bluuebunny/crossref_metadata_2025 huggingface dataset:
Probative Value of the d-Dimer Assay for Diagnosis of Deep Venous Thrombosis in the Coronavirus Disease 2019 Syndrome
Authors: Gibson Cameron J. , Alqunaibit Dalia , Smith Kira E. , Bronstein Matthew , Eachempati Soumitra R. , Kelly Anton G. , Lee Christina , Minneman Jennifer A. , Narayan Mayur , Shou Jian , Villegas Cassandra V. , Winchell Robert J. , Barie Philip S.
Published: September 2020

Objectives:

To describe the predictive utility of the d-dimer assay among patients with the coronavirus disease 2019 syndrome for unprovoked lower extremity deep venous thrombosis.

Design:

Prospective observational study with retrospective data analysis.

Setting:

Academic medical center surgical ICU.

Patients:

Seventy-two intubated patients with critical illness from coronavirus disease 2019.

Interventions:

Therapeutic anticoagulation after imaging diagnosis of the first three deep venous thrombosis cases was confirmed; therapeutic anticoagulation as prophylaxis thereafter to all subsequent ICU admissions.

Measurements and Main Results:

Seventy-two patients with severe coronavirus disease 2019 were screened for deep venous thrombosis after ICU admission with 102 duplex ultrasound examinations, with 12 cases (16.7%) of lower extremity deep venous thrombosis identified. There were no differences between groups with respect to age, renal function, or biomarkers except for d-dimer (median, 12,858 ng/mL [interquartile range, 3,176–30,770 ng/mL] for lower extremity deep venous thrombosis vs 2,087 ng/mL [interquartile range, 638–3,735 ng/mL] for no evidence of deep venous thrombosis; p < 0.0001). Clinical screening tools (Wells score and Dutch Primary Care Rule) had no utility. The C-statistic for d-dimer concentration was 0.874 ± 0.065. At the model-predicted cutoff value of 3,000 ng/mL, sensitivity was 100%, specificity was 51.1%, positive predictive value was 21.8%, and negative predictive value was 100%.

Conclusions:

Lower extremity deep venous thrombosis is prevalent in coronavirus disease 2019 disease and can be present on ICU admission. Screening has been recommended in the context of the pro-inflammatory, hypercoagulable background milieu. d-dimer concentrations are elevated in nearly all coronavirus disease 2019 patients, and the test appears reliable for screening for lower extremity deep venous thrombosis at or above a concentration of 3,000 ng/mL (more than 13-fold above the normal range). Full anticoagulation is indicated if the diagnosis is confirmed, and therapeutic anticoagulation should be considered for prophylaxis, as all coronavirus disease 2019 patients are at increased risk.
Effects of Positive End-Expiratory Pressure in “High Compliance” Severe Acute Respiratory Syndrome Coronavirus 2 Acute Respiratory Distress Syndrome*
Authors: Grasso Salvatore , Mirabella Lucia , Murgolo Francesco , Di Mussi Rossella , Pisani Luigi , Dalfino Lidia , Spadaro Savino , Rauseo Michela , Lamanna Angela , Cinnella Gilda
Published: September 2020

Objectives:

Clinical observation suggests that early acute respiratory distress syndrome induced by the severe acute respiratory syndrome coronavirus 2 may be “atypical” due to a discrepancy between a relatively unaffected static respiratory system compliance and a significant hypoxemia. This would imply an “atypical” response to the positive end-expiratory pressure.

Design:

Single-center, unblinded, crossover study.

Setting:

ICU of Bari Policlinico Academic Hospital (Italy), dedicated to care patients with confirmed diagnosis of novel coronavirus disease 2019.

Patients:

Eight patients with early severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and static respiratory compliance higher than or equal to 50 mL/cm H2O.

Interventions:

We compared a “lower” and a “higher” positive end-expiratory pressure approach, respectively, according to the intervention arms of the acute respiratory distress syndrome network and the positive end-expiratory pressure setting in adults with acute respiratory distress syndrome studies.

Measurements and Main Results:

Patients were ventilated with the acute respiratory distress syndrome network and, subsequently, with the ExPress protocol. After 1 hour of ventilation, for each protocol, we recorded arterial blood gas, respiratory mechanics, alveolar recruitment, and hemodynamic variables. Comparisons were performed with analysis of variance for repeated measures or Friedman test as appropriate. Positive end-expiratory pressure was increased from 9 ± 3.5 to 17.7 ± 1.7 cm H2O (p < 0.01). Alveolar recruitment was 450 ± 111 mL. Static respiratory system compliance decreased from 58.3 ± 7.6 mL/cm H2O to 47.4 ± 14.5 mL/cm H2O (p = 0.018) and the “stress index” increased from 0.97 ± 0.03 to 1.22 ± 0.07 (p < 0.001). The Pao
2/Fio
2 ratio increased from 131 ± 22 to 207 ± 41 (p < 0.001), and the Paco
2 increased from 45.9 ± 12.7 to 49.8 ± 13.2 mm Hg (p < 0.001). The cardiac index went from 3.6 ± 0.4 to 2.9 ± 0.6 L/min/m2 (p = 0.01).

