bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients
Authors: Hultström Michael , Fromell Karin , Larsson Anders , Quaggin Susan E , Betsholtz Christer , Frithiof Robert , Lipcsey Miklos , Jeansson Marie 
Published: January 2021

AbstractSeveral studies suggest that hypercoagulation and endothelial dysfunction play central roles in severe forms of COVID-19 infections. We hypothesized that the high levels of the inflammatory cytokine Angiopoietin-2 (ANGPT2) reported in hospitalized COVID-19 patients might promote hypercoagulation through ANGPT2 binding to thrombomodulin with resulting inhibition of thrombin/thrombomodulin-mediated physiological anticoagulation. Plasma was collected from critically ill COVID-19 patients treated in the intensive care unit (ICU) at Uppsala University Hospital and ANGPT2 was measured at admission (61 patients) and after ten days (40 patients). ANGPT2 levels were compared with biochemical parameters, clinical outcome, and survival. We found that ANGPT2 levels were increased in COVID-19 patients in correlation with disease severity, hypercoagulation, and mortality. To test causality, we administered ANGPT2 to wildtype mice and found that it shortened bleeding time in a tail injury model. In further support of a role for ANGPT2 in physiological coagulation, bleeding time was increased in endothelial-specificAngpt2knockout mice. Usingin vitroassays, we found that ANGPT2 inhibited thrombomodulin-mediated anticoagulation and protein C activation in human donor plasma. Our data reveal a novel mechanism for ANGPT2 in hypercoagulation and suggest that Angiopoietin-2 inhibition may be tested in the treatment of hypercoagulation in severe COVID-19 infection.
The impact of the first wave of COVID-19 on those with lifelong conditions: a case study of congenital heart disease
Authors: Wray Jo , Pagel Christina , Chester Adrian H. , Kennedy Fiona , Crowe Sonya 
Published: January 2021

AbstractObjectivesGlobally, health care systems have been stretched to the limit by the COVID-19 pandemic. Significant changes have had to be made to the way in which non-COVID-19 related care has been delivered. Our objective was to understand, from the perspective of patients with a chronic, life-long condition (congenital heart disease, CHD) and their parents/carers, the impact of COVID-19 on the delivery of care, how changes were communicated and whether health care providers should do anything differently in a subsequent wave of COVID-19 infections.Design and settingA series of asynchronous discussion forums set up and moderated by three patient charities via their Facebook pages.ParticipantsPatients with CHD and parents/carers of patients with CHD.Main outcome measuresQualitative responses to questions posted on the discussion forums.ResultsThe forums ran over a 6-week period and involved 111 participants. Following thematic analysis of the transcripts, we identified three themes and ten subthemes related to individual condition-related factors, patient-related factors and health professional/centre factors that may have influenced how patients and parents/carers experienced changes to service delivery as a result of COVID-19.ConclusionsOur findings, whilst collected in relation to patients with CHD, are not necessarily specific to this population and we believe reflect the experiences of many thousands of people with life-long conditions in the UK. Drawing on what participants told us in the discussion forums, we have developed recommendations related to communication, service delivery and support during the pandemic that would, we think, improve patients’ experience of care and, potentially, their outcomes. Although the data were collected specifically in relation to COVID-19, a number of these recommendations are relevant to the wider delivery of care to patients with chronic underlying health conditions and reflect principles of good communication and service delivery.
Neurocognitive measures of self-blame and risk prediction models of recurrence in major depressive disorder
Authors: Lawrence Andrew J. , Stahl Daniel , Duan Suqian , Fennema Diede , Jaeckle Tanja , Young Allan H. , Dazzan Paola , Moll Jorge , Zahn Roland 
Published: January 2021

