bluuebunny/crossref_metadata_2025_split huggingface dataset:
BACILLARY LAYER DETACHMENT IN ACUTE VOGT–KOYANAGI–HARADA DISEASE
Authors: Agarwal Aniruddha , Freund K. Bailey , Kumar Aman , Aggarwal Kanika , Sharma Deeksha , Katoch Deeksha , Bansal Reema , Gupta Vishali ,   for the OCTA Study Group
Published: July 2020

Purpose:
To report the frequency, optical coherence tomography (OCT) findings, and visual and anatomic outcomes of patients with acute Vogt–Koyanagi–Harada disease presenting with the bacillary layer detachment (BLD) (intraretinal split at the photoreceptor inner segment myoid).

Methods:
This was a retrospective analysis of a consecutive series of patients with Vogt–Koyanagi–Harada disease having a minimum follow-up of 6 months. All patients had swept-source OCT, fluorescein angiography, and indocyanine green angiography performed at baseline. The characteristics of serial swept-source OCT were recorded and analyzed.

Results:
Sixty-two subjects (42 women; age: 34.2 ± 12 years) with Vogt–Koyanagi–Harada disease were included. 118 eyes (95.2%) had serous retinal detachment at presentation. 112 eyes (94.9%) showed the BLD at baseline. In 8 of 112 (7.1%) eyes with the BLD, the external limiting membrane at the anterior aspect of the BLD showed focal discontinuity. The interdigitation zone at the base of the BLD showed discontinuity in 53 of 112 (47.3%) eyes with the BLD. The ellipsoid zone could not be identified as a separate hyperreflective line at the base of the BLD in 102 of 112 eyes (91.1%). Bacillary layer detachments resolved within 3.4 ± 1.3 days after intravenous methylprednisolone therapy with improvement in the best-corrected visual acuity from 0.96 to 0.4 logarithm of the minimum angle of resolution (20/184 Snellen's equivalent) (P < 0.001). Resolution of serous retinal detachment was observed after 5.9 ± 2.6 days.

Conclusion:
In eyes with acute Vogt–Koyanagi–Harada disease, the BLD is a common finding and represents a split in the photoreceptor layer at the inner segment myoid and can be differentiated from serous retinal detachment using swept-source OCT. In addition, resolution of the BLD and photoreceptor recovery can be evaluated using serial swept-source OCT.
The Trans-omics Landscape of COVID-19
Authors: Wu Peng , Chen Dongsheng , Ding Wencheng , Wu Ping , Hou Hongyan , Bai Yong , Zhou Yuwen , Li Kezhen , Xiang Shunian , Liu Panhong , Ju Jia , Guo Ensong , Liu Jia , Yang Bin , Fan Junpeng , He Liang , Sun Ziyong , Feng Ling , Wang Jian , Wu Tangchun , Wang Hao , Cheng Jin , Xing Hui , Meng Yifan , Li Yongsheng , Zhang Yuanliang , Luo Hongbo , Xie Gang , Lan Xianmei , Tao Ye , Yuan Hao , Huang Kang , Sun Wan , Qian Xiaobo , Li Zhichao , Huang Mingxi , Ding Peiwen , Wang Haoyu , Qiu Jiaying , Wang Feiyue , Wang Shiyou , Zhu Jiacheng , Ding Xiangning , Chai Chaochao , Liang Langchao , Wang Xiaoling , Luo Lihua , Sun Yuzhe , Yang Ying , Zhuang Zhenkun , Li Tao , Tian Lei , Zhang Shaoqiao , Zhu Linnan , Chen Lei , Wu Yiquan , Ma Xiaoyan , Chen Fang , Ren Yan , Xu Xun , Liu Siqi , Wang Jian , Yang Huanming , Wang Lin , Sun Chaoyang , Ma Ding , Jin Xin , Chen Gang 
Published: July 2020

