bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function and regulation of an aldehyde dehydrogenase essential for ethanol and methanol metabolism of the yeast,Komagataella phaffii
Authors: Rao Kamisetty Krishna , Sahu Umakant , Rangarajan Pundi N 
Published: June 2020

AbstractThe genome of the methylotrophic yeast,Komagataella phaffiiharbours multiple genes encoding putative alcohol dehydrogenases and aldehyde dehydrogenases (ALDs). Here, we demonstrate that one of the ALDs denoted as ALD-A is essential for ethanol metabolism. A zinc finger transcription factor known as Mxr1p regulatesALD-Atranscription by binding to Mxr1p response elements (MXREs) in theALD-Apromoter. Mutations which abrogate Mxr1p binding toALD-AMXREsin vitroabolish transcriptional activation fromALD-Apromoterin vivo. Mxr1p regulatesALD-Aexpression during ethanol as well as methanol metabolism. ALD-A is essential for the utilization of methanol andΔald-ais deficient in alcohol oxidase (AOX), a key enzyme of methanol metabolism. AOX protein but not mRNA levels are down regulated inΔald-a.ALD-A and AOX localize to cytosol and peroxisomes respectively during methanol metabolism suggesting that they are unlikely interact with each otherin vivo. This study has led to the identification of Mxr1p as a key regulator ofALD-Atranscription during ethanol and methanol metabolism ofK. phaffii. Post-transcriptional regulation of AOX protein levels by ALD-A during methanol metabolism is another unique feature of this study.
Rubisco activase remodels plant Rubisco via the large subunit N-terminus
Authors: Ng Jediael , Mueller-Cajar Oliver 
Published: June 2020

ABSTRACTThe photosynthetic CO2fixing enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) forms inhibited complexes with multiple sugar phosphates, including its substrate ribulose 1,5-bisphosphate. At least three classes of ATPases associated with diverse cellular activities (AAA+ proteins) termed Rubisco activases (Rcas) have evolved to remodel inhibited Rubisco complexes. The mechanism of green-type Rca found in higher plants has proved elusive, because until recently higher plant Rubiscos could not be expressed recombinantly. Towards identifying interaction sites between Rubisco and Rca, here we produce and characterize a suite of 33 Arabidopsis Rubisco mutants for their ability to be activated by Rca. We find that Rca activity is highly sensitive to truncations and mutations in the conserved N-terminus of the Rubisco large subunit. Both T5A and T7A substitutions cannot be activated by Rca, but present with increased carboxylation velocities. Our results are consistent with a model where Rca functions by transiently threading the Rubisco large subunit N-terminus through the axial pore of the AAA+ hexamer.
Genome sequence ofHydrangea macrophyllaand its application in analysis of the double flower phenotype
Authors: Nashima K , Shirasawa K , Ghelfi A , Hirakawa H , Isobe S , Suyama T , Wada T , Kurokura T , Uemachi T , Azuma M , Akutsu M , Kodama M , Nakazawa Y , Namai K 
Published: June 2020

AbstractOwing to its high ornamental value, the double flower phenotype of hydrangea (Hydrangea macrophylla) is one of its most important traits. In this study, genome sequence information was obtained to explore effective DNA markers and the causative genes for double flower production in hydrangea. Single molecule real-time sequencing data followed by a HiC analysis was employed. The resultant haplotype-phased sequences consisted of 3,779 sequences (2.256 Gb in length and N50 of 1.5 Mb), and 18 pseudomolecules comprising 1.08 Gb scaffold sequences along with a high-density SNP genetic linkage map. Using the genome sequence data obtained from two breeding populations, the SNPs linked to double flower loci (DjoandDsu), were discovered for each breeding population. DNA markers J01 linked toDjoand S01 linked toDsuwere developed, and these could be used successfully to distinguish the recessive double flower allele for each locus respectively. TheLEAFYgene was suggested as the causative gene forDsu,since frameshift was specifically observed in double flower accession withdsu. The genome information obtained in this study will facilitate a wide range of genomic studies on hydrangea in the future.
Development and validation of a knowledge-driven risk calculator for critical illness in COVID-19 patients
Authors: Cahan Amos , Gottesman Tamar , Katz Michal Tzuchman , Masad Roee , Azulay Gal , Dicker Dror , Zeidman Aliza , Berkov Evgeny , Levin Gal sahaf , Tadmor Boaz , Lev Shaul 
Published: June 2020

