bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthrophic interactions between Bacteroides and Bifidobacterium on yeast beta-glucan
Authors: Fernandez-Julia Pedro , Munoz Jose
Published: July 2020

The Human Gut Microbiota (HGM) comprises two major phyla, the Bacteroidetes and Firmicutes, although important members of the Actinobacteria (Bifidobacterium) and Verrucomicrobia (Akkemansia) also make an important contribution to this ecosystem.

Accumulating datasupport the notionthat the HGM can be modulated by probiotics and prebiotics to prevent or revert common diseases of the gastrointestinal tract (GIT) such as Inflammatory Bowel Disease. Because it is believed that these GIT diseases are linked to the fact that current Western populations follow a more fat-based diet, significant efforts have been made to search for novel prebiotics/probiotics in order to restore and improve gut health.

So far, no publications have described probiotic properties of Bacteroidetes. Nonetheless, a case can be made that certain Bacteroides species present primary glycan degraders that interact in a syntrophic manner with other members of the microbiota, such as bifidobacteria, which are considered beneficial members of the microbiota.

In this study, we present the simbiotic interactions between Bacteroides and Bifidobacterium spp. acting on yeast beta-glucan (1,3/1,6 mixed linkage beta-glucan). Bacteroides cellulosilyticus and Bacteroides ovatus act as keystone organism to share beta-1,3/1,6-glucooligosaccharides with other members of the HGM, including Bifidobacterium breve UCC2003 and Bifidobacterium bifidum. We show in these Bifidobacterium spp. a specific beta-1,3-glucosidase, which degrade some of these sharing oligosaccharides. Also, we have identified the specific sugar symporter, which incorporate these oligosaccharides into the cytoplasm of B. breve UCC2003. With the help of RT-qPCR, we have quantified and monitored how these two members of the HGM are able to symbioticly use this dietary glycan.
Spectral analysis of the daily evolution of deaths due to Covid-19 in France and in the world shows a weekend effect: myth or reality?
Authors: Constantinesco André , Israel-Jost Vincent , Choquet Philippe
Published: July 2020

Background

The weekend effect has been extensively observed for different diseases and countries and recognized as a fact but without obvious causes.

Objectives

In this paper we first aimed at investigating the existence of a periodicity in the death count due to Covid-19, and second, at opening the discussion concerning the reality of this effect in this particular context.

Methods

Daily statistics of deaths due to the Covid-19 pandemic were subjected to a discrete Fourier transform spectral analysis for France and the world, over the periods from March 29 to May 16, 2020 and from January 22 to May 18, 2020 respectively.

Results

In both cases, a frequency peak of one harmonic corresponding to a period of 7.11 days was observed for France and the world. In France, this weekly frequency corresponds to a decrease in deaths every Sunday, whereas for the world the systematic decrease is shifted on average by 1.5 days and corresponds to Saturday or Friday.

Conclusion

At the world scale and for the epidemic period we confirm the existence of a consecutive weekend effect in the context of the Covid-19 pandemic.
Clinical and epidemiological characteristics of children with SARS-CoV-2 infection: case series in Sinaloa
Authors: Pérez Gaxiola Giordano , Rocha Rosalino Flores , Valadez Vidarte Julio César , Alcaraz Melissa Hernández , Mendoza Gilberto Herrera , Del Real Lugo Miguel Alejandro
Published: July 2020

Background

The SARS-CoV-2 virus may affect both adults and children. Although the disease, named COVID-19, has a lower prevalence in infancy and has been described as mild, the clinical characteristics may vary and there is a possibility of complications.

Objectives

To describe the clinical and epidemiological characteristics of pediatric cases confirmed in the state of Sinaloa, Mexico, during the first three months of the pandemic, and of children admitted with COVID-19 to a secondary hospital.

Methods

This case series includes all patients with SARS-CoV-2 infection confirmed by PCR testing, identified in the state epidemiological surveillance system between March 1 and May 31, 2020. Confirmed patients admitted to the Sinaloa Pediatric Hospital (HPS) during the same dates are also described.

Results

Fifty one children with SARS-CoV-2 were included, 10 of the admitted to HPS. The median age was 10 years. The more frequent symptoms were fever (78%), cough (67%) and headache (57%). Most cases were mild or asymptomatic. Three patients with comorbidities died. Only 4 of 10 patients identified in HPS had been admitted with the diagnosis of possible COVID-19.