SummarySystem-wide molecular characteristics of COVID-19, especially in those patients without comorbidities, have not been fully investigated. We compared extensive molecular profiles of blood samples from 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Amongst the major findings, asymptomatic patients were characterized by highly activated anti-virus interferon, T/natural killer (NK) cell activation, and transcriptional upregulation of inflammatory cytokine mRNAs. However, given very abundant RNA binding proteins (RBPs), these cytokine mRNAs could be effectively destabilized hence preserving normal cytokine levels. In contrast, in critically ill patients, cytokine storm due to RBPs inhibition and tryptophan metabolites accumulation contributed to T/NK cell dysfunction. A machine-learning model was constructed which accurately stratified the COVID-19 severities based on their multi-omics features. Overall, our analysis provides insights into COVID-19 pathogenesis and identifies targets for intervening in treatment.
Quantifying Evolutionary Importance of Protein Sites: A Tale of Two Measures
Authors: Sharir-Ivry Avital , Xia Yu 
Published: July 2020

AbstractA key challenge in evolutionary biology is the accurate quantification of selective pressure on proteins and other biological macromolecules at single-site resolution. The evolutionary importance of a protein site under purifying selection is typically measured by the degree of conservation of the protein site itself. A possible alternative measure is the strength of the site-induced conservation gradient in the rest of the protein structure. However, the quantitative relationship between these two measures remains unknown. Here, we show that despite major differences, there is a strong linear relationship between the two measures such that more conserved protein sites also induce stronger conservation gradient in the rest of the protein. This linear relationship is universal as it holds for different types of proteins and functional sites in proteins. Our results show that the strong selective pressure acting on the functional site in general percolates through the rest of the protein via residue-residue contacts. Surprisingly however, catalytic sites in enzymes are the principal exception to this rule. Catalytic sites induce significantly stronger conservation gradients in the rest of the protein than expected from the degree of conservation of the site alone. The unique requirement for the active site to selectively stabilize the transition state of the catalyzed chemical reaction imposes additional selective constraints on the rest of the enzyme.
A disynaptic circuit in the globus pallidus controls locomotion inhibition
Authors: Aristieta Asier , Barresi Massimo , Lindi Shiva A. , Barriere Gregory , Courtand Gilles , de la Crompe Brice , Guilhemsang Lise , Gauthier Sophie , Fioramonti Stéphanie , Baufreton Jérôme , Mallet Nicolas P. 
Published: July 2020

AbstractBasal ganglia (BG) inhibit movement through two independent pathways, the indirect- and the hyperdirect-pathways. The globus pallidus (GP) has always been viewed as a simple relay within these two pathways, but its importance has changed drastically with the discovery of two functionally-distinct cell types, namely the prototypic and the arkypallidal neurons. Classic BG models suggest that all GP neurons receive GABAergic inputs from striato-pallidal indirect spiny projection neurons and glutamatergic inputs from subthalamic neurons. However, whether this synaptic connectivity scheme applies to both GP cell-types is currently unknown. Here, we optogenetically dissect the input organization of prototypic and arkypallidal neurons and further define the circuit mechanism underlying action inhibition in BG. Our results highlight that an increased activity of arkypallidal neurons is required to inhibit locomotion. Finally, this work supports the view that arkypallidal neurons are part of a novel disynaptic feedback loop that broadcast inhibitory control on movement execution.
Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles
Authors: Miyakawa Kei , Jeremiah Sundararaj Stanleyraj , Ohtake Norihisa , Matsunaga Satoko , Yamaoka Yutaro , Nishi Mayuko , Morita Takeshi , Saji Ryo , Nishii Mototsugu , Kimura Hirokazu , Hasegawa Hideki , Takeuchi Ichiro , Ryo Akihide 
Published: July 2020

AbstractSARS-CoV-2 neutralizing antibodies confer protective immunity against reinfection. We have developed a rapid test for screening SARS-CoV-2 neutralization antibodies using genome-free virus-like particles incorporated with a small luciferase peptide, HiBiT. Their entry into LgBiT-expressing target cells reconstitutes NanoLuc luciferase readily detected by a luminometer. This newly developed HiBiT-tagged Virus-like particle-based Neutralization Test (hiVNT) can readily quantify SARS-CoV-2 neutralizing antibodies within three hours with a high-throughput in a low biosafety setting. Moreover, the neutralizing activity obtained from hiVNT was highly consistent with that measured by the conventional neutralization test using authentic SARS-CoV-2. Furthermore, antibody responses to both viral spike and nucleocapsid proteins correlated with the neutralization activity assessed by hiVNT. Our newly-developed hiVNT could be instrumental to survey individuals for the presence of functional neutralizing antibody against SARS-CoV-2.
Importation of SARS-CoV-2 following the“semaine de relâche”and Québec’s COVID-19 burden - a mathematical modeling study
Authors: Godin A , Xia Y , Buckeridge DL , Mishra S , Douwes-Schultz D , Shen Y , Lavigne M , Drolet M , Schmidt AM , Brisson M , Maheu-Giroux M 
Published: July 2020

