bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of adequate COVID-19 case definitions in the SARS-CoV-2 pandemic
Authors: Núñez Isaac , Caro-Vega Yanink , Belaunzarán-Zamudio Pablo F. 
Published: June 2021

AbstractBackgroundEpidemiologic case definitions serve a myriad of purposes during a pandemic, including contact tracing and monitoring disease trends. It is unknown how any COVID-19 case definition fares against the current gold standard of molecular or antigen tests.MethodsWe calculated the diagnostic properties of five COVID-19 definitions (three of the Mexican government and two of the WHO) using open data of suspected COVID-19 cases in Mexico City from March 24th 2020 until January 31st 2021.ResultsAll 1,632,420 people included in the analysis met the WHO suspected case definition (sensitivity 100%, specificity 0%). The WHO probable case definition was met by 1.4%, while the first and second Mexican suspected case had sensitivities of 61 and 62% and specificities of 58 and 62%, respectively. Confirmed case by epidemiological contact had a low sensitivity (33%) but slightly higher specificity (77%).ConclusionsCase definitions should maximize sensitivity, especially in a high-transmission area such as Mexico City. The WHO suspected case definition has the potential for detecting most symptomatic cases. We underline the need for routine evaluation of case definitions as new evidence arises to maximize their usefulness.
White Matter is Increased in the Brains of Adults with Neurofibromatosis 1
Authors: Wang Su , Friedman Jan M. , Suppa Per , Buchert Ralph , Mautner Victor-Felix 
Published: June 2021

ABSTRACTObjectiveTo characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with neurofibromatosis 1 (NF1).MethodsWe obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients.ResultsTotal brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1.InterpretationsOur findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.
Electoral processes and COVID-19 infections in Japan
Authors: Murata Shunsuke , Nagata Takashi , Ogata Soshiro , Nishimura Kunihiro , Hagihara Akihito 
Published: June 2021

AbstractElection campaigns and polling stations might be areas of potential infections; however, it is unknown whether elections can impact the spread of coronavirus disease (COVID-19). This study aimed to evaluate the association between election process and COVID-19 infection in Japan. Quasi-experimental design using time-series COVID-19 cases data with an election intervention. We chose the cities where elections for major and/or city/ward assembly members were held in 2021 January in Japan. The study period for each city spans one weeks before the start date of the election campaign and three weeks after the voting day (36 days). The daily number of patients testing positive for COVID-19. We used Poisson regression analysis with sandwich estimator to evaluate the association between election and the spread of COVID-19 infections. For Miyakojima City, we assessed the relationship between election and COVID-19 infections by using the Box-Jenkins autoregressive integrated moving average (ARIMA) model. We also estimated the instantaneous reproduction number (Rt) in the city. There were 17 cities that met the inclusion criteria. In all models with three types of different lag effects (i.e., 4, 9, and 14 days), election was not a significant predictor of COVID-19 infections in the 17 cities. For Miyakojima City, the autoregressive integrated moving average (0, 0, 0) with a lag of 14 (α=14) was the best model. The partial coefficient (ω) of the election was 11.91 (95% confidence interval: 3.10–20.72,P<0.001), indicating that the election was associated with an increase in the number of COVID-19 cases 14 days after the election campaign (mean: 12 cases/day). Rthovered far above 1 during and after the election campaign in Miyakojima. Although elections were associated with an increased number of COVID-19 cases in Miyakojima, this association was not verified in the analysis including all 17 cities. Therefore, if preventive measures prescribed by election guidelines are followed, elections do not necessarily relate to a spread of COVID-19 as long as the election process does not involve activities necessitating close contact.
Optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus controls locomotor movements in a mouse model of Parkinson’s disease
Authors: Fougère Maxime , van der Zouwen Cornelis Immanuel , Boutin Joël , Neszvecsko Kloé , Sarret Philippe , Ryczko Dimitri 
Published: June 2021