Conclusions

SARS-CoV-2 infection in children was mostly mild or asymptomatic, but with a wide range of clinical presentations.
Creating Red Light-Controlled Protein Dimerization Systems as Genetically Encoded Actuators with High Specificity
Authors: Huang Zhimin , Li Zengpeng , Zhang Xiao , Dong Runze , Kang Shoukai , Sun Li , Fu Xiaonan , Vaisar David , Watanabe Kurumi , Gu Liangcai
Published: July 2020

Protein dimerization systems that can be controlled by red light with increased tissue penetration depth are a highly needed optogenetic tool for clinical applications such as cell and gene therapies. However, existing red light-induced dimerization systems are all based on phytochrome photoreceptors and naturally occurring binding partners with complex structures and suboptimalin vivoperformance, limiting mammalian applications. Here, we introduce an efficient, generalizable method (COMBINES-LID) for creating highly specific light-induced dimerization systems. Proof-of-principle was provided by creatingnanobody-based,red light-induceddimerization (nanoReD) systems comprising a truncated bacterial phytochrome sensory module using a mammalian endogenous chromophore, biliverdin, and light-form specific nanobodies. Selected nanoReD systems were biochemically characterized and exhibited low dark activity and high induction specificity forin vivoactivation of gene expression. Overall, COMBINES-LID opens new opportunities for creating genetically encoded actuators for the optical manipulation of biological processes.
Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection
Authors: Seow Jeffrey , Graham Carl , Merrick Blair , Acors Sam , Steel Kathyrn J.A. , Hemmings Oliver , O’Bryne Aoife , Kouphou Neophytos , Pickering Suzanne , Galao Rui Pedro , Betancor Gilberto , Wilson Harry D. , Signell Adrian W. , Winstone Helena , Kerridge Claire , Temperton Nigel , Snell Luke , Bisnauthsing Karen , Moore Amelia , Green Adrian , Martinez Lauren , Stokes Brielle , Honey Johanna , Izquierdo-Barras Alba , Arbane Gill , Patel Amita , O’Connell Lorcan , O’Hara Geraldine , MacMahon Eithne , Douthwaite Sam , Nebbia Gaia , Batra Rahul , Martinez-Nunez Rocio , Edgeworth Jonathan D. , Neil Stuart J.D. , Malim Michael H. , Doores Katie J
Published: July 2020

Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy’s and St Thomas’ Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection.
Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome
Authors: Rühlemann Malte Christoph , Hermes Britt Marie , Bang Corinna , Doms Shauni , Moitinho-Silva Lucas , Thingholm Louise Bruun , Frost Fabian , Degenhardt Frauke , Wittig Michael , Kässens Jan , Weiss Frank Ulrich , Peters Annette , Neuhaus Klaus , Völker Uwe , Völzke Henry , Homuth Georg , Weiss Stefan , Laudes Matthias , Lieb Wolfgang , Haller Dirk , Lerch Markus M. , Baines John F. , Franke Andre
Published: July 2020

The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory,1,2 neurologic,3 and neoplastic diseases.4 Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains uncertain.5–11 Nevertheless, twin-studies clearly suggest host-genetics as driver of microbiome composition.11 In a genome-wide association analysis of 8,956 German individuals, we identified 32 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium. Mendelian randomization analysis suggests causative and protective effects of gut microbes, with clade-specific effects on inflammatory bowel disease. This holistic investigative approach of the host, its genetics, and its associated microbial communities as a ‘metaorganism’ broadens our understanding of disease aetiology and emphasizes the potential for implementing microbiota in disease treatment and management.
Non contrast-enhanced imaging as a replacement for contrast-enhanced imaging for MRI automatic delineation of nasopharyngeal carcinoma
Authors: Wong Lun M. , Ai Qi-yong H. , Mo Frankie K.F. , Poon Darren M.C. , King Ann D.
Published: July 2020

Convolutional neural networks (CNNs) show potential for delineating cancers on contrast-enhanced MRI. However, there is world-wide interest in reducing the administration of MRI contrast agents. We aim to determine if CNNs can automatically delineate primary nasopharyngeal carcinoma (NPC) using the non contrast-enhanced (NE) T2-weighted fat-suppressed T1-weighted (CE-T1W) sequence. We retrospectively analyzed primary tumors in 201 patients with NPC. Six patients were randomly sampled as the training-validation group to avoid over-fitting, and the remaining 195 patients underwent validation analysis. We trained and tested a well-established two-dimensional CNN, U-Net, for tumor delineation on CE-T1W and T2W-FS sequences. CNN-derived delineations on CE-T1W and T2W-FS were compared with manual delineation using the dice similarity coefficient (DSC) and average surface distance (ASD). Differences in DSC and ASD of CNN-derived delineations between CE-T1W and T2W-FS sequences were compared using the Wilcoxon rank test. CNN-derived primary tumor volumes (PTVs) on CE-T1W and T2W-FS were also compared with manual delineation using the Wilcoxon rank test. The CNN’s tumor delineation performance on CE-T1W and T2W-FS showed no differences in DSC (0.71±0.09 vs. 0.71±0.09, p=0.50) and ASD (0.21±0.48cm vs. 0.17±0.19cm, p=0.34). The CNN-derived PTVs were larger than those from manual delineation on both CE-T1W (26.3±25.5cm3 vs. 23.5±26.6cm3, p<0.001) and T2W-FS (24.2±23.7cm3 vs. 23.2 ± 26.2 cm3, p<0.001). In conclusion, CNN can automatically delineate primary NPC using the NE T2W-FS sequence which has the potential to be a substitute for the CE-T1W sequence. (T2W-FS) sequence and compare the performance with that from the contrast-enhanced
In vivodemonstration of microvascular thrombosis in severe Covid-19
Authors: do Espírito Santo Douglas Alexandre , Lemos Anna Cristina Bertoldi , Miranda Carlos Henrique
Published: July 2020