AbstractBackgroundThe Canadian epidemics of COVID-19 exhibit distinct early trajectories, with Québec bearing a very high initial burden. Thesemaine de relâche, or March break, took place two weeks earlier in Québec as compared to the rest of Canada. This event may have played a role in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to examine the role of case importation in the early transmission dynamics of SARS-CoV-2 in Québec.MethodsUsing detailed surveillance data, we developed and calibrated a deterministic SEIR-type compartmental model of SARS-CoV-2 transmission. We explored the impact of altering the number of imported cases on hospitalizations. Specifically, we investigated scenarios without case importation after March break, and as scenarios where cases were imported with the same frequency/timing as neighboring Ontario.ResultsA total of 1,544 and 1,150 returning travelers were laboratory-confirmed in Québec and Ontario, respectively (with symptoms onset before 2020-03-25). The cumulative number of hospitalizations could have been reduced by 55% (95%CrI: 51-59%) had no cases been imported after Québec’s March break. However, had Québec experienced Ontario’s number of imported cases, cumulative hospitalizations would have only been reduced by 12% (95%CrI: 8-16%).InterpretationOur results suggest that case importation played an important role in the early spread of COVID-19 in Québec. Yet, heavy importation of SARS-CoV-2 in early March could be insufficient to resolve interprovincial heterogeneities in cumulative hospitalisations. The importance of other factors-public health preparedness, responses, and capacity-should be investigated.
Examining COVID19 Positivity-Ratio Trends in US States from April-July: Are Rising Caseloads Attributable to ‘More Testing’ and Do State Political-Affiliations Play a Role?
Authors: Sen Bisakha P. , Padalabalanarayanan Sangeetha 
Published: July 2020

AbstractImportanceRising Covid19 cases in the US are attributed by some political leaders to more testing. Positivity-ratios (cases to tests ratio) in conjunction with cases and tests provide a better overview. However, comprehensive overviews of positivity-ratio patterns are scarce.ObjectiveTo examine trends in positivity-ratios, tests and cases by state from mid-April-mid-July. Further, to examine whether positivity-ratio patters are associated with state political-affiliations.MethodsState-level publicly available data on Covid19 is used. Seven-day moving averages (MA7) of positivity-ratio are computed for April 21-July 15. States are assigned to four groups based on patterns of change in positivity-ratio – higher at end of study period than beginning (Group 1), initial decline but subsequent increase starting Memorial Day weekend (Group 2), initial decrease but an upturn in last 14 days (Group 3), and consistent downward trend (Group 4). ‘Political-affiliation’ is categorized as ‘Republican-leaning’ if President Trump won the state and the governor is Republican. Additionally, a proxy measure is used to indicate intensity of Black Lives Matter (BLM) protests in the state. Associations are tested using chi-square analysis.ResultsFourteen states are in Group 1, fifteen states in Group 2, fifteen states in Group 3, and six states and DC in Group 4. 78.57% of Group 1, 33.33% of Group 2, 40% of group 3, and none in Group 4 were Republican-leaning. The difference in distribution was statistically significant (p<0.01). Distribution of ‘high’ intensity BLM protests across the four groups was not statistically different (p>0.10).ConclusionIncreased Covid19 cases cannot be attributed to more testing. Indeed, the high positivity-ratios in most states indicate current testing is failing to capture actual infection rates. The association between state political-affiliation and positivity-ratios suggests Republican voters may be somewhat more skeptical of the gravity of the disease and emphasizes the importance of messaging by political leaders.
Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study
Authors: Nolan Amber L. , Petersen Cathrine , Iacono Diego , Mac Donald Christine L. , Mukherjee Pratik , van der Kouwe Andre , Jain Sonia , Stevens Allison , Diamond Bram R. , Wang Ruopeng , Markowitz Amy J. , Fischl Bruce , Perl Daniel P. , Manley Geoffrey T. , Keene C. Dirk , Diaz-Arrastia Ramon , Edlow Brian L. ,   the TRACK-TBI Investigators
Published: July 2020

