bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospitalized COVID-19 Patients treated with Convalescent Plasma in a Mid-size City in the Midwest
Authors: Hartman William , Hess Aaron S , Connor Joseph P 
Published: June 2020

AbstractBackgroundSARS-CoV-2 and its associated disease, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease. Here we report our experience of using convalescent plasma at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge.MethodsHospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease according to the Mayo Clinic Emergency Access Protocol were screened, consented, and treated with convalescent plasma collected from local donors recovered from COVID-19 infection. Clinical data and outcomes were collected retrospectively.Results31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease died. 94% of transfused patients with severe disease avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma transfusion.ConclusionOur results demonstrate that convalescent plasma is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease, but appears to be most beneficial when administered early in the course of disease when patients meet the criteria for severe illness.
Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
Authors: Chen Lan , Zhang Zhen-Yu , Fu Jian-Guo , Feng Zhi-Peng , Zhang Su-Zhen , Han Qiu-Ying , Zhang Xiao-Bin , Xiao Xiong , Chen Hui-Min , Liu Li-Long , Chen Xian-Li , Lan Yu-Pei , Zhong De-Jin , Hu Lan , Wang Jun-Hui , Yu Xing-Hua , She Dan-Yang , Zhu Yong-Hong , Yin Zhen-Yu 
Published: June 2020

ABSTRACTThe outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19.Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12).Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.
U2AF1is a haplo-essential gene required for cancer cell survival
Authors: Wadugu Brian A. , Heard Amanda , Srivatsan Sridhar N. , Alberti Michael O. , Ndonwi Matthew , Grieb Sarah , Bradley Joseph , Shao Jin , Ahmed Tanzir , Shirai Cara L. , Khanna Ajay , Fei Dennis L. , Miller Christopher A. , Graubert Timothy A. , Walter Matthew J. 
Published: June 2020

AbstractSomatic mutations in the spliceosome geneU2AF1are common in patients with myelodysplastic syndromes.U2AF1mutations that code for the most common amino acid substitutions are always heterozygous, and the retained wild-type allele is expressed, suggesting that mutant hematopoietic cells may require the residual wild-type allele to be viable and cause disease. We show that hematopoiesis and RNA splicing inU2af1heterozygous knock-out mice was similar to control mice, but that deletion of the wild-type allele in U2AF1(S34F) heterozygous mutant expressing hematopoietic cells (i.e., hemizygous mutant) was lethal. These results confirm that U2AF1 mutant hematopoietic cells are dependent on the expression of wild-type U2AF1 for survivalin vivoand thatU2AF1is a haplo-essential cancer gene. Mutant U2AF1 (S34F) expressing cells were also more sensitive to reduced, but not absent, expression of wild-type U2AF1 than non-mutant cells. Furthermore, mice transplanted with leukemia cells expressing mutant U2AF1 had significantly reduced tumor burden and improved survival after the wild-typeU2af1allele was deleted compared to when it was not deleted. These results suggest that selectively targeting the wild-typeU2AF1allele in heterozygous mutant cells could induce cancer cell death and be a therapeutic strategy for patients harboringU2AF1mutations.
Characterizing super-spreading events and age-specific infectiousness of SARS-CoV-2 transmission in Georgia, USA
Authors: Lau Max SY , Grenfell Bryan , Thomas Michael , Bryan Michael , Nelson Kristin , Lopman Ben 
Published: June 2020

It is imperative to advance our understanding of heterogeneities in the transmission of SARS-CoV-2 such as age-specific infectiousness and super-spreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatio-temporal mechanistic framework to integrate individual surveillance data with geo-location data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of SARS-CoV-2. We analyze reported cases, between March and early May 2020, in five (urban and rural) counties in the State of Georgia USA. First, our results show that the reproductive number reduced to below 1 in about two weeks after the shelter-in-place order. Super-spreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in rural areas and an increasing importance towards later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases were directly responsible for 20% of all infections. We estimate that the infected non-elderly cases (<60) may be 2.78 [2.10, 4.22] times more infectious than the elderly, and the former tend to be the main driver of super-spreading. Our results improve our understanding of the natural history and transmission dynamics of SARS-CoV-2. More importantly, we reveal the roles of age-specific infectiousness and characterize systematic variations and associated risk factors of super-spreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.Significance StatementThere is still considerable scope for advancing our understanding of the epidemiology and ecology of COVID-19. In particular, much is unknown about individual-level transmission heterogeneities such as super-spreading and age-specific infectiousness. We statistically synthesize multiple valuable datastreams, including surveillance data and mobility data, that are available during the current COVID-19 pandemic. We show that age is an important factor in the transmission of the virus. Super-spreading is ubiquitous over space and time, and has particular importance in rural areas and later stages of an outbreak. Our results improve our understanding of the natural history the virus and have important implications for designing optimal control measures.
Comparison of primer-probe sets among different master mixes for laboratory screening of Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2)
Authors: Cuong Hoang Quoc , Hai Nguyen Duc , Linh Hoang Thuy , Anh Nguyen Hoang , Hieu Nguyen Trung , Thang Cao Minh , Thao Nguyen Thi Thanh , Lan Phan Trong 
Published: June 2020