Several autopsies studies showed the presence of microthrombi in the pulmonary circulation of the severe COVID-19. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final common pathway of the multisystem organ failure exhibited in the critical patient. We report the preliminary results of an invivoevaluation of the sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation at the beginning of the hospitalization. They did not have any laboratorial DIC evidence. We observed multiple filling defects moving within the sublingual microvessels indicative of microthrombi in 11 (85%) patients. This is the first imaging documentation of microvascular thrombosis in living patients with severe COVID-19. The clinical relevance of microvascular thrombosis in this disease requires further research.

Highlights

The presence of microthrombi in the pulmonary circulation is a common finding in autopsies of severe COVID-19.

In vivo evaluation of the sublingual microcirculation of severe COVID-19 showed multiple filling defects moving within the microvessels indicative of thrombi in most of these patients.

This is the first imaging documentation of microvascular thrombosis in living patients with severe COVID-19.

The clinical relevance of microvascular thrombosis in COVID-19 requires further research.
Evidence accumulation determines conscious access
Authors: Pereira Michael , Megevand Pierre , Tan Mi Xue , Chang Wenwen , Wang Shuo , Rezai Ali , Seeck Margitta , Corniola Marco , Momjian Shahan , Bernasconi Fosco , Blanke Olaf , Faivre Nathan
Published: July 2020

A fundamental scientific question concerns the neuronal basis of perceptual consciousness, which encompasses the perceptual experience and reflexive monitoring associated with a sensory event. Although recent human studies identified individual neurons reflecting stimulus visibility, their functional role for perceptual consciousness remains unknown. Here, we provide neuronal and computational evidence indicating that perceptual and reflexive consciousness are governed by an all-or-none process involving accumulation of perceptual evidence. We recorded single-neuron activity in a participant with a microelectrode implant in the posterior parietal cortex, considered a substrate for evidence accumulation, while he detected vibrotactile stimuli around detection threshold and provided confidence estimates. We found that detected stimuli elicited firing rate patterns resembling evidence accumulation during decision-making, irrespective of response effectors. Similar neurons encoded the intensity of task-irrelevant stimuli, suggesting their role for consciousness per se, irrespective of report. We generalized these findings in healthy volunteers using electroencephalography and reproduced their behavioral and neural responses with a computational model. This model considered stimulus detection if accumulated evidence reached a bound, and confidence as the distance between maximal evidence and that bound. Applying this mechanism to our neuronal data, we were able to decode single-trial confidence ratings both for detected and undetected stimuli. Our results show that the specific gradual changes in neuronal dynamics during evidence accumulation govern perceptual consciousness and reflexive monitoring in humans.
Entrainment of network activity by closed-loop microstimulation in healthy ambulatory rats
Authors: Averna Alberto , Hayley Page , Murphy Maxwell D , Nguyen Jimmy , Buccelli Stefano , Barban Federico , Nudo Randolph J. , Chiappalone Michela , Guggenmos David J.
Published: July 2020

As our understanding of how motor output is generated increases, it is clear that there is a need to understand the interactions of multiple distinct regions rather than just the output properties of primary motor cortex. This becomes even more imperative when trying to understand how different regions may contribute to recovery following injury. In this study we used a technique that promotes functional motor recovery after injury, activity-dependent stimulation (ADS), to determine the short- and long-term effects on network activity and neuroplasticity of intracortical connections. ADS uses recorded neural activity to trigger stimulation of the brain and may be utilized to manipulate neuronal connectivityin vivo, representing a novel technique to shape intrinsic neuroplasticity. The aim of this work was to compare the effect of ADS to randomly-generated stimulation (RS) of the somatosensory area (S1) on the single units’ patterns of activity taking place in the premotor cortex (RFA) and to investigate whether synaptic plasticity changes occur in S1 as a consequence of 21 consecutive days of stimulation. In particular, we examined both firing rate changes and correlation between spiking activity and stimuli in chronically-implanted healthy ambulatory rats during both spontaneous and evoked activity, resulting from the two stimulation paradigms. Finally, we evaluated changes in expression of synaptophysin at the end of the treatment. This experimental procedure demonstrated the ability of ADS to modulate firing properties of RFA within daily recording sessions and to promote synaptogenesis in S1, further strengthening the idea that this Hebbian-inspired protocol can be used to effectively modulate cortical connectivity and thus suggesting its translational potential for promoting recovery after brain injury.
Modelling cell guidance and curvature control in evolving biological tissues
Authors: Hegarty-Cremer Solene G.D. , Simpson Matthew J. , Andersen Thomas L. , Buenzli Pascal R.
Published: July 2020

