bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular insights into meningococcal carriage isolates from Burkina Faso 7 years after introduction of a serogroup A meningococcal conjugate vaccine
Authors: Topaz Nadav , Kristiansen Paul Arne , Schmink Susanna , Congo-Ouédraogo Malika , Kambiré Dinanibè , Mbaeyi Sarah , Paye Marietou , Sanou Mahamoudou , Sangaré Lassana , Ouédraogo Rasmata , Wang Xin
Published: December 2020

In 2010, Burkina Faso completed the first nationwide mass-vaccination campaign of a meningococcal A conjugate vaccine, drastically reducing the incidence of disease caused by serogroup A meningococci. Since then, other strains, such as those belonging to serogroups W, X and C, have continued to cause outbreaks within the region. A carriage study was conducted in 2016 and 2017 in the country to characterize the meningococcal strains circulating among healthy individuals following the mass-vaccination campaign. Four cross-sectional carriage evaluation rounds were conducted in two districts of Burkina Faso, Kaya and Ouahigouya. Oropharyngeal swabs were collected for the detection of

Neisseria meningitidis

by culture. Confirmed

N. meningitidis

isolates underwent whole-genome sequencing for molecular characterization. Among 13 758 participants, 1035 (7.5 %)

N

.

meningitidis

isolates were recovered. Most isolates (934/1035; 90.2 %) were non-groupable and primarily belonged to clonal complex (CC) 192 (822/934; 88 %). Groupable isolates (101/1035; 9.8 %) primarily belonged to CCs associated with recent outbreaks in the region, such as CC11 (serogroup W) and CC10217 (serogroup C); carried serogroup A isolates were not detected. Phylogenetic analysis revealed several CC11 strains circulating within the country, several of which were closely related to invasive isolates. Three sequence types (STs) were identified among eleven CC10217 carriage isolates, two of which have caused recent outbreaks in the region (ST-10217 and ST-12446). Our results show the importance of carriage studies to track the outbreak-associated strains circulating within the population in order to inform future vaccination strategies and molecular surveillance programmes.
Interleukin 1 beta is associated with depression in Multiple Sclerosis patients
Authors: Aguilar-Talamantes Hugo , Islas-Hernandez Azul , Rodriguez-Castañenda Aleida , Bertado-Cortés Brenda , Corlay-Noriega Irma , Garcia-delaTorre Paola
Published: December 2020

Depressive and anxiety symptoms occur more frequently in chronic encephalomyelitis. Inflammatory diseases are highly associated with psychiatric comorbidities, which has been well established in Multiple Sclerosis. However, no biomarkers have been found with the capacity to discern between MS and depression. Thirty-six individuals with a diagnosis of MS according to the revised McDonald criteria, were recruited from an outpatient Neurology and Psychiatry from the medical unit of high specialty in Mexico. We measured the association between BDNF, IL-1β, and TNFα in serum with the presence of depression and anxiety using the semi-structured psychiatric interview, the Beck Depression Inventory (IDB), and Hospital Anxiety and Depression Scale (HADS). This was a cross-sectional study. The Logistic Regression was used for the multivariate analysis adjusted by the Multiple Sclerosis Severity Score (MSSS). With a power of 0.75 in the final model, patients with multiple sclerosis, depression, and anxiety obtained the highest values of IL-1 β in our study.
Identifying Synergistic Interventions to Address COVID-19 Using a Large Scale Agent-Based Model
Authors: Li Junjiang , Giabbanelli Philippe J.
Published: December 2020

There is a range of public health tools and interventions to address the global pandemic of COVID-19. Although it is essential for public health efforts to comprehensively identifywhichinterventions have the largest impact on preventing new cases, most of the modeling studies that support such decision-making efforts have only considered a very small set of interventions. In addition, previous studies predominantly considered interventions as independent or examined a single scenario in which every possible intervention was applied. Reality has been more nuanced, as a subset of all possible interventions may be in effect for a given time period, in a given place. In this paper, we use cloud-based simulations and a previously published Agent-Based Model of COVID-19 (Covasim) to measure the individual and interacting contribution of interventions on reducing new infections in the US over 6 months. Simulated interventions include face masks, working remotely, stay-at-home orders, testing, contact tracing, and quarantining. Through a factorial design of experiments, we find that mask wearing together with transitioning to remote work/schooling has the largest impact. Having sufficient capacity to immediately and effectively perform contact tracing has a smaller contribution, primarily via interacting effects.
CD177, a specific marker of neutrophil activation, is a hallmark of COVID-19 severity and death
Authors: Lévy Yves , Wiedemann Aurélie , Hejblum Boris P. , Durand Mélany , Lefebvre Cécile , Surénaud Mathieu , Lacabaratz Christine , Perreau Matthieu , Foucat Emile , Déchenaud Marie , Tisserand Pascaline , Blengio Fabiola , Hivert Benjamin , Gautier Marine , Cervantes-Gonzalez Minerva , Bachelet Delphine , Laouénan Cédric , Bouadma Lila , Timsit Jean-François , Yazdanpanah Yazdan , Pantaleo Giuseppe , Hocini Hakim , Thiébaut Rodolphe ,   the French COVID cohort study group
Published: December 2020

