bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction models for cardiovascular disease risk in the hypertensive population: a systematic review
Authors: Cai Ruixue , Wu Xiaoli , Li Chuanbao , Chao Jianqian
Published: April 2020

Objective:

The aim of this study was to identify, describe, and evaluate the available cardiovascular disease risk prediction models developed or validated in the hypertensive population.

Methods:

MEDLINE and the Web of Science were searched from database inception to March 2019, and all reference lists of included articles were reviewed.

Results:

A total of 4766 references were screened, of which 18 articles were included in the review, presenting 17 prediction models specifically developed for hypertensive populations and 25 external validations. Among the 17 prediction models, most were constructed based on randomized trials in Europe or North America to predict the risk of fatal or nonfatal cardiovascular events. The most common predictors were classic cardiovascular risk factors such as age, diabetes, sex, smoking, and SBP. Of the 17 models, only one model was externally validated. Among the 25 external validations, C-statistics ranged from 0.58 to 0.83, 0.56 to 0.75, and 0.64 to 0.78 for models developed in the hypertensive population, the general population and other specific populations, respectively. Most of the development studies and validation studies had an overall high risk of bias according to PROBAST.

Conclusion:

There are a certain number of cardiovascular risk prediction models in patients with hypertension. The risk of bias assessment showed several shortcomings in the methodological quality and reporting in both the development and validation studies. Most models developed in the hypertensive population have not been externally validated. Compared with models developed for the general population and other specific populations, models developed for the hypertensive population do not display a better performance when validated among patients with hypertension. Research is needed to validate and improve the existing cardiovascular disease risk prediction models in hypertensive populations rather than developing completely new models.
Cutaneous Leishmaniasis in Syrian Refugee Children
Authors: Van Kesteren Lydia , Maniewski Ula , Bottieau Emmanuel , Cnops Lieselotte , Huits Ralph
Published: April 2020

Cutaneous leishmaniasis is the most common presentation of infection by protozoan parasites of the genus Leishmania. Patients with cutaneous leishmaniasis may have one or several disfiguring skin lesions that resemble other dermatologic diseases. Old World cutaneous leishmaniasis is a major public health problem in the World Health Organization Eastern Mediterranean Region. Conflict and ensuing collapse of health systems leads to migration of leishmaniasis patients from countries like Syria. Pediatricians in nonendemic countries should be aware of this disease entity. We identify knowledge gaps and summarize treatment options for cutaneous leishmaniasis.
Effects of Aspirin on Postoperative Bruising and Bleeding Complications in Upper Eyelid Surgery
Authors: Winkler Kathryn P. , Beaulieu Robert , Bevill Lauren , Mishulin Aleksey , Black Evan H.
Published: April 2020

Purpose:

We evaluated the effects of aspirin versus placebo in patients undergoing upper eyelid blepharoplasty and/or levator advancement or plication blepharoptosis repair in this randomized, prospective study.

Methods:

Patients who presented between October 2017 and April 2019 requiring blepharoptosis repair and/or upper eyelid blepharoplasty who were taking 81 mg aspirin were randomized to receive 1 week of aspirin tablets or 1 week of placebo tablets prior to surgery. Postoperative complications, such as bleeding, hematoma, or hemorrhage, were noted as well as perioperative thromboembolic complications. Photos were obtained at the patient’s first postoperative visit and later judged on bruising severity. The 2 groups were subsequently compared.

Results:

A total of 48 patients and 89 eyelids were evaluated in this study. Fifty-two eyelids were included in the aspirin group and 37 eyelids were included in the placebo group. There was no statistically significant difference in bruising rating between groups. There was no statistically significant difference in the number of patients who experienced mild postoperative bleeding. No patients experienced vision loss. No patients experienced a thromboembolic event. There were no patients who experienced hemorrhage, hematoma, or retrobulbar hemorrhage.

Conclusions:

Continuation of aspirin does not appear to effect outcomes with respect to postoperative bruising in patients undergoing upper eyelid blepharoplasty or blepharoptosis repair. The study was not powered to determine statistical significance with regard to bleeding complications and would require a significantly higher sample size. We suggest changing the current guidelines to recommend routine continuation of low dose 81 mg aspirin before upper eyelid surgery.
Identifiable relatives in the family history: not without individual consent
Authors: Nunes José Pedro L. , Faria Maria do Sameiro , Abreu Amorim Carlos
Published: April 2020

The family history is a traditional section of the clinical record. Data on family members in the clinical record may be anonymous but yet these may be easily identifiable; therefore, exposing the relatives of the patient to the fact that a written record is produced, mentioning them, without their consent. This is in direct contradiction with European data protection and other regulations and in contradiction with a reasonable ethical perspective. For the purpose of obtaining an image of the present state of affairs, we used as a convenience sample, the series of Case Records published in 2019 in The New England Journal of Medicine (January to December). From a total number of 40 reports, identifiable relatives were present in 30. The number of identifiable relatives varied between none and 6. It is not the right of each individual to disclose sensitive clinical information regarding other persons, without consent from these latter. Family history should no longer include identifiable relatives, unless consent is obtained from each identifiable person. The authors offer the following guidelines on this topic: (1) Do not mention any identifiable relative of the patient in the medical history without consent from the said relative; (2) Do not mention in the family history clinical conditions seemingly unrelated to the present clinical situation; (3) Do not mention in the family history clinical conditions that the patient does not (him/) herself have and that may be seen as social stigmata; (4) Consult the institutional Ethics committee in case of reasonable doubt.
NursE led Atrial Fibrillation Management: The NEAT Study
Authors: Gallagher Celine , Orchard Jessica , Nyfort-Hansen Karin , Sanders Prashanthan , Neubeck Lis , Hendriks Jeroen M.
Published: April 2020

Background

Atrial fibrillation (AF) is a growing epidemic. Current models of care delivery are inadequate in meeting the needs of the population with AF. Furthermore, quality of life is known to be poor in patients with AF and is associated with adverse patient outcomes.

