bluuebunny/crossref_metadata_2025 huggingface dataset:
Translating COVID-19 Evidence to Maximize Physical Therapists’ Impact and Public Health Response
Authors: Dean Elizabeth , Jones Alice , Yu Homer Peng-Ming , Gosselink Rik , Skinner Margot
Published: June 2020

Coronavirus disease 2019 (COVID-19) has sounded alarm bells throughout global health systems. As of late May, 2020, over 100,000 COVID-19–related deaths were reported in the United States, which is the highest number of any country. This article describes COVID-19 as the next historical turning point in the physical therapy profession’s growth and development. The profession has had over a 100-year tradition of responding to epidemics, including poliomyelitis; 2 world wars and geographical regions experiencing conflicts and natural disasters; and, the epidemic of noncommunicable diseases (NCDs). The evidence-based role of noninvasive interventions (nonpharmacological/nonsurgical) that hallmark physical therapist practice has emerged as being highly relevant today in addressing COVID-19 in 2 primary ways. First, despite some unique features, COVID-19 presents as acute respiratory distress syndrome in its severe acute stage. Acute respiratory distress syndrome is very familiar to physical therapists in intensive care units. Body positioning and mobilization, prescribed based on comprehensive assessments/examinations, counter the negative sequelae of recumbency and bedrest; augment gas exchange and reduce airway closure, deconditioning, and critical illness complications; and maximize long-term functional outcomes. Physical therapists have an indisputable role across the contiuum of COVID-19 care. Second, over 90% of individuals who die from COVID-19 have comorbidities, most notably cardiovascular disease, hypertension, chronic lung disease, type 2 diabetes mellitus, and obesity. Physical therapists need to redouble their efforts to address NCDs by assessing patients for risk factors and manifestations and institute evidence-based health education (smoking cessation, whole-food plant-based nutrition, weight control, physical activity/exercise), and/or support patients’ efforts when these are managed by other professionals. Effective health education is a core competency for addressing risk of death by COVID-19 as well as NCDs. COVID-19 is a wake-up call to the profession, an opportunity to assert its role throughout the COVID-19 care continuum, and augment public health initiatives by reducing the impact of the current pandemic.
Porous silicon carbide coated with tantalum as potential material for bone implants
Authors: Ma Zhijie , Li Jingyu , Cao Fang , Yang Jiahui , Liu Rong , Zhao Dewei
Published: June 2020

Porous silicon carbide (SiC) has a specific biomorphous microstructure similar to the trabecular microstructure of human bone. Compared with that of bioactive ceramics, such as calcium phosphate, SiC does not induce spontaneous interface bonding to living bone. In this study, bioactive tantalum (Ta) metal deposited on porous SiC scaffolds by chemical vapour deposition was investigated to accelerate osseointegration and improve the bonding to bones. Scanning electron microscopy indicated that the Ta coating evenly covered the entire scaffold structure. Energy-dispersive spectroscopy and X-ray diffraction analysis showed that the coating consisted of Ta phases. The bonding strength between the Ta coating and the SiC substrate is 88.4 MPa. The yield strength of porous SiC with a Ta coating (pTa) was 45.8 ± 2.9 MPa, the compressive strength was 61.4 ± 3.2 MPa and the elastic modulus was ∼4.8 GPa. When MG-63 human osteoblasts were co-cultured with pTa, osteoblasts showed good adhesion and spreading on the surface of the pTa and its porous structure, which showed that it has excellent bioactivity and cyto-compatibility. To further study the osseointegration properties of pTa. PTa and porous titanium (pTi) were implanted into the femoral neck of goats for 12 weeks, respectively. The Van-Gieson staining of histological sections results that the pTa group had better osseointegration than the pTi group. These results indicate that coating bioactive Ta metal on porous SiC scaffolds could be a potential material for bone substitutes.
Adiposity covaries with signatures of asymmetric feedback learning during adaptive decisions
Authors: Verstynen Timothy , Dunovan Kyle , Walsh Catherine , Kuan Chieh-Hsin , Manuck Stephen B , Gianaros Peter J
Published: June 2020

Unhealthy weight gain relates, in part, to how people make decisions based on prior experience. Here we conducted post hoc analysis on an archival data set to evaluate whether individual differences in adiposity, an anthropometric construct encompassing a spectrum of body types, from lean to obese, associate with signatures of asymmetric feedback learning during value-based decision-making. In a sample of neurologically healthy adults (N = 433), ventral striatal responses to rewards, measured using fMRI, were not directly associated with adiposity, but rather moderated its relationship with feedback-driven learning in the Iowa gambling task, tested outside the scanner. Using a biologically inspired model of basal ganglia-dependent decision processes, we found this moderating effect of reward reactivity to be explained by an asymmetrical use of feedback to drive learning; that is, with more plasticity for gains than for losses, stronger reward reactivity leads to decisions that minimize exploration for maximizing long-term outcomes. Follow-up analysis confirmed that individual differences in adiposity correlated with signatures of asymmetric use of feedback cues during learning, suggesting that reward reactivity may especially relate to adiposity, and possibly obesity risk, when gains impact future decisions more than losses.
The COVID-19 Pandemic: Lessons for Financially Fragile and Aging Societies
Authors: van Dalen Hendrik P , Henkens Kène
Published: June 2020

