bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing dropout-and-batch effect normalization for single-cell mRNA profiles: a survey and comparative analysis
Authors: Lan Tian , Hutvagner Gyorgy , Lan Qing , Liu Tao , Li Jinyan 
Published: September 2020

AbstractSingle-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver–Beer tool combination and the Baynorm–Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.
Burden of Culture Confirmed Enteric Fever Cases in Karachi, Pakistan: Surveillance For Enteric Fever in Asia Project (SEAP), 2016–2019
Authors: Yousafzai Mohammad T , Irfan Seema , Thobani Rozina S , Kazi Abdul M , Hotwani Aneeta , Memon Ashraf M , Iqbal Khalid , Qazi Saqib H , Saddal Nasir S , Rahman Najeeb , Dehraj Irum F , Hunzai Mohammed J , Mehmood Junaid , Garrett Denise O , Saha Samir K , Andrews Jason R , Luby Stephen P , Qamar Farah N 
Published: September 2020

AbstractBackgroundThe Surveillance for Enteric Fever in Asia Project (SEAP) is a multicenter, multicountry study conducted in Pakistan, Nepal, and Bangladesh. The objectives of the study were to characterize disease incidence among patients with enteric fever. We report the burden of enteric fever at selected sites of Karachi, Pakistan.MethodsDuring September 2016 to September 2019, prospective surveillance was conducted at inpatient, outpatient, surgical departments, and laboratory networks of Aga Khan University Hospital, Kharadar General Hospital, and surgery units of National Institute of Child Health and Jinnah Postgraduate Medical Centre. Socio-demographic, clinical, and laboratory data were obtained from all suspected or confirmed enteric fever cases.ResultsOverall, 22% (2230/10 094) of patients enrolled were culture-positive for enteric fever. 94% (2093/2230) of isolates were Salmonella Typhi and 6% (137/2230) were S. Paratyphi. 15% of isolates multi-drug resistant (MDR) to first-line antibiotics and 60% were extensively drug-resistant (XDR), resistant to first-line antibiotics, fluoroquinolones and third generation cephalosporin.ConclusionEnteric fever cases have increased during the last 3 years with large proportion of drug resistant S. Typhi cases. However, the burden of paratyphoid is still relatively low. Strengthening the existing surveillance system for enteric fever and antimicrobial resistance at the national level is recommended in Pakistan to inform prevention measures. While typhoid vaccination can significantly decrease the burden of typhoid and may also impact antimicrobial resistance, water, sanitation, and hygiene improvement is highly recommended to prevent the spread of enteric fever.
Reconsidering Assumptions of Adolescent and Young Adult Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Dynamics
Authors: Guilamo-Ramos Vincent , Benzekri Adam , Thimm-Kaiser Marco , Hidalgo Andrew , Perlman David C 
Published: September 2020

Abstract
Evidence regarding the important role of adolescents and young adults (AYA) in accelerating and sustaining coronavirus disease 2019 (COVID-19) outbreaks is growing. Furthermore, data suggest that 2 known factors that contribute to high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissibility—presymptomatic transmission and asymptomatic case presentations—may be amplified in AYA. However, AYA have not been prioritized as a key population in the public health response to the COVID-19 pandemic. Policy decisions that limit public health attention to AYA and are driven by the assumption of insignificant forward transmission from AYA pose a risk of inadvertent reinvigoration of local transmission dynamics. In this viewpoint, we highlight evidence regarding the increased potential of AYA to transmit SARS-CoV-2 that, to date, has received little attention, discuss adolescent and young adult–specific considerations for future COVID-19 control measures, and provide applied programmatic suggestions.
Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety?
Authors: Dilworth Thomas J , Schulz Lucas T , Rose Warren E 
Published: September 2020

Abstract
Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.
Ventricular arrhythmia risk is associated with myocardial scar but not with response to cardiac resynchronization therapy
Authors: Linhart Markus , Doltra Adelina , Acosta Juan , Borràs Roger , Jáuregui Beatriz , Fernández-Armenta Juan , Anguera Ignasi , Bisbal Felipe , Martí-Almor Julio , Tolosana Jose M , Penela Diego , Soto-Iglesias David , Villuendas Roger , Perea Rosario J , Ortiz Jose T , Bosch Xavier , Auricchio Angelo , Mont Lluis , Berruezo Antonio 
Published: September 2020

Abstract

Aims
Sudden cardiac death (SCD) risk estimation in patients referred for cardiac resynchronization therapy (CRT) remains a challenge. By CRT-mediated improvement of left ventricular ejection fraction (LVEF), many patients loose indication for primary prevention implantable cardioverter-defibrillator (ICD). Increasing evidence shows the importance of myocardial scar for risk prediction. The aim of this study was to investigate the prognostic impact of myocardial scar depending on the echocardiographic response in patients undergoing CRT.

