bluuebunny/crossref_metadata_2025 huggingface dataset:
Preserving nature: domestic thrift and techniques of conservation in early modern England
Authors: Werrett Simon
Published: September 2021

Against an assumption that conservation practices only became ‘scientific’ in the late nineteenth and early twentieth centuries, this essay shows how, on the contrary, preservation techniques in early modern England were an inspiration for new forms of scientific inquiry and knowledge. Following the framework of ‘thrifty science’, the essay demonstrates how the thrifty value of making use and extending the life of goods encouraged a variety of preservation practices, which some scholars identified as valuable resources for a new experimental philosophy. In practice, preserving techniques crossed between domestic, experimental and academic sites. Since ‘thrifty science’ included the preservation of human and non-human ‘bodies’, the essay argues that an appreciation of early modern conservation necessitates an interdisciplinary approach.
Time's teeth: narratives of preservation in the eighteenth-century Cotton Library
Authors: Burgess W. G.
Published: September 2021

In 1701, the Cotton Library became Britain's first nationally owned manuscript collection, before entering the newly instituted British Museum in 1757. In the intervening years it was threatened by damp, neglect, inadequate organization, and a fire that wrought havoc on its material's survival. Through a detailed analysis of the content, form and language of contemporary inventories and catalogues, this essay explores how the library could sustain a hybrid identity as both a durable, nationally significant repository and a precarious assemblage of fragile paper and parchment during the eighteenth century. Analysing the ways in which custodians of the Cotton Library articulated their work reveals a historically repeating narrative of neglect, loss and recovery that echoed from the collection's seventeenth-century inception to the major restoration work carried out in the mid-nineteenth century. Instrumental in shaping the Cotton Library's identities, as well as how the discipline of antiquarianism perceived itself, this dialectic of preservation depended on, and was threatened by, the eroding forces of time's teeth.
The control effort to steer self-propelled microswimmers depends on their morphology: comparing symmetric spherical versus asymmetric
L
-shaped particles
Authors: Riede Julia M. , Holm Christian , Schmitt Syn , Haeufle Daniel F. B.
Published: September 2021

Active goal-directed motion requires real-time adjustment of control signals depending on the system’s status, also known as control. The amount of information that needs to be processed depends on the desired motion and control, and on the system’s morphology. The morphology of the system may directly effectuate or support the desired motion. This morphology-based reduction to the neuronal ‘control effort’ can be quantified by a novel information-entropy-based approach. Here, we apply this novel measure of ‘control effort’ to active microswimmers of different morphology. Their motion is a combination of directed deterministic and stochastic motion. In spherical microswimmers, the active propulsion leads to linear velocities. Active propulsion of asymmetric
L
-shaped particles leads to circular or—on tilted substrates—directed motion. Thus, the difference in shape, i.e. the morphology of the particles, directly influence the motion. Here, we quantify how this morphology can be exploited by control schemes for the purpose of steering the particles towards targets. Using computer simulations, we found in both cases a significantly lower control effort for
L
-shaped particles. However, certain movements can only be achieved by spherical particles. This demonstrates that a suitably designed microswimmer’s morphology might be exploited to perform specific tasks.
Mathematical model of STAT signalling pathways in cancer development and optimal control approaches
Authors: Lee Jonggul , Lee Donggu , Kim Yangjin
Published: September 2021

In various diseases, the STAT family display various cellular controls over various challenges faced by the immune system and cell death programs. In this study, we investigate how an intracellular signalling network (STAT1, STAT3, Bcl-2 and BAX) regulates important cellular states, either anti-apoptosis or apoptosis of cancer cells. We adapt a mathematical framework to illustrate how the signalling network can generate a bi-stability condition so that it will induce either apoptosis or anti-apoptosis status of tumour cells. Then, we use this model to develop several anti-tumour strategies including IFN-β infusion. The roles of JAK-STATs signalling in regulation of the cell death program in cancer cells and tumour growth are poorly understood. The mathematical model unveils the structure and functions of the intracellular signalling and cellular outcomes of the anti-tumour drugs in the presence of IFN-β and JAK stimuli. We identify the best injection order of IFN-β and DDP among many possible combinations, which may suggest better infusion strategies of multiple anti-cancer agents at clinics. We finally use an optimal control theory in order to maximize anti-tumour efficacy and minimize administrative costs. In particular, we minimize tumour volume and maximize the apoptotic potential by minimizing the Bcl-2 concentration and maximizing the BAX level while minimizing total injection amount of both IFN-β and JAK2 inhibitors (DDP).
Laguerre polynomial-based operational matrix of integration for solving fractional differential equations with non-singular kernel
Authors: Baishya Chandrali , Veeresha P.
Published: September 2021