Objective

The aim of this study was to determine if nurse-led education and cardiovascular risk factor modification, undertaken using the principles of motivational interviewing, facilitated by an electronic decision support tool to ensure the appropriate use of oral anticoagulation (OAC), could improve health-related quality of life (HRQoL), guideline adherence to OAC, and cardiovascular risk factor profiles in individuals with AF.

Methods

This was a multicenter, prospective, randomized controlled feasibility study of 72 individuals with AF. The intervention involved 1 face-to-face nurse-delivered education and risk factor management session with 4 follow-up telephone calls over a 3-month period to monitor progress. The primary outcome measure was HRQoL as assessed by the Short Form-12 survey.

Results

A total of 72 participants were randomized, with 36 individuals in each arm completing follow-up. Mean age was 65 ± 11 years and 44% were women. At 3 months follow-up, no significant differences between groups were observed for the physical or mental component summary scores of the Short Form-12, nor any of the subscales. Appropriate use of OAC did not differ between groups at final follow-up.

Conclusions

A brief nurse-delivered educational intervention did not significantly impact on HRQoL or risk factor status in individuals with AF. Further research should focus on interventions of greater intensity to improve outcomes in this population.

Trial Registration: ACTRN12615000928516
Cardiac Iron Overload by MRI in Children With B-Thalassemia Major and its Correlation With Cardiac Function by Echocardiography
Authors: El-Shanshory Mohammed , Tolba Osama , El-Shafiey Rasha , Elgamasy Mohamed , Hablas Nahed , Mawlana Wegdan
Published: April 2020

Background:

Serial echocardiography is strongly recommended in asymptomatic B-thalassemia major (TM) patients for early detection of subtle cardiac dysfunction. T2*magnetic resonance imaging (MRI) is a noninvasive measurement of myocardial iron burden. Yet, it is not always available in many centers. Our study aimed to evaluate the myocardial function in TM patients using different echocardiographic modalities and to correlate these findings with cardiac T2*MRI.

Patients and Methods:

This is a cross-sectional study that was carried out on 140 children with a mean age of 10.9±3.7 years. One hundred children with TM and 40 healthy children were matched for age and sex as a control group. Serum ferritin, serum iron, and iron-binding capacity were measured. Cardiac iron overload was assessed by T2*MRI and cardiac function was assessed by echocardiography. The local ethics committee approved the study.

Results:

Among 100 children with TM, only 32% had cardiac iron overload of 8.525±5.45 detected by cardiac T2*MRI. Iron deposition correlated significantly with age. Markers of iron overload were significantly correlated with cardiac T2*MRI. There were significantly lower values of myocardial performance index, longitudinal strain, circumferential strain, area strain, and radial strain in TM patients compared with the controls (P<0.001). Only the myocardial performance index was correlated with T2*MRI.

Conclusions:

This study confirms that some parameters measured by tissue Doppler imaging such as the myocardial performance index could be useful for the early detection of cardiac impairment in asymptomatic TM patients when cardiac MRI is lacking. Further studies on a large scale to identify other parameters with high sensitivity are recommended.
Septic Polyarthritis by Staphylococcus aureus of “Unknown Origin”
Authors: Azevedo Soraia , Sousa-Neves Joana , Santos-Faria Daniela , Silva Joana Leite , Rodrigues Joana Ramos , Peixoto Daniela , Alcino Sérgio , Teixeira Filipa , Afonso Carmo , Tavares-Costa José
Published: April 2020

More than 90% of septic arthritis cases are monoarticular. Joint infection can occur through several mechanisms such as hematogenous dissemination, by contiguity from adjacent infected soft tissue, surgical contamination, direct inoculation, or joint trauma.

We report the case of a 69-year-old man admitted to our hospital with septic polyarthritis. The presented case is remarkable given its atypical presentation. The patient had no known risk factors for septic arthritis, comorbidities, or history of recurrent infections that could suggest some degree of immunosuppression. The atypical polyarticular involvement at presentation, the absence of sustained fever, and the good general condition of the patient delayed the diagnosis and treatment.
X-ray Dark-Field Radiography
Authors: Braig Eva-Maria , Roiser Nathalie , Kimm Melanie A. , Busse Madleen , Andrejewski Jana , Scholz Josef , Petrich Christian , Gustschin Alex , Sauter Andreas , Bodden Jannis , Meurer Felix , Korbel Rüdiger , Pfeiffer Franz , Herzen Julia , Pfeiffer Daniela
Published: April 2020

Objective

The aim of this study was to evaluate the potential of x-ray dark-field radiography for the noninvasive detection of monosodium urate (MSU) crystals as a novel diagnostic tool for gout.