Methods and results
Patients with indication for CRT were prospectively enrolled. Decision about ICD or pacemaker implantation was based on clinical criteria. All patients underwent delayed-enhancement cardiac magnetic resonance imaging. Median follow-up duration was 45 (24–75) months. Primary outcome was a composite of sustained ventricular arrhythmia, appropriate ICD therapy, or SCD. A total of 218 patients with LVEF 25.5 ± 6.6% were analysed [158 (73%) male, 64.9 ± 10.7 years]. Myocardial scar was observed in 73 patients with ischaemic cardiomyopathy (ICM) (95% of ICM patients); in 62 with non-ischaemic cardiomyopathy (45% of these patients); and in all but 1 of 36 (17%) patients who reached the primary outcome. Myocardial scar was the only significant predictor of primary outcome [odds ratio 27.7 (3.8–202.7)], independent of echocardiographic CRT response. A total of 55 (25%) patients died from any cause or received heart transplant. For overall survival, only a combination of the absence of myocardial scar with CRT response was associated with favourable outcome.

Conclusion
Malignant arrhythmic events and SCD depend on the presence of myocardial scar but not on CRT response. All-cause mortality improved only with the combined absence of myocardial scar and CRT response.
Herring Trade, Quality Controls and Diplomacy in Cologne in the Fifteenth Century*
Authors: Brunmayr Nicolas 
Published: September 2020

Abstract
The importance of herring to Cologne’s medieval economy is well-known and the need to control the quality of this long-distance and perishable product has also been widely recognized. The interregional quality norms that Cologne negotiated with Low Countries fishing towns in 1481 have been neglected, however. This article offers the first reconstruction of the diplomatic process that led to the edict and an analysis of the motives that impelled the diverse stakeholders to reach an agreement. The article demonstrates that in addition to herring’s commercial significance, its quality control was a major issue and was used as an instrument of influence by Cologne and other powers in the politically decentralized Holy Roman Empire. Comprehensive analysis of Cologne’s abundant sources shows how exchanges of letters and complaints gradually fed into formal negotiations, culminating in the publication of a crucial edict that established an interregional quality control system and took account of the interests of the different stakeholders in the herring trade. The article suggests that this push for regulation was also an element of Cologne’s economic strategy since it helped justify the taxes the city levied on goods in transit at the expense of competing actors in the Rhine region. In short, the example of quality controls on herring shows how food trade studies can shed light on power relations in the Empire during the late Middle Ages.
Predictors of Olfactory Decline in Aging: A Longitudinal Population-Based Study
Authors: Ekström Ingrid , Larsson Maria , Rizzuto Debora , Fastbom Johan , Bäckman Lars , Laukka Erika J 
Published: September 2020

Abstract

Background
Olfactory dysfunction is common in aging and associated with dementia and mortality. However, longitudinal studies tracking change in olfactory ability are scarce. We sought to identify predictors of interindividual differences in rate of olfactory identification change in aging.

Method
Participants were 1780 individuals, without dementia at baseline and with at least 2 olfactory assessments over 12 years of follow-up (mean age = 70.5 years; 61.9% female), from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Odor identification was assessed with the Sniffin’ Sticks. We estimated the impact of demographic, health, and genetic factors on rate of olfactory change with linear mixed effect models.

Results
Advancing age, manufacturing profession, history of cerebrovascular disease, higher cardiovascular disease burden, diabetes, slower walking speed, higher number of medications, and the APOE ε4 allele were associated with accelerated odor identification decline (ps &lt; .014). Multi-adjusted analyses showed unique associations of age, diabetes, and ε4 to olfactory decline (ps &lt; .017). In 1531 participants who remained free of dementia (DSM IV criteria) during follow-up, age, cardiovascular disease burden, and diabetes were associated with accelerated decline (ps &lt; .011). Of these, age and diabetes remained statistically significant in the multi-adjusted model (ps &lt; .001).