Conclusions:

Our data suggest that the “higher” positive end-expiratory pressure approach in patients with severe acute respiratory syndrome coronavirus 2 acute respiratory distress syndrome and high compliance improves oxygenation and lung aeration but may result in alveolar hyperinflation and hemodynamic alterations.
Assessment of Materials to Prevent Sutures Cutting Through Atrophic Skin
Authors: Xiong Michael Y. , Bennett Richard G.
Published: September 2020

BACKGROUND

Sutures can tear through thin skin, especially in the elderly. To reinforce thin skin, several materials have been suggested through which sutures may be placed.

OBJECTIVE

To evaluate the relative tear-through resistance to suture provided by various materials applied to a skin substitute.

MATERIALS/METHODS

We measured the force needed for 3-0 polypropylene suture to tear through an artificial skin substitute, both alone and after various materials were applied. These materials included wound closure tapes, nonwoven polyester tape, hydrocolloid dressing, polyethylene film, and cyanoacrylate glue. The Student t-test and one-way analysis of variance were used to determine differences in the mean forces.

RESULTS

Reinforced wound closure tape and nonwoven polyester tape were superior to the other materials, and provided a 3.1-fold and 3.6-fold increase in tear-through resistance, respectively, compared with skin substitute alone (p < .001). Orientation of wound closure tape and nonwoven polyester tape with their reinforcing fibers placed parallel to the skin substitute edge provided increased tear-through resistance compared with perpendicular placement. Affixing these latter materials with liquid adhesive also improved holding strength.

CONCLUSION

Reinforced wound closure tape and nonwoven polyester tape, when applied to a skin substitute, provide significantly increased tear-through resistance to suture compared with skin substitute alone.
A Case of Postmalaria Neurologic Syndrome and Pediatric Literature Review
Authors: Faivre Benjamin , Bessis Simon , Bergounioux Jean , Duran Clara , Dinh Aurélien , Essid Aben
Published: September 2020

Postmalaria neurologic syndrome is an under-recognized self-resolving acute neuropsychiatric condition, usually occurring after complete recovery from malaria. We describe the case of a 7-year-old child who presented with an afebrile lymphocytic meningoencephalitis. The notion of a previously treated malaria episode and the absence of malaria during current episode led us postmalaria neurologic syndrome diagnosis with secondary spontaneous outcome.
Hand-Held Dynamometry in the Inpatient Care Setting After Total Knee Arthroplasty
Authors: Eymir Musa , Yuksel Ertugrul , Unver Bayram , Karatosun Vasfi
Published: September 2020

Objective

The aim of the study was to determine intrarater and interrater reliabilities for static strength assessment of knee flexors and knee extensors in patients with total knee arthroplasty, during the acute postoperative rehabilitation.

Design

Forty-five total knee arthroplasty patients were included in the study. Two physical therapists performed strength assessments by using hand-held dynamometry. Patients performed three trials and a 30-sec rest was provided between each trial. After this, a 5-min rest was provided, and then, a second investigator performed the same procedure for interrater reliability. Assessments for intrarater reliability were performed 1 hr later.

Results

The intrarater reliability of knee extensors and knee flexors strength measurements were 0.96 and 0.94, respectively. The standard error of measurement and minimal detectable change 95% confidence level were 6.17 and 17.01 Nm for knee extensors and were 8.89 and 24.51 Nm for knee flexors, respectively. The interrater reliability of knee flexors and knee extensors strength measurement was 0.96 for both. The standard error of measurement and minimal detectable change values at 95% confidence level were 6.00 and 16.54 Nm for knee extensors and were 6.32 and 17.42 Nm for knee flexors, respectively.

Conclusions

Hand-held dynamometry is a reliable method to assess static knee strength. Hand-held dynamometry assessment can be implemented during acute postoperative rehabilitation. Our results may assist the clinicians in determining an accurate postoperative rehabilitation program after total knee arthroplasty surgery.
Differential utilization of CD4+ by transmitted/founder and chronic envelope glycoproteins in a MSM HIV-1 subtype B transmission cluster
Authors: Bouvin-Pley Mélanie , Leoz Marie , Roch Emmanuelle , Moreau Alain , Migraine Julie , Bellini Nicolas , Blake Olivia , Mammano Fabrizio , Braibant Martine , Plantier Jean-Christophe , Brand Denys
Published: September 2020

Objective:

HIV-1 transmission leads to a genetic bottleneck, with one or a few variants of the donor quasispecies establishing an infection in the new host. We aimed to characterize this bottleneck in more detail, by comparing the properties of HIV envelope glycoproteins from acute and chronic infections within the particular context of a male-to-male transmission cluster.

Design:

We compared the genotypic and phenotypic properties of envelope glycoproteins from viral variants derived from five study participants from the same transmission cluster.