ABSTRACTIn Parkinson’s disease (PD), the loss of midbrain dopaminergic cells results in severe locomotor deficits such a gait freezing and akinesia. Growing evidence indicates that these deficits can be attributed to decreased activity in the Mesencephalic Locomotor Region (MLR), a brainstem region controlling locomotion. Clinicians are exploring deep brain stimulation of the MLR as a treatment option to improve locomotor function. The results are variable, from modest to promising. However, within the MLR, clinicians have targeted the pedunculopontine nucleus exclusively, while leaving the cuneiform nucleus unexplored. To our knowledge, the effects of cuneiform nucleus stimulation have never been determined in parkinsonian conditions in any animal model. Here, we addressed this issue in a mouse model of Parkinson’s disease based on bilateral striatal injection of 6-hydroxydopamine (6-OHDA), which damaged the nigrostriatal pathway and decreased locomotor activity. We show that selective optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus in mice expressing channelrhodopsin in a Cre-dependent manner in Vglut2-positive neurons (Vglut2-ChR2-EYFP mice) increased the number of locomotor initiations, increased the time spent in locomotion, and controlled locomotor speed. Using deep learning-based movement analysis, we found that limb kinematics of optogenetic-evoked locomotion in pathological conditions were largely similar to those recorded in freely moving animals. Our work identifies the glutamatergic neurons of the cuneiform nucleus as a potentially clinically relevant target to improve locomotor activity in parkinsonian conditions. Our study should open new avenues to develop targeted stimulation of these neurons using deep brain stimulation, pharmacotherapy or optogenetics.SIGNIFICANCE STATEMENTIn Parkinson’s disease, alleviating locomotor deficits is a challenge. Clinicians are exploring deep brain stimulation of the Mesencephalic Locomotor Region, a brainstem region controlling locomotion, but results are mixed. However, the best target in this region in Parkinson’s disease remains unknown. Indeed, this region which comprises the pedunculopontine and cuneiform nuclei, contains different cell types with opposing effects on locomotor output. Here, using a mouse model where midbrain dopaminergic cells were damaged by a neurotoxin, we demonstrate that optogenetic activation of glutamatergic neurons in the cuneiform nucleus increases locomotion, controls speed, and evokes limb movements similar to those observed during spontaneous locomotion in intact animals. Our study identifies a potentially clinically relevant target to improve locomotor function in Parkinson’s disease.
Eye-hand coordination during online reach corrections is task-dependent
Authors: de Brouwer Anouk J. , Spering Miriam 
Published: June 2021

AbstractTo produce accurate movements, the human motor system needs to deal with errors that can occur due to inherent noise, changes in the body, or disturbances in the environment. Here, we investigated the temporal coordination of rapid corrections of the eye and hand in response to a change in visual target location during the movement. In addition to a ‘classic’ double-step task in which the target stepped to a new position, participants performed a set of modified double-step tasks in which the change in movement goal was indicated by the appearance of an additional target, or by a spatial or symbolic cue. We found that both the absolute correction latencies of the eye and hand and the relative eye-hand correction latencies were dependent on the visual characteristics of the target change, with increasingly longer latencies in tasks that required more visual and cognitive processing. Typically, the hand started correcting slightly earlier than the eye, especially when the target change was indicated by a symbolic cue, and in conditions where visual feedback of the hand position was provided during the reach. Our results indicate that the oculomotor and limb-motor system can be differentially influenced by processing requirements of the task and emphasize that temporal eye-hand coordination is flexible rather than rigid.New & NoteworthyEye movements support hand movements in many situations. Here we used variations of a double-step task to investigate temporal coupling of corrective hand and eye movements in response to target displacements. Correction latency coupling depended on the visual and cognitive processing demands of the task. The hand started correcting before the eye, especially when the task required decoding a symbolic cue. These findings highlight the flexibility and task-dependency of eye-hand coordination.
A comprehensive series of temporal transcription factors in the fly visual system
Authors: Konstantinides Nikolaos , Rossi Anthony M. , Escobar Aristides , Dudragne Liébaut , Chen Yen-Chung , Tran Thinh , Jaimes Azalia Martinez , Özel Mehmet Neset , Simon Félix , Shao Zhiping , Tsankova Nadejda M. , Fullard John F. , Walldorf Uwe , Roussos Panos , Desplan Claude 
Published: June 2021