COVID-19 SARS-CoV-2 infection exhibits wide inter-individual clinical variability, from silent infection to severe disease and death. The identification of high-risk patients is a continuing challenge in routine care. We aimed to identify factors that influence clinical worsening. We analyzed 52 cell populations, 71 analytes, and RNA-seq gene expression in the blood of severe patients from the French COVID cohort upon hospitalization (n = 61). COVID-19 patients showed severe abnormalities of 27 cell populations relative to healthy donors (HDs). Forty-two cytokines, neutrophil chemo-attractants, and inflammatory components were elevated in COVID-19 patients. Supervised gene expression analyses showed differential expression of genes for neutrophil activation, interferon signaling, T- and B-cell receptors, EIF2 signaling, and ICOS-ICOSL pathways in COVID-19 patients. Unsupervised analysis confirmed the prominent role of neutrophil activation, with a high abundance of CD177, a specific neutrophil activation marker. CD177 was the most highly differentially-expressed gene contributing to the clustering of severe patients and its abundance correlated with CD177 protein serum levels. CD177 levels were higher in COVID-19 patients from both the French and “confirmatory” Swiss cohort (n = 203) than in HDs (P< 0.01) and in ICU than non-ICU patients (P< 0.001), correlating with the time to symptoms onset (P = 0.002). Longitudinal measurements showed sustained levels of serum CD177 to discriminate between patients with the worst prognosis, leading to death, and those who recovered (P = 0.01). These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.
Effectiveness and Cost-Effectiveness of TeleStroke Consultations to Support the Care of Stroke Patients Presenting to Regional Emergency Departments in Western Australia: An Economic Evaluation Case Study Protocol
Authors: Tsou Christina , Robinson Suzanne , Boyd James , Kamath Shruthi , Yeung Justin , Waters Stephanie , Gifford Karen , Jamieson Andrew , Hendrie Delia
Published: December 2020

Introduction

The Western Australia Acute TeleStroke Programme commenced incrementally across regional Western Australia (WA) during 2016-2017. Since the introduction of the TeleStroke Programme, there has been monitoring of service outputs including regional patient access to tertiary stroke specialist advice and reperfusion treatment, however, the impact of consultation with a stroke specialist via telehealth (videoconferencing or telephone) on the effectiveness and cost-effectiveness of stroke care, and the drivers of cost-effectiveness has not been systematically evaluated.

Methods and Analysis

The aim of the case study is to examine the impact of consultation with a stroke specialist via telehealth on the effectiveness and cost-effectiveness of stroke and TIA care using a mixed methods approach. A categorical decision tree model will be constructed in collaboration with clinicians and programme managers. A before and after comparison using State-wide administrative datasets will be used to run the base model. If sample size and statistical power permits, the cases and comparators will be matched by stroke type and presence of CT scan at the initial site of presentation, age category and presenting hospital. The drivers of cost-effectiveness will be explored through stakeholder interviews. Data from the qualitative analysis will be cross-referenced with trends emerging from the quantitative dataset and used to guide the factors to be involved in sub-group and sensitivity analysis.

Ethics and Dissemination

Ethics approval for this case study has been granted from the WACHS Human Research and Ethics Committee (RGS3076). Reciprocal approval has been granted from Curtin University Human Research Ethics Office (HRE2019-0740). Findings will be disseminated publicly through conference presentation and peer-review publications. Interim findings will be released as internal reports to inform the service development.

Strengths and Limitations of This Study

Comparison of the impact of stroke specialist consultation via telehealth in regional Australia in supporting the management of different stroke subtypes

The decision tree model will be constructed in collaboration with clinicians and programme administrators directly involved in the delivery of the TeleStroke Programme

Use of local administrative data as model inputs enables the base model to reflect the reality of the regional WA Health service delivery

Collaboration with WA Health stakeholders involved in TeleStroke Programme design and implementation to optimise utility of the case study to inform service development and expansion

Conversion of the functional outcome modified Rankin Scale score (mRS) to quality adjusted life years (QALY) relies on national or international averages
Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
Authors: Naseem Maleeha , Arshad Hajra , Hashmi Syeda Amrah , Irfan Furqan , Ahmed Fahad Shabbir
Published: December 2020

Background

The second wave of COVID-19 pandemic is anticipated to be worse than the initial one and will strain the healthcare systems even more during the winter months. Our aim was to develop a machine learning-based model to predict mortality using the deep learning Neo-V framework. We hypothesized this novel machine learning approach could be applied to COVID-19 patients to predict mortality successfully with high accuracy.