The Atangana–Baleanu derivative and the Laguerre polynomial are used in this analysis to define a new computational technique for solving fractional differential equations. To serve this purpose, we have derived the operational matrices of fractional integration and fractional integro-differentiation via Laguerre polynomials. Using the derived operational matrices and collocation points, we reduce the fractional differential equations to a system of linear or nonlinear algebraic equations. For the error of the operational matrix of the fractional integration, an error bound is derived. To illustrate the accuracy and the reliability of the projected algorithm, numerical simulation is presented, and the nature of attained results is captured in diverse order. Finally, the achieved consequences enlighten that the solutions obtained by the proposed scheme give better convergence to the actual solution than the results available in the literature.
The Archean origin of oxygenic photosynthesis and extant cyanobacterial lineages
Authors: Fournier G. P. , Moore K. R. , Rangel L. T. , Payette J. G. , Momper L. , Bosak T.
Published: September 2021

The record of the coevolution of oxygenic phototrophs and the environment is preserved in three forms: genomes of modern organisms, diverse geochemical signals of surface oxidation and diagnostic Proterozoic microfossils. When calibrated by fossils, genomic data form the basis of molecular clock analyses. However, different interpretations of the geochemical record, fossil calibrations and evolutionary models produce a wide range of age estimates that are often conflicting. Here, we show that multiple interpretations of the cyanobacterial fossil record are consistent with an Archean origin of crown-group Cyanobacteria. We further show that incorporating relative dating information from horizontal gene transfers greatly improves the precision of these age estimates, by both providing a novel empirical criterion for selecting evolutionary models, and increasing the stringency of sampling of posterior age estimates. Independent of any geochemical evidence or hypotheses, these results support oxygenic photosynthesis evolving at least several hundred million years before the Great Oxygenation Event (GOE), a rapid diversification of major cyanobacterial lineages around the time of the GOE, and a post-Cryogenian origin of extant marine picocyanobacterial diversity.
Positive selection on mitochondria may eliminate heritable microbes from arthropod populations
Authors: Fenton Andy , Camus M. Florencia , Hurst Gregory D. D.
Published: September 2021

Diverse eukaryotic taxa carry facultative heritable symbionts, microbes that are passed from mother to offspring. These symbionts are coinherited with mitochondria, and selection favouring either new symbionts, or new symbiont variants, is known to drive loss of mitochondrial diversity as a correlated response. More recently, evidence has accumulated of episodic directional selection on mitochondria, but with currently unknown consequences for symbiont evolution. We therefore employed a population genetic mean field framework to model the impact of selection on mitochondrial DNA (mtDNA) upon symbiont frequency for three generic scenarios of host–symbiont interaction. Our models predict that direct selection on mtDNA can drive symbionts out of the population where a positively selected mtDNA mutation occurs initially in an individual that is uninfected with the symbiont, and the symbiont is initially at low frequency. When, by contrast, the positively selected mtDNA mutation occurs in a symbiont-infected individual, the mutation becomes fixed and in doing so removes symbiont variation from the population. We conclude that the molecular evolution of symbionts and mitochondria, which has previously been viewed from a perspective of selection on symbionts driving the evolution of a neutral mtDNA marker, should be reappraised in the light of positive selection on mtDNA.
Expansion of 5’ UTR CGG repeat in RILPL1 is associated with oculopharyngodistal myopathy
Authors: Yang Xinzhuang , Zhang Dingding , Li Pidong , Niu Jingwen , Xu Dan , Guo Xueyu , Wang Zhen , Zhao Yanhuan , Ren Haitao , Ling Chao , Wang Yang , Shen Jianxiong , Zhu Yicheng , Wang Depeng , Cui Liying , Chen Lin , Dai Yi
Published: September 2021

Oculopharyngodistal myopathy is an adult-onset degenerative muscle disorder characterized by ptosis, ophthalmoplegia and weakness of the facial, pharyngeal and limb muscles. Trinucleotide repeat expansions in non-coding regions of LRP12, G1PC1and NOTCH2NLC were recently reported to be the etiologies for OPDM. However, a significant portion of OPDM patients still have unknown genetic causes. In this study, we performed long-read whole-genome sequencing in a large five-generation family of 156 individuals, including 22 patients diagnosed with typical OPDM and identified CGG repeat expansions in RILPL1 gene in all patients we tested while not in unaffected family members. Methylation analysis indicated that methylation levels of the RILPL1 gene were unaltered in OPDM patients, which was in consistent with previous reports. Our findings first provided evidences that RILPL1 were associated OPDM which we suggested as OPDM type 4.
Implementation, interrupted: Identifying and leveraging factors that sustain after a program interruption
Authors: Hennein Rachel , Ggita Joseph , Ssuna Bashir , Shelley Donna , Akiteng Ann R. , Davis J. Lucian , Katamba Achilles , Armstrong-Hough Mari
Published: September 2021

Background

Many implementation efforts experience interruptions, especially in settings with developing health systems. Approaches for evaluating interruptions are needed to inform targeted re-implementation strategies.

Methods

This study took place in two public health centers with tuberculosis (TB) units in Uganda that previously implemented diabetes mellitus (DM) screening in 2017. In 2019, we conducted interviews with clinic staff to determine current DM practices. We mapped themes identified in the interviews to a Social Ecological Model with three levels: outer setting, inner setting, and individuals.