Tissue geometry is an important influence on the evolution of many biological tissues. The local curvature of an evolving tissue induces tissue crowding or spreading, which leads to differential tissue growth rates, and to changes in cellular tension, which can influence cell behaviour. Here, we investigate how directed cell motion interacts with curvature control in evolving biological tissues. Directed cell motion is involved in the generation of angled tissue growth and anisotropic tissue material properties, such as tissue fibre orientation. We develop a new cell-based mathematical model of tissue growth that includes both curvature control and cell guidance mechanisms to investigate their interplay. The model is based on conservation principles applied to the density of tissue synthesising cells at or near the tissue’s moving boundary. The resulting mathematical model is a partial differential equation for cell density on a moving boundary, which is solved numerically using a hybrid front-tracking method called the cell-based particle method. The inclusion of directed cell motion allows us to model new types of biological growth, where tangential cell motion is important for the evolution of the interface, or for the generation of anisotropic tissue properties. We illustrate such situations by applying the model to simulate both the resorption and infilling components of the bone remodelling process, and to simulate root hair growth. We also provide user-friendly MATLAB code to implement the algorithms.
Structure-informed functional connectivity driven by identifiable and state-specific control regions
Authors: Chiêm Benjamin , Crevecoeur Frédéric , Delvenne Jean-Charles
Published: July 2020

Abstract

A challenge in neuroscience is to describe the contribution of the brain anatomical wiring to the emergence of coordinated neural activity underlying complex behavior. Indeed, patterns of remote coactivations that adjust with the ongoing task-demand do not systematically match direct, static anatomical links. Here, we propose that observed coactivation patterns, known as Functional Connectivity (FC), can be explained by a linear diffusion dynamics defined on the brain architecture and driven by control regions. Our model, termedstructure-informedFC, is based on a novel interpretation of functional connectivity according to which different sets of brain regions controlling the information flow on a fixed anatomical wiring enable the emergence of state-specific FC. This observation leads us to introduce a framework for the identification of potential control centers in the brain. We find that well-defined, sparse and robust sets of control regions, which partially overlap across several task conditions and resting-state, produce FC patterns comparable to empirical ones. In conclusion, this work introduces a principled method for identifying brain regions underlying the task-specific control of brain activity.

Significance statement

Understanding how brain anatomy promotes particular patterns of coactivations among neural regions is a key challenge in neuroscience. This challenge can be addressed using network science and systems theory. Here, we propose that coactivations result from the diffusion of information through the network of anatomical links connecting brain regions, with certain regions controlling the dynamics. We translate this hypothesis into a model calledstructure-informed functional connectivity, and we introduce a framework for identifying control regions based on empirical data. We find that our model produces coactivation patterns comparable to empirical ones, and that distinct sets of control regions are associated with different functional states. These findings suggest that controllability is an important feature allowing the brain to reach different states.
4-1BB is a target for immunotherapy in patients with undifferentiated pleomorphic sarcoma
Authors: Melake MJ , Smith HG , Mansfield D , Davies E , Dillon MT , Wilkins AC , Patin EC , Pedersen M , Buus R , Miah AB , Zaidi SH , Thway K , Melcher AA , Hayes AJ , Fenton TR , Harrington KJ , McLaughlin M
Published: July 2020

Systemic relapse, after treatment of a localised primary tumour with neo-adjuvant radiotherapy and surgery, is the major cause of disease related mortality in patients with sarcoma. As with other cancers, many sarcoma patients derive no benefit from anti-PD-1 treatment. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates and control metastatic disease. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data to explore patient stratification for immunotherapy and therapeutic targets of relevance to sarcoma. We show a group of patients with immune-hot undifferentiated pleomorphic sarcoma as one of the highest-ranking candidates for emerging 4-1BB targeting agents. A binary hot/cold classification method indicates 4-1BB-high hot sarcomas share many characteristics with immunotherapy responsive cancers of other pathologies. Hot tumours in sarcoma are however substantially less prevalent. Patient stratification, of intense interest for immunotherapies, is therefore even more important in sarcoma.
Cortical propagation as a biomarker for recovery after stroke
Authors: Cecchini Gloria , Scaglione Alessandro , Mascaro Anna Letizia Allegra , Checcucci Curzio , Conti Emilia , Adam Ihusan , Fanelli Duccio , Livi Roberto , Pavone Francesco Saverio , Kreuz Thomas
Published: July 2020