Methods:

We used single-genome amplification to generate a collection of full-length env sequences. We then constructed pseudotyped viruses expressing selected Env variants from the quasispecies infecting each study participant and compared their infectivities and sensitivities to various entry inhibitors.

Results:

The genotypic analyses confirmed the genetic bottleneck expected after HIV transmission, with a limited number of variants identified in four study participants during acute infection. However, the transmitted sequences harbored no evident common signature and belonged to various genetic lineages. The phenotypic analyses revealed no difference in infectivity, susceptibility to the CCR5 antagonist maraviroc, the fusion inhibitor enfurvitide or type-I interferon between viruses from participants with acute and chronic infections. The key property distinguishing transmitted viruses was a higher resistance to soluble CD4+, correlated with greater sensitivity to occupation of the CD4+ receptor by the anti-CD4+ antibodies LM52 and SK3.

Conclusion:

These results suggest that envelope glycoproteins from transmitted/founder viruses bind CD4+ less efficiently than those of viruses from chronic infections.
Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection
Authors: Anderson Albert M. , Jang Jeong Hoon , Easley Kirk A. , Fuchs Dietmar , Gisslen Magnus , Zetterberg Henrik , Blennow Kaj , Ellis Ronald J. , Franklin Donald , Heaton Robert K. , Grant Igor , Letendre Scott L.
Published: September 2020

Background:

Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH).

Methods:

We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time.

Results:

At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease.

Conclusion:

Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.
Oceanipulchritudo coccoides gen. nov., sp. nov., isolated from marine sediment within the family Puniceicoccaceae
Authors: Feng Xi , Zou Qi-Hang , Zhang Xiao-Yu , Ye Meng-Qi , Du Zong-Jun
Published: September 2020

A Gram-stain-negative, aerobic coccus, designated CK1056T, was isolated from coastal sediment of Xiaoshi Island, Weihai, PR China. Strain CK1056T was found to grow at 15–37 °C (optimum, 30 °C), with 0.5–6.5 % (w/v) NaCl (optimum, 3.5 %) and displayed alkaliphilic growth within the pH range of pH 6.5–10.0 (optimum, pH 8.0). The major fatty acids identified were iso-C15 : 0 and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c). The main polar lipids consisted of aminophosphoglycolipid and phosphatidylethanolamine. The predominant respiratory quinone was MK-7. The G+C content of the genomic DNA was 54.0 mol%. The result of the 16S rRNA gene sequence analysis confirmed the affiliation of this micro-organism to the family

Puniceicoccaceae

, with

Coraliomargarita akajimensis

KCTC 12865T as its closest relative with only 88.0 % sequence similarity. From the taxonomic data obtained in this study, we propose that the new marine isolate be placed into a novel species within a novel genus in the family

Puniceicoccaceae

, phylum

Verrucomicrobia

, for which the name Oceanipulchritudo coccoides gen. nov., sp. nov. is proposed. The type strain is CK1056T (=KCTC 72798T=MCCC 1H00425T).
Mitochondrial induced T cell apoptosis and aberrant myeloid metabolic programs define distinct immune cell subsets during acute and recovered SARS-CoV-2 infection
Authors: Thompson Elizabeth A. , Cascino Katherine , Ordonez Alvaro A. , Zhou Weiqiang , Vaghasia Ajay , Hamacher-Brady Anne , Brady Nathan R. , Sun Im-Hong , Wang Rulin , Rosenberg Avi Z. , Delannoy Michael , Rothman Richard , Fenstermacher Katherine , Sauer Lauren , Shaw-Saliba Kathyrn , Bloch Evan M. , Redd Andrew D. , Tobian Aaron AR , Horton Maureen , Smith Kellie , Pekosz Andrew , D’Alessio Franco R. , Yegnasubramanian Srinivasan , Ji Hongkai , Cox Andrea L. , Powell Jonathan D.
Published: September 2020

By interrogating metabolic programs in the peripheral blood mononuclear cells (PBMC) of acutely infected COVID-19 patients, we identified novel and distinct immune cell subsets Our studies identified a non-clonal population of T cells expressing high H3K27me3 and voltage-dependent anion channel (VDAC) with mitochondrial dysfunction and increased susceptibility to cell death. Characterized by dysmorphic mitochondria and increased cytoplasmic cytochromec, apoptosis of these cells was inhibited by preventing VDAC aggregation or blocking caspase activation. Further, we observed a marked increase in Hexokinase II+polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC). While PMN-MDSC were also found in the PBMC of patients with other viral infections, the Hexokinase II+PMN-MDSC were found exclusively in the acute COVID-19 patients with moderate or severe disease. Finally, we identified a population of monocytic MDSC (M-MDSC) expressing high carnitine palmitoyltransferase I (CPT1a) and VDAC, which were present in the PBMC of the acute COVID-19 patients, but not recovered COVID-19 patients and whose presence correlated with severity of disease. Overall, these unique populations of immune cells provide insight into the pathogenesis of SARS-CoV-2 infection and provide a means to predict and track disease severity as well as an opportunity to design and evaluate novel therapeutic regimens.