AbstractThe brain consists of thousands of different neuronal types that are generated through multiple divisions of neuronal stem cells. These stem cells have the capacity to generate different neuronal types at different stages of their development. In Drosophila, this temporal patterning is driven by the successive expression of temporal transcription factors (tTFs). While a number of tTFs are known in different animals and across various parts of the nervous system, these have been mostly identified by informed guesses and antibody availability. We used single-cell mRNA sequencing to identify the complete series of tTFs that specify most Drosophila medulla neurons in the optic lobe. We tested the genetic interactions among these tTFs. While we verify the general principle that tTFs regulate the progression of the series by activating the next tTFs in the series and repressing the previous ones, we also identify more complex regulations. Two of the tTFs, Eyeless and Dichaete, act as hubs integrating the input of several upstream tTFs before allowing the series to progress and in turn regulating the expression of several downstream tTFs. Moreover, we show that tTFs not only specify neuronal identity by controlling the expression of cell type-specific genes. Finally, we describe the very first steps of neuronal differentiation and find that terminal differentiation genes, such as neurotransmitter-related genes, are present as transcripts, but not as proteins, in immature larval neurons days before they are being used in functioning neurons; we show that these mechanisms are conserved in humans. Our results offer a comprehensive description of a temporal series of tTFs in a neuronal system, offering mechanistic insights into the regulation of the progression of the series and the regulation of neuronal diversity. This represents a proof-of-principle for the use of single-cell mRNA sequencing for the comparison of temporal patterning across phyla that can lead to an understanding of how the human brain develops and how it has evolved.
Emerging Hantaviruses in Central Argentina: first case of Hantavirus Pulmonary Syndrome caused by Alto Paraguay Virus and a novel orthohantavirus in Scapteromys aquaticus rodent
Authors: Bellomo Carla M , Alonso Daniel , Ricardo Tamara , Coelho Rocío , Kehl Sebastián , Periolo Natalia , Casas Natalia , Bergero Laura Cristina , Previtali María Andrea , Martinez Valeria Paula 
Published: June 2021

AbstractOrthohantaviruses are emerging rodent-borne pathogens that cause Hantavirus Pulmonary Syndrome in humans. They have a wide range of rodent reservoir hosts and are transmitted to humans through aerosolized viral particles generated by the excretions of infected individuals. Since the first description of HPS in Argentina, new hantaviruses have been reported throughout the country, most of which are pathogenic to humans.We present here the first HPS case infected with Alto Paraguay virus reported in Argentina. Until now, Alto Paraguay virus was considered a non-pathogenic orthohantavirus since it was identified in a rodent, Hollochilus chacarius. In addition to this, with the goal of identifying potential hantavirus host species in the province of Santa Fe, we finally describe a novel orthohantavirus found in the native rodent Scapteromys aquaticus, which differed from other hantaviruses described in the country so far.Our findings implicate an epidemiological warning regarding these new orthohantaviruses circulating in Central Argentina as well as new rodent species that must be considered as hosts from now on.
Perioperative antimicrobial prophylaxis in patients receiving antibiotic therapy
Authors: Yin Yiwei , Tesoro Eljim P , Gross Alan E , Mucksavage Jeffrey J 
Published: June 2021