The current COVID-19 crisis teaches organizations and households harsh lessons about the necessity of having buffers, to deal with the consequences of the COVID-19 virus. The financial fragility of households and the rising proportion of people becoming obese calls for intensified efforts, both by individuals and employers to create financial buffers and keep on investing in health. The financial fragility of organizations is a wake-up call that a short-term focus on efficiency can be counterproductive and may overturn the efforts to start working longer.
The osteology of the early-diverging dinosaurDaemonosaurus chauliodus(Archosauria: Dinosauria) from theCoelophysisQuarry (Triassic: Rhaetian) of New Mexico and its relationships to other early dinosaurs
Authors: Nesbitt Sterling J , Sues Hans-Dieter
Published: June 2020

The early evolution of dinosaurs is documented by abundant postcranial material, but cranial material is much rarer and comparisons of cranial features among early dinosaurs are limited to only a few specimens. Here, we fully detail the osteology of the unusual early-diverging dinosaur Daemonosaurus chauliodus from the latest Triassic Coelophysis Quarry in northern New Mexico, USA. The taxon possesses a unique and curious suite of character states present in a variety of early dinosaurs, and the morphology of D. chauliodus appears to link the morphology of Herrerasaurus with that of later diverging eusaurichians. Our phylogenetic analyses places D. chauliodus at the base of dinosaurs and our interpretation of the unusual mix of character states of D. chauliodus does not lead to a firm conclusion about its nearest relationships or its implications for the evolution of character state transitions at the base of Dinosauria. The combination of character states of D. chauliodus should not be ignored in future considerations of character evolution in early dinosaurs. As one of the last members of the earliest radiation of saurischians in the Carnian–early Norian, D. chauliodus demonstrates that members of the original diversification of dinosaurs survived until nearly the end of the Triassic Period.
Recovery from Mosaic Caused by Sorghum Mosaic Virus in Sugarcane and Impact on Yield
Authors: Rice J. L. , Hoy J. W.
Published: June 2020

Mosaic is a historically important viral disease of sugarcane in Louisiana caused by Sugarcane mosaic virus and, currently, by Sorghum mosaic virus (SrMV). Sugarcane clones can have variable responses to mosaic for different traits, including susceptibility to infection and yield loss. Disease incidence and rate of increase within a multiple-year crop cycle is affected by susceptibility and other epidemiological factors, possibly including recovery from symptom expression and virus infection. Recovery (defined as the emergence of asymptomatic plants from buds on planted symptomatic stalks) and the impact of mosaic on yield components were evaluated in two sugarcane cultivars, HoCP 09-804 and L 10-147. Recovery varied between the two cultivars. Across two experiments, L 10-147 had a higher frequency of recovery (range 9.4 to 19.8%) than HoCP 09-804 (range 0.9 to 2.3%). A reverse-transcription PCR assay did not detect SrMV in 96.5% of 143 L 10-147 leaf samples and 83.3% of 6 HoCP 09-804 leaf samples collected from recovered plants. When comparing symptomatic and asymptomatic plantings, mosaic reduced cane and sucrose yield in HoCP 09-804 but not L 10-147, suggesting a possible association between recovery and tolerance to virus infection.
Prognostic factors of pacing-induced cardiomyopathy
Authors: Zhang Hong , Zhou Yu-Jie , Zeng Yu-Jie
Published: June 2020

Background:

The detrimental outcomes of right ventricular pacing on left ventricular electromechanical function ultimately result in heart failure, a phenomenon termed pacing-induced cardiomyopathy (PICM) in clinical research. This study aimed to validate prognostic factors that can be used to identify patients with higher susceptibility to progress to the stage of cardiomyopathy before pacemaker implantation.

Methods:

This observational analysis enrolled 256 patients between January 2013 and June 2016, 23 (8.98%) of whom progressed to PICM after 1 year of follow-up. A Cox proportional hazard model was used to analyze the prognostic factors associated with PICM. Dose-response analysis was used to evaluate the relationship between significant indicators in multifactor analysis and PICM.

Results:

The mean values of left ventricular ejection fraction before and after pacemaker implantation in 23 patients diagnosed with PICM were 62.3% and 42.7%, respectively. Univariate analysis showed that sex, atrio-ventricular block, paced QRS duration, and ventricular pacing percentage were significantly associated with PICM. In the multivariate analysis, male sex (hazard ratio: 1.20, 95% confidence interval [CI]: 1.09–1.33,P < 0.005), paced QRS duration (hazard ratio: 1.95 per 1 ms increase, 95% CI: 1.80–2.12,P < 0.001), and ventricular pacing percentage (hazard ratio: 1.65 per 1% increase, 95% CI: 1.51–1.79,P < 0.001) were independent prognostic factors associated with the development of PICM. The ventricular pacing percentage and paced QRS duration level defined by the dose-response analysis were positively associated with PICM (P < 0.05).

Conclusions:

Our findings indicated that paced QRS duration and ventricular pacing percentage were the most sensitive prognostic factors for PICM.
Risk factors for surgical-site infections after radical gastrectomy for gastric cancer: a study in China
Authors: Qiao Yong-Qi , Zheng Li , Jia Bei , Wang Wei-Hua , Zheng Xiao-Hao , Fan Lin-Lin , Xie Yi-Bin , Tian Yan-Tao
Published: June 2020

Background

About 10% of patients get a surgical-site infection (SSI) after radical gastrectomy for gastric cancer, but SSI remains controversial among surgeons. The aim of this study was to explore the risk factors for SSIs after radical gastrectomy in patients with gastric cancer to guide clinical therapies and reduce the incidence of SSI.