Methods

The current Deep-Neo-V model is built on our previously statistically rigorous machine learning framework [Fahad-Liaqat-Ahmad Intensive Machine (FLAIM) framework] that evaluated statistically significant risk factors, generated new combined variables and then supply these risk factors to deep neural network to predict mortality in RT-PCR positive COVID-19 patients in the inpatient setting. We analyzed adult patients (≥18 years) admitted to the Aga Khan University Hospital, Pakistan with a working diagnosis of COVID-19 infection (n=1228). We excluded patients that were negative on COVID-19 on RT-PCR, had incomplete or missing health records. The first phase selection of risk factor was done using Cox-regression univariate and multivariate analyses. In the second phase, we generated new variables and tested those statistically significant for mortality and in the third and final phase we applied deep neural networks and other traditional machine learning models like Decision Tree Model, k-nearest neighbor models and others.

Results

A total of 1228 cases were diagnosed as COVID-19 infection, we excluded 14 patients after the exclusion criteria and (n=)1214 patients were analyzed. We observed that several clinical and laboratory-based variables were statistically significant for both univariate and multivariate analyses while others were not. With most significant being septic shock (hazard ratio [HR], 4.30; 95% confidence interval [CI], 2.91-6.37), supportive treatment (HR, 3.51; 95% CI, 2.01-6.14), abnormal international normalized ratio (INR) (HR, 3.24; 95% CI, 2.28-4.63), admission to the intensive care unit (ICU) (HR, 3.24; 95% CI, 2.22-4.74), treatment with invasive ventilation (HR, 3.21; 95% CI, 2.15-4.79) and laboratory lymphocytic derangement (HR, 2.79; 95% CI, 1.6-4.86). Machine learning results showed our DNN (Neo-V) model outperformed all conventional machine learning models with test set accuracy of 99.53%, sensitivity of 89.87%, and specificity of 95.63%; positive predictive value, 50.00%; negative predictive value, 91.05%; and area under the curve of the receiver-operator curve of 88.5.

Conclusion

Our novel Deep-Neo-V model outperformed all other machine learning models. The model is easy to implement, user friendly and with high accuracy.
Exploring virtual and augmented reality simulation in obstetrics and gynaecology training; a qualitative study
Authors: Ryan R , Ryan G , Higgins MF
Published: December 2020

Introduction

The scope and use of simulation in medical education and healthcare training has increased considerably over the past 20 years, as technology has advanced rapidly and increasing fidelity has become standard.

This study aims to explore O&G trainees’ attitudes and beliefs regarding augmented reality (AR) and virtual reality (VR), and their attitudes towards their incorporation into relevant curricula.

Methods

This was a qualitative descriptive study using thematic analysis. An initial pilot focus group was followed by semi-structured interviews. Data was analysed using iterative content analysis. Relevant themes were identified during the focus ground and explored in greater detail during semi-structured interviews.

Results

Nine trainees participated in total; one focus group and two individual interviews were conducted. Five key themes were identified: the value and importance of education, ‘what works’, the importance of a supportive educator and peer, the difference between simulation and real-life, and VR-associated hope.

Conclusions

Trainees had little experience or knowledge of AR and VR simulation. They believe that simulation will be more important in future, and that it has potential for training. Further exposure and education involving AR and VR will be required for it to become an integral part of education and training.
Risk compensation after HIV-1 vaccination may accelerate viral adaptation and reduce cost-effectiveness: a modeling study
Authors: Peebles Kathryn , Mittler John E. , Goodreau Steven M. , Murphy James T. , Reid Molly C. , Abernethy Neil , Gottlieb Geoffrey S. , Barnabas Ruanne V. , Herbeck Joshua T.
Published: December 2020

Pathogen populations can evolve in response to selective pressure from vaccine-induced immune responses. For HIV, models predict that viral adaptation, either via strain replacement or selection on de novo mutation, may rapidly reduce the effectiveness of an HIV vaccine. We hypothesized that behavioral risk compensation after vaccination may accelerate the transmission of vaccine resistant strains, increasing the rate of viral adaptation and leading to a more rapid decline in vaccine effectiveness. To test our hypothesis, we modeled: a) the impact of risk compensation on rates of HIV adaptation via strain replacement in response to a partially effective vaccine; and b) the combined impact of risk compensation and viral adaptation on vaccine-mediated epidemic control. We used an agent-based epidemic model that was calibrated to HIV-1 trends in South Africa, and includes demographics, sexual network structure and behavior, and within-host disease dynamics. Our model predicts that risk compensation can increase the rate of HIV viral adaptation in response to a vaccine. In combination, risk compensation and viral adaptation can, under certain scenarios, reverse initial declines in prevalence due to vaccination, and result in HIV prevalence at 15 years equal to or greater than prevalence without a vaccine.
Public good exploitation in natural bacterioplankton communities
Authors: Pollak Shaul , Gralka Matti , Sato Yuya , Schwartzman Julia , Lu Lu , Cordero Otto X.
Published: December 2020