Stroke is a debilitating condition affecting millions of people worldwide. The development of improved rehabilitation therapies rests on finding biomarkers suitable for tracking functional damage and recovery. To achieve this goal, we perform a spatiotemporal analysis of cortical activity obtained by wide-field calcium images in mice before and after stroke. We compared spontaneous recovery with three different post-stroke rehabilitation paradigms, motor training alone, pharmacological contralesional inactivation and both combined. We identify three novel indicators that are able to track how movement-evoked global activation patterns are impaired by stroke and evolve during rehabilitation: the duration, the smoothness, and the angle of individual propagation events. Results show that, compared to pre-stroke conditions, propagation of cortical activity in the acute phase right after stroke is slowed down and more irregular. When comparing rehabilitation paradigms, we find that mice treated with both motor training and pharmacological intervention, the only group associated with generalized recovery, manifest new propagation patterns, that are even faster and smoother than before the stroke. In conclusion, our new spatiotemporal propagation indicators act as biomarkers that are able to uncover neural correlates not only of motor deficits caused by stroke but also of functional recovery during rehabilitation. These insights could pave the way towards more targeted post-stroke therapies.
Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS-S and MERS-S pseudotyped particles
Authors: Chen Catherine Z. , Xu Miao , Pradhan Manisha , Gorshkov Kirill , Petersen Jennifer , Straus Marco R. , Zhu Wei , Shinn Paul , Guo Hui , Shen Min , Klumpp-Thomas Carleen , Michael Samuel G. , Zimmerberg Joshua , Zheng Wei , Whittaker Gary R.
Published: July 2020

While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection, thus reducing viral burden in COVID-19 patients.

Abstract Figure
Characteristics and transmission dynamics of COVID-19 in healthcare workers at a London teaching hospital
Authors: Zheng Charlotte , Hafezi-Bakhtiari Nema , Cooper Victoria , Davidson Harriet , Habibi Maximillian , Riley Peter , Breathnach Aodhan
Published: July 2020

Background

Healthcare worker (HCW) associated COVID-19 is of global concern due to the potential for nosocomial spread and depletion of staff numbers. However, the literature on transmission routes and risk factors for COVID-19 in HCWs is limited.

Aim

To examine the characteristics and transmission dynamics of SARS-CoV-2 in HCWs in a university teaching hospital in London, UK.

Methods

Staff records and virology testing results were combined to identify staff sickness and COVID-19 rates from March to April 2020. Comparisons were made with staff professional groups, department of work and ethnicity. Analysis was performed using Microsoft Excel™.

Findings

COVID-19 rates in our HCWs largely rose and declined in parallel with the number of community cases. White and non-white ethnic groups among our HCWs had similar rates of infection. Clinical staff had a higher rate of laboratory-confirmed COVID-19 than non-clinical staff, but total sickness rates were similar. Doctors had the highest rate of infection, but took the fewest sickness days. Critical Care had lower rates than the Emergency Department (ED), but rates in the ED declined once all staff were advised to use Personal Protective Equipment (PPE).

Conclusion

These findings show that sustained transmission of SARS-CoV-2 among our hospital staff did not occur, beyond the community outbreak, even in the absence of strict infection control measures in non-clinical areas. The results also suggest that current PPE is effective when used appropriately. In addition, our findings emphasise the importance of testing both clinical and non-clinical staff groups during a pandemic.
A framework for making predictive models useful in practice
Authors: Jung Kenneth , Kashyap Sehj , Avati Anand , Harman Stephanie , Shaw Heather , Li Ron , Smith Margaret , Shum Kenny , Javitz Jacob , Vetteth Yohan , Seto Tina , Bagley Steven C. , Shah Nigam H.
Published: July 2020

Objective

To analyze the impact of factors in healthcare delivery on the net benefit of triggering an Advanced Care Planning (ACP) workflow based on predictions of 12-month mortality.

Materials and Methods

We built a predictive model of 12-month mortality using electronic health record data and evaluated the impact of healthcare delivery factors on the net benefit of triggering an ACP workflow based on the models’ predictions. Factors included non-clinical reasons that make ACP inappropriate, limited capacity for ACP, inability to follow up due to patient discharge, and availability of an outpatient workflow to follow up on missed cases. We also quantified the relative benefits of increasing capacity for inpatient ACP versus outpatient ACP.