Results

We conducted nine interviews with clinic staff. Respondents explained that DM screening ceased due to disruptions in the supply chain for glucose test strips. This outer setting interruption had cascading effects on the inner setting and individuals. The lack of screening supplies limited the staff’s opportunities to perform DM screening within the inner setting level, which was associated with diminished self-efficacy within the individual level. However, culture, compatibility and individual beliefs about DM screening sustained throughout the interruption.

Conclusions

We identified factors that diminished and sustained within and between ecological levels during a program interruption. Using this approach, other programs facing interruptions can identify factors and cascading effects of the interruption to target them for re-implementation.
AnFiSA: An open-source computational platform for the analysis of sequencing data for rare genetic disease
Authors: Bouzinier M.A. , Etin D. , Trifonov S.I. , Evdokimova V.N. , Ulitin V. , Shen J. , Kokorev A. , Ghazani A. A. , Chekaluk Y. , Albertyn Z. , Giersch A. , Morton C.C. , Abraamyan F. , Bendapudi P.K. , Sunyaev S. ,   Undiagnosed Diseases Network,   Brigham Genomic Medicine,   SEQuencing a Baby for an Optimal Outcome, Quantori, Krier J.B.
Published: September 2021

Despite genomic sequencing rapidly transforming from being a bench-side tool to a routine procedure in a hospital, there is a noticeable lack of genomic analysis software that supports both clinical and research workflows as well as crowdsourcing. Furthermore, most existing software packages are not forward-compatible in regards to supporting ever-changing diagnostic rules adopted by the genetics community. Regular updates of genomics databases pose challenges for reproducible and traceable automated genetic diagnostics tools. Lastly, most of the software tools score low on explainability amongst clinicians.

We have created a fully open-source variant curation tool, AnFiSA, with the intention to invite and accept contributions from clinicians, researchers and professional software developers. The design of AnFiSA addresses the aforementioned issues via the following architectural principles: using a multidimensional database management system (DBMS) for genomic data to address reproducibility, curated decision trees adaptable to changing clinical rules, and a crowdsourcing-friendly interface to address difficult-to-diagnose cases. We discuss how we have chosen our technology stack and describe the design and implementation of the software. Finally, we show in detail how selected workflows can be implemented using the current version of AnFiSA by a medical geneticist.

All software is available at https://github.com/ForomePlatform under the Apache 2.0 license.

The public demo instance with the public data sets can be accessed via https://github.com/ForomePlatform/AnFiSA#public-demo
Usual Source of Primary Care and Preventive Care Measures in a Pandemic: A Nationwide Study in Japan
Authors: Aoki Takuya , Fujinuma Yasuki , Matsushima Masato
Published: September 2021

Objectives

In a pandemic when there are many barriers to providing preventive care by health care workers, it is unclear whether primary care contributes to the quality of preventive care and what type of preventive care delivery is a challenge for primary care providers. This study aimed to assess multiple preventive care measures and to examine their associations with having a usual source of primary care and primary care performance during the COVID-19 pandemic in Japan.

Design

Nationwide cross-sectional study.

Setting

Japanese general adult population.

Participants

1,757 adult residents.

Primary outcome measures

Fourteen preventive care measures aggregated the overall, screening, immunization, and counseling composites.

Results

Depression screening, zoster vaccination, and tetanus vaccination had low implementation rates even among participants with a usual source of primary care. After adjustment for possible confounders, having a usual source of primary care was positively associated with all preventive care composites. Primary care performance assessed by the Japanese version of Primary Care Assessment Tool Short Form was also dose-dependently associated with an increase in all composites. Results of the sensitivity analyses using a different calculation of preventive care composite were similar to those of the primary analyses.

Conclusions

Receipt of primary care, particularly high-quality primary care, contributed to increased preventive care utilization even during the COVID-19 pandemic. However, the rate of mental health screening in primary care was at a very low level. Therefore, addressing mental health issues should be a major challenge for primary care providers during and after the pandemic.
Evaluation of Correlation between CD44, Radiotherapy Response and Survival Rate in Patients with Advanced Stage of Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Dubey Parul , Gupta Rajeev , Mishra Anupam , Kumar Vijay , Bhadauria Smrati , Bhatt Madan Lal Brahma
Published: September 2021

Purpose

Cancer stem cells (CSCs) constitute a distinctive subpopulation of cancer cells that are competent in tumor initiation, invasion, recurrence, and resistance to chemo-radiotherapy. CD44, a hyaluronic acid (HA) receptor has been considered as a potential CSC marker in head and neck cancer. The purpose of this study is to evaluate the correlation between CD44 and clinicopathological parameters, treatment response, survival, and recurrence.

Methods

CD44 expression was examined by immunohistochemistry (IHC) in 90 samples of head and neck squamous cell carcinoma (HNSCC) confirmed patients. Expression of CD44 and its association with clinicopathological parameters, treatment response, and survival was determined.