Microorganisms such as bacteria often interact with their environment through extracellular molecules that increase access to limiting resources. These secretions can act as public goods, creating incentives for exploiters, a.k.a cheaters, to invade and ‘steal’ public goods away from producers. This phenomenon has been studied extensively in microbiology due to its implications for the evolution of cooperation, but little is known about the occurrence and impact of public good exploiters in the environment. Here, we develop a new genomic approach to systematically identify bacteria that can exploit public goods produced during the degradation of polysaccharides. Focusing on chitin – the second most abundant biopolymer on the planet, we show that public good exploiters are active in natural marine microbial communities that assemble on chitin particles, invading during early stages of colonization and potentially hindering degradation. Unlike in classical studies of social evolution, exploiters and polysaccharide degraders are not isogenic and instead belong to distant lineages, facilitating their coexistence. Our approach opens novel avenues to use the wealth of genomic data available to infer ecological roles and interactions among microbes.
Acceptability and feasibility of strategies to shield the vulnerable during the COVID-19 outbreak: a qualitative study in six Sudanese communities
Authors: Abdelmagid Nada , Ahmed Salma A.E. , Nurelhuda Nazik , Zainalabdeen Israa , Ahmed Aljaile , Fadlallah Mahmoud Ali , Dahab Maysoon
Published: December 2020

Background

Shielding of high-risk groups from coronavirus disease (COVID-19), either within their households or safe communal structures, has been suggested as a realistic alternative to severe movement restrictions in response to the COVID-19 epidemic in low-income countries. To our knowledge, this concept has not been tested or evaluated in resource-poor settings. This study aimed to explore the acceptability and feasibility of strategies to shield persons at higher risk of severe COVID-19 outcomes, during the COVID-19 epidemic in six communities in Sudan.

Methods

We purposively sampled participants from six communities, illustrative of urban, rural and forcibly-displaced settings. In-depth telephone interviews were held with 59 members of households with one or more members at higher risk of severe COVID-19 outcomes. Follow-up interviews were held with 30 community members after movement restrictions were eased across the country. All interviews were audio-recorded, transcribed verbatim, and analysed using a two-stage deductive and inductive thematic analysis.

Results

Most participants were aware that some people are at higher risk of severe COVID-19 outcomes but were unaware of the concept of shielding. Most participants found shielding acceptable and consistent with cultural inclinations to respect elders and protect the vulnerable. However, extra-household shielding arrangements were mostly seen as socially unacceptable. Participants reported feasibility concerns related to the social isolation of shielded persons and loss of income for shielding families. The acceptability and feasibility of shielding strategies were reduced after movement restrictions were eased, as participants reported lower perception of risk in their communities and increased pressure to comply with social commitments outside the house.

Conclusion

Shielding is generally acceptable in the study communities. Acceptability is influenced by feasibility, and by contextual changes in the epidemic and associated policy response. The promotion of shielding should capitalise on the cultural and moral sense of duty towards elders and vulnerable groups. Communities and households should be provided with practical guidance to implement feasible shielding options. Households must be socially, psychologically and financially supported to adopt and sustain shielding effectively.
Remote olfactory assessment using the NIH Toolbox Odor Identification Test and the Brain Health Registry
Authors: Jaen Cristina , Maute Christopher , Mackin Scott , Camacho Monica R , Truran Diana , Nosheny Rachel , Weiner Michael M , Dalton Pamela
Published: December 2020

Objective: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. However, unlike hearing and vision, olfactory function is rarely tested outside of a research laboratory. The purpose of this study is to determine the feasibility of remotely testing olfactory performance using the National Institutes of Health's Toolbox odor identification test (NIH Toolbox Odor ID Test).

Methods: Participants were recruited using the Brain Health Registry (BHR), an online assessment platform which connects participants with researchers. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses.

Results: Data obtained from subjects who performed the test at home was comparable to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting. Age-dependent olfactory decline and gender-dependent sensitivity could be detected using the NIH Toolbox Odor ID Test remotely.

Conclusions: The NIH Toolbox Odor ID Test is a valid instrument to measure olfactory performance via self-administration at home. This approach can be useful for longitudinal studies or as a screening tool for studies that require testing the sense of smell.
Mathematical model for the mitigation of the economic effects of Covid-19 in the Democratic Republic of the Congo
Authors: Balike Zirhumanana Dieudonne
Published: December 2020

A mathematical model of the spread of the Covid-19 in the Democratic Republic of the Congo taking into account the vulnerability of the economy is proposed. The reproduction number of the Covid-19 is calculated and numerical simulations are performed using Python software. Clear advice for the policymakers is deduced from the forecasting of the model.
Vaccine Prioritisation Using Bluetooth Exposure Notification Apps
Authors: Penney Mark D , Yargic Yigit , Smolin Lee , Thommes Edward W , Anand Madhur , Bauch Chris T.
Published: December 2020