Materials and Methods

Contrast-to-noise ratios of MSU crystals in conventional radiography and dark-field radiography have been compared in a proof of principle measurement. Monosodium urate crystals have been injected into mouse legs in an ex vivo experimental gout setup. Three radiologists independently evaluated the images for the occurrence of crystal deposits in a blinded study for attenuation images only, dark-field images only, and with both images available for a comprehensive diagnosis. All imaging experiments have been performed at an experimental x-ray dark-field setup with a 3-grating interferometer, a rotating anode tube (50 kVp), and a photon-counting detector (effective pixel size, 166 μm).

Results

X-ray dark-field radiography provided a strong signal increase for MSU crystals in a physiological buffer solution compared with conventional attenuation radiography with a contrast-to-noise ratio increase from 0.8 to 19.3. Based on conventional attenuation images only, the reader study revealed insufficient diagnostic performance (sensitivity, 11%; specificity, 92%) with poor interrater agreement (Cohen's coefficient κ = 0.031). Based on dark-field images, the sensitivity increased to 100%, specificity remained at 92%, and the interrater agreement increased to κ = 0.904. Combined diagnosis based on both image modalities maximized both sensitivity and specificity to 100% with absolute interrater agreement (κ = 1.000).

Conclusions

X-ray dark-field radiography enables the detection of MSU crystals in a mouse-based gout model. The simultaneous avaliability of a conventional attenuation image together with the dark-field image provides excellent detection rates of gout deposits with high specificity.
177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma
Authors: Liu Qingxing , Zhang Jingjing , Kulkarni Harshad R. , Baum Richard P.
Published: April 2020

Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)–targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on 68Ga-DOTATOC PET/CT, and remarkably partial remission after 177Lu-DOTATOC PRRT.
Low-Grade Versus High-Grade Glioma… That Is the Question. 18F-Fluorocholine PET in the Detection of Anaplastic Focus
Authors: García Vicente Ana María , Cordero García José Manuel , López Menéndez Carlos , Borrás Moreno Jose María , Soriano Castrejón Angel
Published: April 2020

Gliomas are characterized by intratumoral histological heterogeneity, coexisting foci of low and high grade. First, in low-grade gliomas, neoangiogenesis has not yet developed and cellularity is low, so alterations on perfusion MRI may not be present. Second, a non-negligible number of high-grade gliomas show none, patchy, or weak contrast enhancement on MRI, so they can be misdiagnosed as low-grade glioma, preventing their correct management. We present 4 cases of patients in which 18F-fluorocholine PET defined the anaplastic tumor component and therefore the tumor aggressiveness, solving the limitations of MRI.
Radiation Dose Reduction Using a Novel Fluoroscopy System in Patients Undergoing Diagnostic Invasive Coronary Angiography
Authors: Kraemer Bjoern F. , Tesche Christian , Hapfelmeier Alexander , Finsterer Sebastian , Ebersberger Ullrich , Schlüter Mathis , Ziegler Martin , Martens Eimo , Laugwitz Karl-Ludwig , Schmidt Martin
Published: April 2020

Background:

Invasive coronary angiography (ICA) still causes a significant amount of radiation exposure for patients and operators. In February 2017, the Azurion system was introduced, a new-generation fluoroscopy image acquisition and processing system. Radiation exposure in patients undergoing ICA was assessed comparing the novel Azurion 7 F12 angiography system to its predecessor Allura Xper in a randomized manner.

Methods:

Radiation exposure was prospectively analyzed in 238 patients undergoing diagnostic ICA. Patients were randomly assigned to the novel Azurion system (119 patients) or its predecessor Allura Xper system (119 patients). In each patient, 8 predefined standard projections (5 left coronary artery, 3 right coronary artery) were performed. Image quality was quantified by grading of the images on the basis of a 5-point grading system.

Results:

Radiation dose area product was significantly lower in the Azurion group 109 (interquartile range [IQR 75-176] cGy cm2) compared with the Allura Xper group 208 [IQR 134-301] cGy cm2 (P<0.001). Body mass index (26.6 [IQR 23.9-29.7] kg/m2 vs. 26.2 [IQR 24.2-29.4] kg/m2; P=0.607), body surface area (1.96 [IQR 1.81-2.11] m2 vs. 1.90 [IQR 1.77-20.4] m2; P=0.092), and procedure duration (1.5 [IQR 1.2-2.3] min vs. 1.6 [IQR 1.2-2.5] min; P=0.419) were similar in both groups. Images from the Azurion system were at least of equal quality compared with Allura Xper (image quality grade 4.82±0.45 vs. 4.75±0.52, P=0.43).