Results

In all HNSCC patient samples, CD44 was expressed consistently at different intensities. Tumor size (p<0.001), stage (p<0.001) and treatment response (p<0.001) showed statistically significant association with CD44 expression. Alcohol and CD44 were observed as independent predictors of response to radiotherapy by using multivariate ordinal logistic regression analysis. Analysis of 2 years overall survival (OS) showed that CD44 expression (p=0.02), tumor size (p=0.001), lymph node status (p<0.001), stage (p<0.001) and grade (p=0.007) were significantly associated with OS. By using Cox regression analysis, lymph node status (p=0.001), grade (p<0.001), recurrence (p<0.001) and CD44 expression (p=0.003) were found to be potential independent predictors of OS.

Conclusion

Our findings suggest that CD44 contributes to resistance to radiotherapy and poor OS. The results also suggest that except for CD44 there could be other factors such as lymph node metastasis, grade, and alcohol which should be investigated as potential targets for therapy.
Pre-referral rectal artesunate and referral completion among children with suspected severe malaria in the Democratic Republic of the Congo, Nigeria and Uganda
Authors: Brunner Nina C. , Omoluabi Elizabeth , Awor Phyllis , Okitawutshu Jean , Tshefu Antoinette , Signorell Aita , Akano Babatunde , Ayodeji Kazeem , Okon Charles , Yusuf Ocheche , Athieno Proscovia , Kimera Joseph , Tumukunde Gloria , Angiro Irene , Kalenga Jean-Claude , Delvento Giulia , Lee Tristan T. , Lambiris Mark , Ross Amanda , Cereghetti Nadja , Visser Theodoor , Napier Harriet G. , Buj Valentina , Burri Christian , Lengeler Christian , Hetzel Manuel W.
Published: September 2021

Background

Children who receive pre-referral rectal artesunate (RAS) require urgent referral to a health facility where appropriate treatment for severe malaria can be provided. However, the rapid improvement of a child’s condition after RAS administration may influence a caregiver’s decision to follow this recommendation. Currently, the evidence on the effect of RAS on referral completion is limited. In this study, we investigated the relationship between RAS implementation and administration and referral completion.

Methods and Findings

An observational study accompanied the roll-out of RAS in three malaria endemic settings in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Community health workers and primary health centres enrolled children under five years with suspected severe malaria before and after the roll-out of RAS. All children were followed up 28 days after enrolment to assess their treatment seeking pathways, treatments received, and their health outcome. In total, 8,365 children were enrolled, 77% of whom fulfilled all inclusion criteria and had a known referral completion status. Referral completion was 67% (1,408/2,104) in DRC, 48% (287/600) in Nigeria and 58% (2,170/3,745) in Uganda. In DRC and Uganda, RAS users were less likely to complete referral than RAS non-users in the pre-roll-out phase (adjusted odds ratio [aOR] = 0.48, 95% CI 0.30–0.77 and aOR = 0.72, 95% CI 0.58–0.88, respectively). Among children seeking care from a primary health centre in Nigeria, RAS users were less likely to complete referral compared to RAS non-users in the post-roll-out phase (aOR = 0.18, 95% CI 0.05–0.71). In Uganda, among children who completed referral, RAS users were significantly more likely to complete referral on time than RAS non-users enrolled in the pre-roll-out phase (aOR = 1.81, 95% CI 1.17–2.79).

Conclusions

The findings of this study raise legitimate concerns that the roll-out of RAS may lead to lower referral completion in children who were administered pre-referral RAS. To ensure that community-based programmes are effectively implemented, barriers to referral completion need to be addressed at all levels. Alternative effective treatment options should be provided to children unable to complete referral.
CovRNN—A recurrent neural network model for predicting outcomes of COVID-19 patients: model development and validation using EHR data
Authors: Rasmy Laila , Nigo Masayuki , Kannadath Bijun Sai , Xie Ziqian , Mao Bingyu , Patel Khush , Zhou Yujia , Zhang Wanheng , Ross Angela , Xu Hua , Zhi Degui
Published: September 2021

Background

Predicting outcomes of COVID-19 patients at an early stage is critical for optimized clinical care and resource management, especially during a pandemic. Although multiple machine learning models have been proposed to address this issue, based on the need for extensive data pre-processing and feature engineering, these models have not been validated or implemented outside of the original study site.

Methods

In this study, we propose CovRNN, recurrent neural network (RNN)-based models to predict COVID-19 patients’ outcomes, using their available electronic health record (EHR) data on admission, without the need for specific feature selection or missing data imputation. CovRNN is designed to predict three outcomes: in-hospital mortality, need for mechanical ventilation, and long length of stay (LOS >7 days). Predictions are made for time-to-event risk scores (survival prediction) and all-time risk scores (binary prediction). Our models were trained and validated using heterogeneous and de-identified data of 247,960 COVID-19 patients from 87 healthcare systems, derived from the Cerner® Real-World Dataset (CRWD). External validation was performed using three test sets (approximately 53,000 patients). Further, the transferability of CovRNN was validated using 36,140 de-identified patients’ data derived from the Optum® de-identified COVID-19 Electronic Health Record v. 1015 dataset (2007–2020).

