bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter cohort study of multisystem inflammatory syndrome in children (MIS-C)
Authors: Merckx Joanna , Cooke Suzette , Tal Tala El , Laxer Ronald M. , Bitnun Ari , Morris Shaun K. , Yeh E. Ann , Yea Carmen , Gill Peter , Papenburg Jesse , Lefebvre Marie-Astrid , Ulloa-Gutierrez Rolando , Brenes-Chacon Helena , Yock-Corrales Adriana , Ivankovich-Escoto Gabriela , Soriano-Fallas Alejandra , Mezerville Marcela Hernandez-de , Dewan Tammie , Restivo Lea , Nateghian Alireza , Aski Behzad Haghighi , Manafi Ali , Dwilow Rachel , Bullard Jared , Lopez Alison , Sadarangani Manish , Roberts Ashley , Barton Michelle , Petel Dara , Saux Nicole Le , Bowes Jennifer , Purewal Rupeena , Lautermilch Janell , Tehseen Sarah , Bayliss Ann , Wong Jacqueline K. , Leifso Kirk , Foo Cheryl , Robinson Joan 
Published: May 2021

AbstractBACKGROUNDSARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We investigated risk factors for severe disease and explored changes in severity over time.METHODSChildren up to 17 years of age admitted March 1, 2020 through March 7th, 2021 to 15 hospitals in Canada, Iran and Costa Rica with confirmed or probable MIS-C were included. Descriptive analysis and comparison by diagnostic criteria, country, and admission date was performed. Adjusted absolute average risks (AR) and risk differences (RD) were estimated for characteristics associated with ICU admission or cardiac involvement.RESULTSOf 232 cases (106 confirmed) with median age 5.8 years, 56% were male, and 22% had comorbidities. ICU admission occurred in 73 (31%) but none died. Median length of stay was 6 days (inter-quartile range 4-9). Children 6 to 12 years old had the highest AR for ICU admission (44%; 95% confidence interval [CI] 34-53). Initial ferritin greater than 500 mcg/L was associated with ICU admission. When comparing cases admitted up to October 31, 2020 to those admitted later, the AR for ICU admission increased from 25% (CI 17-33) to 37% (CI 29-46) and for cardiac involvement from 44% (CI 35-53) to 75% (CI 66-84). Risk estimates for ICU admission in the Canadian cohort demonstrated a higher risk in December 2020-March 2021 compared to March-May 2020 (RD 25%; 95%CI 7-44).INTERPRETATIONMIS-C occurred primarily in previously well children. Illness severity appeared to increase over time. Despite a high ICU admission incidence, most children were discharged within one week.
Will there be a third COVID-19 wave? A SVEIRD model based study of India’s situation
Authors: Kannan Dwarakesh , Gurusriram R , Banerjee Rudra , Bhattacharjee Srijit , Varadwaj Pritish Kumar 
Published: May 2021

AbstractSince first patient detected in India in late February, 2020, SARS-CoV-II virus is playing havoc on India. After the first wave, India is now riding the 2nd wave. As was in the case of European countries like Italy and UK, the 2nd wave is more contagious and at the time of writing this paper, the per day infection is as high as 400,000. The alarming thing is it is not uncommon that people is getting infected multiple time. On the other hand, mass vaccination has started step by step. There is also growing danger of potential 3rd wave is unavoidable, which can even infect kids and minors.In this situation, an estimation of the dynamics of SARS-CoV-2 is absolutely necessary to combat the pandemic. We have used a modified SEIRD model, that includes vaccination and repeat infection as well. We have studied India and 8 Indian states with varying SARS-CoV-2 infection. We have shown that, Covid-19 wave will be repeated time to time, but the intensity will slow down with time. In most possible situation, our calculation shows COVID-19 will remain as endemic for foreseeable future, unless we are able to increase our vaccination rate manifold.
Comparison of dried blood spots and venous blood for the detection of SARS-CoV-2 antibodies in a population of nursing home residents
Authors: Meyers Eline , Heytens Stefan , Formukong Asangwing , Vercruysse Hanne , De Sutter An , Geens Tom , Hofkens Kenneth , Janssens Heidi , Nys Eveline , Padalko Elizaveta , Deschepper Ellen , Cools Piet 
Published: May 2021