Methods

The study was a retrospective cohort study in patients who underwent radical gastrectomy for gastric cancer. SSI was defined in accordance with the National Nosocomial Infection Surveillance System. We evaluated patient-related and peri-operative variables that could be risk factors for SSIs. The Chi-squared test and logistic regression analysis were used to assess the association between these risk factors and SSI.

Results

Among the 590 patients, 386 were men and 204 were women. The mean age was 56.6 (28–82) years and 14.2% (84/590) of these patients had an SSI. Among them, incisional SSI was observed in 23 patients (3.9%) and organ/space SSI in 61 patients (10.3%). Multivariate logistic regression analysis identified sex (odds ratios [ORs] = 2.548, and 95% confidence interval [CI]: 1.268–5.122, P = 0.009), total gastrectomy (OR = 2.327, 95% CI: 1.352–4.004, P = 0.002), albumin level (day 3 after surgery) <30 g/L (OR = 1.868, 95% CI: 1.066–3.274, P = 0.029), and post-operative total parenteral nutrition (OR = 2.318, 95% CI: 1.026–5.237, P = 0.043) as independent risk factors for SSI.

Conclusions

SSI was common among patients after radical gastrectomy for gastric cancer. The method supporting post-operative nutrition and the duration of prophylactic antibiotics may be important modifiable influencing factors for SSI.
Long-term Results of Intraocular Pressure Elevation and Post-DMEK Glaucoma After Descemet Membrane Endothelial Keratoplasty
Authors: Maier Anna-Karina B. , Pilger Daniel , Gundlach Enken , Winterhalter Sibylle , Torun Necip
Published: June 2020

Purpose:

Intraocular pressure (IOP) elevation occurs regularly after Descemet membrane endothelial keratoplasty (DMEK). This study evaluated the long-term incidence of IOP elevation and post-DMEK glaucoma after DMEK.

Methods:

A total of 463 consecutive DMEKs in 352 patients performed between September 2011 and September 2014 at the Universitätsmedizin-Charité Berlin were reviewed. Data of the second treated eye of each patient and of re-DMEKs during the follow-up were excluded. The 12- and 36-month incidence of IOP elevation and post-DMEK glaucoma was analyzed using the Kaplan–Meier survival analysis. IOP elevation was defined as IOP ≥22 mm Hg or ≥10 mm Hg from preoperative baseline. COX regression analysis was used to evaluate the risk factors for IOP elevation and the development of a post-DMEK glaucoma.

Results:

The 12-month incidence of IOP elevation was 15.9% [95 confidence interval (CI), 12.0%–19.8%] and that of post-DMEK glaucoma was 3.9% (95 CI, 1.7%–6.1%); the 36-month incidence was 18.8% (95 CI, 14.5%–23.1%) and that of post-DMEK glaucoma was 6.6% (95 CI, 3.7%–9.5%). The most frequent cause was steroid-induced IOP elevation with a 12-month incidence of 11.7% (95 CI, 8.2%–15.2%) and a 36-month incidence of 12.9% (95 CI, 9.2%–16.6%), respectively. The incidence of postoperative pupillary block IOP elevation was 7.5% (95 CI, 4.8%–10.2%). A preexisting glaucoma increased the risk of IOP elevation [P < 0.001, hazard ratio (HR) 3.331; 95% CI, 1.919–5.782] and the development of a post-DMEK glaucoma (P < 0.001, HR 6.633; 95% CI, 2.556–17.215). The preoperative diagnosis also influenced the risk of IOP elevation [Fuchs corneal dystrophy (FED) vs. bullous keratopathy; P = 0.012, HR 2.354; 95% CI, 1.203–4.608] and post-DMEK glaucoma (FED vs. graft failure; P = 0.01, HR 4.412; 95% CI, 1.419–13.723, FED vs. bullous keratopathy; P = 0.09, HR 2.679; 95% CI, 0.858–8.358).

Conclusions:

Incidence of IOP elevation is high in the first 12 months after DMEK, especially steroid-induced IOP elevation. Steroid-induced IOP elevation could be treated effectively by tapering down the steroid medication or changing the steroid drug. A preexisting glaucoma and the preoperative diagnosis increase the risk for an IOP elevation and a post-DMEK glaucoma.
Ubiquinol Supplementation of Donor Tissue Enhances Corneal Endothelial Cell Mitochondrial Respiration
Authors: Skeie Jessica M. , Aldrich Benjamin T. , Nishimura Darryl Y. , Schmidt Gregory A. , Zimmerman M. Bridget , Ling Jennifer J. , Naguib Youssef W. , Salem Aliasger K. , Greiner Mark A.
Published: June 2020

Purpose:

To determine whether ubiquinol improves mitochondrial function and cell viability in human donor corneal endothelial cells during hypothermic corneal tissue storage.

Methods:

Endothelial cell Descemet membrane tissues were treated with 10 μM ubiquinol, the reduced form of the antioxidant coenzyme Q10, for 5 days in Optisol-GS storage media before assaying for mitochondrial activity using extracellular flux analysis of oxygen consumption. In addition, endothelial cell Descemet membrane tissues were analyzed for cell viability using apoptosis and necrosis assays. Control tissues from mate corneas were treated with diluent only, and comparisons were analyzed for differences.