Conclusion:

Use of the novel Azurion 7 F12 angiography system resulted in a significant reduction of dose area product in patients undergoing diagnostic ICA by 56%.
Fatigue, Physical Activity, and Mental Health in People Living With Inflammatory Bowel Disease, Fibromyalgia, and in Healthy Controls
Authors: Olive Lisa S. , Emerson Catherine A. , Cooper Eliza , Rosenbrock Emily M. , Mikocka-Walus Antonina A.
Published: April 2020

This study aimed to identify biopsychosocial factors associated with fatigue, physical activity, and perceived benefits of and barriers to exercise in adults with inflammatory bowel disease and to compare them with those with fibromyalgia and healthy controls. A cross-sectional online survey was conducted. Hierarchical linear regressions were used to examine correlates of fatigue and physical activity. Analysis of variance and Kruskal–Wallis tests were used to compare levels of fatigue and physical activity between the groups. Overall, 387 participants completed the study (inflammatory bowel disease: n = 232; fibromyalgia: n = 102; healthy controls: n = 53). Significant correlates of fatigue included pain catastrophizing (p = .006), sleep quality (p = .003), and depressive symptoms (p < .001). Perceived barriers to exercise were associated with depressive symptoms (p = .003). Correlates of perceived benefits of exercise included anxiety (p = .036), depressive symptoms (p = .014), coping (positive reframing) (p = .018), and social support (from family) (p = .033). The fibromyalgia group had the greatest fatigue interference and the lowest score for physical activity, followed by the inflammatory bowel disease group and healthy controls (p < .05). Given the interplay between depressive symptoms, fatigue, and benefits/barriers to exercise, there is a need for more psychological interventions to be developed and tested in order to reduce fatigue and increase physical activity to better manage disease-related outcomes.
COVID-19 related social distancing measures and reduction in city mobility
Authors: Malik Amyn A. , Couzens Chandra , Omer Saad B.
Published: April 2020

In the absence of any pharmacological intervention, one approach to slowing the COVID-19 pandemic is reducing the contact rate in the population through social distancing. Governments the world over have instituted different measures to increase social distancing but information on their effectiveness in reducing mobility is lacking. We analyzed the mobility data from 41 cities to look at the effect of these interventions. The median mobility across cities on March 2, 2020 was 100% (IQR: 94%, 107%), which decreased to a median of 10% (IQR: 7%, 17%) on March 26, 2020. We found that the mobility decreased on average by 3.4% (95%CI: 3.3%, 3.6%) per day from March 2 through March 26. Social distancing measures decreased the mobility by an additional 23% (95%CI: 20%, 27%). Our study provides initial evidence for the reduction in mobility in cities instituting social distancing measures.
Estimating effects of intervention measures on COVID-19 outbreak in Wuhan taking account of improving diagnostic capabilities using a modelling approach
Authors: Liang Jingbo , Yuan Hsiang-Yu , Wu Lindsey , Pfeiffer Dirk U.
Published: April 2020

Background

Although by late February 2020 the COVID-19 epidemic was effectively controlled in Wuhan, China, the virus has since spread around the world and been declared a pandemic on March 11. Estimating the effects of interventions, such as transportation restrictions and quarantine measures, on the early COVID-19 transmission dynamics in Wuhan is critical for guiding future virus containment strategies. Since the exact number of COVID-19 infected cases is unknown, the number of documented cases was used by many disease transmission models to infer epidemiological parameters. However, this means that it would not be possible to adequately estimate epidemiological parameters and the effects of intervention measures, because the percentage of all infected cases that were documented changed during the first 2 months of the epidemic as a consequence of a gradually increasing diagnostic capability.

Methods

To overcome the limitations, we constructed a stochastic susceptible-exposed-infected-quarantined-recovered (SEIQR) model, accounting for intervention measures and temporal changes in the proportion of new documented infections out of total new infections, to characterize the transmission dynamics of COVID-19 in Wuhan across different stages of the outbreak. Pre-symptomatic transmission was taken into account in our model, and all epidemiological parameters were estimated using Particle Markov-chain Monte Carlo (PMCMC) method.

Results

Our model captured the local Wuhan epidemic pattern as a two-peak transmission dynamics, with one peak on February 4 and the other on February 12, 2020. The impact of intervention measures determined the timing of the first peak, leading to an 86% drop in the Re from 3.23 (95% CI, 2.22 to 4.20) to 0.45 (95% CI, 0.20 to 0.69). An improved diagnostic capability led to the second peak and a higher proportion of documented infections. Our estimated proportion of new documented infections out of the total new infections increased from 11% (95% CI 1% - 43%) to 28% (95% CI 4% - 62%) after January 26 when more detection kits were released. After the introduction of a new diagnostic criterion (case definition) on February 12, a higher proportion of daily infected cases were documented (49% (95% CI 7% - 79%)).
LesionQuant for assessment of MRI in multiple sclerosis - a promising supplement to the visual scan inspection
Authors: Brune Synne , Høgestøl Einar A. , Cengija Vanja , Berg-Hansen Pål , Sowa Piotr , Nygaard Gro O. , Harbo Hanne F. , Beyer Mona K.
Published: April 2020

Background and goals

Multiple sclerosis (MS) is a central nervous system inflammatory disease where magnetic resonance imaging (MRI) is an important tool for diagnosis and disease monitoring. Quantitative measurements of lesion volume, lesion count, distribution of lesions and brain atrophy have a potentially significant value for evaluating disease progression. We hypothesize that utilizing software designed for evaluating MRI data in MS will provide more accurate and detailed analyses compared to the visual neuro-radiological evaluation.