Findings

CovRNN shows higher performance than do traditional models. It achieved an area under the receiving operating characteristic (AUROC) of 93% for mortality and mechanical ventilation predictions on the CRWD test set (vs. 91·5% and 90% for light gradient boost machine (LGBM) and logistic regression (LR), respectively) and 86.5% for prediction of LOS > 7 days (vs. 81·7% and 80% for LGBM and LR, respectively). For survival prediction, CovRNN achieved a C-index of 86% for mortality and 92·6% for mechanical ventilation. External validation confirmed AUROCs in similar ranges.

Interpretation

Trained on a large heterogeneous real-world dataset, our CovRNN model showed high prediction accuracy, good calibration, and transferability through consistently good performance on multiple external datasets. Our results demonstrate the feasibility of a COVID-19 predictive model that delivers high accuracy without the need for complex feature engineering.
RESEARCH PROTOCOL: Large-scale evidence generation and evaluation across a network of databases for type 2 diabetes mellitus
Authors: Khera Rohan , Scheumie Martijn J , Lu Yuan , Ostropolets Anna , Chen Ruijun , Hripcsak George , Ryan Patrick B , Krumholz Harlan M , Suchard Marc A
Published: September 2021

Background

Therapeutic options for type 2 diabetes mellitus (T2DM) have expanded over the last decade with the emergence of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists, which reduced the risk of major cardiovascular events in randomized controlled trials (RCTs). Cardiovascular evidence for older second-line agents, such as sulfonylureas, and direct head-to-head comparisons, including with dipeptidyl peptidase 4 (DPP4) inhibitors, are lacking, leaving a critical gap in our understanding of the relative effects of T2DM agents on cardiovascular risk and on patient-centered safety outcomes.

Methods and Analysis

The Large-Scale Evidence Generations Across a Network of Databases for T2DM (LEGEND-T2DM) initiative is a series of systematic, large-scale, multinational, real-world comparative cardiovascular effectiveness and safety studies of all 4 major second-line anti-hyperglycemic agents including SGLT2 inhibitor, GLP1 receptor agonist, DPP4 inhibitor and sulfonylureas. LEGEND-T2DM will leverage the Observational Health Data Science and Informatics (OHDSI) community that provides access to a global network of administrative claims and electronic health record (EHR) data sources. Committed data partners represent 190 million patients in the US and about 50 million internationally. LEGEND-T2DM will identify all adult, T2DM patients who newly initiate a traditionally second-line T2DM agent, including individuals with and without established cardiovascular disease. Using an active comparator, new-user cohort design, LEGEND-T2DM will execute all pairwise class-vs-class and drug-vs-drug comparisons in each data source that meet a minimum patient count of 1,000 per arm and extensive study diagnostics that assess reliability and generalizability through cohort balance and equipoise to examine the relative risk of cardiovascular and safety outcomes. The primary cardiovascular outcomes include a 3-point and a 4-point composite of major adverse cardiovascular events, and series of safety outcomes. The study will pursue data-driven, large-scale propensity adjustment for measured confounding, a large set of negative control outcome experiments to address unmeasured and systematic bias.

Ethics and Dissemination

The study ensures data safety through a federated analytic approach and follows research best practices, including prespecification and full disclosure of hypotheses tested and their results. LEGEND-T2DM is dedicated to open science and transparency and will publicly share all our analytic code from reproducible cohort definitions through turn-key software, enabling other research groups to leverage our methods, data, and results in order to verify and extend our findings.
Understanding the evidence for climate concerns, negative emotions and climate-related mental ill-health in young people: a scoping review
Authors: Ramadan Reem , Randell Alicia , Lavoie Suzie , Gao Caroline X , Manrique Paula Cruz , Anderson Rebekah , Zbukvic Isabel
Published: September 2021

Background

Human-induced climate change represents a serious threat to human health, including mental health, due to both the traumatising effects of extreme climate events and the psychological effect of worry about climate change. The present scoping review aims to systematically search and synthesise original research related to mental health and climate related concerns, negative emotions and mental ill-health in young people. Findings will help to understand the current landscape, gaps in the literature, and to provide recommendations for future youth mental health research and practice.

Methods

A systematic search and narrative synthesis of the literature published prior to October 2020 examining negative emotions associated with climate change in young people was undertaken. Studies were included if they examined mental ill-health (e.g. symptoms of depression or anxiety) or negative emotions (e.g. distress, worry, concern) associated with the threat of climate change.

Findings

Of the 3329 peer-reviewed articles screened, 12 met the inclusion criteria. Together, included studies show that young people are worried about climate change. Studies also explored the coping strategies young people use to manage their distress caused by climate change.

Interpretations

The limited literature in this area indicates a key gap in youth mental health research. Available evidence suggests that young people are concerned about climate change, which may increase risk of mental ill-health. Thus, clinicians should assess for and address climate anxiety in young people. Mental health leaders are urged to advocate for urgent climate action to mitigate the effects of climate anxiety in young people.