Results:

A total of 13 donor corneal tissues with a mean (SEM) preservation time of 11.8 days (0.4) were included for the analysis. Treatment with 10 μM ubiquinol increased spare respiratory capacity by 174% (P = 0.001), maximal respiration by 93% (P = 0.003), and proton leak by 80% (P = 0.047) compared with controls. Cells treated with ubiquinol had no significant change in cell necrosis or apoptosis.

Conclusions:

Preliminary testing in donor corneal tissue at specified doses indicates that ubiquinol may be a useful biocompatible additive to hypothermic corneal storage media that increases corneal endothelial cell mitochondrial function. Additional investigations are indicated to further study and optimize the dose and formulation of ubiquinol for use in preserving donor corneal tissue function during hypothermic storage.
Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial
Authors: Ma Ke , Jin Yi , Wang Lin , Feng Zhi-Ying , Song Tao , Yang Xiao-Qiu , Chen Fu-Qiang , Duan Bao-Lin , Huang You-Qing , Xie Guang-Lun , Bao Hong-Guang , Wang Kun , Xu Jiang-Tao , Lu Yan , Liu Yan-Qing
Published: June 2020

Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥50% pain relief. The noninferiority margin was defined as −0.15. Other outcomes included daily visual analogue scale score, breakthrough pain (BTP) incidence, intrathecal dose change, and patient-controlled analgesia bolus count change, GAD-7/PHQ-9. Clinical success was achieved in 85 and 79 of the 121 ITHM patients (70.2%) and 112 ITMO patients (70.5%), respectively. Compared to the corresponding baseline findings, significantly decreased visual analogue scale scores and BTP incidence were noted in both groups. The dose change rate decreased and increased with time in the ITHM and ITMO groups, respectively (ITHM −3.33% vs ITMO 35.4%, P < 0.01, t test) from the third week. The patient-controlled analgesia bolus change rate was lower in the ITHM group than in the ITMO group (ITHM −19.88% vs ITMO 7.79%, P < 0.01, t test) from first week. Our result shows that ITHM is noninferior to ITMO on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase, whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling BTP.
The Potential for Preserved Cochleovestibular Function in the Setting of Prolonged Pneumolabyrinth
Authors: Breen Joseph T. , Sweeney Alex D. , Vrabec Jeffrey T.
Published: June 2020

Objective:

To discuss the natural history and management of pneumolabyrinth, with particular attention to illustrative cases where hearing improved after a fluid-filled vestibule was restored.

Patients:

Adults at two academic medical centers with documented pneumolabyrinth on computed tomography (CT) imaging.

Intervention:

Middle ear surgery or observation.

Main Outcome Measures:

Cochlear and vestibular symptoms are reported. Inner ear function was documented with audiometry and vestibular testing. Resolution of pneumolabyrinth was documented on imaging for a subset of patients.

Results:

All patients presented with severe hearing loss following temporal bone fracture (three cases), penetrating trauma (one case), or stapedectomy (three cases). The radiographic finding was typically seen when imaging was obtained in the first few days after the injury. In two cases, vestibular symptoms resolved and partial recovery of hearing was seen despite a relatively long time interval between the inciting event and repair.

Conclusion:

Management of pneumolabyrinth is individualized based on the mechanism of injury, severity of symptoms, and timing of the imaging study. In most cases, the barrier between the middle ear and inner ear is expected to heal with rapid resolution of pneumolabyrinth. Late repair is demonstrated to result in favorable recovery in selected cases. The presence of air in the vestibule cannot be assumed to be indicative of irreversible inner ear damage.
Quality of Otology and Neurotology Research in Otolaryngology Journals
Authors: Socolovsky Leandro D. , Krishnan Pavan , Ramraj Rahul , Retnam Reuben , Sima Adam , Bauschard Michael J. , Coelho Daniel H.
Published: June 2020

Objective:

To identify trends in the quality of otology studies published in general otolaryngology journals over a 20-year period.

Study Design:

Retrospective analysis.

Methods:

Otologic and neurotologic papers from 1997, 2007, and 2017 were identified in the three general otolaryngology journals with the highest Eigenfactor scores: the Laryngoscope, European Archives of Otorhinolaryngology, and Otolaryngology–Head and Neck Surgery. The studies were reviewed and assigned level of evidence (LoE) based on standards set by the Centres for Evidence Based Medicine (CEBM). One-way analysis of variance were calculated with a 95% bootstrap sensitivity analysis performed.

Results:

A total of 786 otology articles were reviewed for level of evidence, of which 557 (70.8%) were original, clinical research, eligible for LoE assignation. Total publications increased for each year in all three journals. Both the absolute number and proportion of high evidence studies (level of evidence 1 and 2) increased with respect to time in all three journals. Lower evidence studies (level of evidence 3, 4, or 5) made up 66.8% of total publications in 2017. There was a reduction in average level of evidence (towards higher quality evidence) by 0.431 units from 1997 to 2017 (Diff = –0.431 between 1997 and 2017, p < 0.001). There was no significant difference in rate of change of level of evidence between 1997 and 2007 and 2007 and 2017 (0.033, p = 0.864).