Results

Work capacity constraints and discharge timing can significantly reduce the net benefit of triggering the ACP workflow based on a model’s predictions. However, the reduction can be mitigated by creating an outpatient ACP workflow. Given limited resources to either add capacity for inpatient ACP versus developing outpatient ACP capability, the latter is likely to provide more benefit to patient care.

Discussion

The benefit of using a predictive model for identifying patients for interventions is highly dependent on the capacity to execute the workflow triggered by the model. We provide a framework for quantifying the impact of healthcare delivery factors and work capacity constraints on achieved benefit.

Conclusion

An analysis of the sensitivity of the net benefit realized by a predictive model triggered clinical workflow to various healthcare delivery factors is necessary for making predictive models useful in practice.
White matter hyperintensities classified according to intensity and spatial location reveal specific associations with cognitive performance
Authors: Melazzini Luca , Mackay Clare E , Bordin Valentina , Suri Sana , Zsoldos Enikő , Filippini Nicola , Mahmood Abda , Sundaresan Vaanathi , Codari Marina , Duff Eugene , Singh-Manoux Archana , Kivimäki Mika , Ebmeier Klaus P , Jenkinson Mark , Sardanelli Francesco , Griffanti Ludovica
Published: July 2020

White matter hyperintensities (WMHs) on T2-weighted images are radiological signs of cerebral small vessel disease. As their total volume is variably associated with cognition, a new approach that integrates multiple radiological criteria is warranted. Location may matter, as periventricular WMHs have been shown to be associated with cognitive impairments. WMHs that appear as hypointense in T1-weighted images (T1w) may also indicate the most severe component of WMHs. We developed an automatic method that classifies WMHs into four categories (periventricular/deep and T1w-hypointense/nonT1w-hypointense) using MRI data from 684 community-dwelling older adults from the Whitehall II study. To test if location and intensity information can impact cognition, we derived two general linear models using either overall or subdivided volumes. Results showed that periventricular T1w-hypointense WMHs were significantly associated with poorer performance in several cognitive tests. We found no association between total WMH volume and cognition. These findings suggest that classifying WMHs according to both location and intensity in T1w adds value over and above total WMH volume.

HIGHLIGHTS

Heterogeneous measures of WMHs are used in research and clinical practice.

Location and image intensity should be considered in the assessment of WMHs.

T1-hypointense WMHs were found to be associated with poorer cognitive performance.

Sub-classes of WMHs provide promising results for translation into the clinic.
No benefits of prolonged vitamin D3 supplementation for adaptations to resistance training in old adults
Authors: Mølmen KS , Hammarström D , Pedersen K , Lie AC Lian , Steile RB , Nygaard H , Khan Y , Hamarsland H , Koll L , Hanestadhaugen M , Eriksen A Lie , Grindaker E , Whist JE , Buck D , Ahmad R , Strand TA , Rønnestad BR , Ellefsen S
Published: July 2020

Background

Lifestyle therapy with resistance training is a potent measure to counteract age-related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those chronically diseased (e.g. chronic obstructive pulmonary disease, COPD), and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored.

Methods

Ninety-five male and female participants (healthy, n=71; COPD, n=24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double-blinded manner (latitude 61°N, September-May). Seventy-eight participants completed the RCT, which was initiated by 12 weeks of supplementation-only (in average, 3333 IU.day-1), followed by 13 weeks of combined supplementation (2000 IU.day-1) and supervised whole-body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (n=7), endurance performance (n=6), and muscle mass (n=3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health-related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments.

Results

Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%) and endurance performance (one-legged, 23% ± 15%; whole-body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, − 6% ± 21%; [LDL]serum, −4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, −3%-points), myonuclei·fibre-1 (30% ± 65%), total RNA/rRNA abundances (15%/6-19%), and transcriptome profiles (e.g. ∼336 differentially expressed genes). Vitamin D3 supplementation led to robust increases in [25(OH)D]serum (Δ49% vs placebo), but did not affect training-associated changes for any of the main outcome domains, with no interaction being evident with disease status or pre-RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue, strength gains in participants with high fat mass, and [cortisol]serum (Δ20%), all of which advocate further study.