AbstractBackgroundThere is a shortage of chemical reagents for severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) diagnosis and a surge of SARS-CoV-2cases, especially in limited-resource settings. Therefore, the combination of an optimal assay kit is necessary.MethodsWe compared the ability to screen SARS-CoV-2 among three primer-probe sets in two different master mixes, Invitrogen™ SuperScript™ III One-Step RT-PCR and LightCycler Multiplex RNA Virus Master.ResultsThe assay with TIB-Molbiol, IDT, and Phu Sa sets for LightCycler Multiplex RNA Virus Master or Invitrogen™ SuperScript™ III One-Step RT-PCR showed positive results from a single reaction of triplicate in the three days of 4.8 copies per reaction. R-squared and amplification efficiency were 0.97 and ranged from 107 to 108%, respectively.ConclusionsOur findings indicated that TIB-Molbiol, IDT, and Phu Sa primer-probe sets could be beneficial for the laboratory screening of SARS-CoV-2 by RT-qPCR assay of E gene. There is a need to consider the combination of these reagent sets as a new strategy to increase the testing capacity of screening programs for COVID-19.
Spring Weather and COVID-19 Deaths in the U.S.
Authors: Karimi Seyed M. , Majbouri Mahdi , White Kelsey , Little Bert , McKinney W. Paul , DuPre Natalie 
Published: June 2020

AbstractThis study used statistically robust regression models to control for a large set of confounders (including county-level time-invariant factors and time trends, regional-level daily variation, state-level social distancing measures, ultraviolet light, and levels of ozone and fine particulate matter, PM2.5) to estimate a reliable rather than simple regression for the impact of weather on the most accurately measured outcome of COVID-19, death. When the average minimum temperature within a five-day window increased by one degree Fahrenheit in spring 2020, daily death rates in northern U.S. counties increased by an estimated 5.1%. When ozone concentration over a five-day window rose by one part per billion, daily death rates in southern U.S. counties declined by approximately 2.0%. Maximum temperature, precipitation, PM2.5, and ultraviolet light did not significantly associate with COVID-19 mortality. The mechanism that may drive the observed association of minimum temperature on COVID-19 deaths in spring months may be increased mobility and contacts. The effect of ozone may be related to its disinfectant properties, but this requires further confirmation.
Arsenic trioxide resistance in acute promyelocytic leukemia: More to it than PML mutations
Authors: Balasundaram Nithya , Ganesan Saravanan , Chendamarai Ezhilarasi , Palani Hamenth Kumar , Venkatraman Arvind , Alex Ansu Abu , David Sachin , Krishna Sanjeev , Korula Anu , Janet Nancy Beryl , Balasubramanian Poonkuzhali , Mathews Vikram 
Published: June 2020