AbstractObjectiveAntimicrobial prophylaxis is administered perioperatively to prevent surgical site infections. However, in patients who have already received antibiotics for the treatment of active infections prior to surgery, the risks and benefits of administering prophylactic antibiotics are unknown. We aimed to assess the necessity of perioperative prophylactic antibiotic administration in patients receiving antibiotic treatment for active infections.MethodThis was a retrospective, chart-review cohort study. Between January 2018 to May 2018, adult patients who underwent inpatient surgery at the University of Illinois Hospital and Health Sciences System, and were prescribed prophylactic antibiotics based on institutional protocol, while receiving antibiotic treatment within 48 hours prior to surgery, were included in the study. The primary endpoint was the rate of duplicative antibiotic therapy, which was defined as the administered prophylactic antibiotic (1) exhibiting similar or narrower bacterial coverage as the treatment antibiotic(s), and (2) given within the dose interval of the treatment antibiotic(s).ResultsA total of 158 patients were included in the study, of which 70 (44.3%) received duplicative antibiotic therapy, whereas 88 (55.7%) did not. Differences in the incidence of acute kidney injury, C. difficile infection, and surgery site infections were not statistically significant between the two groups.ConclusionWe found that it was common for patients receiving therapeutic systematic antibiotics to perioperatively be prescribed additional prophylactic antibiotics at our institution. However, additional prophylactic antibiotics can be unnecessary in decreasing the incidence of surgical site infections but may increase the risk of adverse reaction.
SARS-CoV-2 Spike protein binding of glycated serum albumin - its potential role in the pathogenesis of the COVID-19 clinical syndromes and bias towards individuals with pre-diabetes/type 2 diabetes & metabolic diseases
Authors: IIes Jason K , Zmuidinaite Raminta , Sadee Christoph , Gardiner Anna , Lacey Jonathan , Harding Stephen , Ule Jernej , Roblett Debra , Iles Ray K 
Published: June 2021

AbstractSince the immune response to SARS-CoV2 infection requires antibody recognition of the Spike protein, we used MagMix, a semi-automated magnetic rack to reproducibly isolate patient plasma proteins bound to a pre-fusion stabilised Spike and nucleocapsid proteins conjugated to magnetic beads. Once eluted, MALDI-ToF mass spectrometry identified a range of immunoglobulins, but also in Spike protein magnetic beads we found a high affinity for human serum albumin. Careful mass comparison revealed a preferential capture of advanced glycation end product (AGE) glycated human serum albumin by the pre-fusion Spike protein.The ability of bacteria and viruses to surround themselves with serum proteins is a recognised process of immune evasion. A lower serum albumin concentration is a reported feature of COVID-19 patients with severe symptoms and high probability of death. This binding preference of the Spike protein for AGE glycated serum albumin may contribute to immune evasion and influence the severity & pathology of SARS-COV2 towards acute respiratory distress. Thus, it can be hypothesised, contributing to the symptom severity bias and mortality risk for the elderly and those with (pre)diabetic and atherosclerotic/metabolic diseases who contract SARS-CoV2 infections.Graphic abstract
SOD1 Mediates Lysosome-to-Mitochondria Communication and its Dysregulation by Amyloid-β Oligomers
Authors: Norambuena Andrés , Sun Xuehan , Wallrabe Horst , Cao Ruofan , Sun Naidi , Pardo Evelyn , Shivange Nutan , Wang Dora Bigler , Post Lisa A. , Ferris Heather A. , Hu Song , Periasamy Ammasi , Bloom George S. 
Published: June 2021