Methods

A group of 56 MS patients (mean age 35 years, 70% females and 96% relapsing-remitting MS) was examined with brain MRI one and five years after diagnosis. The T1 and FLAIR brain MRI sequences for all patients were analysed using the LesionQuant(LQ) software. These data were compared with data from structured visual evaluations of the MRI scans performed by a neuro-radiologist, including assessments of atrophy and lesion count. Correlations with clinical tests like the timed 25-foot walk test (T25FT) were performed to explore additional value of LQ analyses.

Results

Lesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor=0.92, p=2.2×10−16) and five years (cor=0.84, p=2.7×10−16) after diagnosis. LQ detected a reduction in whole brain percentile >10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8-28) in the LQ analysis. Significant positive correlation was identified between lesion volume measured by LQ and test performance on the T25FT both at one year and five years after diagnosis.

Conclusion

For the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radiologist. Lesion volume evaluated with LQ correlated with T25FT performance. LQ-analyses were more sensitive in capturing brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions and brain volume in MS patients in both a longitudinal and cross-sectional setting.
Simulation of trajectories in the illness-death model for chronic diseases: discrete event simulation, Doob-Gillespie algorithm and coverage of Wald confidence intervals
Authors: Brinks Ralph , Hoyer Annika
Published: April 2020

We compare two approaches for simulating events in the illness-death model in a test example about type 2 diabetes in Germany. The first approach is a discrete event simulation, where relevant events, i.e., onset of disease and death, are simulated for each subject individually. The second approach is the Doob-Gillespie algorithm, which simulates the number of people in each state of the illness-death model at each point in time. The algorithms are compared in terms of bias, variance and speed. Based on the results of the comparison in the test example, we assess coverage of the corresponding Wald confidence intervals.
Dynamic Estimation of Epidemiological Parameters of COVID-19 Outbreak and Effects of Interventions on Its Spread
Authors: Zhang Hongzhe , Zhao Xiaohang , Yin Kexin , Yan Yiren , Qian Wei , Chen Bintong , Fang Xiao
Published: April 2020

A key challenge for estimating the epidemiological parameters of the COVID-19 out-break in Wuhan is the discrepancy between the officially reported number of infections and the true number of infections. A common approach to tackling the challenge is to use the number of infections exported from Wuhan to infer the true number in the city. This approach can only provide a static estimate of the epidemiological parameters before Wuhan lockdown on January 23, 2020, because there are almost no exported cases thereafter. Here, we propose a method to dynamically estimate the epidemiological parameters of the COVID-19 outbreak in Wuhan by recovering true numbers of infections from day-to-day official numbers. Using the method, we provide a comprehensive retrospection on how the disease had progressed in Wuhan from January 19 to March 5, 2020. Particularly, we estimate that the outbreak sizes by January 23 and March 5 were 11,239 [95% CI 4,794–22,372] and 124,506 [95% CI 69,526–265,113], respectively. The effective reproduction number attained its maximum on January 24 (3.42 [95% CI 3.34–3.50]) and became less than 1 from February 7 (0.76 [95% CI 0.65–0.92]). We also estimate the effects of two major government interventions on the spread of COVID-19 in Wuhan. In particular, transportation suspension and large scale hospitalization respectively prevented 33,719 and 90,072 people from getting infected in the nine-day time period right after its implementation.
Synchronized travel restrictions across cities can be effective in COVID-19 control
Authors: Liu Haiyan , Bai Xuemei , Shen Huanfeng , Pang Xiaoping , Liang Zeyu , Liu Yue
Published: April 2020

The COVID-19 outbreak is under control in China. Mobility interventions, including both the Wuhan lockdown and travel restrictions in other cities, have been undertaken in China to mitigate the epidemic. However, the impact of mobility restrictions in cites outside Wuhan has not been systematically analyzed. Here we ascertain the relationships between all mobility patterns and the epidemic trajectory in Chinese cities outside Hubei Province, and we estimate the impact of local travel restrictions. We estimate local inter-city travel bans averted 22.4% (95% PI: 16.8–27.9%) more infections in the two weeks after the Wuhan lockdown, while local intra-city travel prevented 32.5% (95% PI: 18.9–46.1%) more infections in the third and fourth weeks. More synchronized implementation of mobility interventions would further decrease the number of confirmed cases in the first two weeks by 15.7% (95% PI:15.4–16.0%). This study shows synchronized travel restrictions across cities can be effective in COVID-19 control.
Could SARS-CoV-2 be transmitted via speech droplets?
Authors: Anfinrud Philip , Bax Christina E. , Stadnytskyi Valentyn , Bax Adriaan
Published: April 2020

Speaking may be a primary mode of transmission of SARS-CoV-2. Considering that reports of asymptomatic transmission account for 50-80% of COVID-19 cases and that saliva has peak viral loads at time of patient presentation, droplet emission while speaking could be a significant factor driving transmission and warrants further study. We used a planar beam of laser light passing through a dust-free enclosure to detect saliva droplets emitted while speaking. We found that saying the words ‘Stay Healthy’ generates thousands of droplets that are otherwise invisible to the naked eye. A damp homemade cloth face mask dramatically reduced droplet excretion, with none of the spoken words causing a droplet rise above the background. Our preliminary findings have important implications for pandemic mitigation efforts.
Modelling fatality curves of COVID-19 and the effectiveness of intervention strategies
Authors: Vasconcelos Giovani L. , Macêdo Antônio M. S. , Ospina Raydonal , Almeida Francisco A. G. , Duarte-Filho Gerson C. , Brum Arthur A. , Souza Inês C. L.
Published: April 2020