One Sentence Summary

Metabolic programs define unique immune cells among COVID-19 patients with severe diease.
Biochemical and Biophysical Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections
Authors: Kratochvil Michael J. , Kaber Gernot , Cai Pamela C. , Burgener Elizabeth B. , Barlow Graham L. , Nicolls Mark R. , Ozawa Michael G. , Regula Donald P. , Pacheco-Navarro Ana E. , Milla Carlos E. , Nagy Nadine , Yang Samuel ,   Stanford COVID-19 Biobank Study Group, Rogers Angela J. , Spakowitz Andrew J. , Heilshorn Sarah C. , Bollyky Paul L.
Published: September 2020

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percent solids and protein content are all greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis (CF), a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibited heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. These results highlight the dramatic biophysical properties of COVID-19 respiratory secretions and suggest that DNA and hyaluronan may be viable therapeutic targets in COVID-19 infection.
Saliva as a potential clinical specimen for diagnosis of SARS-CoV-2
Authors: Bhattacharya Debdutta , Parai Debaprasad , Rout Usha Kiran , Nanda Rashmi Ranjan , Kanungo Srikanta , Dash Girish Chandra , Palo Subrat Kumar , Giri Sidharth , Choudhary Hari Ram , Kshatri Jaya Singh , Turuk Jyotirmayee , Mishra Bijay Kumar , Dash Saroj , Pati Sanghamitra
Published: September 2020

Background

It is almost nine months, still there is no sign to stop the spreading of the COVID-19 pandemic. Rapid and early detection of the virus is the master key to cease the rapid spread and break the human transmission chain. There are very few studies in search of an alternate and convenient diagnostic tool which can substitute nasopharyngeal swab (NPS) specimen for detection of SARS-CoV-2. We aimed to analyse the comparison and agreement between the feasibility of using the saliva in comparison to NPS for diagnosis of SARS-CoV-2.

Methods

A total number of 74 patients were enrolled for this study. We analysed and compared the NPS and saliva specimen collected within 48 h after the symptom onset. We used real time quantitative polymerase chain reaction (RT-qPCR), gene sequencing for the detection and determination SARS-CoV-2 specific genes. Phylogenetic tree was constructed to establish the isolation of viral RNA from saliva. We use Bland-Altman model to identify the agreement between two specimens.

Findings

This study shows a lower CTmean value for the detection of SARS-CoV-2 ORF1 gene (27.07; 95% CI, 25.62 to 28.52) in saliva methods than that of NPS (28.24; 95% CI, 26.62 to 29.85) sampling method. Bland-Altman analysis produces relatively smaller bias and high agreement between these specimen tools. Phylogenetic analysis with the RdRp and Spike gene confirmed the presence of SARS-CoV-2 in the saliva samples.

Interpretation

In conclusion, our study highlights that saliva represents a promising tool in COVID-19 diagnosis and would reduce the exposure risk of frontline health workers which is one of biggest concern in primary healthcare settings.
A Comparative Study to Find a Suitable Model for an Improved Real-Time Monitoring of The Interventions to Contain COVID-19 Outbreak in The High Incidence States of India
Authors: Amrutha G.S , Sharma Abhibhav , Sharma Anudeepti
Published: September 2020

Background

On March 11, 2020, The World Health Organization (WHO) declared coronavirus disease (COVID-19) as a global pandemic. There emerged a need for reliable models to estimate the imminent incidence and overall assessment of the outbreak, in order to develop effective interventions and control strategies. One such vital metrics for monitoring the transmission trends over time is the time-dependent effective reproduction number (Rt). Rt is an estimate of secondary cases caused by an infected individual at a time t during the outbreak, given that a certain population proportion is already infected. Misestimated Rt is particularly concerning when probing the association between the changes in transmission rate and the changes in the implemented policies. In this paper, we substantiate the implementation of the instantaneous reproduction number (Rins) method over the conventional method to estimate Rt viz case reproduction number (Rins), by unmasking the real-time estimation ability of both methodologies using credible datasets.

Materials & Methods

We employed the daily incidence dataset of COVID-19 for India and high incidence states to estimate Rins and Rcase. We compared the real-time projection obtained through these methods by corroborating those states that are containing high number of COVID-19 cases and are conducting high and efficient COVID-19 testing. The Rins and Rcase were estimated using R0 and EpiEstim packages respectively in R software 4.0.0.

Results

Although, both the Rins and Rcase. for the selected states were higher during the lockdown phases (March 25 - June 1, 2020) and subsequently stabilizes co-equally during the unlock phase (June 1-August 23, 2020), Rins demonstrated variations in accordance with the interventions while Rcase. remained generalized and under- & overestimated. A larger difference in Rins and Rcase. estimates was also observed for states that are conducting high testing.

