Meta-Analysis
Authors: Karam Mohammad , Abul Ahmad , Althuwaini Abdulwahab , Alenezi Talal , Aljadi Ali , Almuhanna Abdulredha , AlNaseem Abdulrahman , Alsaif Abdulmalik , Alwael Athari 
Published: September 2020

AbstractObjectiveTo compare the outcomes of coblation versus bipolar in pediatric patients undergoing tonsillectomy.MethodsA systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and an electronic search of information was conducted to identify all Randomized Controlled Trials (RCTs) comparing the outcomes of coblation versus bipolar in pediatric patients undergoing tonsillectomy. Intraoperative bleeding, reactionary hemorrhage, delayed hemorrhage and post-operative pain were primary outcome measures. Secondary outcome measures included return to normal diet, effects on tonsillar bed, operation time and administration of analgesia. Fixed and random effects models were used for the analysis.ResultsSeven studies enrolling 1328 patients were identified. There was a significant difference between coblation and bipolar groups in terms of delayed hemorrhage (Odds Ratio [OR] = 0.25, P = 0.0007) and post-operative pain (standardized mean difference [MD] = -2.13, P = 0.0007). Intraoperative bleeding (MD = -43.26, P = 0.11) and reactionary hemorrhage did not show any significant difference. For secondary outcomes, coblation group had improved outcomes in terms of administration of analgesia, diet and tonsillar tissue recovery and thermal damage. No significant difference was reported in terms of operation time.ConclusionsCoblation is a superior option when compared to bipolar technique for pediatric patients undergoing tonsillectomy as it improves post-operative pain and delayed hemorrhage and does not worsen intraoperative bleeding and reactionary hemorrhage.Highlights-Coblation tonsillectomy was less painful than bipolar diathermy.-Coblation tonsillectomy was associated with less delayed hemorrhage than bipolar diathermy.-Tonsillar tissue recovery, thermal damage and return to normal diet were better in the coblation group.
Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome
Authors: Song Yuyao , Yang Hongbo , Wang Linjie , Gong Fengying , Pan Hui , Zhu Huijuan 
Published: September 2020

AbstractIntroductionShort stature and thyroid autoimmunity are among the most common traits in Turner syndrome (TS). Recombinant human growth hormone (rhGH) treatment benefits height growth in Turner syndrome individuals when applicable. This study aims to investigate the association of thyroid autoimmunity and the response to rhGH treatment in Turner Syndrome patients.MethodsMedical records of 494 patients with TS were reviewed. Among 126 patients who regularly tested for thyroid autoantibodies, 108 patients had received rhGH treatment. Clinical characteristics, including karyotype and the presence of autoimmune thyroid diseases, as well as rhGH treatment records were analyzed. Height velocity (HV) of patients with or without thyroid autoimmunity was compared to assess the response to rhGH treatment. For patients who received rhGH treatment and positive for thyroid autoantibodies, height velocity before and after antibody presence was compared.Results45XO monosomy presented in 36% (176/496) of patients. 42.1% of patients (53/126) had elevated circulating anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb). In 108 patients who received rhGH treatment, a negative correlation was found between circulating TPOAb concentration and HV (n=53, r = -0.276, P<0.05). For patients who developed thyroid autoantibodies during rhGH treatment, HVs after thyroid autoantibody presence significantly decreased compared with HVs before thyroid autoantibody detection (n=44, p=0.0017).ConclusionsOur data suggested that in preadult TS patients who developed thyroid autoantibodies during rhGH treatment, the response to rhGH is negatively associated with the development of thyroid autoimmunity.
A Full-Scale Agent-Based Model of Lombardy COVID-19 Dynamics to Explore Social Networks Connectivity and Vaccine Impact on Epidemic
Authors: Giacopelli Giuseppe 
Published: September 2020

ABSTRACTSeptember 13, 2020COVID-19 outbreak is an awful event. However it gives to the scientists the possibility to test theories about epidemic. The aim of this contribution is to propose a individual-based model of Lombardy COVID-19 outbreak at full-scale, where full-scale means that will be simulated all the 10 millions inhabitant population of Lombardy person by person, in a commercial computer. All this to test the impact of our daily actions in epidemic, investigate social networks connectivity and in the end have an insight on the impact of an hypothetical vaccine.
Screening electrocardiogram in young athletes and military members: a systematic review and meta-analysis
Authors: Lear Aaron , Patel Niraj , Mullen Chanda , Simonson Marian , Leone Vince , Koshiaris Constantinos , Nunan David 
Published: September 2020

AbstractObjectiveTo determine the effect of electrocardiogram (ECG) screening on prevention of sudden cardiac arrest and death (SCA/D) in young athletes and military members.DesignSystematic review and meta-analysisData SourcesMEDLINE, Embase, Cochrane CENTRAL, Web of Science, BIOSIS, Scopus, SPORT discus, PEDro, were searched from inception to date searched between 2/21/19 and 3/1/19, and Clinicaltrials.gov on 7/29/19. All databases were searched without limits on language.Eligibility criteria for selected studiesRandomized and non-randomized controlled trials, where pre-participation examination including ECG was the primary intervention used to screen athletes or military 40 years of age or younger. Accepted controls were no screening, usual care, or pre-participation examination without ECGResults4 studies (11,689,172 participants) were included, all at high risk of bias. Pooled data from two studies (n= 3,869,274; very low quality) showed a 42% relative decrease in sudden cardiac death, equating to an absolute risk reduction of.0016%. Uncertainty was high, with a potential 67% relative decrease to a 45% relative increase in those screened with ECG based on 95% confidence intervals (RR 0.58; 95%CI 0.23, 1.45). Heterogeneity was found to be high as measured with I2statistic (71%).ConclusionThere is very low quality evidence ECG screening decreases risk of sudden cardiac death in young athletes and military members. Decisions need to consider evidence that ECG screening could also increase risk of sudden cardiac death based on the findings of meta-analysis.PROSPERO Registration:CRD42019125560
Q-STARZ: Quantitative Spatial and Temporal Assessment of Regulatory element activity in Zebrafish
Authors: Bhatia Shipra , Kleinjan Dirk Jan , Uttley Kirsty , Mann Anita , Dellepiane Nefeli , Bickmore Wendy A. 
Published: September 2020

ABSTRACTNoncoding regions of the genome harbouring cis-regulatory elements (CREs) or enhancers drive spatial and temporal gene expression. Mutations or single nucleotide polymorphisms (SNPs) in enhancers have been widely implicated in human diseases and disease-predispositions. However, our ability to assay the regulatory potential of genetic variants in enhancers is currently very limited, in part because of the need to assay these elements in an appropriate biological context. Here, we describe a method for simultaneous quantitative assessment of the spatial and temporal activity of wild-type (Wt) and disease-associated, mutant (Mut) human CRE alleles using live imaging in zebrafish embryonic development. We generated transgenic lines harbouring a dual-CRE dual-reporter cassette in a pre-defined neutral docking site in the zebrafish genome. Using this single transgenic cassette, the functional activity of each CRE allele is reported via expression of a specific fluorescent reporter, allowing the simultaneous visualisation of the activity of both alleles. This can reveal where and when in embryonic development the wild-type allele is active and how this activity is altered by the disease-associated mutation.