Funding

this project was not funded.
A Novel Retinal Vascular Feature and Machine Learning-based Brain White Matter Lesion Prediction Model
Authors: Bhuiyan Alauddin , Roy Pallab Kanti , Bhuiyan Tasin , Storey Elsdon , Abhayaratna Walter P , Dhamoon Mandip , Smith R. Theodore , Ramamohanarao Kotagiri
Published: September 2021

White matter lesion (WML) is one of the common cerebral abnormalities, it indicates changes in the white matter of human brain and have shown significant association with stroke, dementia and deaths. Magnetic resonance imaging (MRI) of the brain is frequently used to diagnose white matter lesion (WML) volume. Regular screening can detect WML in early stage and save from severe consequences. Current option of MRI based diagnosis is impractical for regular screening because of its high expense and unavailability. Thus, earlier screening and prediction of the WML volume/load specially in the rural and remote areas becomes extremely difficult. Research has shown that changes in the retinal micro vascular system reflect changes in the cerebral micro vascular system. Using this information, we have proposed a retinal image based WML volume and severity prediction model which is very convenient and easy to operate.

Our proposed model can help the physicians to detect the patients who need immediate and further MRI based detail diagnosis of WML. Our model uses quantified measurement of retinal micro-vascular signs (such as arteriovenular nicking (AVN), Opacity (OP) and focal arteriolar narrowing (FAN)) as input and estimate the WML volume/load and classify its severity. We evaluate our proposed model on a dataset of 111 patients taken from the ENVISion study which have retinal and MRI images for each patient. Our model shows high accuracy in estimating the WML volume, mean square error (MSE) between our predicted WML load and manually annotated WML load is 0.15. The proposed model achieves an F1 score of 0.92 in classifying the patients having mild and severe WML load.

The preliminary results of our study indicate that quantified measurement of retinal micro-vascular features (AVN, OP and FAN) can more accurately identify the patients who have high risk of cardio-vascular diseases and dementia.
Calibrating an SIR model for South Korea COVID-19 infections and predicting vaccination impact
Authors: Pae Brandon
Published: September 2021

In the span of 1.5 years, COVID-19 has caused more than 4 million deaths worldwide. To prevent such a catastrophe from reoccurring, it is necessary to test and refine current epidemiological models that impact policy decisions. Thus, we developed a deterministic SIR model to examine the long-term transmission dynamics of COVID-19 in South Korea. Using this model, we analyzed how vaccines would affect the number of cases. We found that a 70% vaccination coverage with a 100% effective vaccine would effectively eliminate the number of cases and herd immunity would have been obtained approximately 85 days after February 15 had there not been a reintroduction of cases.
Contact tracing can explain counter-intuitive COVID-19 trajectories, mitigate disease transmission and provide an early warning indicator - a mathematical modeling study
Authors: Shayak B , Sharma Mohit Manoj
Published: September 2021

The COVID-19 trajectories worldwide have shown several surprising features which are outside the purview of classical epidemiological models. These include (a) almost constant and low daily case rates over extended periods of time, (b) sudden waves emerging from the above solution despite no or minimal change in the level of non-pharmaceutical interventions (NPI), and (c) reduction or flattening of case counts even after relaxation of NPI. To explain these phenomena, we add contact tracing to our recently developed cluster seeding and transmission (CST) model, which is predicated on heterogeneous rather than homogeneous mixing of people in society. With this addition, we find no fewer than four effects which make prediction of epidemic trajectories uncertain. These are (a) cryptogenic instability, where a small increase in population-averaged contact rate causes a large increase in cases, (b) critical mass effect, where a wave can manifest after weeks of quiescence with no change in parameter values, (c) knife-edge effect, where a small change in parameter across a critical value can cause a huge change in the response of the system, and (d) hysteresis effect, where the timing and not just the strength of a particular NPI determines the subsequent evolution of the epidemic. Despite these effects however, it is a robust conclusion that a good contact tracing program can effectively substitute for much more invasive measures. We further find that the contact tracing capacity ratio - a metric of the stress to which the tracers are subject - can act as a reliable early warning indicator of an imminent epidemic wave. Extensive simulations demonstrate that whenever there is a drop in capacity ratio during a period of low daily infections, there is a very high probability of the case counts rising significantly in the immediate future.
Mental Health Concerns Related to the COVID-19 Pandemic on Twitter in the UK
Authors: Zhang Daiwei , Liu Yue , Zhang Senqi , Sun Li , Li Pin , Anand Ajay , Xie Zidian , Li Dongmei
Published: September 2021

Background

Amid the COVID-19 pandemic, mental health-related symptoms (such as depression and anxiety) have been actively mentioned on social media.

Objective

In this study, we aimed to monitor mental health concerns on Twitter during the COVID-19 pandemic in the United Kingdom (UK), and assess the potential impact of the COVID-19 pandemic on mental health concerns of Twitter users.

Methods

We collected COVID-19 and mental health-related tweets from the UK between March 5, 2020 and January 31, 2021 through the Twitter Streaming API. We conducted topic modeling using Latent Dirichlet Allocation model to examine discussions about mental health concerns. Deep learning algorithms including Face++ were used to infer the demographic characteristics (age and gender) of Twitter users who expressed mental health concerns related to the COVID-19 pandemic.