Conclusion

Of the two methods, Rins elucidated a better real-time progression of the COVID-19 outbreak conceptually and empirically, than that of Rcase. However, we also suggest considering the assumptions corroborated in the implementations which may result in misleading conclusions in the real world.
Joint hypermobility and its relevance to common mental illness in adolescents: a population-based longitudinal study
Authors: Eccles Jessica A , Scott Hannah E , Davies Kevin A , Bond Rod , David Anthony S , Harrison Neil A. , Critchley Hugo D
Published: September 2020

Importance

Depression and anxiety are common mood disorders that show higher prevalence in adults with joint hypermobility, a consequence of a constitutional variant of connective tissue structure. In adolescents, an association between mood disorder and hypermobility may enhance the potential understanding of risk factors for emotional disorder and provide opportunities for early intervention approaches.

Objective

To test the hypothesis that joint hypermobility, a consequence of constitutional variant of connective tissue, is associated with common mental illness in adolescents.

Design

This was a longitudinal prospective study.

Setting

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective ongoing general population birth cohort study based in Avon County, England.

Participants

The original data set comprised 6105 individuals from the cohort with data available on joint hypermobility at age 14 years; a sub-sample (n=3803) had later psychiatric assessments.

Measurement of Exposure

Joint hypermobility was measured by physical examination at age 14 and 18 years, using the Beighton Scale

Main Outcome and Measures

Participants were assessed at age 18 years. ICD-10 diagnoses of Depression and Anxiety were obtained using the Clinical Interview Schedule-Revised (CIS-R) and levels of anxiety quantified using the Anxiety Sensitivity Index (ASI)

Results

Presence of generalized joint hypermobility (GJH) at age 14 years predicted depression at 18 years in males (Odds Ratio (OR) 2.10; 95%CI, 1.17-3.76) but not females After accounting for missing data it was determined that this relationship was mediated by heart rate, a potential measure of physiological arousal. Symptomatic hypermobility ((GJH plus chronic widespread pain (CWP)) at age 18 years was further associated with the presence of anxiety disorder (OR 3.13; 95% CI 1.52-6.46) and level of anxiety (Beta = 0.056, t(3315)=3.27), depressive disorder (adjusted OR 3.52; 95%CI, 1.67 – 7.40) and degree of psychiatric symptomatology (Beta 0.096, t(2064)=4.38)

Conclusions and relevance

Generalized joint hypermobility and symptomatic hypermobility are associated with common mental disorders in adolescence. Consideration of hypermobility may provide important opportunities for intervention to mitigate psychiatric disorder.

KEY POINTS

Question

Is joint hypermobility related to depression and anxiety in adolescence?

Findings

In this longitudinal study presence of generalized joint hypermobility at 14 predicted subsequent adolescent depression in males only and this relationship was mediated by heart rate. At age 18 symptomatic hypermobility was associated with both presence of anxiety and depression and psychiatric symptom severity.

Meaning

Generalized joint hypermobility and symptomatic hypermobility are associated with common mental disorders in adolescence.
LOW BIRTH WEIGHT AS A RISK FACTOR FOR SEVERE COVID-19 IN ADULTS
Authors: Crispi Fàtima , Crovetto Francesca , Larroya Marta , Camacho Marta , Tortajada Marta , Sibila Oriol , Badia Joan Ramon , López Marta , Vellvé Kilian , Garcia Ferran , Trilla Antoni , Faner Rosa , Blanco Isabel , Borràs Roger , Agustí Alvar , Gratacós Eduard
Published: September 2020

The identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18-70y) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤2,500 g. Age (adjusted OR (aOR) 1.04 [1-1.07], P=0.012), male sex (aOR 3.39 [1.72-6.67], P<0.001), hypertension (aOR 3.37 [1.69-6.72], P=0.001), and LBW (aOR 3.61 [1.55-8.43], P=0.003) independently predicted admission to ICU. The area under the receiver-operating characteristics curve (AUC) of this model was 0.79 [95% CI, 0.74-0.85], with positive and negative predictive values of 29.1% and 97.6% respectively. Results were reproduced in an independent cohort, from a web-based survey in 1,822 subjects who self-reported laboratory-positive SARS-CoV-2 infection, where 46 patients (2.5%) needed ICU admission (AUC 0.74 [95% CI 0.68-0.81]). LBW seems to be an independent risk factor for severe COVID-19 in non-elderly adults and might improve the performance of risk stratification algorithms.
Early-life socioeconomic position and the accumulation of health-related deficits by midlife in the 1958 British birth cohort study
Authors: Rogers Nina T , Blodgett Joanna M , Searle Samuel D , Cooper Rachel , Davis Daniel H J , Pinto Pereira Snehal M
Published: September 2020