Conclusion:

Over a 20-year period the number of total publications increased with time. The majority of otology publications in 2017 were lower evidence studies, though significant increases in the number and proportion of high evidence studies in general otolaryngology journals were observed throughout the study period.
microRNA in inflammatory bowel disease at a glance
Authors: Alamdari-Palangi Vahab , Vahedi Farzaneh , Shabaninejad Zahra , Dokeneheifard Sadat , Movehedpour Ahmad , Taheri-Anganeh Mortaza , Savardashtaki Amir
Published: June 2020

Inflammatory bowel disease (IBD) as a chronic inflammation in colon and small intestine has two subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). Genome studies have shown that UC and CD are related to microRNAs (miRNAs) expression in addition to environmental factors. This article reviews important researches that have recently been done on miRNAs roles in CD and UC disease. First, miRNA is introduced and its biogenesis and function are discussed. Afterward, roles of miRNAs in inflammatory processes involved in IBD are showed. Finally, this review proposes some circulating and tissue-specific miRNAs, which are useful for CD and UC fast diagnosis and grade prediction. As a conclusion, miRNAs are efficient diagnostic molecules especially in IBD subtypes discrimination and can be used by microarray and real time PCR methods for disease detection and classification.
Cerebrospinal Fluid Norepinephrine and Neurocognition in HIV and Methamphetamine Dependence
Authors: Saloner Rowan , Cherner Mariana , Iudicello Jennifer E. , Heaton Robert K. , Letendre Scott L. , Ellis Ronald J.
Published: June 2020

Objective:

HIV disease and methamphetamine (METH) dependence share overlapping mechanisms of neurotoxicity that preferentially compromise monoamine-rich frontostriatal circuitry. However, norepinephrine (NE) function is poorly understood in HIV and METH dependence. We evaluated associations between cerebrospinal fluid (CSF) NE and HIV, METH dependence, and neurocognition.

Methods:

Participants included 125 adults, stratified by HIV serostatus (HIV+/HIV−) and recent METH dependence (METH+/METH−), who underwent comprehensive neurocognitive testing and lumbar puncture. CSF NE was assayed using high-performance liquid chromatography. Multivariable regression modelled NE as a function of HIV, METH, and their interaction, adjusting for demographic and clinical factors. Pearson correlations examined relationships between NE and demographically-adjusted neurocognitive domain scores.

Results:

HIV significantly interacted with METH (P< 0.001) such that compared with HIV−/METH−, CSF NE was markedly elevated in the single risk-groups (HIV+/METH−:d= 0.96; HIV−/METH+:d= 0.79) and modestly elevated in the dual-risk group (HIV+/METH+:d= 0.48). This interaction remained significant after adjustment for lifetime depression, antidepressant use, and race/ethnicity. In the full sample, higher NE levels significantly correlated with worse global function (r= −0.19), learning (r= −0.23), and delayed recall (r= −0.18). Similar relationships between higher NE and worse neurocognition were detected in the METH− groups (ie, HIV−/METH− and HIV+/METH−) and in the virally-suppressed persons HIV+ subgroup, but not in the METH+ groups (ie, HIV−/METH+, HIV+/METH+).

Discussion:

HIV and METH independently, but not additively, relate to noradrenergic excess in the central nervous system, and perturbations to noradrenergic function may represent a pathophysiological mechanism of HIV-related neurocognitive dysfunction. Consistent with prior reports that noradrenergic excess compromises hippocampal and prefrontal function, higher NE related to worse neurocognition, even among successfully treated persons with HIV. Pharmacological and psychosocial interventions that stabilize NE function may improve neurocognition in persons with HIV.
The evolution of complex life and the stabilization of the Earth system
Authors: Payne Jonathan L. , Bachan Aviv , Heim Noel A. , Hull Pincelli M. , Knope Matthew L.
Published: June 2020

The half-billion-year history of animal evolution is characterized by decreasing rates of background extinction. Earth's increasing habitability for animals could result from several processes: (i) a decrease in the intensity of interactions among species that lead to extinctions; (ii) a decrease in the prevalence or intensity of geological triggers such as flood basalt eruptions and bolide impacts; (iii) a decrease in the sensitivity of animals to environmental disturbance; or (iv) an increase in the strength of stabilizing feedbacks within the climate system and biogeochemical cycles. There is no evidence that the prevalence or intensity of interactions among species or geological extinction triggers have decreased over time. There is, however, evidence from palaeontology, geochemistry and comparative physiology that animals have become more resilient to an environmental change and that the evolution of complex life has, on the whole, strengthened stabilizing feedbacks in the climate system. The differential success of certain phyla and classes appears to result, at least in part, from the anatomical solutions to the evolution of macroscopic size that were arrived at largely during Ediacaran and Cambrian time. Larger-bodied animals, enabled by increased anatomical complexity, were increasingly able to mix the marine sediment and water columns, thus promoting stability in biogeochemical cycles. In addition, body plans that also facilitated ecological differentiation have tended to be associated with lower rates of extinction. In this sense, Cambrian solutions to Cambrian problems have had a lasting impact on the trajectory of complex life and, in turn, fundamental properties of the Earth system.
Evaluation of methods for detecting human reads in microbial sequencing datasets
Authors: Bush Stephen J. , Connor Thomas R. , Peto Tim E.A. , Crook Derrick W. , Walker A. Sarah
Published: June 2020