The main objective of the present paper is twofold: first, to model the fatality curves of the COVID-19 disease, as represented by the cumulative number of deaths as a function of time; and second, to use the corresponding mathematical model to study the effectiveness of possible intervention strategies. We applied the Richards growth model (RGM) to the COVID-19 fatality curves from several countries, where we used the data from the Johns Hopkins University database up to May 8, 2020. Countries selected for analysis with the RGM were China, France, Germany, Iran, Italy, South Korea, and Spain. The RGM was shown to describe very well the fatality curves of China, which is in a late stage of the COVID-19 outbreak, as well as of the other above countries, which supposedly are in the middle or towards the end of the outbreak at the time of this writing. We also analysed the case of Brazil, which is in an initial sub-exponential growth regime, and so we used the generalised growth model which is more appropriate for such cases. An analytic formula for the efficiency of intervention strategies within the context of the RGM is derived. Our findings show that there is only a narrow window of opportunity, after the onset of the epidemic, during which effective countermeasures can be taken. We applied our intervention model to the COVID-19 fatality curve of Italy of the outbreak to illustrate the effect of several possible interventions.
COVID-19 pandemic: Power law spread and flattening of the curve
Authors: Verma Mahendra K. , Asad Ali , Chatterjee Soumyadeep
Published: April 2020

In this paper, we analyze the real-time infection data of COVID-19 epidemic for nine nations. Our analysis is up to 7 April 2020. For China and South Korea, who have already flattened their infection curves, the number of infected individuals (I(t)) exhibits power-law behavior before flattening of the curve. Italy has transitioned to the power-law regime for some time. For the other six nations—USA, Spain, Germany, France, Japan, and India—a power-law regime is beginning to appear after exponential growth. We argue that the transition from an exponential regime to a power-law regime may act as an indicator for flattening of the epidemic curve. We also argue that long-term community transmission and/or the transmission by asymptomatic carriers traveling long distances may be inducing the power-law growth of the epidemic.
Prediction and Evolution of B Cell Epitopes of Surface Protein in SARS-CoV-2
Authors: Lon Jerome R , Bai Yunmeng , Zhong Bingxu , Cai Fuqaing , Du Hongli
Published: April 2020

The discovery of epitopes is helpful to the development of SARS-CoV-2 vaccine. The sequences of the surface protein of SARS-CoV-2 and its proximal sequences were obtained by BLAST, the sequences of the whole genome of SARS-CoV-2 were obtained from the GenBank. Based on the NCBI Reference Sequence: NC_045512.2, the conformational and linear B cell epitopes of the surface protein were predicted separately by various prediction methods. Furthermore, the conservation of the epitopes, the adaptability and other evolutionary characteristics were also analyzed. 7 epitopes were predicted, including 5 linear epitopes and 2 conformational epitopes, one of the linear and one of the conformational were coincide. The epitope D mutated easily, but the other epitopes were very conservative and the epitope C was the most conservative. It is worth mentioning that all of the 6 dominated epitopes were absolutely conservative in nearly 1000 SARS-CoV-2 genomes, and they deserved further study. The findings would facilitate the vaccine development, had the potential to be directly applied on the treatment in this disease, but also have the potential to prevent the possible threats caused by other types of coronavirus.
Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase
Authors: Jockusch Steffen , Tao Chuanjuan , Li Xiaoxu , Anderson Thomas K. , Chien Minchen , Kumar Shiv , Russo James J. , Kirchdoerfer Robert N. , Ju Jingyue
Published: April 2020

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. We previously demonstrated that four nucleotide analogues (specifically, the active triphosphate forms of Sofosbuvir, Alovudine, AZT and Tenofovir alafenamide) inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Tenofovir and emtricitabine are the two components in DESCOVY and TRUVADA, the two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. This is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. PrEP can stop HIV from replicating and spreading throughout the body. We report here that the triphosphates of tenofovir and emtricitabine, the two components in DESCOVY and TRUVADA, act as terminators for the SARS-CoV-2 RdRp catalyzed reaction. These results provide a molecular basis to evaluate the potential of DESCOVY and TRUVADA as PrEP for COVID-19.
Genomic evaluation of circulating proteins for drug target characterisation and precision medicine
Authors: Folkersen Lasse , Gustafsson Stefan , Wang Qin , Hansen Daniel Hvidberg , Hedman Åsa K , Schork Andrew , Page Karen , Zhernakova Daria V , Wu Yang , Peters James , Ericsson Niclas , Bergen Sarah E , Boutin Thibaud , Bretherick Andrew D , Enroth Stefan , Kalnapenkis Anettne , Gådin Jesper R , Suur Bianca , Chen Yan , Matic Ljubica , Gale Jeremy D , Lee Julie , Zhang Weidong , Quazi Amira , Ala-Korpela Mika , Choi Seung Hoan , Claringbould Annique , Danesh John , Davey-Smith George , de Masi Federico , Elmståhl Sölve , Engström Gunnar , Fauman Eric , Fernandez Celine , Franke Lude , Franks Paul , Giedraitis Vilmantas , Haley Chris , Hamsten Anders , Ingason Andres , Johansson Åsa , Joshi Peter K , Lind Lars , Lindgren Cecilia M. , Lubitz Steven , Palmer Tom , Macdonald-Dunlop Erin , Magnusson Martin , Melander Olle , Michaelsson Karl , Morris Andrew P. , Mägi Reedik , Nagle Michael , Nilsson Peter M , Nilsson Jan , Orho-Melander Marju , Polasek Ozren , Prins Bram , Pålsson Erik , Qi Ting , Sjögren Marketa , Sundström Johan , Surendran Praveen , Võsa Urmo , Werge Thomas , Wernersson Rasmus , Westra Harm-Jan , Yang Jian , Zhernakova Alexandra , Ärnlöv Johan , Fu Jingyuan , Smith Gustav , Esko Tonu , Hayward Caroline , Gyllensten Ulf , Landen Mikael , Siegbahn Agneta , Wilson Jim F , Wallentin Lars , Butterworth Adam S , Holmes Michael V , Ingelsson Erik , Mälarstig Anders
Published: April 2020