ABSTRACTFacing the rapidly spreading novel coronavirus disease (COVID-19), evidence to inform decision-making at both the clinical and policy-making level is highly needed. Based on the results of a study by Petrilli et al, we have developed a calculator using patient data at admission to predict the risk of critical illness (intensive care unit admission, use of mechanical ventilation, discharge to hospice, or death).We report a retrospective validation of the risk calculator on 145 consecutive patients admitted with COVID-19 to a single hospital in Israel. Of the 18 patients with critical illness, 17 were correctly identified by the model(sensitivity: 94.4%, 95% CI, 72.7% to 99.9%; specificity: 81.9%, 95% CI, 74.1% to 88.2%). Of the 127 patients with non-critical illness, 104 were correctly identified. This, despite considerable differences between the original and validation study populations.Our results show that data from published knowledge can be used to provide reliable, patient level, automated risk assessment, potentially reducing the cognitive burden on physicians and helping policy makers better prepare for future needs.
Publish or perish: reporting characteristics of peer-reviewed publications, pre-prints and registered studies on the COVID-19 pandemic
Authors: Gianola S , Jesus TS , Bargeri S , Castellini G 
Published: June 2020

AbstractBackgroundThe COVID-19 pandemic has resulted in a mass of academic papers being published in a very brief span of time. Our aim was to compare the amount and reporting characteristics of COVID-19 related peer-reviewed and pre-prints publications. We also investigated the amount of ongoing trials and systematic reviews.Methods and findingsA cross-sectional study of publications covering the COVID-19 pandemic time frame, up to May 20, 2020 was conducted. PubMed with appropriate combinations of Medical Subject Headings and COVID-19 section of MedRxiv and BioRxiv archives were searched. We examined Clinicaltrial.gov, Chinese Clinical Trial Registry, EU Register and 15 other trial registers as well as the international prospective register of systematic reviews (PROSPERO). Characteristics of each publication source were extracted. Regression analyses and Z tests were used to analyze publication trends over the weeks and compare their relative proportions.We found 3635 peer-reviewed publications and 3805 pre-prints, of which 8.6% (n=329) were published in indexed journals. Peer-reviewed and pre-print publications amount both increased significantly over time (p<0.001). Case reports (peer-reviewed: 6% vs pre-prints: 0.9%,p<0.001) and letters (17.4% vs 0.5%,p<0.001) accounted for a greater share of the peer-reviewed compared to pre-print publications. In turn, randomized controlled trials (0.22% vs 0.63%p<0.001) and systematic reviews (0.08% vs 5%) accounted for a significantly greater share of the pre-print publications. Clinicaltrials.gov, Chinese Clinical Trial Registry and EU register included 57.9%, 49.5 % and 98.9% trials mostly still “recruiting”. PROSPERO amounted to 962 systematic review protocols.ConclusionPre-prints were slightly more prevalent than peer-reviewed publications, yet both are growing. To fill the void given by the absence of published primary studies, immediate opinions (i.e., letters) has virulently been published in PubMed. However, preprints has been promoted as rapid responses to give direct and promptly access at scientific findings in this pandemic.
High temperature has no impact on the reproduction number and new cases of COVID-19 in Bushehr, Iran
Authors: Sahafizadeh Ebrahim , Sartoli Samaneh 
Published: June 2020

AbstractBackgroundCOVID-19 was first reported in Iran on February 19, 2020. Bushehr, one of the warmest provinces of Iran, was the last province confirmed to be infected on March 5, 2020. In the beginning of April, Bushehr was announced as a ‘white’, coronavirus-free, province. However, increasing the temperature in the next months did not affect the spread of coronavirus and the number of confirmed cases increased during the next months, so that Bushehr was announced as a ‘Red’ province on June 13, 2020.MethodsThis paper aims 1) to estimate the reproduction number of COVID-19 in Bushehr considering COVID-19 reported cases of Bushehr from April to June 12, 2020, using exponential function and SIR epidemic model, and 2) to investigate the impact of temperature on the reproduction number and the spread of coronavirus in Bushehr using the temperature data.ResultsThe reproduction number was estimated to be 2.564, 2.641 and 2.573 at the beginning of April, May and June 2020 respectively. Regarding the increase in the temperature from April to June, the results showed that not only was the spread of COVID-19 not reduced but it also increased.ConclusionData analysis on this study showed that high temperature has no impact on the reproduction number and does not slow down the spread of coronavirus in Bushehr.
Clinical Characteristics and Outcomes of Venous Thromboembolism in Patients Hospitalized for COVID-19: Systematic Review and Meta-Analysis
Authors: Henrina Joshua , Santosa Putra Iwan Cahyo , Cahyadi Irvan , Hadi Gunawan Hoo Felicia , Cahyadi Alius , Suciadi Leonardo Paskah 
Published: June 2020