Conclusions

Vitamin D3 supplementation did not affect muscular responses to resistance training in old adults with or without COPD.
Wastewater SARS-CoV-2 RNA Concentration and Loading Variability from Grab and 24-Hour Composite Samples
Authors: Curtis Kyle , Keeling David , Yetka Kathleen , Larson Allison , Gonzalez Raul
Published: July 2020

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a significant, coordinated public health response. Assessing case density and spread of infection is critical and relies largely on clinical testing data. However, clinical testing suffers from known limitations, including test availability and a bias towards enumerating only symptomatic individuals. Wastewater-based epidemiology (WBE) has gained widespread support as a potential complement to clinical testing for assessing COVID-19 infections at the community scale. The efficacy of WBE hinges on the ability to accurately characterize SARS-CoV-2 RNA concentrations in wastewater. To date, a variety of sampling schemes have been used without consensus around the appropriateness of grab or composite sampling. Here we address a key WBE knowledge gap by examining the variability of SARS-CoV-2 RNA concentrations in wastewater grab samples collected every 2 hours for 72 hours compared with three corresponding 24-hour flow-weighted composite samples collected over the same period. Results show relatively low variability (respective means for N1, N2, N3 assays = 608, 847.9, 768.4 copies 100 mL-1, standard deviations = 501.4, 500.3, 505.8 copies 100 mL-1) for grab sample concentrations, and good agreement between most grab samples and their respective composite (mean deviation from composite = 159 copies 100 mL-1). When SARS-CoV-2 RNA concentrations are used to calculate viral load (RNA concentration * total influent flow the sample day), the discrepancy between grabs (log10range for all grabs = 11.9) or a grab and its associated 24-hour composite (log10difference = 11.6) are amplified. A similar effect is seen when estimating carrier prevalence in a catchment population with median estimates based on grabs ranging 63-1885 carriers. Findings suggest that grab samples may be sufficient to characterize SARS-CoV-2 RNA concentrations, but additional calculations using these data may be sensitive to grab sample variability and warrant the use of flow-weighted composite sampling. These data inform future WBE work by helping determine the most appropriate sampling scheme and facilitate sharing of datasets between studies via consistent methodology.
A comprehensive estimation and analysis of the basic reproduction number (R0) of novel corona virus in India: A comparative study with different lockdown phase of COVID-19
Authors: Agrawal Tushant , Chhabra Mayank
Published: July 2020

Background

World Health organization declared Covid-19 as an outbreak, hence preventive measure like lockdown should be taken to control the spread of infection. This study offers an exhaustive analysis of the reproductive number (R0) in India with major intervention for COVID-19 outbreaks and analysed the lockdown effects on the Covid-19.

Methodology

Covid-19 data extracted from Ministry of Health and Family Welfare, Government of India. Then, a novel method implemented in the incidence and Optimum function in desolve package to the data of cumulative daily new confirmed cases for robustly estimating the reproduction number in the R software.

Result

Analysis has been seen that the lockdown was really quite as effective, India has already shown a major steady decline. The growth rate has fluctuated about 20 percent with trend line projections in various lockdown. A comparative analysis gives an idea of decline in value of R0 from 1.73 to 1.08. Annotation plot showing the predicted R0 values based on previous lockdown in month of June and July.

Conclusion

Without lockdown, the growth might not have been contained in India and may have gone into the exponential zone. We show that, the lockdown in India was fairly successful. The effect partial lifting of the lockdown (unlock) is also seen in the results, in terms of increment in R0 values. Hence this study provides a platform for policy makers and government authorities for implementing the strategies to prevent the spread of infection.
What effect might border screening have on preventing importation of COVID-19 compared with other infections? A modelling study
Authors: Bays Declan , Bennett Emma , Finnie Thomas
Published: July 2020

The effectiveness of screening travellers during times of international disease outbreak is contentious, especially as the reduction in the risk of disease importation can be very small. Border screening typically consists of travellers being thermally scanned for signs of fever and/or completing a survey declaring any possible symptoms prior to admission to their destination country; while more thorough testing typically exists, these would generally prove more disruptive to deploy. In this paper, we describe a simple Monte Carlo based model that incorporates the epidemiology of COVID-19 to investigate the potential benefit of requiring all travellers to undergo thorough screening upon arrival. This is a purely theoretical study to investigate whether a single test at point of entry might ever prove to be a way of significantly decreasing risk of importation. We therefore assume ideal conditions such as 100% compliance among travellers and the use of a “perfect” test. In addition to COVID-19, we also apply the presented model to simulated outbreaks of Influenza, SARS and Ebola for comparison. Our model only considers screening implemented at airports, being the predominant method of international travel. Primary results showed that in the best-case scenario, screening may expect to detect 8.8% of travellers infected with COVID-19, compared to 34.8.%, 9.7% and 3.0% for travellers infected with influenza, SARS and Ebola respectively. While results appear to indicate that screening is more effective at preventing disease ingress when the disease in question has a shorter average incubation period, our results indicate that screening alone does not represent a sufficient method to adequately protect a nation from the importation of COVID-19 cases.