AbstractBackgroundOvergeneralised self-blaming emotions, such as self-disgust, are core symptoms of major depressive disorder (MDD) and prompt specific actions (i.e. “action tendencies”), which are more functionally relevant than the emotions themselves. We have recently shown, using a novel cognitive task, that when feeling self-blaming emotions, maladaptive action tendencies (feeling like “hiding” and like “creating a distance from oneself”) and an overgeneralised perception of control are characteristic of MDD, even after remission of symptoms. Here, we probed the potential of this cognitive signature, and its combination with previously employed fMRI measures, to predict individual recurrence risk. For this purpose, we developed a user-friendly hybrid machine-/statistical-learning tool which we make freely available.Methods52 medication-free remitted MDD patients, who had completed the Action Tendencies Task and our self-blame fMRI task at baseline, were followed up clinically over 14-months to determine recurrence. Prospective prediction models included baseline maladaptive self-blame-related action tendencies and anterior temporal fMRI connectivity patterns across a set of fronto-limbic a priori regions of interest, as well as established clinical and standard psychological predictors. Prediction models used elastic-net regularised logistic regression with nested 10-fold cross-validation.ResultsCross-validated discrimination was highly promising (AuC≥0.86), and positive predictive values over 80% were achieved when including fMRI in multi-modal models, but only up to 71% (AuC≤.74) when solely relying on cognitive and clinical measures.ConclusionsThis shows the high potential of multi-modal signatures of self-blaming biases to predict recurrence risk at an individual level, and calls for external validation in an independent sample.
Mucoricin is a Ricin-Like Toxin that is Critical for the Pathogenesis of Mucormycosis
Authors: Soliman Sameh S. M. , Baldin Clara , Gu Yiyou , Singh Shakti , Gebremariam Teclegiorgis , Swidergall Marc , Alqarihi Abdullah , Youssef Eman G. , Alkhazraji Sondus , Pikoulas Antonis , Perske Christina , Venkataramani Vivek , Rich Abigail , Bruno Vincent M. , Hotopp Julie Dunning , Mantis Nicolas J. , Edwards John E. , Filler Scott G. , Chamilos Georgios , Vitetta Ellen S. , Ibrahim Ashraf S. 
Published: January 2021

AbstractFungi of the order Mucorales cause mucormycosis, a lethal infection with an incompletely understood pathogenesis. We now demonstrate that Mucorales fungi produce a toxin that plays a central role in virulence. Polyclonal antibodies against this toxin inhibit its ability to damage human cellsin vitro,and prevent hypovolemic shock, organ necrosis, and death in mice with mucormycosis. RNAi inhibition of the toxin inRhizopus delemar,compromises the ability of the fungus to damage host cells and attenuates virulence in mice. This 17 kDa toxin has structural and functional features of the plant toxin, ricin, including the ability to inhibit protein synthesis by its N-glycosylase activity, the existence of a motif that mediates vascular leak, and a lectin sequence. Antibodies against the toxin inhibitR. delemar-or toxin-mediated vascular permeabilityin vitroand cross-react with ricin. A monoclonal anti-ricin B chain antibody binds to the toxin and also inhibits its ability to cause vascular permeability. Therefore, we propose the name “mucoricin” for this toxin. Not only is mucoricin important in the pathogenesis of mucormycosis but our data suggest that a ricin- like toxin is produced by organisms beyond the plant and bacterial kingdoms. Importantly, mucoricin should be a promising therapeutic target.
Prevalence of floating toe and its relationship with static postural stability in children: The Yamanashi adjunct study of the Japan Environment and Children’s Study (JECS-Y)
Authors: Fujimaki Taro , Wako Masanori , Koyama Kensuke , Furuya Naoto , Shinohara Ryoji , Otawa Sanae , Kobayashi Anna , Horiuchi Sayaka , Kushima Megumi , Yamagata Zentaro , Haro Hirotaka 
Published: January 2021