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. By mapping and replicating protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, we identified 467 pQTLs for 85 proteins. The pQTLs were used in combination with other sources of information to evaluate known drug targets, and suggest new target candidates or repositioning opportunities, underpinned by a) causality assessment using Mendelian randomization, b) pathway mapping usingtrans-pQTL gene assignments, and c) protein-centric polygenic risk scores enabling matching of plausible target mechanisms to sub-groups of individuals enabling precision medicine.
TMEM70 forms oligomeric scaffolds within mitochondrial cristae promotingin situassembly of mammalian ATP synthase proton channel
Authors: Bahri Hela , Buratto Jérémie , Rojo Manuel , Dompierre Jim , Salin Bénédicte , Blancard Corinne , Cuvellier Sylvain , Rose Marie , Elgaaied Amel Ben Ammar , Tetaud Emmanuel , di Rago Jean-Paul , Devin Anne , Duvezin-Caubet Stéphane
Published: April 2020

Mitochondrial ATP-synthesis is catalyzed by a F1Fo-ATP synthase, an enzyme of dual genetic origin enriched at the edge of cristae where it plays a key role in their structure/stability. The enzyme’s biogenesis remains poorly understood, both from a mechanistic and a compartmentalization point of view. The present study provides novel molecular insights into this process through investigations on a human protein called TMEM70 with an unclear role in the assembly of ATP synthase. A recent study has revealed the existence of physical interactions between TMEM70 and the subunit c (Su.c), a protein present in 8 identical copies forming a transmembrane oligomeric ring (c-ring) within the ATP synthase proton translocating domain (FO). Herein we analyzed the ATP-synthase assembly in cells lacking TMEM70, mitochondrial DNA or F1 subunits and observe a reciprocal dependence of TMEM70 and Su.c levels, regardless of the status of other ATP synthase subunits or of mitochondrial bioenergetics. Immunoprecipitation and two-dimensional blue-native/SDS-PAGE reveal that TMEM70 forms large oligomers composed of 8 TMEM70 dimers and that TMEM70 oligomers interact with Su.c not yet incorporated into ATP synthase complexes. Moreover, discrete TMEM70-Su.c complexes with increasing Su.c contents can be detected, suggesting a role for TMEM70 oligomers in the gradual assembly of the c-ring. Furthermore, we demonstrate using expansion super-resolution microscopy the specific localization of TMEM70 at the inner cristae membrane, distinct from the MICOS component MIC60. Taken together, our results show that TMEM70 oligomers provide a scaffold for c-ring assembly and that mammalian ATP synthase is assembled within inner cristae membranes.
Deep whole genome sequencing of multiple proband tissues and parental blood reveals the complex genetic etiology of congenital diaphragmatic hernias
Authors: Bogenschutz EL , Fox ZD , Farrell A , Wynn J , Moore B , Yu L , Aspelund G , Marth G , Yandell MY , Shen Y , Chung WK , Kardon G
Published: April 2020

The diaphragm is a mammalian muscle critical for respiration and separation of the thoracic and abdominal cavities. Defects in the development of the diaphragm are the cause of congenital diaphragmatic hernia (CDH), a common birth defect. In CDH, weaknesses in the developing diaphragm allow abdominal contents to herniate into the thoracic cavity and impair lung development, leading to a high neonatal mortality. The genetic etiology of CDH is complex. Single nucleotide variants (SNVs), insertion/deletions (indels), and structural/copy number variants in more than 150 genes have been associated with CDH, although few genes are recurrently mutated in multiple patients and recurrently mutated genes can be incompletely penetrant. This suggests that multiple genetic variants in combination, other not yet investigated classes of variants, and/or nongenetic factors contribute to CDH susceptibility. However, to date no studies have comprehensively investigated the contribution of all possible classes of variants throughout the genome to the etiology of CDH. In our study, we used a unique cohort of four patients with isolated CDH with samples from blood, skin, and diaphragm connective tissue and parental blood samples and deep whole genome sequencing to assess germline and somaticde novoand inherited variants of various sizes (SNVs, indels, and structural variants) in exons, introns, UTRs, and intergenic regions. In each patient we found a different mutational landscape that included germlinede novo,and inherited SNVs and indels in multiple genes. We also found in two patients an inherited 343 bp deletion interrupting an annotated enhancer of the CDH associated gene,GATA4, and we hypothesize that this common deletion (found in 1-2% of the population) acts as a sensitizing allele for CDH. Overall, our comprehensive reconstruction of the genetic architecture of four CDH individuals demonstrates that the etiology of CDH is heterogeneous and multifactorial.