Results

We showed a positive correlation between COVID-19-related mental health concerns on Twitter and the severity of the COVID-19 pandemic in the UK. Geographic analysis showed that populated urban areas have a higher proportion of Twitter users with mental health concerns compared to England as a whole. Topic modeling showed that general concerns, COVID-19 skeptics, and Death toll were the top topics discussed in mental health-related tweets. Demographic analysis showed that middle-aged and older adults might be more likely to suffer from mental health issues or express their mental health concerns on Twitter during the COVID-19 pandemic.

Conclusions

The COVID-19 pandemic has noticeable effects on mental health concerns on Twitter in the UK, which varied among demographic and geographic groups.
Preoperative optimisation in fast-track and enhanced recovery after surgery (ERAS) programs for total hip and knee joint replacement: a systematic review protocol
Authors: Chang Wei-Ju , Naylor Justine , Liu Victor , Monuja Masiath , Adie Sam
Published: September 2021

Introduction

Emerging evidence suggests that fast-track and enhanced recovery after surgery (ERAS) targeting modifiable risk factors reduce complications after total hip (THR) and knee replacement (TKR). However, what constitutes an effective preoperative optimisation protocol for THR and TKR remains unclear. The aims are to: (1) describe pre-operative optimisation protocols for THR and TKR; (2) evaluate the effects of pre-operative optimisation protocols for THR and TKR on morbidity, and patient-reported outcomes.

Methods and analysis

Systematic review and meta-analysis. Electronic databases will be searched using pre-determined search terms to identify relevant studies and evaluate the study eligibility and risks of bias. Two independent reviewers will select the eligible studies and any disagreement will be resolved through a third reviewer. We will include studies investigated pre-operative optimisation protocols administered prior to participants receiving primary THR or TKR to improve post-operative outcomes. Primary outcomes are hospital readmission, complications and patient-reported pain and function. Risk of bias will be assessed using the Cochrane RoB 1 tool and strength of evidence will be examined using the GRADE approach. Pre-operative optimisation protocols will be summarised qualitatively. Meta-analyses on the effects of included protocols will be conducted if appropriate.

Ethics and dissemination

This systematic review does not require ethics approval. The findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.

Registration

This protocol has been submitted to the International Prospective Register of Systematic Reviews on 30 August 2021.

ARTICLE SUMMARY

Strength and Limitations

This systematic review aims to describe pre-operative optimisation protocols for total hip and knee replacement and to synthesise evidence for the effects of pre-operative optimisation protocols on hospital readmission, complications and patient-reported outcomes.

Two independent reviewers will conduct study selection, data extraction and risk of bias assessment.

Meta-analyses, sub-group and sensitivity analyses will be performed where appropriate.
SARS-Cov-2 Infection versus Vaccine-Induced Immunity among Veterans
Authors: Young-Xu Yinong , Smith Jeremy , Korves Caroline
Published: September 2021

Background

With over 40 million cases of SARS-CoV-2 infection reported in the US and discussion of both vaccine mandates as well as boosters ongoing, we aim to examine protection conferred by previous infection compared with vaccination so that citizens and policy makers can make informed decisions.

Objectives

To compare mRNA COVID-19 vaccine-induced immunity against immunity induced by previous infection with SARS-CoV-2 between June and August 2021 when the Delta variant became dominant in the US.

We conducted a retrospective observational study comparing two groups whose incident vaccination or infection occurred within the first two months of 2021: (1) SARS-CoV-2-naive individuals who received a full mRNA vaccination - 2 doses of either Pfizer or Moderna vaccine, (2) newly infected individuals who were subdivided into those have not been vaccinated and those have been vaccinated after their infection. Matched multivariable Cox proportional hazards model was applied. We evaluated laboratory (RT-PCR) confirmed SARS-CoV-2 infection during follow-up, COVID-related hospitalization, and deaths.

Setting

Veterans Health Administration (VHA).

Main outcomes

Positive SARS-CoV-2 PCR test, COVID-related hospitalization, and deaths. Protection was estimated from hazard ratios with 95% confidence intervals (CI).

Results

A total of 9,539 patients with SARS-CoV-2 infection during the first two months of 2021 were matched to 14,458 and 23,105 patients fully vaccinated with Moderna and Pfizer mRNA vaccines, during the same two months. 3,917 (41%) of patients with SARS-CoV-2 infection were subsequently vaccinated. We plan to study this group separately. Consequently, protections were estimated among those with infection but were not subsequently vaccinated and those vaccinated with a mRNA vaccine. Among seniors, Moderna and Pfizer mRNA vaccines offered stronger protection against infection, lowering the risk by an additional 66% [HR: 0.34 (95% CI, 0.14-0.78)] and 68% [HR: 0.32 (95% CI, 0.14-0.70)]; stronger protection against hospitalization, lowering the risk by an additional 61% [HR: 0.34 (95% CI, 0.14-0.78)] and 45% [HR: 0.34 (95% CI, 0.14-0.78)]; and stronger protection against deaths lowering the risk by an additional 95% [HR: 0.05 (95% CI, 0.004-0.62)] and 99% [HR: 0.01 (95% CI, 0.001-0.44)]. Among young adults (age < 65), the protections offered by vaccines were statistically equivalent to that provided by previous infection, especially in terms of absolute incidence rate.