Reducing population levels of frailty is an important goal and preventing its development in mid-adulthood could be pivotal. Childhood socioeconomic position (SEP) is associated with a myriad of adult health outcomes but evidence is limited on associations with frailty. Using 1958 British birth cohort data (N=8711), we aimed to: (i) establish the utility of measuring frailty in mid-life, by examining associations between a 34-item frailty index at 50y (FI50y) and mortality over an eight-year follow-up period and (ii) examine associations between early-life SEP and FI50y and investigate whether these associations were explained by adult SEP. Hazard ratios (HRs) for mortality increased with increasing levels of frailty, e.g., HRsex-adjusted was 4.07(95% CI:2.64,6.25) for highest vs. lowest fifth of FI50y. Lower early-life SEP was associated with higher FI50y: per unit decrease in early-life SEP (on a 4-point scale), FI50y increased by 12.7%(10.85%,14.6%) in a model adjusted for early-life covariates. After additional adjustment for adult occupational class and education, the association attenuated to 5.71%(3.71%,7.70%). Findings suggest that early-life SEP is associated with frailty and that adult SEP only partially explains this association. Results highlight the importance of improving socioeconomic circumstances across the life course to reduce inequalities in frailty from mid-adulthood.
Increased rate of joint hypermobility in autism and related neurodevelopmental conditions is linked to dysautonomia and pain
Authors: Csecs Jenny L L , lodice Valeria , Rae Charlotte L , Brooke Alice , Simmons Rebecca , Dowell Nicholas G , Prowse Fenella , Themelis Kristy , Critchley Hugo D , Eccles Jessica A
Published: September 2020

Objective

Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social and emotional functioning. Vulnerability to chronic physical symptoms, including fatigue and pain, are also recognised. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts vulnerability to psychological symptoms alongside recognised physical symptoms. Here, we tested for increased rates of joint hypermobility, autonomic dysfunction and pain in 109 adults with neurodevelopmental diagnoses.

Method

Rates of generalized joint laxity in those individuals with neurodevelopmental conditions were compared to those in the general population in UK. Levels of orthostatic intolerance and musculoskeletal symptoms were compared to a neurotypical control group.

Results

Adults with neurodevelopmental diagnoses manifest elevated rates of joint hypermobility (50%) compared to the general population rate of 20% and a matched control population of 10%. Odds ratio for hypermobility in individuals with neurodevelopmental diagnoses, compared to the general population was 4.51 (95%CI 2.17-9.37), with greater odds in females rather than males. Neurodevelopmental patients reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than controls

Conclusions

In adults with neurodevelopmental conditions, there is a strong link between the expression of joint hypermobility, autonomic dysfunction and pain, more so than in healthy controls. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties including comorbid stress-sensitive physical symptoms.
Predicting morbidity by Local Similarities in Multi-Scale Patient Trajectories
Authors: Carrasco-Ribelles Lucía A , Pardo-Mas Jose Ramón , Tortajada Salvador , Sáez Carlos , Valdivieso Bernardo , García-Gómez Juan M
Published: September 2020

Healthcare predictive models generally rely on static snapshots of patient information. Patient Trajectories (PTs) model the evolution of patient conditions over time and are a promising source of information for predicting future morbidities. However, PTs are highly heterogeneous among patients in terms of length and content, so only aggregated versions that include the most frequent events have been studied. Further, the use of longitudinal multiscale data such as integrating EHR coded data and laboratory results in PT models is yet to be explored. Our hypothesis is that local similarities on small chunks of PTs can identify similar patients with respect to their future morbidities. The objectives of this work are (1) to develop a methodology to identify local similarities between PTs prior to the occurrence of morbidities to predict these on new query individuals; and (2) to validate this methodology to impute risk of cardiovascular diseases (CVD) in patients with diabetes.

We have proposed a novel formal definition of PTs based on sequences of multi-scale data over time, so each patient has their own PT including every data available in their EHR. Thus, patients do not need to follow partly or completely one pre-defined trajectory built by the most frequent events in a population but having common events with any another patient. A dynamic programming methodology to identify local alignments on PTs for predicting future morbidities is proposed. The proposed methodology for PT definition and the alignment algorithm are generic to be applied on any additional clinical domain. We tested this solution for predicting CVD in patients with diabetes and we achieved a positive predictive value of 0.33, a recall of 0.72 and a specificity of 0.38. Therefore, the proposed solution in the diabetes use case can result of utmost utility to patient screening.

Highlights

Local similarities between patient trajectories can potentially be used to predict morbid conditions.

A formal definition of patient trajectories comprising heterogeneous clinical observations, biomedical tests and time gaps is proposed.

A novel dynamic programming methodology is proposed to find similar patients based on the Smith-Waterman alignment algorithm and a set of customized scoring matrices.
PreQual: An automated pipeline for integrated preprocessing and quality assurance of diffusion weighted MRI images
Authors: Cai Leon Y. , Yang Qi , Hansen Colin B. , Nath Vishwesh , Ramadass Karthik , Johnson Graham W. , Conrad Benjamin N. , Boyd Brian D. , Begnoche John P. , Beason-Held Lori L. , Shafer Andrea T. , Resnick Susan M. , Taylor Warren D. , Price Gavin R. , Morgan Victoria L. , Rogers Baxter P. , Schilling Kurt G. , Landman Bennett A.
Published: September 2020

Purpose

Diffusion weighted MRI imaging (DWI) is often subject to low signal-to-noise ratios (SNRs) and artifacts. Recent work has produced software tools that can correct individual problems, but these tools have not been combined with each other and with quality assurance (QA). A single integrated pipeline is proposed to perform DWI preprocessing with a spectrum of tools and produce an intuitive QA document.