ABSTRACTObjectiveTo investigate the clinical characteristics and outcomes of Coronavirus Disease of 2019 (COVID-19) patients complicated with venous thromboembolism (VTE)MethodWe performed a comprehensive literature search of several databases to find studies that assessed VTE in hospitalized COVID-19 patients with a primary outcome of all-cause mortality and secondary outcomes of intensive care unit (ICU) admission and mechanical ventilation. We also evaluated the clinical characteristics of VTE sufferers.ResultsEight studies have been included with a total of 1237 pooled subjects. Venous thromboembolism was associated with higher mortality (RR 2.48 (1.35, 4.55),p=0.003;I25%,p=0.35) after we performed sensitivity analysis, ICU admission (RR 2.32 (1.53, 3.52),p<0.0001;I280%,p<0.0001), and mechanical ventilation need (RR 2.73 (1.56, 4.78),p=0.0004;I277%,p=0.001). Furthermore, it was also associated to male gender (RR 1.21 (1.08, 1.35),p=0.0007;I212%,p=0.34), higher white blood cells count (MD 1.24 (0.08, 2.41), 0.04;I20%; 0.26), D-dimer (MD 4.49 (2.74, 6.25),p<0.00001;I267%,p=0.009) and LDH levels (MD 70.93 (19.33, 122.54),p<0.007;I221%, p=0.28). In addition, after sensitivity analysis was conducted, VTE also associated with older age (MD 2.79 (0.06, 5.53),p=0.05;I225%,p=0.24) and higher CRP levels (MD 2.57 (0.88, 4.26);p=0.003;I20%,p=0.96).ConclusionVenous thromboembolism in COVID-19 patients was associated with increased mortality, ICU admission, and mechanical ventilation requirement. Male gender, older age, higher levels of biomarkers, including WBC count, D-Dimer, and LDH were also being considerably risks for developing VTE in COVID-19 patients during hospitalization.
Clinical characteristics of Coronavirus Disease 2019 (COVID-19) patients in Kuwait
Authors: Alshukry Abdullah , Ali Hamad , Ali Yaseen , Taweel Talal Al , Abu-Farha Mohammad , AbuBaker Jehad , Devarajan Sriraman , Dashti Ali A. , Bandar Ali , Taleb Hessah , Bader Abdullah Al , Aly Nasser Y. , Al-Ozairi Ebaa , Al-Mulla Fahd , Abbas Mohammad Bu 
Published: June 2020

AbstractThis is a retrospective single-center study of 417 consecutive patients with coronavirus disease 2019 (COVID-19) admitted to Jaber Al-Ahmad Hospital in Kuwait between February 24, 2020 and May 24, 2020. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild/moderate symptoms, 5.3% were admitted to the intensive care unit (ICU) and recovered, and 14.4% died. The mean age of death cases was 54.20 years (± 11.09). Comorbidities were more prevalent in patients who died compared with others. Key findings include abnormal levels of markers assicated with infection, inflammation, abnormal blood clotting, heart problems and kidney problems in patients with severe form of the disease and poor putcome. We report a rapidly deteriorating estimated glomerular filtration rate (eGFR) in deaths during ICU stay with kidney injury complications reported in 65% of deaths (p < 0.05). Our dynamic profiling of eGFR in ICU highlights the potential role of renal markers in forecasting disease outcome that could perhaps identify patients at risk of poor outcome.
Detecting space-time clusters of COVID-19 in Brazil: mortality, inequality, socioeconomic vulnerability, and the relative risk of the disease in Brazilian municipalities
Authors: Martines M. R , Ferreira R.V , Toppa R. H. , Assunção L. M. , Desjardins M.R. , Delmelle E.M. 
Published: June 2020