AbstractAcquired genetic mutations can confer resistance to arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL). However, such resistance-conferring mutations are rare and do not explain the majority of disease recurrence seen in the clinic. We have generated a stable ATO resistant promyelocytic cell from a ATO sensitive NB4 cell line. We also noted that another ATRA resistant cell line (UF1) was cross resistant to ATO. We have characterized these resistant cell lines and observed that they significantly differed in their immunophenotype, drug transporter expression, drug resistance mutation profile and were also cross-resistant to other conventional chemotherapeutic agents. The NB4 derived resistant cell line had the classical A216VPML-B2domain mutation while the UF1 cell line did not. Gene expression profiling revealed prominent dysregulation of the cellular metabolic pathways in the resistant cell lines. Glycolytic inhibition by 2-DG was efficient and comparable to the standard of care (ATO) in targeting the sensitive APL cell lines and was also effective in the in vivo transplantable APL mouse model; however, it did not affect the ATO resistant cell lines. The survival of the resistant cell lines was significantly affected by compounds targeting the mitochondrial respiration irrespective of the existence of ATO resistance-conferring genetic mutations. Our data demonstrate the addition of mitocans can overcome ATO resistance. We further demonstrated that the combination of ATO and mitocans has the potential in the treatment of non-M3 AML and the translation of this approach in the clinic needs to be explored further.Key pointsMetabolic rewiring promotes ATO resistance, which can be overcome by targeting mitochondrial oxidative phosphorylation.Combination of ATO and mitocans can be exploited as a potential therapeutic option for relapsed APL and in non-M3 AML patients.
ADA2 is a lysosomal DNase regulating the type-I interferon response
Authors: Greiner-Tollersrud Ole Kristian , Boehler Vincent , Bartok Eva , Krausz Máté , Polyzou Aikaterini , Schepp Johanna , Seidl Maximilian , Olsen Jan Ole , Smulski Cristian R. , Raieli Salvatore , Hübscher Katrin , Trompouki Eirini , Link Regina , Ebersbach Hilmar , Srinivas Honnappa , Marchant Martine , Staab Dieter , Guerini Danilo , Baasch Sebastian , Henneke Philipp , Kochs Georg , Hartmann Gunther , Geiger Roger , Grimbacher Bodo , Warncke Max , Proietti Michele 
Published: June 2020

AbstractDeficiency of adenosine deaminase 2 (DADA2) is a severe, congenital syndrome, which manifests with hematologic, immunologic and inflammatory pathologies. DADA2 is caused by biallelic mutations inADA2, but the function of ADA2, and the mechanistic link between ADA2 deficiency and the severe inflammatory phenotype remains unclear. Here, we show that monocyte-derived proteomes from DADA2 patients are highly enriched in interferon response proteins. Using immunohistochemistry and detailed glycan analysis we demonstrate that ADA2 is post-translationally modified for sorting to the lysosomes. At acidic, lysosomal pH, ADA2 acts as a novel DNase that degrades cGAS/Sting-activating ligands. Furthermore, we define a clear structure-function relationship for this acidic DNase activity. Deletion of ADA2 increased the production of cGAMP and type I interferons upon exposure to dsDNA, which was reverted by ADA2 overexpression or deletion ofSTING.Our results identify a new level of control in the nucleic acid sensing machinery and provide a mechanistic explanation for the pathophysiology of autoinflammation in DADA2.One Sentence SummaryADA2 is a lysosomal nuclease controlling nucleic acid sensing and type I interferon production.
Lift observation conveys object weight distribution but partly enhances predictive lift planning
Authors: Rens Guy , de Xivry Jean-Jacques Orban , Davare Marco , van Polanen Vonne 
Published: June 2020

AbstractObservation of object lifting allows updating of internal object representations for object weight, in turn enabling accurate scaling of fingertip forces when lifting the same object. Here, we investigated whether lift observation also enables updating of internal representations for an object’s weight distribution. We asked participants to lift an inverted T-shaped manipulandum, of which the weight distribution could be changed, in turns with an actor. Participants were required to minimize object roll (i.e., ‘lift performance’) during lifting and were allowed to place their fingertips at self-chosen locations. The center of mass changed unpredictably every third to sixth trial performed by the actor and participants were informed that they would always lift the same weight distribution as the actor. Participants observed either erroneous (i.e., object rolling towards its heavy side) or skilled (i.e., minimized object roll) lifts. Lifting performance after observation was compared to lifts without prior observation and to lifts after active lifting, which provided haptic feedback about the weight distribution. Our results show that observing both skilled and erroneous lifts convey an object’s weight distribution similar to active lifting, resulting in altered digit positioning strategies. However, minimizing object roll on novel weight distributions was only improved after observing error lifts and not after observing skilled lifts. In sum, these findings suggest that although observing motor errors and skilled motor performance enables updating of digit positioning strategy, only observing error lifts enables changes in predictive motor control when lifting objects with unexpected weight distributions.New and noteworthyIndividuals are able to extract an object’s size and weight by observing interactions with objects and subsequently integrate this information in their own motor repertoire. Here, we show that this ability extrapolates to weight distributions. Specifically, we highlighted that individuals can perceive an object’s weight distribution during lift observation but can only partially embody this information when planning their own actions.
Live imaging of chromatin distribution in muscle nuclei reveals novel principles of nuclear architecture and chromatin compartmentalization
Authors: Amiad-Pavlov Daria , Lorber Dana , Bajpai Gaurav , Safran Samuel , Volk Talila 
Published: June 2020