AbstractDiffusion tractography MRI can infer changes in network connectivity in patients with traumatic brain injury (TBI), but pathological substrates of disconnected tracts have not been well-defined due to a lack of high-resolution imaging with histopathological validation. We developed anex vivoMRI protocol to analyze tract terminations at 750 μm resolution, followed by histopathologic evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein and loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with neurofilament loss.Ex vivodiffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.
A Visuomotor Model Enhances Human Position Sense
Authors: Omprakash Charitha , Razavizadeh Seyedsina , Stenner Max-Philipp 
Published: July 2020

AbstractIntegrating information from multiple sources reduces uncertainty. Besides sensory input, animals have access to another source of information about their body and the environment, i.e., their own motor commands, which alter the body and environment in a predictable way. Does this predictability reduce perceptual uncertainty, i.e., variance? Participants moved their unseen arm and reported movement endpoint locations. In two conditions, a predictive model of visuomotor contingencies could either be fully formed, and used for this estimation, or remained incomplete. This was achieved through context trials that provided visual endpoint feedback at a predictable vs. unpredictable latency, while carrying identical spatial information. In two experiments, we found that endpoint estimation was less variable when a full, spatiotemporal, model could be formed. Higher perceptual precision was paralleled by enhanced movement accuracy. We conclude that a visuomotor model provides a separate source of information, additional to sensory input, which enhances human position sense.
An aberrant cytoplasmic intron retention programme is a blueprint for ALS-related RBP mislocalization
Authors: Tyzack Giulia E. , Neeves Jacob , Klein Pierre , Crerar Hamish , Ziff Oliver , Taha Doaa M. , Luisier Raphaëlle , Luscombe Nicholas M , Patani Rickie 
Published: July 2020

SUMMARYWe recently described aberrant cytoplasmic SFPQ intron-retaining transcripts (IRTs) and concurrent SFPQ protein mislocalization as a new hallmark of amyotrophic lateral sclerosis (ALS). However the generalizability and potential roles of cytoplasmic IRTs in health and disease remain unclear. Here, using time-resolved deep-sequencing of nuclear and cytoplasmic fractions of hiPSCs undergoing motor neurogenesis, we reveal that ALS-causing VCP gene mutations lead to compartment-specific aberrant accumulation of IRTs. Specifically, we identify >100 IRTs with increased cytoplasmic (but not nuclear) abundance in ALS samples. Furthermore, these aberrant cytoplasmic IRTs possess sequence-specific attributes and differential predicted binding affinity to RNA binding proteins (RBPs). Remarkably, TDP-43, SFPQ and FUS – RBPs known for nuclear-to-cytoplasmic mislocalization in ALS – avidly and specifically bind to this aberrant cytoplasmic pool of IRTs, as opposed to any individual IRT. Our data are therefore consistent with a novel role for cytoplasmic IRTs in regulating compartment-specific protein abundance. This study provides new molecular insight into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets.Abstract Figure
V-ATPase controls tumor growth and autophagy in aDrosophilamodel of gliomagenesis
Authors: Formica Miriam , Storaci Alessandra , Bertolini Irene , Vaira Valentina , Vaccari Thomas 
Published: July 2020

AbstractGlioblastoma (GBM), a very aggressive and incurable tumor, often results from constitutive activation of EGFR (epidermal growth factor receptor) and of PI3K (phosphoinositide 3-kinase). To understand the role of autophagy in the pathogenesis of glial tumorsin vivo, we used an establishedDrosophila melanogastermodel of glioma based on overexpression in larval glial cells of an active humanEGFRand of the PI3K homologDp110. Interestingly, the resulting hyperplastic glia expresses high levels of ref(2)P (refractory to Sigma P), theDrosophilahomolog of p62/SQSTM1. However, cellular clearance of autophagic cargoes appears inhibited upstream of autophagosome formation. Remarkably, downregulation of subunits of the vacuolar-H+-ATPase (V-ATPase) prevents overgrowth, reduces PI3K signaling and restores clearance. Consistent with evidence in flies, neurospheres from patients with high V-ATPase subunit expression show inhibition of autophagy. Altogether, our data suggest that autophagy is repressed during glial tumorigenesis and that V-ATPase could represent a therapeutic target against GBM.
Identifying loci under selection via explicit demographic models
Authors: Luqman Hirzi , Widmer Alex , Fior Simone , Wegmann Daniel 
Published: July 2020