AbstractIntroductionIn the current SARS-CoV-2 pandemic, testing for SARS-CoV-2 specific antibodies is paramount to monitor immune responses in post-authorization vaccination and sero-epidemiology studies. However, large scale and iterative serological testing by venipuncture in older persons can be challenging. Capillary blood sampled using a finger prick and collected on protein saver cards, i.e., dried blood spots (DBS), has already proven to be a promising alternative. However, elderly persons have a reduced cutaneous microvasculature, which may affect DBS-based antibody testing. Therefore, we aimed to evaluate the performance of DBS for the detection of SARS-CoV-2 antibodies in nursing homes residents.Materials and methodsWe collected venous blood and paired Whatman and EUROIMMUN DBS from nursing home residents, and from staff as a reference population. Venous blood samples were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Abbot chemiluminescent microparticle immunoassay (CMIA). DBS were analyzed by the EUROIMMUN enzyme-linked immuno sorbent assay (ELISA) for SARS-CoV-2 IgG antibodies. We performed a statistical assessment to optimize the ELISA cut-off value for the DBS using the Youden’s J index.ResultsA total of 273 paired DBS-serum samples were analyzed, of which 129 were positive as assessed by the reference test. The sensitivities and specificities of DBS ranged from 95.0% to 97.1% and from 97.1% to 98.8%, respectively, depending on population (residents or staff) or DBS card type.ConclusionDBS sampling is a valid alternative to venipuncture for the detection of SARS-CoV-2 antibodies in the elderly.
Local prevalence of transmissible SARS-CoV-2 infection: an integrative causal model for debiasing fine-scale targeted testing data
Authors: Nicholson George , Lehmann Brieuc , Padellini Tullia , Pouwels Koen B , Jersakova Radka , Lomax James , King Ruairidh E , Mallon Ann-Marie , Diggle Peter J , Richardson Sylvia , Blangiardo Marta , Holmes Chris 
Published: May 2021

AbstractTargeted surveillance testing schemes for SARS-CoV-2 focus on certain subsets of the population, such as individuals experiencing one or more of a prescribed list of symptoms. These schemes have routinely been used to monitor the spread of SARS-CoV-2 in countries across the world. The number of positive tests in a given region can provide local insights into important epidemiological parameters, such as prevalence and effective reproduction number. Moreover, targeted testing data has been used inform the deployment of localised non-pharmaceutical interventions. However, surveillance schemes typically suffer from ascertainment bias; the individuals who are tested are not necessarily representative of the wider population of interest. Here, we show that data from randomised testing schemes, such as the REACT study in the UK, can be used to debias fine-scale targeted testing data in order to provide accurate localised estimates of the number of infectious individuals. We develop a novel, integrative causal framework that explicitly models the process underlying the selection of individuals for targeted testing. The output from our model can readily be incorporated into longitudinal analyses to provide local estimates of the reproduction number. We apply our model to characterise the size of the infectious population in England between June 2020 and January 2021. Our local estimates of the effective reproduction number are predictive of future changes in positive case numbers. We also capture local increases in both prevalence and effective reproductive number in the South East from November 2020 to December 2020, reflecting the spread of the Kent variant. Our results illustrate the complementary roles of randomised and targeted testing schemes. Preparations for future epidemics should ensure the rapid deployment of both types of schemes to accurately monitor the spread of emerging and ongoing infectious diseases.
Screening of renal function among a group of physicians working in a hospital who are often self neglected
Authors: Kashem MA , Ullah Ahsan , Biswas Rajat Sanker Roy 
Published: May 2021