AbstractFloating toe (FT) is a frequently seen condition in which a toe is inadequately in contact with the ground. Although toes play an important role in stabilizing standing posture and walking, many aspects of the effects of FT on the body remain unclear. To our knowledge, there have been no reports about the relationship between FT and postural stability, especially in children. This study aimed to clarify the prevalence of FT and its relationship with static postural stability in children. Of the 400 children aged 8 years who participated in our cohort study, 396, who were examined for static postural stability, were included in this study. Postural stability and FT were assessed using a foot pressure plate. The sway path length of the center of pressure and the area of the ellipse defined as the size of the area marked by the center of pressure were measured as an evaluation of static postural stability. We calculated the “floating toe score (FT score: small FT score indicates insufficient ground contact of the toes)” using the image of the plantar footprint obtained at the postural stability measurement. The FT rate was very high at more than 90%, and the FT score in the eyes-closed condition was significantly higher than that in the eyes-open condition in both sexes. The FT score significantly correlated with the center of pressure path and area. Our results suggest that ground contact of the toes is not directly related to static postural stability in children, but it may function to stabilize the body when the condition becomes unstable, such as when the eyes are closed.
Assessing biomass and primary production of microphytobenthos in depositional coastal systems using spectral information
Authors: Jacobs Pascalle , Pitarch Jaime , Kromkamp Jacco C. , Philippart Catharina J.M. 
Published: January 2021

ABSTRACTIn depositional intertidal coastal systems, primary production is dominated by benthic microalgae (microphytobenthos) inhabiting the mudflats. This benthic productivity is supporting secondary production and supplying important services to humans including food provisioning. Increased frequencies of extreme events in weather (such as heatwaves, storm surges and cloudbursts) are expected to strongly impact the spatiotemporal dynamics of the microphytobenthos and subsequently their contribution to coastal food webs. Within north-western Europe, the years 2018 and 2019 were characterized by record-breaking summer temperatures and accompanying droughts. Field-calibrated satellite data (Sentinel 2) were used to quantify the seasonal dynamics of microphytobenthos biomass and production at an unprecedented spatial and temporal resolution during these years. We demonstrate that the Normalized Difference Vegetation Index (NDVI) should be used with caution in depositional coastal intertidal systems, because it may reflect import of remains of allochthonous pelagic productivity rather than local benthic biomass. We show that the reduction in summer biomass of the benthic microalgae cannot be explained by grazing but was most probably due to the high temperatures. The fivefold increase in salinity from January to September 2018, resulting from reduced river run-off during this exceptionally dry year, cannot have been without consequences for the vitality of the microphytobenthos community and its resistance to wind stress and cloud bursts. Comparison to historical information revealed that primary productivity of microphytobenthos may vary at least fivefold due to variations in environmental conditions. Therefore, ongoing changes in environmental conditions and especially extreme events because of climate change will not only lead to changes in spatiotemporal patterns of benthic primary production but also to changes in biodiversity of life under water and ecosystem services including food supply. Satellite MPB data allows for adequate choices in selecting coastal biodiversity conservation and coastal food supply.HIGHLIGHTSExpected seasonality changes require large-scale and high-resolution coastal dataNDVI of tidal flats reflects local benthic biomass and allochthonous phytoplanktonHigh summer temperatures reduced biomass and productivity of benthic microalgaeLong-term data revealed a five-fold variation in MPB biomass and productionSatellite MPB data allow for adequate conservation of coastal biodiversity
Female gametophyte expressedArabidopsis thalianalipid transfer proteins AtLtpI.4 and AtLtpI.8 provide a link between callose homeostasis, pollen tube guidance, and fertilization success
Authors: Kumari Khushbu , Zhao Meng , Britz Sebastian , Weiste Christine , Dröge-Laser Wolfgang , Stigloher Christian , Deeken Rosalia , Becker Dirk 
Published: January 2021

ABSTRACTNon-specific lipid transfer proteins (LTPs) represent a sub-class among the large family of Cysteine-rich proteins (CRPs) specific to land plants. LTPs possess a hydrophobic cavity, enabling them to bind and stabilize a variety of lipid molecules outside membranes. In line with the existence of an N-terminal signal peptide, secreted LTPs represent a well-suited mobile signal carrier in the plant’s extracellular matrix. Thus, LTPs are currently considered as key players to mediate the bulk flow of lipids between membranes/compartments as well as the buildup of lipid barrier polymers including cutin and suberin.Here, we show that floral expressedArabidopsis thalianaAtLtpI.4 (AtLTP2) and AtLtpI.8 (AtLTP5), mutually control cell-cell communication between growing pollen tubes and ovules during fertilization. Arabidopsis mutants lacking functional AtLtpI.4 and AtLtpI.8 exhibit significantly reduced fertilization success. Cross-pollination and cell biological analyses revealed thatAtLtpI.4/I.8double mutants are impaired in pollen tube guidance towards ovules. Our finding that theAtLtpI.4/I.8phenotype correlates with aberrant callose depositions in the micropylar region during ovule development suggests that both LTPs represent novel players of a joint signaling pathway that controls callose homeostasis in the female gametophyte.
Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational change greater than N501Y mutant alone, potentially resulting in an escape mutant
Authors: Nelson Gard , Buzko Oleksandr , Spilman Patricia , Niazi Kayvan , Rabizadeh Shahrooz , Soon-Shiong Patrick 
Published: January 2021