Sequencing data from host-associated microbes can often be contaminated by the body of the investigator or research subject. Human DNA is typically removed from microbial reads either by subtractive alignment (dropping all reads that map to the human genome) or by using a read classification tool to predict those of human origin, and then discarding them. To inform best practice guidelines, we benchmarked eight alignment-based and two classification-based methods of human read detection using simulated data from 10 clinically prevalent bacteria and three viruses, into which contaminating human reads had been added. While the majority of methods successfully detected >99 % of the human reads, they were distinguishable by variance. The most precise methods, with negligible variance, were Bowtie2 and SNAP, both of which misidentified few, if any, bacterial reads (and no viral reads) as human. While correctly detecting a similar number of human reads, methods based on taxonomic classification, such as Kraken2 and Centrifuge, could misclassify bacterial reads as human, although the extent of this was species-specific. Among the most sensitive methods of human read detection was BWA, although this also made the greatest number of false positive classifications. Across all methods, the set of human reads not identified as such, although often representing <0.1 % of the total reads, were non-randomly distributed along the human genome with many originating from the repeat-rich sex chromosomes. For viral reads and longer (>300 bp) bacterial reads, the highest performing approaches were classification-based, using Kraken2 or Centrifuge. For shorter (c. 150 bp) bacterial reads, combining multiple methods of human read detection maximized the recovery of human reads from contaminated short read datasets without being compromised by false positives. A particularly high-performance approach with shorter bacterial reads was a two-stage classification using Bowtie2 followed by SNAP. Using this approach, we re-examined 11 577 publicly archived bacterial read sets for hitherto undetected human contamination. We were able to extract a sufficient number of reads to call known human SNPs, including those with clinical significance, in 6 % of the samples. These results show that phenotypically distinct human sequence is detectable in publicly archived microbial read datasets.
On Identifying and Mitigating Bias in the Estimation of the COVID-19 Case Fatality Rate
Authors: Angelopoulos Anastasios Nikolas , Pathak Reese , Varma Rohit , Jordan Michael I.
Published: June 2020

The relative case fatality rates (CFRs) between groups and countries are key measures of relative risk that guide policy decisions regarding scarce medical resource allocation during the ongoing COVID-19 pandemic. In the middle of an active outbreak when surveillance data is the primary source of information, estimating these quantities involves compensating for competing biases in time series of deaths, cases, and recoveries. These include time- and severity-dependent reporting of cases as well as time lags in observed patient outcomes. In the context of COVID-19 CFR estimation, we survey such biases and their potential significance. Further, we analyze theoretically the effect of certain biases, like preferential reporting of fatal cases, on naive estimators of CFR. We provide a partially corrected estimator of these naive estimates that accounts for time lag and imperfect reporting of deaths and recoveries. We show that collection of randomized data by testing the contacts of infectious individuals regardless of the presence of symptoms would mitigate bias by limiting the covariance between diagnosis and death. Our analysis is supplemented by theoretical and numerical results and a simple and fast open-source codebase.1
Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma
Authors: Farrera-Soler Lluc , Daguer Jean-Pierre , Barluenga Sofia , Cohen Patrick , Pagano Sabrina , Yerly Sabine , Kaiser Laurent , Vuilleumier Nicolas , Winssinger Nicolas
Published: June 2020

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients, we identified immunodominant linear epitopes corresponding to key proteolytic sites on the spike protein.
Discovery and biosynthesis of gladiochelins: unusual lipodepsipeptide siderophores fromBurkholderia gladioli
Authors: Dashti Yousef , Nakou Ioanna T. , Mullins Alex J. , Webster Gordon , Jian Xinyun , Mahenthiralingam Eshwar , Challis Gregory L.
Published: June 2020

Burkholderiais a genus of diverse Gram-negative bacteria that includes several opportunistic pathogens. Siderophores, which transport iron from the environment into microbial cells, are important virulence factors in most pathogenicBurkholderiaspecies. However, it is widely believed thatBurkholderia gladioli, which can infect the lungs of cystic fibrosis (CF) sufferers, does not produce siderophores.B. gladioliBCC0238, isolated from the lung of a CF patient, produces two novel metabolites in a minimal medium containing glycerol and ribose as carbon sources. HPLC purification, followed by detailed spectroscopic analyses, identified these metabolites as unusual lipodepsipeptides containing a unique citrate-derived fatty acid and a rare dehydro-β-alanine residue. The absolute configurations of the amino acid residues in the two metabolites was elucidated using Marfey’s method and the gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of mostB. gladioliisolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S (CAS) assay showed the metabolites bind ferric iron and that this supresses their production when added to the growth medium. Moreover, a gene encoding a TonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes. Together, these observations suggest that these metabolites likely function as siderophores inB. gladioli.
scRNA-Sequencing uncovers a TCF-4-dependent transcription factor network regulating commissure development
Authors: Wittmann Marie-Theres , Kirchner Philipp , Ekici Arif B. , Sock Elisabeth , Lie D. Chichung , Reis André
Published: June 2020