Conclusions

Among the elderly (age 65 or older), two-dose mRNA vaccines provided stronger protection against infection, hospitalization, and death, compared to natural immunity. Among young adults (age < 65), the protections offered between natural immunity and vaccine-induced immunity were similar.
The effects of communicating uncertainty around statistics on public trust: an international study
Authors: Kerr John R. , van der Bles Anne Marthe , Schneider Claudia , Dryhurst Sarah , Chopurian Vivien , Freeman Alexandra L.J. , van der Linden Sander
Published: September 2021

A growing body of research indicates that transparent communication of statistical uncertainty around facts and figures does not undermine credibility. However, the extent to which these findings apply in the context of the COVID-19 pandemic—rife with uncertainties—is unclear. In a large international survey experiment, (Study 1;N= 10,519) we report that communicating uncertainty around COVID-19 statistics in the form of a numeric range (vs. no uncertainty) may lead to slightly lower trust in the number presented but has no impact on trust in the source of the information. We also report the minimal impact of numeric uncertainty on trust is consistent across estimates of current or future COVID-19 statistics (Study 2) and figures relating to environmental or economic research, rather than the pandemic (Study 3). Conversely, we find imprecise statements about the mere existence of uncertainty without quantification can undermine both trust in the numbers and their source – though effects vary across countries and contexts. Communicators can be transparent about statistical uncertainty without concerns about undermining perceptions of their trustworthiness, but ideally should aim to use numerical ranges rather than verbal statements.
Comammox Nitrospira bacteria outnumber canonical nitrifiers irrespective of nitrogen source and availability
Authors: Vilardi Katherine J. , Cotto Irmarie , Rivera Maria Sevillano , Dai Zihan , Anderson Christopher L. , Pinto Ameet
Published: September 2021

Complete ammonia oxidizing bacteria coexist with canonical ammonia and nitrite oxidizing bacteria in a wide range of environments. Whether this is due to competitive or cooperative interactions, or a result of niche separation is not yet clear. Understanding the factors driving coexistence of nitrifiers is critical to manage nitrification processes occurring in engineered and natural ecosystems. In this study, microcosm-based experiments were used to investigate the impact of nitrogen source and loading on the population dynamics of nitrifiers in drinking water biofilter media. Shotgun sequencing of DNA followed by co-assembly and reconstruction of metagenome assembled genomes revealed clade A2 comammox bacteria were likely the primary nitrifiers within microcosms and increased in abundance over Nitrsomonas-like ammonia and Nitrospira-like nitrite oxidizing bacteria irrespective of nitrogen source type or loading. Changes in comammox bacterial abundance did not correlate with either ammonia or nitrite oxidizing bacterial abundance in urea amended systems where metabolic reconstruction indicated potential for cross feeding between ammonia and nitrite oxidizing bacteria. In contrast, comammox bacterial abundance demonstrated a negative correlation with nitrite oxidizers in ammonia amended systems. This suggests potentially weaker synergistic relationships between ammonia and nitrite oxidizers might enable comammox bacteria to displace nitrite oxidizers from complex nitrifying communities.
MNPmApp: An image analysis tool to quantify mononuclear phagocyte distribution in mucosal tissuesa, b
Authors: Potts Catherine , Schearer Julia , Bair Dominic , Ayler Becky , Love Jordan , Dankoff Jennifer , Harris Paul R. , Zosso Dominique , Bimczok Diane
Published: September 2021

Mononuclear phagocytes (MNPs) such as dendritic cells and macrophages perform key sentinel functions in mucosal tissues and are responsible for inducing and maintaining adaptive immune responses to mucosal pathogens. Positioning of MNPs at the mucosal epithelial interface facilitates their access to luminally-derived antigens and may regulate MNP function through soluble mediators or surface receptor interactions. Therefore, accurately quantifying the distribution of MNPs within mucosal tissues as well as their spatial relationship with other cells is important to infer functional cellular interactions in health and disease. In this study, we developed and validated a MATLAB-based tissue cytometry platform, termed “MNP mapping application” (MNPmApp), that performs high throughput analyses of MNP density and distribution in the gastrointestinal mucosa based on digital multicolor fluorescence microscopy images and that integrates a Monte Carlo modeling feature to assess randomness of MNP distribution. MNPmApp identified MNPs in tissue sections of the human gastric mucosa with a specificity of 98.3 ± 1.6% and a sensitivity of 76.4 ± 15.1%. Monte Carlo modeling revealed that mean MNP-MNP distances were significantly lower than anticipated based on random cell placement, whereas MNP-epithelial distances did not significantly differ from those of randomly placed cells. Interestingly, H. pylori infection had no significant impact on MNP density or distribution with regards to MNP-epithelial distances or MNP-MNP distances in gastric tissue. Overall, our analysis demonstrates that MNPmApp is a useful tool for unbiased quantitation of MNPs and their distribution at mucosal sites.