Methods

The proposed pipeline, built around the FSL, MRTrix3, and ANTs software packages, performs DWI denoising; inter-scan intensity normalization; susceptibility-, eddy current-, and motion-induced artifact correction; and slice-wise signal drop-out imputation. To perform QA on the raw and preprocessed data and each preprocessing operation, the pipeline documents qualitative visualizations, quantitative plots, gradient verifications, and tensor goodness-of-fit and fractional anisotropy analyses.

Results

Raw DWI data were preprocessed and quality checked with the proposed pipeline and demonstrated improved SNRs; physiologic intensity ratios; corrected susceptibility-, eddy current-, and motion-induced artifacts; imputed signal-lost slices; and improved tensor fits. The pipeline identified incorrect gradient configurations and file-type conversion errors and was shown to be effective on externally available datasets.

Conclusion

The proposed pipeline is a single integrated pipeline that combines established diffusion preprocessing tools from major MRI-focused software packages with intuitive QA.
rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins
Authors: Lang Benjamin , Yang Jae-Seong , Garriga-Canut Mireia , Speroni Silvia , Gili Maria , Hoffmann Tobias , Tartaglia Gian Gaetano , Maurer Sebastian P.
Published: September 2020

RNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactionsin vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacentlyin vivo. We further find that the mRNA binding region and motif preferences of RBPs can deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks.

Graphical abstract
Evolution and Ecology in Widespread Acoustic Signaling Behavior Across Fishes
Authors: Rice Aaron N. , Farina Stacy C. , Makowski Andrea J. , Kaatz Ingrid M. , Lobel Philip S. , Bemis William E. , Bass Andrew H.
Published: September 2020

Acoustic signaling by fishes has been recognized for millennia, but is typically regarded as comparatively rare within ray-finned fishes; as such, it has yet to be integrated into broader concepts of vertebrate evolution. We map the most comprehensive data set of volitional sound production of ray-finned fishes (Actinopterygii) yet assembled onto a family level phylogeny of the group, a clade representing more than half of extant vertebrate species. Our choice of family-level rather than species-level analysis allows broad investigation of sonifery within actinopterygians and provides a conservative estimate of the distribution and ancestry of a character that is likely far more widespread than currently known. The results show that families with members exhibiting soniferous behavior contain nearly two-thirds of actinopterygian species, with potentially more than 20,000 species using acoustic communication. Sonic fish families also contain more extant species than those without sounds. Evolutionary analysis shows that sound production is an ancient behavior because it is present in a clade that originating circa 340 Ma, much earlier than any evidence for sound production within tetrapods. Ancestral state reconstruction indicates that sound production is not ancestral for actinopterygians; instead, it independently evolved at least 27 times, compared to six within tetrapods. This likely represents an underestimate for actinopterygians that will change as sonifery is recognized in ever more species of actinopterygians. Several important ecological factors are significantly correlated with sonifery – including physical attributes of the environment, predation by members of other vertebrate clades, and reproductive tactics – further demonstrating the broader importance of sound production in the life history evolution of fishes. These findings offer a new perspective on the role of sound production and acousticcommunication during the evolution of Actinopterygii, a clade containing more than 34,000 species of extant vertebrates.
Time-restricted feeding prolongs lifespan inDrosophilain a peripheral clock-dependent manner
Authors: Cabrera Daniel , Young Michael W. , Axelrod Sofia
Published: September 2020

Time-restricted feeding/eating (TRF/TRE) – limiting not the amount of food but the daily time window of food intake – is a dietary intervention that has been shown to improve health markers in model organisms and humans, but whether these benefits translate into positive effects on aging and longevity is not clear. We demonstrate here that TRF robustly prolongs lifespan in the short-lived genetically tractable model organismDrosophila melanogaster. Median TRF lifespan extensions range between ∼10% and ∼50% dependent on sex, reproductive status, TRF duration, and genotype. TRF’s positive effect on longevity is independent of food intake and at least in part relies on a functioning circadian clock: TRF benefits on longevity are abolished in arrhythmicper0andtim01mutants as well as in constant light, suggesting that timed feeding acts as a zeitgeber partitioning eating and associated metabolic processes into certain phases of day and night. TRF-mediated longevity extension is unaffected in flies whose neural circadian clocks have been abolished genetically, pointing towards peripheral clocks as the target of TRF mediating lifespan extension.
Phylogenomics reveals multiple introductions and early spread of SARS-CoV-2 into Peru
Authors: Juscamayta-López Eduardo , Tarazona David , Valdivia Faviola , Rojas Nancy , Carhuaricra Dennis , Maturrano Lenin , Gavilán Ronnie
Published: September 2020