AbstractBackgroundPrevalence of chronic kidney disease (CKD) has been increasing rapidly worldwide and early screening to detect kidney disease, particularly at its early stages is pivotal to stop its further deterioration. Population based study on detection at early stage of kidney disease and it’s prevalence are scanty in our country, especially among the medical professional personnel. Hence taking advantage of the observance of World Kidney Day 2020, we conducted a screening program for kidney disease organized at the Chattogram Maa O Shishu Hospital (CMOSH) premises among a group of physicians of the hospital.MethodsThis was a cross sectional observational study among 67 physicians of different ranks (medical officer to professor), working at our hospital in different discipline. Age, body weight, height, Body Mass Index (BMI), blood pressure were documented, and urinary protein and serum creatinine were measured at a single sitting. Kidney function was estimated by calculating the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula. Kidney function was classified according to estimated GFR (eGFR) and Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines.ResultsA total of 67 working physicians of the hospital were studied. Among them majority subjects (30) were in the age group of 20 to 29 years. Among all 11.9% participants had proteinuria (trace to 1 plus). The distribution of eGFR was symmetrical, with the majority (70.10%) of subjects in the 60 to 89 ml/min category; 11.90% had 30 to 59 ml/min category and only 17.90% of the study population had eGFR > 90 ml/min. An inverse relation between eGFR and age, and a direct relation between eGFR and BMI were observed.ConclusionProteinuria, low eGFR levels might be related with future decline in renal function among the studied subjects and so regular health check-up is important to abate the potential epidemic of kidney disease among the health professionals.
Trait mindfulness is associated with less amyloid, tau, and cognitive decline in individuals at risk for Alzheimer’s disease
Authors: Strikwerda-Brown Cherie , Ozlen Hazal , Binette Alexa Pichet , Chapleau Marianne , Marchant Natalie L. , Breitner John C. S. , Villeneuve Sylvia ,   for the PREVENT-AD Research Group
Published: May 2021

AbstractBACKGROUND AND OBJECTIVESMindfulness, defined as non-judgmental awareness of the present moment, has been associated with an array of mental and physical health benefits, including improved cognitive functioning and changes to brain structure and function. Mindfulness may also represent a protective factor for Alzheimer’s disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk for AD dementia.METHODSTwo hundred sixty-one nondemented older adults with a family history of AD dementia were included from the PREVENT-AD observational cohort study, including 124 with Aβ- and tau-positron emission tomography (PET) scans. All participants completed measures of trait mindfulness and longitudinal cognitive assessments. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and (1) cognitive decline, (2) Aβ, and (3) tau.RESULTSHigher levels of mindful nonjudgment, describing, and nonreactivity were associated with less cognitive decline in attention, global cognition, and immediate and delayed memory. Higher levels of mindful nonjudgment and nonreactivity were related to less Aβ-PET signal in bilateral medial and lateral temporoparietal and frontal regions. Higher levels of mindful acting with awareness, describing, nonjudgment, and nonreactivity were associated with less tau-PET signal in bilateral temporal regions, namely entorhinal cortex, amygdala, and parahippocampal, fusiform, and inferior temporal gyri. These relationships remained significant when additional demographic (age, sex, education and APOE status) and psychological (personality traits and neuropsychiatric symptoms) were included in analyses. When mindfulness, personality traits, and neuropsychiatric symptoms were entered into the same model, mindful nonjudgment showed the strongest association with cognitive decline and Aβ.DISCUSSIONTrait mindfulness is associated with less cognitive decline and less Aβ and tau in the brain in older adults at risk for AD dementia. In addition to its other health benefits, trait mindfulness may also represent a psychological protective factor for AD dementia. Longitudinal studies examining the temporal relationship between trait mindfulness and AD markers, along with mindfulness intervention studies with cognition and pathology as outcome variables, will be important for further clarifying the potential protective benefits of mindfulness on AD risk.
Frailty is a predictor of medication-related harm requiring healthcare utilisation: a multicentre prospective cohort study
Authors: Stevenson Jennifer M. , Parekh Nikesh , Chua Kia-Chong , Davies J. Graham , Schiff Rebekah , Rajkumar Chakravarthi , Ali Khalid 
Published: May 2021