After vaccinating health care workers and vulnerable groups against COVID-19, authorities will need to decide how to vaccinate everyone else. Prioritising individuals with more contacts can be disproportionately effective, in theory, but identifying these individuals is difficult. Here we show that the technology underlying Bluetooth exposure notification applications, such as used for digital contact tracing, can be leveraged to prioritise vaccination based on individual contact data. Our approach is based on the insight that these apps also act as local sensing devices measuring each user’s total exposure time to other users, thereby enabling the implementation of a previously impossible strategy that prioritises potential super-spreaders. Furthermore, by generalising percolation theory and introducing a novel measure of vaccination efficiency, we demonstrate that this “hot-spotting” strategy can achieve herd immunity with up to half as many vaccines as a non-targeted strategy, and is attractive even for relatively low rates of app usage.
Anosmia and other SARS-CoV-2 positive test-associated symptoms, across three national, digital surveillance platforms as the COVID-19 pandemic and response unfolded: an observation study
Authors: Sudre Carole Helene , Keshet Ayya , Graham Mark S , Joshi Amit D , Shilo Smadar , Rossman Hagai , Murray Benjamin , Molteni Erika , Klaser Kerstin , Canas Liane S , Antonelli Michela , Modat Marc , Capdevila Pujol Joan , Ganesh Sajaysurya , Wolf Jonathan , Meir Tomer , Chan Andrew T , Steves Claire , Spector Timothy , Brownstein John S , Segal Eran , Ourselin Sebastien , Astley Christina
Published: December 2020

Background: Multiple participatory surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of community-wide COVID-19 epidemiology. During this time, testing criteria broadened and healthcare policies matured. We sought to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three national surveillance platforms, during periods of testing and policy changes, and whether inconsistencies could better inform our understanding and future studies as the COVID-19 pandemic progresses.
Methods: Four months (1st April 2020 to 31st July 2020) of observation through three volunteer COVID-19 digital surveillance platforms targeting communities in three countries (Israel, United Kingdom, and United States). Logistic regression of self-reported symptom on self-reported SARS-CoV-2 test status (or test access), adjusted for age and sex, in each of the study cohorts. Odds ratios over time were compared to known changes in testing policies and fluctuations in COVID-19 incidence.
Findings: Anosmia/ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test, based on 658325 tests (5% positive) from over 10 million respondents in three digital surveillance platforms using longitudinal and cross-sectional survey methodologies. During higher-incidence periods with broader testing criteria, core COVID-19 symptoms were more strongly associated with test status. Lower incidence periods had, overall, larger confidence intervals.
Interpretation: The strong association of anosmia/ageusia with self-reported SARS-CoV-2 test positivity is omnipresent, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform or testing policy. This analysis highlights that precise effect estimates, as well as an understanding of test access patterns to interpret differences, are best done only when incidence is high. These findings strongly support the need for testing access to be as open as possible both for real-time epidemiologic investigation and public health utility.
Emergence and rising of ceftazidime-avibactam resistant KPC-producing Pseudomonas aeruginosa in China: a molecular epidemiology study
Authors: Zhu Yiwei , Chen Jie , Shen Han , Chen Zhongju , Yang Qiwen , Zhu Jin , Li Xi , Yang Qing , Zhao Feng , Ji Jingshu , Cai Heng , Li Yue , Zhang Linghong , Leptihn Sebastian , Hua Xiaoting , Yu Yunsong
Published: December 2020

Background: Infections by Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are difficult to treat and novel antibiotics are desperately needed. Till today, ceftazidime-avibactam (CAZ-AVI) has been used to treat infections caused by multidrug resistant (MDR) Gram-negative bacteria, including Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Although cases of KPC-producing P. aeruginosa (KPC-PA) have been reported sporadically, data about KPC-PA susceptibility to CAZ-AVI and its molecular characteristics are limited.
Methods: CRPA were collected from seven hospitals in China from 2017 to 2018. PCR was deployed to screen for the blaKPC gene. Antimicrobial susceptibility of KPC-PA was determined by broth microdilution method or agar dilution method. We combined Illumina sequencing and Nanopore long-read sequencing to elucidate the genomic characteristics of KPC-PA strains.
Results: KPC-PA strains were found in six out of seven hospitals. 151/374 (40.4%) CRPA clinical isolates harbored the blaKPC-2 gene. Among KPC-PA, ST463 (107/151) was predominant, followed by ST485 (14/151) and ST1212 (12/151). Approximately half of all KPC-PA (50.3%) were susceptible to CAZ-AVI. We found that the blaKPC-2 gene copy number correlated with CAZ-AVI MIC. In more than 90% (136/151) of the strains, we found plasmids that belonged to two types carrying blaKPC-2 gene. The Type 1 plasmid, predominant in East China, was identified in 118 strains and the Type 2 plasmid, belonged to a megaplasmid family spreading globally, was identified in 19 strains. In addition, we identified IS26-ΔTn6296 and IS6100-ΔTn6296-Tn1403 as two mobile genetic elements that mediated blaKPC-2 gene transmission.
Conclusion: Our results suggest that the blaKPC-2 gene is becoming a remarkable mediator of carbapenem resistance in P. aeruginosa in China. The emergence and spread of such KPC-PA strains poses a threat on clinical therapy as CAZ-AVI becomes inefficient. It would be beneficial to screen for the blaKPC gene in CRPA strains for antimicrobial surveillance.
The low-cost Shifter microscope stage transforms the speed and robustness of protein crystal harvesting
Authors: Wright Nathan David , Collins Patrick , Koekemoer Lizbé , Krojer Tobias , Talon Romain , Nelson Elliot , Ye Mingda , Nowak Radosław , Newman Joseph , Ng Jia Tsing , Mitrovich Nick , Wiggers Helton , von Delft Frank
Published: December 2020