AbstractRapidly spreading SARS-CoV-2 variants present not only an increased threat to human health due to the confirmed greater transmissibility of several of these new strains but, due to conformational changes induced by the mutations, may render first-wave SARS-CoV-2 convalescent sera, vaccine-induced antibodies, or recombinant neutralizing antibodies (nAbs) ineffective. To be able to assess the risk of viral escape from neutralization by first-wave antibodies, we leveraged our capability for Molecular Dynamic (MD) simulation of the spike receptor binding domain (S RBD) and its binding to human angiotensin-converting enzyme 2 (hACE2) to predict alterations in molecular interactions resulting from the presence of the E484K, K417N, and N501Y variants found in the South African 501Y.V2 strain – alone and in combination. We report here the combination of E484K, K417N and N501Y results in the highest degree of conformational alterations of S RBD when bound to hACE2, compared to either E484K or N501Y alone. Both E484K and N501Y increase affinity of S RBD for hACE2 and E484K in particular switches the charge on the flexible loop region of RBD which leads to the formation of novel favorable contacts. Enhanced affinity of S RBD for hACE2 very likely underpins the greater transmissibility conferred by the presence of either E484K or N501Y; while the induction of conformational changes may provide an explanation for evidence that the 501Y.V2 variant, distinguished from the B.1.1.7 UK variant by the presence of E484K, is able to escape neutralization by existing first-wave anti-SARS-CoV-2 antibodies and re-infect COVID-19 convalescent individuals.
High prevalence of Plasmodium malariae and Plasmodium ovale in co-infections with Plasmodium falciparum in asymptomatic malaria parasite carriers in Southwest Nigeria
Authors: Abdulraheem Muhydeen Abiodun , Ernest Medard , Ugwuanyi Ifeoma , Abkallo Hussein M. , Nishikawa Saori , Adeleke Mofeyisade , Orimadegun Adebola E. , Culleton Richard 
Published: January 2021

AbstractAsymptomatic malaria parasite carriers do not seek anti-malarial treatment and may constitute a silent infectious reservoir. In order to assess the level of asymptomatic and symptomatic carriage amongst adolescents in a highly endemic area, and to identify the risk factors associated with such carriage, we conducted a cross sectional survey of 1032 adolescents (ages 10-19) from eight schools located in Ibadan, Southwest Nigeria in 2016. Blood films and blood spot filter paper samples were prepared for microscopy and DNA analysis. The prevalence of asymptomatic malaria was determined using microscopy, rapid diagnostic tests and PCR for 658 randomly selected samples. Of these, we found that 80% of asymptomatic schoolchildren were positive for malaria parasites by PCR, compared to 47% and 9% determined by RDT and microscopy, respectively. Malaria parasite species typing was performed using PCR targeting the mitochondrial CoxIII gene, and revealed high rates of carriage of Plasmodium malariae (53%) and Plasmodium ovale (24%). Most asymptomatic infections were co-infections of two or more species (62%), with P. falciparum + P. malariae the most common (35%), followed by P. falciparum + P. malariae + P. ovale (21%) and P. falciparum + P. ovale (6%). Single infections of P. falciparum, P. malariae and P. ovale accounted for 24%, 10% and 4% of all asymptomatic infections respectively. To compare the species composition of asymptomatic and symptomatic infections, further sample collection was carried out in 2017 at one of the previously sampled schools, and at a nearby hospital. Whilst the species composition of the asymptomatic infections was similar to that observed in 2016, the symptomatic infections were markedly different, with single infections of P. falciparum observed in 91% of patients, P. falciparum + P. malariae in 5% and P. falciparum + P. ovale in 4%.
Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study
Authors: Goodfellow Laura , Verwijs Marijn C. , Care Angharad , Sharp Andrew , Ivandic Jelena , Poljak Borna , Roberts Devender , Bronowski Christina , Gill A. Christina , Darby Alistair C. , Alfirevic Ana , Muller-Myhsok Bertram , Alfirevic Zarko , van de Wijgert Janneke H.H.M. 
Published: January 2021