Peru has become one of the countries with the highest mortality rate from the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To investigate early transmission event and genomic diversity of SARS-CoV-2 isolates circulating in Peru, we analyzed a total of 3472 SARS-CoV-2 genomes, from which 149 ones were from Peru. Phylogenomic analysis revealed multiple and independent introductions of the virus mainly from Europe and Asia. In addition, we found evidence for community-driven transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different Peru regions.
Intracellular Optical Doppler Phenotypes of Chemosensitivity in Human Epithelial Ovarian Cancer
Authors: Li Zhe , An Ran , Swetzig Wendy M. , Kanis Margaux , Nwani Nkechiyere , Turek John , Matei Daniela , Nolte David
Published: September 2020

Development of an assay to predict response to chemotherapy has remained an elusive goal in cancer research. We report a phenotypic chemosensitivity assay for epithelial ovarian cancer based on Doppler spectroscopy of infrared light scattered from intracellular motions in living three-dimensional tumor biopsy tissue measuredin vitro. The study analyzed biospecimens from 20 human patients with epithelial ovarian cancer. Matched primary and metastatic tumor tissues were collected for 3 patients, and an additional 3 patients provided only metastatic tissues. Doppler fluctuation spectra were obtained using full-field optical coherence tomography through off-axis digital holography. Frequencies in the range from 10 mHz to 10 Hz are sensitive to changes in intracellular dynamics caused by platinum-based chemotherapy. Metastatic tumor tissues were found to display a biodynamic phenotype that was similar to primary tissue from patients who had poor clinical outcomes. The biodynamic phenotypic profile correctly classified 90% [88% to 91% c.i.] of the patients when the metastatic samples were characterized as having a chemoresistant phenotype. This work suggests that Doppler profiling of tissue response to chemotherapy has the potential to predict patient clinical outcomes based on primary, but not metastatic, tumor tissue.
Experience enhances certainty about olfactory stimuli under bulbar cholinergic control
Authors: Cho Christina , Linster Christiane
Published: September 2020

We present evidence that experience and cholinergic modulation in an early sensory network interact to improve certainty about olfactory stimuli. The data we present are in agreement with existing theoretical ideas about the functional role of acetylcholine but highlight the importance of early sensory networks in addition to cortical networks. We use a simple behavioral paradigm in mice which allows us to measure certainty about a stimulus via the response amplitude to a condition and novel stimuli. We conclude that additional learning increases certainty and that the slope of this relationship can be modulated by activation of muscarinic cholinergic receptors in the olfactory bulb.
(3Z,5E)-2-Amino-4,6-bis(pyridin-3-yl)hepta-1,3,5-triene-1,1,3-tricarbonitrile
Authors: Cai Changting , Lin Bicheng , Wu Wenxuan , Zhu Qingwei
Published: September 2020

In the title compound, C20H14N6, the dihedral angle between the pyridine rings is 37.98 (7)°. In the crystal, N—H...N hydrogen bonds link the molecules into (10\overline{2}) sheets.
Six Sigma quality evaluation of life test data based on Weibull distribution
Authors: A Niveditha , Joghee Ravichandran
Published: September 2020

Purpose

While Six Sigma metrics have been studied by researchers in detail for normal distribution-based data, in this paper, we have attempted to study the Six Sigma metrics for two-parameter Weibull distribution that is useful in many life test data analyses.

Design/methodology/approach

In the theory of Six Sigma, most of the processes are assumed normal and Six Sigma metrics are determined for such a process of interest. In reliability studies non-normal distributions are more appropriate for life tests. In this paper, a theoretical procedure is developed for determining Six Sigma metrics when the underlying process follows two-parameter Weibull distribution. Numerical evaluations are also considered to study the proposed method.

Findings

In this paper, by matching the probabilities under different normal process-based sigma quality levels (SQLs), we first determined the Six Sigma specification limits (Lower and Upper Six Sigma Limits- LSSL and USSL) for the two-parameter Weibull distribution by setting different values for the shape parameter and the scaling parameter. Then, the lower SQL (LSQL) and upper SQL (USQL) values are obtained for the Weibull distribution with centered and shifted cases. We presented numerical results for Six Sigma metrics of Weibull distribution with different parameter settings. We also simulated a set of 1,000 values from this Weibull distribution for both centered and shifted cases to evaluate the Six Sigma performance metrics. It is found that the SQLs under two-parameter Weibull distribution are slightly lesser than those when the process is assumed normal.

Originality/value

The theoretical approach proposed for determining Six Sigma metrics for Weibull distribution is new to the Six Sigma Quality practitioners who commonly deal with normal process or normal approximation to non-normal processes. The procedure developed here is, in fact, used to first determine LSSL and USSL followed by which LSQL and USQL are obtained. This in turn has helped to compute the Six Sigma metrics such as defects per million opportunities (DPMOs) and the parts that are extremely good per million opportunities (EGPMOs) under two-parameter Weibull distribution for lower-the-better (LTB) and higher-the-better (HTB) quality characteristics. We believe that this approach is quite new to the practitioners, and it is not only useful to the practitioners but will also serve to motivate the researchers to do more work in this field of research.