AUTHOR SUMMARY

Deep whole genome sequencing of family trios shows that etiology of congenital diaphragmatic hernias is heterogeneous and multifactorial.
Genome wide analysis of gene dosage in 24,092 individuals shows that 10,000 genes modulate cognitive ability
Authors: Huguet Guillaume , Schramm Catherine , Douard Elise , Petra Tamer , Main Antoine , Monin Pauline , England Jade , Jizi Khadije , Renne Thomas , Poirier Myriam , Nowak Sabrina , Martin Charles-Olivier , Younis Nadine , Knoth Inga Sophia , Jean-Louis Martineau , Saci Zohra , Auger Maude , Tihy Frédérique , Mathonnet Géraldine , Maftei Catalina , Léveillé France , Porteous David , Davies Gail , Redmond Paul , Harris Sarah E. , Hill W. David , Lemyre Emmanuelle , Schumann Gunter , Bourgeron Thomas , Pausova Zdenka , Paus Tomas , Karama Sherif , Lippe Sarah , Deary Ian J. , Almasy Laura , Labbe Aurélie , Glahn David , Greenwood Celia M.T. , Jacquemont Sébastien
Published: April 2020

Genomic Copy Number Variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect-size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect-sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well.

Here, we identified all CNVs >50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect-size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of IQ when duplicated or deleted, respectively. Effect-sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect-sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect-size on intelligence occurde novoat the same frequency.

We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect-sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways.
RIPK2 dictates insulin responses to tyrosine kinase inhibitors in obese mice
Authors: Duggan Brittany M. , Cavallari Joseph F. , Foley Kevin P. , Barra Nicole G. , Schertzer Jonathan D.
Published: April 2020

Tyrosine kinase inhibitors (TKIs) used in cancer are also being investigated in diabetes. TKIs can improve blood glucose control in diabetic cancer patients, but the specific kinases that alter blood glucose or insulin are not clear. We sought to define the role of Receptor Interacting Serine/Threonine Kinase 2 (RIPK2) in mouse models of insulin resistance. We tested the TKI gefitinib, which inhibits RIPK2 activity, in WT,Nod1-/-, Nod2-/-andRipk2-/-mice fed an obesogenic high fat diet. Gefitinib lowered blood glucose during a glucose tolerance test (GTT) in a NOD-RIPK2-independent manner in all obese mice. However, gefitinib lowered glucose-stimulated insulin secretion only in obeseRipk2-/-mice. Gefitinib had no effect on insulin secretion in obese WT,Nodi-/-, orNod2-/-mice. Hence, genetic deletion ofRipk2promoted the insulin sensitizing potential of gefitinib, since this TKI lowered both blood glucose and insulin only inRipk2-/-mice. Gefitinib did not alter the inflammatory profile of pancreas, adipose, liver or muscle tissues in obeseRipk2-/-mice compared to obese WT mice. We also tested imatinib, a TKI which does not inhibit RIPK2 activity, in obese WT mice. Imatinib lowered blood glucose during a GTT, consistent with TKIs lowering blood glucose independently of RIPK2. However, imatinib increased glucose-stimulated insulin secretion during the glucose challenge. These data show that multiple TKIs lower blood glucose, where actions of TKIs on RIPK2 dictate divergent insulin responses, independent of tissue inflammation. Our data shows that RIPK2 limits the insulin sensitizing effect of gefitinib, whereas imatinib increased insulin secretion.
Detecting fine and elaborate movements with piezo sensors, from heartbeat to the temporal organization of behavior
Authors: Carreño-Muñoz Maria Isabel , Medrano Maria Carmen , Leinekugel Thomas , Bompart Maelys , Martins Fabienne , Subashi Enejda , Aby Franck , Frick Andreas , Landry Marc , Grana Manuel , Leinekugel Xavier
Published: April 2020

Behavioral phenotyping devices have been successfully used to build ethograms, but studying the temporal dynamics of individual movements during spontaneous, ongoing behavior, remains a challenge. We now report on a novel device, the Phenotypix, which consists in an open-field platform resting on highly sensitive piezoelectric (electro-mechanical) pressure-sensors, with which we could detect the slightest movements from freely moving rats and mice. The combination with video recordings and signal analysis based on time-frequency decomposition, clustering and machine learning algorithms allowed to quantify various behavioral components with unprecedented accuracy, such as individual heartbeats and breathing cycles during rest, shaking in response to pain or fear, and the dynamics of balance within individual footsteps during spontaneous locomotion. We believe that this device represents a significant progress and offers new opportunities for the awaited advance of behavioral phenotyping.