AbstractAdaptive genetic variation is a function of both selective and neutral forces. To accurately identify adaptive loci, it is thus critical to account for demographic history. Theory suggests that signatures of selection can be inferred using the coalescent, following the premise that genealogies of selected loci deviate from neutral expectations. Here, we build on this theory to develop an analytical framework to identify Loci under Selection via explicit Demographic models (LSD). Under this framework, signatures of selection are inferred through deviations in demographic parameters, rather than through summary statistics directly, and demographic history is accounted for explicitly. Leveraging on the property of demographic models to incorporate directionality, we show that LSD can provide information on the environment in which selection acts on a population. This can prove useful in elucidating the selective processes underlying local adaptation, by characterising genetic trade-offs and extending the concepts of antagonistic pleiotropy and conditional neutrality from ecological theory to practical application in genomic data. We implement LSD via Approximate Bayesian Computation and demonstrate, via simulations, that LSD has i) high power to identify selected loci across a large range of demographic-selection regimes, ii) outperforms commonly applied genome-scan methods under complex demographies, and iii) accurately infers the directionality of selection for identified candidates. Using the same simulations, we further characterise the behaviour of isolation-with-migration models conducive to the study of local adaptation under regimes of selection. Finally, we demonstrate an application of LSD by detecting loci and characterising genetic trade-offs underlying flower colour inAntirrhinum majus.
Dentate spikes and external control of hippocampal function
Authors: Dvorak D. , Chung A. , Park E. H. , Fenton A. A. 
Published: July 2020

AbstractMouse hippocampus CA1 place-cell discharge typically encodes current location but during slow gamma dominance (SGdom), when slow gamma oscillations (30-50 Hz) dominate mid-frequency gamma oscillations (70-90 Hz) in CA1 local field potentials, CA1 discharge switches to represent distant recollected locations. We report that dentate spike type 2 (DSM) events initiated by MECII→DG inputs promote SGdomand change excitation-inhibition coordinated discharge in DG, CA3, and CA1, whereas type 1 (DSL) events initiated by LECII→DG inputs do not. Just before SGdom, LECII-originating slow gamma oscillations in dentate gyrus and CA3-originating slow gamma oscillations in CA1 phase and frequency synchronize at the DSMpeak when discharge within DG and CA3 increases to promote excitation-inhibition cofiring within and across the DG→CA3→CA1 pathway. This optimizes discharge for the 5-10 ms DG-to-CA1 neuro-transmission that coincides with SGdom. DSMproperties identify extrahippocampal control of SGdom, and a cortico-hippocampal mechanism that switches between memory-related modes of information processing.
Optical measurement of physiological sodium currents in the axon initial segment
Authors: Filipis Luiza , Canepari Marco 
Published: July 2020

ABSTRACTIn most neurons of the mammalian central nervous system, the action potential (AP) is triggered in the axon initial segment (AIS) by a fast Na+current mediated by voltage-gated Na+channels. The intracellular Na+increase associated with the AP has been measured using fluorescent Na+indicators, but with insufficient resolution to resolve the Na+current in the AIS. In this article, we report the critical improvement in temporal resolution of the Na+imaging technique allowing the direct experimental measurement of Na+currents in the AIS. We determined the AIS Na+current, from fluorescence measurements at temporal resolution of 100µs and pixel resolution of half a micron, in pyramidal neurons of the layer-5 of the somatosensory cortex from brain slices of the mouse. We identified a subthreshold current before the AP, a fast inactivating current peaking during the rise of the AP and a persistent current during the AP repolarisation. We correlated the kinetics of the current at different distances from the soma with the kinetics of the somatic AP. We quantitatively compared the experimentally measured Na+current with the current obtained by computer simulation of published NEURON models and we show how the present approach can lead to the correct estimate of the native behaviour of Na+channels. Thus, it is expected that the present method will be adopted to investigate the function of different channel types under physiological or pathological conditions.