AbstractThe first case of COVID-19 in South America occurred in Brazil on February 25th, 2020. By June 7th, 2020, there were 691,758 confirmed cases, 36,455 confirmed deaths, and a mortality rate of 5.3%. To assist with the establishment of measures for the strategic planning to combat the COVID-19 pandemic in Brazil, we present the first Brazilian geographic study with the aims to examine “active” hand “emerging” space-time clusters of COVID-19. We examine the associations between clusters and mortality rate, vulnerability, and social inequality. We used the prospective space-time scan statistic to detect daily COVID-19 clusters and examine the relative risk from February 25th - June 7th, 2020 in 5,570 Brazilian municipalities. We apply a Spearman’s statistic to measure correlation between the relative risk of each cluster and mortality rate, GINI index, and social inequality. We detected 11 emerging space-time clusters of COVID-19 occurring in all Brazilian regions, with seven of them with a relative risk greater than one, and the highest in the Amapá state in the northern region of Brazil. We observed a positive and significant correlation between the relative risk and mortality rate, Brazilian Social Vulnerability Index, and GINI Index. The results can be utilized to improve COVID-19 response and planning in all Brazilian states.
Hypokalemia in Patients with COVID-19
Authors: Gaetano Alfano , Annachiara Ferrari , Francesco Fontana , Perrone Rossella , Mori Giacomo , Elisabetta Ascione , Riccardo Magistroni , Giulia Venturi , Pederzoli Simone , Margiotta Gianlulca , Romeo Marilina , Piccinini Francesca , Giacomo Franceschi , Sara Volpi , Matteo Faltoni , Giacomo Ciusa , Erica Bacca , Marco Tutone , Alessandro Raimondi , Marianna Menozzi , Erica Franceschini , Gianluca Cuomo , Gabriella Orlando , Antonella Santoro , Margherita Di Gaetano , Cinzia Puzzolante , Federica Carli , Andrea Bedini , Jovana Milic , Marianna Meschiari , Cristina Mussini , Gianni Cappelli , Giovanni Guaraldi ,   Modena Covid-19 Working Group (MoCo19)
Published: June 2020

AbstractPatients with COVID-19 may experience multiple conditions (e.g., fever, hyperventilation, anorexia, gastroenteritis, acid-base disorder) that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder that may increase the susceptibility to various kinds of arrhythmia. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of non-critically ill patients. A retrospective analysis was conducted on 290 hospitalized patients with confirmed COVID-19 infection at the tertiary teaching hospital of Modena, Italy.Hypokalemia (<3.5 mEq/L) was detected in 119 patients (41%). The decrease of serum potassium level was of mild entity (3-3.4 mEq/L) and occurred in association with hypocalcemia (P=0.001) and lower level of serum magnesium (P=0.028) compared to normokaliemic patients. Urine K: creatinine ratio, measured in a small subset of patients (n=45; 36.1%), showed an increase of urinary potassium excretion in the majority of the cases (95.5%). Causes of kaliuria were diuretic therapy (53.4%) and corticosteroids (23.3%). In the remaining patients, urinary potassium loss was associated with normal serum magnesium, low sodium excretion (FENa< 1%) and metabolic alkalosis. Risk factors for hypokalemia were female gender (P=0.002; HR 0.41, 95%CI 0.23-0.73) and diuretic therapy (P=0.027; HR 1.94, 95%CI 1.08-3.48). Hypokalemia, adjusted for sex, age and SOFA score, resulted not associated with ICU admission (P=0.131, 95% CI 0.228-1.212) and in-hospital mortality (P=0.474; 95% CI 0,170-1,324) in our cohort of patients.Hypokalemia is a frequent disorder in COVID-19 patients and urinary potassium loss may be the main cause of hypokalemia. The disorder was mild in the majority of the patients and was unrelated to poor outcomes. Nevertheless, hypokalemic patients required potassium supplements to dampen the risk of arrhythmias.
Evidence for a pervasive autobiographical memory impairment in Logopenic Progressive Aphasia: clinical and neural correlates
Authors: Ramanan Siddharth , Foxe David , El-Omar Hashim , Ahmed Rebekah M. , Hodges John R. , Piguet Olivier , Irish Muireann 
Published: June 2020