Despite the tremendous success of X-ray cryo-crystallography in recent decades, the transfer of crystals from the drops in which they are grown to diffractometer sample mounts remains a manual process in almost all laboratories. Here, the Shifter, a motorized, interactive microscope stage that transforms the entire crystal-mounting workflow from a rate-limiting manual activity to a controllable, high-throughput semi-automated process, is described. By combining the visual acuity and fine motor skills of humans with targeted hardware and software automation, it was possible to transform the speed and robustness of crystal mounting. Control software, triggered by the operator, manoeuvres crystallization plates beneath a clear protective cover, allowing the complete removal of film seals and thereby eliminating the tedium of repetitive seal cutting. The software, either upon request or working from an imported list, controls motors to position crystal drops under a hole in the cover for human mounting at a microscope. The software automatically captures experimental annotations for uploading to the user's data repository, removing the need for manual documentation. The Shifter facilitates mounting rates of 100–240 crystals per hour in a more controlled process than manual mounting, which greatly extends the lifetime of the drops and thus allows a dramatic increase in the number of crystals retrievable from any given drop without loss of X-ray diffraction quality. In 2015, the first in a series of three Shifter devices was deployed as part of the XChem fragment-screening facility at Diamond Light Source, where they have since facilitated the mounting of over 120 000 crystals. The Shifter was engineered to have a simple design, providing a device that could be readily commercialized and widely adopted owing to its low cost. The versatile hardware design allows use beyond fragment screening and protein crystallography.
TEMPy2: a Python library with improved 3D electron microscopy density-fitting and validation workflows
Authors: Cragnolini Tristan , Sahota Harpal , Joseph Agnel Praveen , Sweeney Aaron , Malhotra Sony , Vasishtan Daven , Topf Maya
Published: December 2020

Structural determination of molecular complexes by cryo-EM requires large, often complex processing of the image data that are initially obtained. Here, TEMPy2, an update of the TEMPy package to process, optimize and assess cryo-EM maps and the structures fitted to them, is described. New optimization routines, comprehensive automated checks and workflows to perform these tasks are described.
Using a partial atomic model from medium-resolution cryo-EM to solve a large crystal structure
Authors: Fàbrega-Ferrer Montserrat , Cuervo Ana , Fernández Francisco J. , Machón Cristina , Pérez-Luque Rosa , Pous Joan , Vega M. Cristina , Carrascosa José L. , Coll Miquel
Published: December 2020

Medium-resolution cryo-electron microscopy maps, in particular when they include a significant number of α-helices, may allow the building of partial models that are useful for molecular-replacement searches in large crystallographic structures when the structures of homologs are not available and experimental phasing has failed. Here, as an example, the solution of the structure of a bacteriophage portal using a partial 30% model built into a 7.8 Å resolution cryo-EM map is shown. Inspection of the self-rotation function allowed the correct oligomerization state to be determined, and density-modification procedures using rotation matrices and a mask based on the cryo-EM structure were critical for solving the structure. A workflow is described that may be applicable to similar cases and this strategy is compared with direct use of the cryo-EM map for molecular replacement.
Primary cutaneous follicle center lymphoma in a 16‐year‐old girl
Authors: Edmonds Nicole , Hernández‐Pérez Marier , Holsinger Michael , Gru Alejandro A.
Published: December 2020