Data availability

All results described in the work, in addition to technical descriptions of methods used, are made available in the supplementary material. The Python package used to implement these methods and obtain our results has been made accessible online[1].
Subsequent waves of viral pandemics, a hint for the future course of the SARS-CoV-2 pandemic
Authors: Standl Fabian , Jöckel Karl-Heinz , Kowall Bernd , Schmidt Börge , Stang Andreas
Published: July 2020

Background

It is unknown if the SARS-CoV-2 pandemic will have a second wave. We analysed published data of five influenza pandemics (such as the Spanish Flu and the Swine Flu) and the SARS-CoV-1 pandemic to describe whether there were subsequent waves and how they differed.

Methods

We reanalysed literature and WHO reports on SARS-CoV-1 and literature on five influenza pandemics. We report frequencies of second and third waves, wave heights, wavelengths and time between subsequent waves. From this, we estimated peak-to-peak ratios to compare the wave heights, and wave-length-to-wave-length ratios to compare the wavelengths differences in days. Furthermore, we analysed the seasonality of the wave peaks and the time between the peak values of two waves.

Results

Second waves, the Spanish Flu excluded, were usually about the same height and length as first waves and were observed in 93% of the 57 described epidemic events of influenza pandemics and in 42% of the 19 epidemic events of the SARS-CoV-1 pandemic. Third waves occurred in 54% of the 28 influenza and in 11% of the 19 SARS-CoV-1 epidemic events. Third waves, the Spanish Flu excluded, usually peaked higher than second waves with a peak-to-peak ratio of 0.5.

Conclusion

While influenza epidemics are usually accompanied by 2nd waves, this is only the case in the minority of SARS-Cov1 epidemics.
Serology in Children with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19
Authors: Rostad Christina A. , Chahroudi Ann , Mantus Grace , Lapp Stacey A. , Teherani Mehgan , Macoy Lisa , Rostad Bradley S. , Milla Sarah S. , Tarquinio Keiko M. , Basu Rajit K. , Kao Carol , Linam W. Matthew , Zimmerman Matthew G. , Shi Pei-Yong , Menachery Vineet D. , Oster Matthew E. , Edupuganti Sri , Anderson Evan J. , Suthar Mehul , Wrammert Jens , Jaggi Preeti
Published: July 2020

Objectives

We aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and other hospitalized pediatric controls.

Methods

From March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children at Children’s Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies by quantitative ELISA and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody titers among groups and performed correlation analyses using linear regression.

Results

All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated strongly with neutralizing antibodies (R2=0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010).

Conclusion

Quantitative SARS-CoV-2 RBD antibody titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.

Table of Contents Summary

Children with MIS-C have high antibody titers to the SARS-CoV-2 spike protein receptor binding domain, which correlate with neutralization, systemic inflammation, and clinical outcomes.

What’s Known on This Subject

Although the clinical features of a multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been recently described, the serologic features of MIS-C are unknown.

What This Study Adds

In this case series, all hospitalized children with MIS-C had significantly higher SARS-CoV-2 binding and neutralizing antibodies than children with COVID-19 or Kawasaki Disease. SARS-CoV-2 antibodies correlated with metrics of systemic inflammation and clinical outcomes, suggesting diagnostic and prognostic value.
Two pathways to self-harm in adolescence
Authors: Uh Stepheni , Dalmaijer Edwin S. , Siugzdaite Roma , Ford Tamsin J. , Astle Duncan E.
Published: July 2020

Background

The behavioural and emotional profiles underlying adolescent self-harm, and its developmental risk factors, are relatively unknown. We aimed to identify sub-groups of young people who self-harm (YPSH) and longitudinal predictors leading to self-harm.

Methods

Participants were from the Millennium Cohort Study (n=10,827). A clustering algorithm identified sub-groups who self-harmed with different behavioural and emotional profiles at age 14. Feature selection analyses were then used to identify longitudinal predictors of self-harming behaviour.

Findings

There were two distinct sub-groups at age 14: a smaller group (n = 379) who reported a long history of psychopathology, and a second group (n = 905) without. Notably, both groups could be predicted almost a decade before the reported self-harm. They were similarly characterised by sleep problems and low self-esteem, but there was developmental differentiation. From an early age, the first group had poorer emotion regulation, were bullied, and their caregivers faced emotional challenges. The second group showed less consistency in early childhood, but later reported more willingness to take risks and less security with peers/family.

Interpretation

Our results uncover two distinct pathways to self-harm: a ‘psychopathology’ pathway, associated with early and persistent emotional difficulties and bullying; and an ‘adolescent risky behaviour’ pathway, where risk-taking and external challenges emerge later into adolescence and predict self-harm. These two pathways have long developmental histories, providing an extended window for interventions as well as potential improvements in the identification of children at risk, biopsychosocial causes, and treatment or prevention of self-harm.

Funding

This study was supported by the UK Medical Research Council, Templeton World Charitable Foundation, and a Gates Cambridge Scholarship awarded to SU.