AbstractObjectivesTo determine the association between frailty and medication-related harm requiring healthcare utilisation.DesignProspective observational cohort study.Setting6 primary and 5 secondary care sites across South East England, September 2013 – November 2015.Participants1280 participants, 65 years old or over, who were due for discharge from general medicine and older persons’ wards following an acute episode of care. Exclusion criteria were limited life expectancy, transfer to another hospital and consent not gained.Main outcome measuresMedication-related harm requiring healthcare utilisation, including adverse drug reactions, non-adherence and medication error determined via triangulation of: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of re-admission to recruiting hospital. Frailty was measured using a Frailty Index, developed using a standardised approach. Marginal estimates were obtained from logistic regression models to examine how probabilities of healthcare service use due to medication-related harm were associated with increasing polypharmacy and frailty.ResultsHealthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06 to 49.26, p = 0.004), independent of age, gender, and polypharmacy. With increasing polypharmacy, the need for healthcare use as a result of MRH increases from a probability of around 0.2 to 0.4. This is also the case for frailty.ConclusionsFrailty is as important as polypharmacy in its association with MRH. Reducing the burden of frailty through an integrated health and social care approach, alongside strategies to reduce inappropriate polypharmacy, may reduce MRH related healthcare utilisation.Trial registrationApproved by the National Research Ethics Service, East of England (REC Reference 13/EE/0075)
Systematic characterization of short intronic splicing-regulatory elements
Authors: Gao Yuan , Lin Kuan-Ting , Yang Yang , Bai Jialin , Wang Li , Sun Junjie , Sheng Lei , Krainer Adrian R. , Hua Yimin 
Published: May 2021

ABSTRACTIntronic splicing enhancers and silencers (ISEs and ISSs) are two groups of splicing-regulatory elements (SREs) that play critical roles in determining splice-site selection, particularly for alternatively spliced introns or exons. SREs are often short motifs; their mutation or dysregulation of their cognate proteins frequently causes aberrant splicing and results in disease. To date, however, knowledge about SRE sequences and how they regulate splicing remains limited. Here, using an SMN2 minigene, we generated a complete pentamer-sequence library that comprises all possible combinations of 5 nucleotides in intron 7, at a fixed site downstream of the 5′ splice site. We systematically analyzed the effects of all 1023 mutant pentamers on exon 7 splicing, in comparison to the wild-type minigene, in HEK293 cells. Our data show that the majority of pentamers significantly affect exon 7 splicing: 584 of them are stimulatory and 230 are inhibitory. To identify actual SREs, we utilized a motif set enrichment analysis (MSEA), from which we identified groups of stimulatory and inhibitory SRE motifs. We experimentally validated several strong SREs in SMN1/2 and MAPT minigene settings. Our results provide a valuable resource for understanding how short RNA sequences regulate splicing. Many novel SREs can be explored further to elucidate their mechanism of action.
Protein cost minimization promotes the emergence of coenzyme redundancy
Authors: Goldford Joshua E. , George Ashish B. , Flamholz Avi I. , Segrè Daniel 
Published: May 2021

AbstractCoenzymes distribute a variety of chemical moieties throughout cellular metabolism, participating in group (e.g., phosphate, acyl) and electron transfer. For a variety of reactions requiring acceptors or donors of specific resources, there often exist degenerate sets of molecules (e.g., NAD(H) and NADP(H)) that carry out similar functions. Although the physiological roles of various coenzyme systems are well established, it is unclear what selective pressures may have driven the emergence of coenzyme redundancy. Here we use genome-wide metabolic modeling approaches to decompose the selective pressures driving enzymatic specificity for either NAD(H) or NADP(H) in the metabolic network ofEscherichia coli. We found that few enzymes are thermodynamically constrained to using a single coenzyme, and in principle, a metabolic network relying on only NAD(H) is feasible. However, structural and sequence analyses revealed widespread conservation of residues that retain selectivity for either NAD(H) or NADP(H), suggesting that additional forces may shape specificity. Using a model accounting for the cost of oxidoreductase enzyme expression, we found that coenzyme redundancy universally reduces the minimal amount of protein required to catalyze coenzyme-coupled reactions, inducing individual reactions to strongly prefer one coenzyme over another when reactions are near thermodynamic equilibrium. We propose that protein minimization generically promotes coenzyme redundancy, and that coenzymes typically thought to exist in a single pool (e.g., CoA) may exist in more than one form (e.g., dephospho-CoA).Significance statementMetabolism relies on a small class of molecules (coenzymes) that serve as universal donors and acceptors of key chemical groups and electrons. Although metabolic networks crucially depend on structurally redundant coenzymes (e.g., NAD(H) and NADP(H)) associated with different enzymes, the criteria that led to the emergence of this redundancy remain poorly understood. Our combination of modeling, and structural and sequence analysis indicates that coenzyme redundancy is not essential for metabolism, but rather an evolved strategy promoting efficient usage of enzymes when biochemical reactions are near equilibrium. Our work suggests that early metabolism may have operated with fewer coenzymes, and that adaptation for metabolic efficiency may have driven the rise of coenzyme diversity in living systems.
The mirror neuron system compensates for amygdala dysfunction-associated social deficits in individuals with higher autistic traits
Authors: Xu Lei , Zheng Xiaoxiao , Yao Shuxia , Li Jialin , Fu Meina , Li Keshuang , Zhao Weihua , Li Hong , Becker Benjamin , Kendrick Keith M. 
Published: May 2021