In the pediatric and adolescent age group, primary cutaneous lymphomas are rare, especially cutaneous B‐cell lymphomas. According to the World Health Organization, the three main subtypes of primary cutaneous B‐cell lymphomas are primary cutaneous marginal zone B‐cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large B‐cell lymphoma, leg type. We present an extraordinary case of PCFCL arising in a 16‐year‐old female, only the sixth case of PCFCL to be reported in the literature in a patient less than 20 years old. Although PCMZL was considered in this case, the finding of lambda light chain restriction in the BCL‐6 and CD10 positive population of lymphocytes established the diagnosis of primary cutaneous follicle center lymphoma. Not many data currently exist on the prognosis of PCFCL in young individuals, but adult PCFCL has a good prognosis with an indolent course and 5‐year survival rates over 95%. Because of its uncommon manifestation in young patients, the diagnosis of PCFCL is often delayed or missed. This case is presented to raise awareness of PCFCL in the pediatric/ adolescent population and to contribute to the ongoing research of this condition.
Burden of increasing opioid use in the treatment of migraine: Results from the Migraine in America Symptoms and Treatment Study
Authors: Lipton Richard B. , Buse Dawn C. , Dodick David W. , Schwedt Todd J. , Singh Preeti , Munjal Sagar , Fanning Kristina , Bostic BS Ryan , Reed Michael L.
Published: December 2020

Objective

We sought to assess factors associated with the frequency of self‐reported prescription opioid use in persons with migraine, including demographic variables, comorbidities, headache characteristics, and patterns of consultation.

Background

Despite the dose‐dependent effect of opioids on migraine progression and the association with negative outcomes, migraine treatment often includes opioids. The Migraine in America Symptoms and Treatment Study focuses on individuals with migraine who receive prescription acute medications, including those receiving and those not receiving opioids.

Methods

This web‐based panel survey identified people in the United States with migraine using a validated screener. This analysis stratified people with migraine into 4 groups based on days of monthly opioid use: non‐opioid users, ≤3 days, 4‒9 days, and ≥10 days per month.

Results

Of 15,133 respondents with migraine, 4701 (31%) reported acute prescription medication use for headache/migraine in the previous 3 months (mean age 45 years, 71.6% [3367/4701] female), of whom 32.5% (1528/4701) reported opioid use. About one‐third of respondents with primary care or neurology consults in the prior 6 months reported receiving an opioid, and more than half of respondents (209/391, 53.5%) with a pain clinic consultation did so. Models compared those using opioids ≤3 days/month (879/4701, 18.7%), 4‒9 days/month (304/4701, 6.5%), ≥10 days/month (345/4701, 7.3%) to non‐opioid users (3173/4701, 67.5%). Compared to non‐opioid users, infrequent users (≤3 days/month) were more likely to be male and less likely to have chronic migraine or to screen positive for anxiety and depression; and frequent opioid users (the 4‒9 days/month and the ≥10 days/month groups) were more likely to be male, to smoke, to be obese, to report greater pain interference, to have moderate to severe disability, to have symptoms of anxiety and depression, to use fewer triptans and nonsteroidal anti‐inflammatory drugs, and to have poor acute treatment optimization.

Conclusion

Among prescription medication users, this cross‐sectional analysis shows that increasing use of prescription opioids is associated with male gender, chronic migraine, more severe disability, anxiety and depression, poor acute treatment optimization, and treatment in a pain clinic.
Timing of native nephrectomy and kidney transplant outcomes in children
Authors: Kizilbash Sarah J. , Huynh Dao , Kirchner Varvara , Lewis Jane , Verghese Priya S.
Published: December 2020

Background

No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking.

Method

We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank‐sum test, Fisher's exact test, and Kaplan‐Meier methods to compare outcomes.

Results

Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P = .049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P = .06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P = .02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P = .05). We observed no difference in 5‐year graft survival between the groups (95.0% vs 91.7%, P = .73). Patient survival was 100% in both groups over a median follow‐up of 44.2 months. Surgical complications were similar between the groups.

Conclusion

Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes.
The novel HLA‐A allele, HLA‐A*01:354, identified in a Buryat individual
Authors: Loginova Maria , Smirnova Daria , Kutyavina Svetlana , Paramonov Igor , Zarubin Maksim
Published: December 2020

HLA‐A*01:354 differs from HLA‐A*01:01:01:01 by a single nonsynonymous change (124G‐>A, glycine 18 to arginine).
CONTINUITY OF GREAT SUMATRAN FAULT IN THE MARINE AREA REVEALED BY 3D INVERSION OF GRAVITY DATA
Authors: Muhammad Yanis , Faisal Abdullah , Yenny Assyifa , Muzakir Zainal , Abubakar Marwan , Nazli Ismail
Published: December 2020

The Great Sumatran Fault (GSF) is a 1900-km-long fault extending from Lampung, Indonesia, to India's Andaman Islands. The fault location is not only on the land but also in the marine area. Previous studies were only focused on the land area of Sumatra and Andaman Islands even though the marine fault has also impacted earthquakes and tsunamis such as in 2004. As an effort to disaster risk mitigation, this study used the gravity method to map and study the continuity of the GSF in the marine area from the Aceh Province, Indonesia, to the Andaman Islands, India. The gravity data were obtained from Topex with a resolution of 1.85 km/px. Based on the Bouguer data, the subduction zone in the western part of the Indian Ocean is observed with the anomaly of 500–700 mGal, while the residual structure of GSF, relative to the subduction zone, only comes to clarity through a horizontal derivative transformation with anomaly 130-250 mGal. To delineate the fault's geometry, the data were inverted by GRABLOX 1.6 using Singular Value Decomposition and Occam methods. The 3D modeling results also clearly show the contrast density between regional faults such as subduction zones on the Westside of the West Andaman Fault (WAF). The GSF faults can also be well demonstrated at 50 km depth. Based on these results, the gravity Topex is potentially used as a preliminary study of the GSF activity in the marine area.
On the Process of Understanding the Reading of Students with Mental Disabilities: An Examination of Teacher Practices
Authors: Uyanık Abdurrahman , Nuri Cahit , Sarı Hakan
Published: December 2020