Intercortical connectivity is important for higher cognitive brain functions by providing the basis for integrating information from both hemispheres. We show that ablation of the neurodevelopmental disorder associated bHLH factorTcf4results in complete loss of forebrain commissural systems in mice. Applying a new bioinformatic strategy integrating transcription factor expression levels and regulon activities from single cell RNA-sequencing data predicted a TCF-4 interacting transcription factor network in intercortical projection neurons regulating commissure formation. This network comprises a number of regulators previously linked to the pathogenesis of intellectual disability, autism-spectrum disorders and schizophrenia, e.g.Foxg1, Sox11andBrg1. Furthermore, we demonstrate that TCF-4 and SOX11 biochemically interact and cooperatively control commissure formationin vivo, and regulate the transcription of genes implied in this process. Our study provides a regulatory transcriptional network for the development of interhemispheric connectivity with potential pathophysiological relevance in neurodevelopmental disorders.
Research on the Trend of the Height of Han Students Aged 7-18 in China
Authors: Hong Chenlu , Rui Zhang , Wu Fei
Published: June 2020

Aims

To make time series analysis on the 29-year (1985−2014) trends in height among Han Students Aged 7-18 in China and predict their future height from the perspective of interdisciplinary studies of demography and physical education.

Methods

The data were from the findings of seven cross-sectional surveys from the Chinese National Survey on Students’ Constitution and Health (CNSSCH). The mean, standard error, variance analysis, trend test, F test, T test, development growth and growth rate were used to make a descriptive analysis of height trends. The ARIMA model in the time series analysis was applied to predict the height development of Han students in 2024.

Results

The height of students aged 7-18 substantially increased from 1985 to2014. The mean of the height of boys increased by 3.99 cm, 8.01 cm, 8.31 cm, 8.63 cm, 9.81 cm, 11.62 cm, 10.38 cm, 9.22 cm, 7.50 cm, 5.59 cm, 4.51 cm, and 3.79 cm, respectively. The mean of the height of girls increased by 6.66 cm, 7.36 cm, 8.00 cm, 8.84 cm, 9.60 cm, 8.66 cm, 5.57 cm, 4.65 cm, 3.95 cm, 3.32 cm, 2.87 cm and 3.32 cm, respectively. The increasing disparity of the sex differential in the mean height was also observed. From 1985 to 2014, the mean of height difference between boys and girls aged 7-18 had been increased constantly. Their mean height differences were 3.27 cm, 4.03 cm, 4.64 cm, and 5.13 cm, respectively in 1985, 1995, 2005, and 2014. A narrowing of the urban−rural differential in the mean height was observed. In 1985, on average, urban boys aged 7-18 were 4.18cm higher than rural boys in the same age group. And the height differences between urban and rural boys in the same age group were 3.58 cm, 3.18 cm and 2.41 cm, respectively in 1995, 2005 and 2014. According to comparison results, the mean height of urban girls was greater than that of rural girls, and the height difference between urban and rural girls had been constantly narrowed as well. The results of 4 comparisons showed that the height differences between urban and rural girls were 3.68 cm, 3.12 cm, 2.62 cm, and 1.98 cm, respectively.

Conclusions

There was a general increase in the height of Chinese Han students aged 7-18 in the past 29 years and difference between sex, rural-urban and age have been observed. In 2024, the height of students will continue to grow.
Progression / remission of Coronavirus disease 2019: Data driven recommendations for repeating SARS-CoV-2 nucleic acid amplification tests
Authors: Williams Kaitlyn , Idriss Reed , Dodge Jessica , Barasch Samuel
Published: June 2020

Aims

This short study was performed to better understand the time frame associated with changes in SARS-CoV-2 nucleic acid testing and provide recommendations for repeat testing. Recommendations were useful as little guidance is available for repeat testing in patients being followed expectantly for changes in disease.

Methods

A review of laboratory data of tests for SARS-CoV-2 nucleic acid was performed selecting patients who had changing results. Time between changes in test results was determined to provide guidance for repeat testing.

Results

The interquartile range of data for patients who had a negative to positive change in lab testing (“progression”) was 6-16 days (Median 9). The interquartile range of data for patients who had a positive to negative change in test results (“remission”) was 9-21 days (Median 14).

Conclusion

Because sampling of the nares or nasopharynx can be variable, repeat testing should be performed swiftly when symptomatic patients are negative. The data in this short study varies widely, so authors recommend repeat testing during a period of time associated with the interquartile range or median (see results above).
HYFI: Hybrid filling of the dead-time gap for faster zero echo time imaging
Authors: Froidevaux Romain , Weiger Markus , Rösler Manuela B. , Brunner David O. , Pruessmann Klaas P.
Published: June 2020

Purpose

To improve the SNR efficiency of zero echo time (ZTE) MRI pulse sequences for faster imaging of short-T2 components at large dead-time gaps.

Methods

HYFI is s strategy of retrieving inner k-space data missed during the dead-time gap arising from radio-frequency excitation and switching in ZTE imaging. It performs hybrid filling of the inner k-space with a small single-point-imaging core surrounded by a stack of shells acquired on radial readouts in an onion-like fashion. The exposition of this concept is followed by translation into guidelines for parameter choice and implementation details. The imaging properties and performance of HYFI are studied in simulations as well as phantom, in-vitro and in-vivo imaging, with an emphasis on comparison with the PETRA technique (pointwise encoding time reduction with radial acquisition).

Results

Simulations predict higher SNR efficiency of HYFI compared to PETRA at preserved image quality with the advantage increasing with the size of the k-space gap. These results are confirmed by imaging experiments with gap sizes of 25 to 50 Nyquist dwells, in which scan times for similar SNR could be reduced by 25 to 60%.