AbstractThe amygdala is a core node in the social brain which exhibits structural and functional abnormalities in Autism spectrum disorder and there is evidence that the mirror neuron system (MNS) can functionally compensate for impaired emotion processing following amygdala lesions. In the current study, we employed an fMRI paradigm in 241 subjects investigating MNS and amygdala responses to observation, imagination and imitation of dynamic facial expressions and whether these differed in individuals with higher as opposed to lower autistic traits. Results indicated that individuals with higher compared to lower autistic traits showed reduced left amygdala responses to imitation and enhanced responses in the left superior temporal sulcus (STS) of the MNS to observation, imagination and imitation. Additionally, functional connectivity between the left amygdala and the left STS as well as some other MNS regions was increased in individuals with higher autistic traits, especially during imitation of fearful expressions. The amygdala-MNS connectivity significantly moderated autistic group differences on recognition memory for fearful faces and real-life social network indices, indicating that increased amygdala-MNS connectivity could diminish the social behavioral differences between higher and lower autistic trait groups. Overall, findings demonstrate decreased imitation-related amygdala activity in individuals with higher autistic traits in the context of increased cortical MNS activity and amygdala-MNS connectivity which may functionally compensate for amygdala dysfunction and social deficits. Training targeting the MNS may capitalize on this compensatory mechanism for therapeutic benefits in Autism spectrum disorder.
Assessment of the infectious threshold of SARS-CoV-2 in primary airway epithelial cells
Authors: Essaidi-Laziosi Manel , Perez Rodriguez Francisco Javier , Sattonnet-Roche Pascale , Hulo Nicolas , Jacquerioz Frederique , Kaiser Laurent , Eckerle Isabella 
Published: May 2021

AbstractComparison of virus isolation success from clinical samples across a range of viral loads inoculated in parallel on Vero E6 and human airway epithelia (HAE) showed lower success of virus isolation in HAE, suggesting an overestimation of actual infectiousness in humans using Vero E6 cell lines, commonly considered as reference.
Interval timing and midfrontal delta oscillations are impaired in Parkinson’s disease patients with freezing of gait
Authors: Bosch Taylor J. , Barsainya Richa , Ridder Andrew , Santosh KC , Singh Arun 
Published: May 2021

AbstractGait abnormalities and cognitive dysfunction are common in patients with Parkinson’s disease (PD) and get worst with disease progression. Recent evidence has suggested a strong relationship between gait abnormalities and cognitive dysfunction in PD patients and impaired cognitive control could be one of the causes for abnormal gait patterns. However, the pathophysiological mechanisms of cognitive dysfunction in PD patients with gait problems are unclear. Here, we collected scalp electroencephalography (EEG) signals during a 7-second interval timing task to investigate the cortical mechanisms of cognitive dysfunction in PD patients with (PDFOG+, n=34) and without (PDFOG–, n=37) freezing of gait, as well as control subjects (n=37). Results showed that the PDFOG+ group exhibited the lowest maximum response density at around 7 seconds compared to PDFOG– and control groups, and this response density peak correlated with gait abnormalities as measured by FOG scores. EEG data demonstrated that PDFOG+ had decreased midfrontal delta-band power at the onset of the target cue, which was also correlated with maximum response density and FOG scores. In addition, our classifier performed better at discriminating PDFOG+ from PDFOG– and controls with an area under the curve of 0.93 when midfrontal delta power was chosen as a feature. These findings suggest that abnormal midfrontal activity in PDFOG+ is related to cognitive dysfunction and describe the mechanistic relationship between cognitive and gait functions in PDFOG+. Overall, these results could advance the development of novel biosignatures and brain stimulation approaches for PDFOG+.