AbstractPackaging of the chromatin within the nucleus serves as an important factor in the regulation of transcriptional output. However, information on chromatin architecture on nuclear scale in fully differentiated cells, under physiological conditions and in live organisms, is largely unavailable. Here, we imaged nuclei and chromatin in muscle fibers of live, intactDrosophilalarvae. In contrast to the common view that chromatin is distributed throughout the nuclear volume, we show that the entire chromatin, including active and repressed regions, forms a peripheral layer underneath the nuclear lamina, leaving a chromatin-devoid compartment at the nucleus center. Importantly, visualization of nuclear compartmentalization required imaging of un-fixed nuclei embedded within their intrinsic tissue environment, with preserved nuclear volume. Upon fixation of similar muscle nuclei, we observed an average of three-fold reduction in nuclear volume caused by dehydration and evidenced by nuclear flattening. In these conditions, the peripheral chromatin layer was not detected anymore, demonstrating the importance of preserving native biophysical tissue environment. We further show that nuclear compartmentalization is sensitive to the levels of lamin C, since over-expression of lamin C-GFP in muscle nuclei resulted in detachment of the peripheral chromatin layer from the lamina and its collapse into the nuclear center. Computer simulations of chromatin distribution recapitulated the peripheral chromatin organization observed experimentally, when binding of lamina associated domains (LADs) was incorporated with chromatin self-attractive interactions. Reducing the number of LADs led to collapse of the chromatin, similarly to our observations following lamin C over-expression. Taken together, our findings reveal a novel mode of mesoscale organization of chromatin within the nucleus in a live organism, in which the chromatin forms a peripheral layer separated from the nuclear interior. This architecture may be essential for robust transcriptional regulation in fully differentiated cells.
Vegetative phase change inPopulus tremula x alba
Authors: Lawrence Erica H. , Leichty Aaron R. , Doody Erin E. , Ma Cathleen , Strauss Steven H. , Poethig R. Scott 
Published: June 2020

SummaryPlants transition through juvenile and adult phases of vegetative development in a process known as vegetative phase change (VPC). In poplars (genusPopulus) the differences between these stages are subtle, making it difficult to determine when this transition occurs. Previous studies of VPC in poplars have relied on plants propagatedin vitro, leaving the natural progression of this process unknown.We examined developmental morphology of seed-grown andin vitroderivedPopulus tremula x alba(clone 717-1B4), and compared the phenotype of these, to transgenics with manipulated miR156 expression, the master regulator of VPC.In seed-grown plants, most traits changed from node-to-node during the first 3 months of development but remained constant after node 25. Many traits remained unchanged in clones over-expressing miR156, or were enhanced when miR156 was lowered, demonstrating their natural progression is regulated by the miR156/SPL pathway. The characteristic leaf fluttering ofPopulusis one of these miR156-regulated traits.Vegetative development in plants grown from culture mirrored that of seed-grown plants, allowing direct comparison between plants often used in research and those found in nature. These results provide a foundation for further research on the role of VPC in the ecology and evolution of this economically important genus.
Diametric Property of Rotational and Spiral Doppler Effect in Human Heart Atrial Fibrillation
Authors: Rubenstein D 
Published: June 2020

AbstractCompass mapping of moving rotors during atrial fibrillation unveiled unique properties of a different form of Doppler phenomenon. New rotational (RDE) and spiral Doppler effect (SDE) equations are derived and explain the diverging frequency changes (increasing and decreasing) that occur simultaneously on either side of passing rotor. These equations confirm that regions of maximal frequency are shifted 90° compared to moving sources that exhibit classical doppler effects. The new SDE equation predicts sequence reversal, side-dependent frequency changes, and an unpaired strong-side wave front strike previously observed in patients with persistent atrial fibrillation. Conclusion: The diametric property of SDE is a mechanism behind dysynchrony of atrial fibrillation when a spinning source of wave fronts moves between two stationary electrodes. The diametric property of SDE in other fields of science are discussed.Statement of SignificanceSpinning sources of periodic wave fronts during atrial fibrillation do NOT exhibit classical Doppler effects when they approach and pass between 2 adjacent equidistant electrodes. The wave front is a spinning single spiral arm and frequency of wave front strikes is not only dependent upon distance between successive WF crests, but it is also dependent upon changes in rotation. Rotational and spiral math were developed and to derive new rotational and spiral wave front Doppler effect equations in two dimensions. These equations predict the unique and profound diametric property that have been observed clinically in which the strong side electrodes record an approaching increasing frequency while the weak side electrodes record an approaching decreasing frequency. The solution opens up many new avenues of research, not only into atrial fibrillation, but at all levels of nature, into objects that spin.