This study aims to examine the teacher adaptations related to the stages of the reading process used in the process of understanding the reading of students with mental disabilities according to different variables. A descriptive survey model which is one of the quantitative research methods was used in the study. In 2018-2019, to ensure the research sample, reliability, and validity of the scale, 361 classroom teachers were gathered from 18 primary schools of Meray and Kartay districts of Konya province. It was applied to 93 more classroom teachers to provide a confirmatory factor analysis of the scale. After ensuring validity and reliability, it was applied to 99 special education teachers working in primary schools in Karatay, Meram, and Selcuklu districts of Konya province for descriptive analysis. Scores of male teachers are a little higher than female teachers in the scale of teacher practices related to the stages of the reading process. Graduate-level teachers, who have received training in the scale of teacher practices related to the stages of the reading process, score at the undergraduate level. Yet, the observed difference was not statistically significant in question.
Coaching Effectiveness: A Personal Discourse on Bringing Clarity to an Overused Concept
Authors: Lyle John
Published: December 2020

Coaching effectiveness is a ubiquitous term in the sport coaching literature, yet it remains ill-defined and challenging to operationalize. This paper explores the concept and provides a polemic intended to generate discussion within the field. Effectiveness is a more nuanced concept than generally accepted and is best considered a superordinate concept that synthesizes other lower order concepts. Feature matching approaches are most common but provide, at best, a partial account of effective practice. This has also led to a focus on ineffective behavior. The simplistic notion of effectiveness as goal achievement is not as straightforward as it seems and in setting the bar too high, effectiveness has been equated with excellence. Effective coaching should imply that coaches have drawn on their expertise to harness appropriately the resources available in the context of environment and ambition. In this sense, effective coaching is a realizable goal for all coaches; it may or may not lead to performance success. It remains a useful “unifying label” for reasoning about sport coaching.
Enhancement of Nitrous Oxide Emissions in Soil Microbial Consortia via Copper Competition between Proteobacterial Methanotrophs and Denitrifiers
Authors: Chang Jin , Kim Daehyun D. , Semrau Jeremy D. , Lee Ju Yong , Heo Hokwan , Gu Wenyu , Yoon Sukhwan
Published: December 2020

Proteobacterial methanotrophs—groups of microorganisms that utilize methane as a source of energy and carbon—have been known to utilize unique mechanisms to scavenge copper, namely, utilization of methanobactin, a polypeptide that binds copper with high affinity and specificity. Previously the possibility that copper sequestration by methanotrophs may lead to alteration of cuproenzyme-mediated reactions in denitrifiers and consequently increase emission of potent greenhouse gas N
2
O has been suggested in axenic and coculture experiments.
Influence of Single Nitrogen Compounds on Growth and Fermentation Performance ofStarmerella bacillarisandSaccharomyces cerevisiaeduring Alcoholic Fermentation
Authors: Englezos Vasileios , Cocolin Luca , Rantsiou Kalliopi , Ortiz-Julien Anne , Bloem Audrey , Seguinot Pauline , Camarasa Carole
Published: December 2020

Mixed fermentations combining non-SaccharomycesandS. cerevisiaestrains are increasingly implemented in the wine sector, as they offer promising opportunities to diversify the flavor profile of end products. However, competition for nutrients between species can cause fermentation problems, which is a severe hindrance to the development of these approaches.
Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II—practical challenges
Authors: Cesano Alessandra , Cannarile Michael A , Gnjatic Sacha , Gomes Bruno , Guinney Justin , Karanikas Vaios , Karkada Mohan , Kirkwood John M , Kotlan Beatrix , Masucci Giuseppe V , Meeusen Els , Monette Anne , Naing Aung , Thorsson Vésteinn , Tschernia Nicholas , Wang Ena , Wells Daniel K , Wyant Timothy L , Rutella Sergio
Published: December 2020

The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated with the infrastructure, technology, workforce, and sustainability required for clinical biomarker data sharing. To provide guidance and assist in the navigation of these challenges, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to outline the challenges that researchers currently face, both at the conceptual level (Volume I) and at the technical level (Volume II). The committee also suggests possible solutions to these problems in the form of professional standards and harmonized requirements for data sharing, assisting in continued progress toward effective, clinically relevant biomarkers in the IO setting.