Conclusion

The HYFI technique provides both high SNR efficiency and image quality, thus outperforming previously known ZTE-based pulse sequences in particular for large k-space gaps. Promising applications include direct imaging of ultra-short T2 components, such as the myelin bilayer or collagen, T2 mapping of ultra-fast relaxing signals, and ZTE imaging with reduced chemical shift artifacts.
Effect of hydroxychloroquine on SARS-CoV-2 viral load in patients with COVID-19
Authors: Faíco-Filho Klinger Soares , Conte Danielle Dias , de Souza Luna Luciano Kleber , Almeida Carvalho Joseane Mayara , Sitta Perosa Ana Helena , Bellei Nancy
Published: June 2020

Background

Some studies have shown that hydroxychloroquine (HCQ) is an effective drug in reducing the in vitro replication of SARS-CoV-2. However, the in vivo effect of HCQ still unclear. This study aims to evaluate viral load clearance in patients with COVID-19 who underwent HCQ treatment in comparison with a control group that did not receive the drug.

Methods

This prospective study comprised consecutive viral load measurements in patients with COVID-19 hospitalized with a moderate illness. Patients received 400 mg of HCQ every 12 hours for 10 days according to the medical decision. Nasal swab samples were collected at the 1st, 7th, and 14th days of the admission.

Results

155 samples were collected from 66 patients with COVID-19 (60% female), with a median age of 58 years. The viral load between studied groups, assumed as a semiquantitative measure of cycle threshold (Ct) values, presented no significant difference within the three consecutive measures (ΔCt) (p>0.05). We also analyzed the ΔCt viral load at different intervals of sample collection (Δt <7; 7-12 and >12 days) without significant differences at any ΔCt (p>0.05).

Conclusion

In this study, we did not observe any change in viral load in vivo with the use of HCQ.

We evaluate viral load clearance in patients with COVID-19 who took hydroxychloroquine (HCQ) for treatment and those who not. Prospective viral load measurements have shown any change in viral load in vivo with the use of HCQ.
Evidence of Increased Hemangioblastic and Early Hematopoietic Potential in Chronic Myeloid Leukemia (CML)-derived Induced Pluripotent Stem Cells (iPSC)
Authors: Telliam G. , Féraud O. , Baykal-Köse S. , Griscelli F. , Imeri J. , Latsis T. , Bennaceur-Griscelli A. , Turhan A.G.
Published: June 2020

Hemangioblasts derived from mesodermal lineage are the earliest precursors of hematopoietic stem cells and endothelial cells. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) are the only experimental systems in which these cells can be assayed and quantified. We show here using CML-derived iPSC and blast-cell colony forming (Bl-CFC) assays that hemangioblasts are highly expanded in CML derived iPSC as compared to human H1-ESC-derived hemangioblasts. BCR-ABL signaling pathway is intact in these cells with evidence of CRK-L phosphorylation which is reduced by the use of Imatinib. Hematopoietic progenitor assays generated using blast-CFC demonstrates also a highly increased hematopoietic progenitor potential of these cells as compared to H1-ESC. The same results were also obtained using hematopoietic progenitor assays via embryoid body formation. In CML iPSC, we have also found a significant reduction of Aryl Hydrocarbon Receptor (AHR) expression which is involved in hematopoietic quiescence. Further inhibition of AHR using StemRegenin (SR1), an AHR antagonist, led to an increase of blast-cell colonies in CML iPSC whereas the use of an AHR agonist inhibited blast cell colonies. Thus, our results show for the first time, the possibility of establishment of a myeloproliferative phenotype using patient-derived iPSC and the presence of a major expansion hemangioblast compartment and derived hematopoietic progenitors in this context. They also suggest that the AHR signaling pathway could represent a novel druggable target in CML.
Reading frame restoration at the EYS locus, and allele-specific chromosome removal after Cas9 cleavage in human embryos
Authors: Zuccaro Michael V. , Xu Jia , Mitchell Carl , Marin Diego , Zimmerman Raymond , Rana Bhavini , Weinstein Everett , King Rebeca T. , Smith Morgan , Tsang Stephen H. , Goland Robin , Jasin Maria , Lobo Rogerio , Treff Nathan , Egli Dieter
Published: June 2020

The correction of disease-causing mutations in human embryos could reduce the burden of inherited genetic disorders in the fetus and newborn, and improve the efficiency of fertility treatments for couples with disease-causing mutations in lieu of embryo selection. Here we evaluate the repair outcomes of a Cas9-induced double-strand break (DSB) introduced on the paternal chromosome at the EYS locus, which carries a frame-shift mutation causing blindness. We show that the most common repair outcome is microhomology-mediated end joining, which occurs during the first cell cycle in the zygote, leading to embryos with non-mosaic restoration of the reading frame. However, about half of the breaks remain unrepaired, resulting in an undetectable paternal allele and, upon entry into mitosis, loss of one or both chromosomal arms. Thus, Cas9 allows for the modification of chromosomal content in human embryos in a targeted manner, which may be useful for the prevention of trisomies.

Highlights

Cas9-mediated DSB induction and repair by end joining occurs within hours

End joining provides an efficient way to restore reading frames without mosaicism

Unrepaired DSBs persist through mitosis and result in frequent chromosome loss