ABSTRACTLogopenic Progressive Aphasia is a rare language disorder characterised by repetition and naming difficulties, reflecting the progressive degeneration of left-lateralized peri-sylvian temporal and inferior parietal regions. Mounting evidence suggests that cognitive impairments in this syndrome extend beyond the language domain to include episodic encoding and retrieval disturbances. To date, it remains unknown whether autobiographical memories from across the lifespan are also subject to decline, yet this information is critical to arrive at a comprehensive understanding of the Logopenic syndrome. The objective of this study was to provide the first in depth examination of autobiographical memory function in Logopenic Progressive Aphasia using the Autobiographical Interview, a validated semi-structured interview which assesses recollection of the past under free and probed recall conditions. Autobiographical memory performance in 10 well-characterised Logopenic Progressive Aphasia patients was contrasted with that of 18 typical amnestic Alzheimer’s disease and 16 healthy Control participants. Relative to Controls, Logopenic Progressive Aphasia cases showed marked impairment in the free recall of episodic details, scoring comparably to disease-matched cases of Alzheimer’s disease. This impairment was evident across all time periods and persisted even when formal structured probing was provided. Importantly, controlling for overall level of language disruption failed to ameliorate the autobiographical memory impairment in the Logopenic Progressive Aphasia group, suggesting a genuine amnesia spanning recent and remote memories. Whole-brain voxel-based morphometry analyses revealed that total episodic information retrieved in Logopenic Progressive Aphasia was associated with decreased grey matter intensity predominantly in a bilateral posterior parietal network. Taken together, our findings reveal for the first time the presence of marked remote and recent autobiographical memory impairments in Logopenic Progressive Aphasia, that cannot be explained solely due to their language difficulties or disease staging. Our findings hold important clinical implications for the accurate characterization of Logopenic Progressive Aphasia, and suggest that episodic memory difficulties should be considered as one of the core clinical features of this syndrome.
Pre-existing immunity provides a barrier to airborne transmission of influenza viruses
Authors: Le Sage Valerie , Jones Jennifer E. , Kormuth Karen A. , Fitzsimmons William J. , Nturibi Eric , Padovani Gabriella H. , Arevalo Claudia P. , French Andrea J. , Avery Annika J. , Manivanh Richard , McGrady Elizabeth E. , Bhagwat Amar R. , Lauring Adam S. , Hensley Scott E. , Lakdawala Seema S. 
Published: June 2020

AbstractHuman-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne viruses is still unknown. Using human seasonal influenza viruses in a ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We found that airborne transmission of seasonal influenza strains is abrogated in recipient animals with pre-existing non-neutralizing immunity, indicating that transmissibility of a given influenza virus strain should be examined in the context of ferrets that are not immunologically naïve.
Spindle scaling is governed by cell boundary regulation of microtubule nucleation
Authors: Rieckhoff Elisa Maria , Berndt Frederic , Golfier Stefan , Decker Franziska , Elsner Maria , Ishihara Keisuke , Brugués Jan 
Published: June 2020

AbstractCellular organelles such as the mitotic spindle adjust their size to the dimensions of the cell. It is widely understood that spindle scaling is governed by regulation of microtubule polymerization. Here we use quantitative microscopy in living zebrafish embryos andXenopusegg extracts in combination with theory to show that microtubule polymerization dynamics are insufficient to scale spindles and only contribute below a critical cell size. In contrast, microtubule nucleation governs spindle scaling for all cell sizes. We show that this hierarchical regulation arises from the partitioning of a nucleation inhibitor to the cell membrane. Our results reveal that cells differentially regulate microtubule number and length using distinct geometric cues to maintain a functional spindle architecture over a large range of cell sizes.
Control of fluid flow by Adgrd1 is essential for mammalian oviductal embryo transport
Authors: Bianchi Enrica , Sun Yi , Almansa-Ordonez Alexandra , Woods Michael , Goulding David , Martinez-Martin Nadia , Wright Gavin J. 
Published: June 2020

AbstractDysfunction of oviductal embryo transport can lead to ectopic pregnancy which affects 1 to 2% of all conceptions in the United States and Europe, and is the most common cause of pregnancy-related death in the first trimester1, 2. Ectopic pregnancies almost always occur in the Fallopian tube, emphasizing the critical role of oviductal transport in human reproduction3. Oviductal transit is regulated and involves a valve-like “tubal-locking” phenomenon that temporarily arrests oocytes at the ampullary-isthmic junction (AIJ) where fertilization occurs4. Here, we show that female mice lacking the orphan adhesion G-protein coupled receptorAdgrd1are sterile because they are unable to unlock the restraining mechanism at the AIJ, inappropriately retaining embryos within the oviduct.Adgrd1is expressed on the oviductal epithelium and the post-ovulatory attenuation of tubal fluid production is dysregulated inAdgrd1-deficient mice. We identified Plxdc2 as an activating ligand for Adgrd1 displayed on the surface of cumulus cells. Our findings suggest that regulating oviductal luminal fluid production by Adgrd1 controls embryo transit, and provides important insights into the genetic regulation and molecular mechanisms involved embryo tubal transport.