AbstractObjectiveTo assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM).DesignNested case-control study.SettingUK tertiary referral hospital.SampleHigh-risk women with previous sPTB/PPROM <34+0 weeks gestation who had a recurrence (n=22) or delivered at ≥37+0 weeks without PPROM (n=87).MethodsVaginal swabs collected between 15-22 weeks gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR.Main outcome measureRecurrent early sPTB/PPROM.Results28/109 high-risk women had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (L. iners 36/109, L. crispatus 23/109, or other 22/109). VMB type, diversity, and stability were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 vs. 7.89 log10 cells/μl, adjusted odds ratio (aOR)=1.90, 95% confidence interval (CI)=1.01-3.56, p=0.047) and estimated Lactobacillus concentration (8.59 vs. 7.48 log10 cells/μl, aOR=2.35, CI=1.20-4.61, p=0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners-domination (aOR=3.44, CI=1.06-11.15, p=0.040). Women with anaerobic dysbiosis or L. iners-domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log10 cells/μl, respectively).ConclusionsVaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts.FundingWellbeing of Women, London, UKTweetable abstractIncreased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.
COVID-19 dynamics in an Ohio prison
Authors: KhudaBukhsh Wasiur R. , Khalsa Sat Kartar , Kenah Eben , Rempala Grzegorz A. , Tien Joseph H. 
Published: January 2021

AbstractImportanceIncarcerated individuals are a vulnerable population for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Understanding SARS-CoV-2 dynamics in prisons is crucial for curbing transmission both within correctional facilities and in the surrounding community.ObjectiveThe purpose of this study was to identify transmission scenarios that could underly rapid, widespread SARS-CoV-2 infection among inmates in Marion Correctional Institution (MCI).DesignPublicly available data reported by the Ohio Department of Rehabilitation and Corrections (ODRC) was analyzed using mathematical and statistical models.SettingWe consider SARS-CoV-2 transmission dynamics among MCI inmates prior to and including April 16, 2020.ParticipantsThis study uses de-identified, publicly available SARS-CoV-2 test result data for MCI inmates.ExposuresInmates at MCI were considered exposed to potential infection with SARS-CoV-2.Main outcome and measuresResults from mass testing conducted on April 16, 2020 were analyzed together with time of first reported SARS-CoV-2 infection among MCI inmates.ResultsRapid, widespread infection of MCI inmates was reported, with nearly 80% of inmates infected within three weeks of first reported inmate case. These data are consistent with i) a basic reproduction number greater than 14, together with a single initially infected inmate, ii) an initial super-spreading event resulting in several hundred initially infected inmates, together with a basic reproduction number of approximately three, and iii) earlier undetected circulation of virus among inmates prior to April.Conclusions and relevanceMass testing data are consistent with extreme transmissibility, super-spreading events, or undetected circulation of virus among inmates. All scenarios consistent with these data attest to the vulnerabilities of prisoners to COVID-19.Key pointsQuestionTo identify transmission characteristics consistent with timing and extent of SARS-CoV-2 infection among inmates in Marion Correctional Institution.FindingsMathematical and statistical modeling finds three scenarios that are consistent with the observed widespread infection in Marion Correctional Institution: i) very high transmissibility corresponding to a basic reproduction number in the double digits, ii) an initial super-spreading event involving exposure of several hundred inmates, iii) undetected circulation of virus prior to the first documented case among inmates.MeaningHigh transmissibility, super-spreading events, and challenges with disease surveillance all attest to the vulnerabilities of prison populations to SARS-CoV-2.