AbstractAltered mitochondrial DNA (mtDNA) occurs in neurodegenerative disorders like Alzheimer’s disease (AD); how mtDNA synthesis is linked to neurodegeneration is poorly understood. We discovered Nutrient-induced Mitochondrial Activity (NiMA), an inter-organelle signaling pathway where nutrient-stimulated lysosomal mTORC1 activity regulates mtDNA replication in neurons by a mechanism sensitive to amyloid-β oligomers (AβOs), a primary factor in AD pathogenesis. Using 5-ethynyl-2’-deoxyuridine (EdU) incorporation into mtDNA of cultured neurons, along with photoacoustic and mitochondrial metabolic imaging of cultured neurons and mouse brains, we show these effects being mediated by mTORC1-catalyzed T40 phosphorylation of superoxide dismutase 1 (SOD1). Mechanistically, tau, another key factor in AD pathogenesis and other tauopathies, reduced the lysosomal content of the tuberous sclerosis complex (TSC), thereby increasing NiMA and suppressing SOD1 activity and mtDNA synthesis. AβOs inhibited these actions. Dysregulation of mtDNA synthesis was observed in fibroblasts derived from TS patients, who lack functional TSC and elevated SOD1 activity was also observed in human AD brain. Together, these findings imply that tau and SOD1 couple nutrient availability to mtDNA replication, linking mitochondrial dysfunction to AD.
Control of Arabidopsis shoot stem cell homeostasis by two antagonistic CLE peptide signalling pathways
Authors: Schlegel Jenia , Denay Grégoire , Pinto Karine Gustavo , Stahl Yvonne , Schmid Julia , Blümke Patrick , Simon Rüdiger 
Published: June 2021

AbstractStem cell homeostasis in plant shoot meristems requires tight coordiantion between stem cell proliferation and cell differentiation. In Arabidopsis, stem cells express the secreted dodecapeptide CLAVATA3 (CLV3), which signals through the leucine-rich repeat (LRR)–receptor kinase CLAVATA1 (CLV1) and related CLV1-family members to downregulate expression of the homeodomain transcription factor WUSCHEL (WUS). WUS protein moves from cells below the stem cell domain to the meristem tip and promotes stem cell identity, together with CLV3 expression, generating a negative feedback loop. How stem cell activity in the meristem centre is coordinated with organ initiation and cell differentiation at the periphery is unknown.We show here that the CLE40 gene, encoding a secreted peptide closely related to CLV3, is expressed in the SAM in differentiating cells in a pattern complementary to that of CLV3. CLE40 promotes WUS expression via BAM1, a CLV1-family receptor, and CLE40 expression is in turn repressed in a WUS-dependent manner. Together, CLE40-BAM1-WUS establish a second negative feedback loop. We propose that stem cell homeostasis is achieved through two intertwined pathways that adjust WUS activity and incorporate information on the size of the stem cell domain, via CLV3-CLV1, and on cell differentiation via CLE40-BAM1.
A need for time-varying models to suppress artefacts of tACS in the M/EEG
Authors: Bland Nicholas S. 
Published: June 2021

ABSTRACTRhythmic modulation of brain activity by transcranial alternating current stimulation (tACS) can entrain neural oscillations in a frequency- and phase-specific manner. However, large stimulation artefacts contaminate concurrent ‘online’ neuroimaging measures, including magneto- and electro-encephalography (M/EEG)—restricting most analyses to periods free from stimulation (‘offline’ aftereffects). While many published methods exist for removing artefacts of tACS from M/EEG recordings, they universally assume linear artefacts: either time-invariance (i.e., an artefact is a scaled version of itself from cycle to cycle) or sensor-invariance (i.e., artefacts are scaled versions of one another from sensor to sensor). However, heartbeat and respiration both nonlinearly modulate the amplitude and phase of these artefacts, predominantly via changes in scalp impedance. The spectral symmetry this introduces to the M/EEG spectra may lead to false-positive evidence for entrainment around the frequency of tACS, if not adequately suppressed. Good electrophysiological evidence for entrainment therefore requires that tACS artefacts are fully accounted for before comparing online spectra to a control (e.g., as might be observed during sham stimulation). Here I outline an approach to linearly solve templates for tACS artefacts, and demonstrate how event-locked perturbations to amplitude and phase can be introduced from simultaneous recordings of heartbeat and respiration—effectively forming time-varying models of tACS artefacts. These models are constructed for individual sensors, and can therefore be used in contexts with few EEG sensors and with no assumption of artefact collinearity. I also discuss the feasibility of this approach in the absence of simultaneous recordings of heartbeat and respiration traces.