Conclusion
Demographic, vascular, and genetic factors are linked to rate of decline in odor identification in aging. Although some olfactory loss may be an inevitable part of aging, our results highlight the importance of vascular factors for the integrity of the olfactory system, even in the absence of dementia.
Anticholinergic/Sedative Drug Burden and Subjective Cognitive Decline in Older Adults at Risk of Alzheimer’s Disease
Authors: Margolis Seth A , Kelly Dana A , Daiello Lori A , Davis Jennifer , Tremont Geoffrey , Pillemer Sarah , Denby Charles , Ott Brian R 
Published: September 2020

Abstract

Background
Anticholinergic/sedative drug use, measured by the Drug Burden Index (DBI), has been linked to cognitive impairment in older adults. Subjective cognitive decline (SCD) may be among the first symptoms patients with Alzheimer’s disease (AD) experience. We examined whether DBI values are associated with SCD in older adults at risk of AD. We hypothesized that increased DBI would be associated with greater SCD at older ages.

Method
Two-hundred-six community-dwelling, English-speaking adults (age = 65 ± 9 years) at risk of AD (42% apolipoprotein ε4 carriers; 78% with AD family history) were administered a single question to ascertain SCD: “Do you feel like your memory is becoming worse?” Response options were “No”; “Yes, but this does not worry me”; and “Yes, this worries me.” DBI values were derived from self-reported medication regimens using older adult dosing recommendations. Adjusting for relevant covariates (comorbidities and polypharmacy), we examined independent effects of age and DBI on SCD, as well as the moderating effect of age on the DBI-SCD association at mean ± 1 SD of age.

Results
Both SCD and anticholinergic/sedative drug burden were prevalent. Greater drug burden was predictive of SCD severity, but age alone was not. A significant DBI*Age interaction emerged with greater drug burden corresponding to more severe SCD among individuals age 65 and older.

Conclusion
Anticholinergic/sedative drug exposure was associated with greater SCD in adults 65 and older at risk for AD. Longitudinal research is needed to understand if this relationship is a pre-clinical marker of neurodegenerative disease and predictive of future cognitive decline.
White Blood Cell Count Mediates the Association Between Periodontal Inflammation and Cognitive Performance Measured by Digit Symbol Substitution Test Among Older U.S. Adults
Authors: Li An , Chen Yuntao , van der Sluis Luc W M , Schuller Annemarie A , Tjakkes Geerten-Has 
Published: September 2020

Abstract

Background
Systemic effects of periodontal infection may increase the risk of central neuroinflammation, aggravating impaired cognition. This study aims to examine whether systemic inflammatory factors mediate the possible association between periodontal inflammation and cognitive function.

Methods
We conducted a cross-sectional analysis of 766 participants aged ≥ 60 years and who had completed periodontal and cognitive examinations in the National Health and Nutrition Examination Survey (NHANES) 2001–2002. We used multivariable linear regression to investigate the overall association between periodontal health and cognitive function as measured by the digit symbol substitution test (DSST). Bleeding on probing (BOP) and periodontal inflamed surface area (PISA) were used to assess the periodontal inflammatory activity and burden, respectively. Mediation analyses were used to test the indirect effects of the BOP/PISA on DSST via C-reactive protein, white blood cell (WBC) count, and fibrinogen.

Results
Participants with superior periodontal health obtained higher DSST scores than those with poorer periodontal health, adjusting for demographic factors and chronic conditions. Concerning the inflammatory activity, WBC count acted as a full mediator in the association between BOP and DSST (β = −0.091; 95% confidence interval [CI] = −0.174 to −0.008) and mediated 27.5% of the total association. Regarding the inflammatory burden, WBC count acted as a partial mediator in the association between PISA and DSST (β = −0.059; 95% CI = −0.087 to −0.031) and mediated 20.3% of the total association.

Conclusion
Our study indicated the potential role of systemic inflammatory factors as a mediator of associations between periodontal inflammation and cognitive function in the U.S. geriatric population.
Novel serine/threonine-O-glycosylation with N-acetylneuraminic acid and 3-deoxy-D-manno-octulosonic acid by bacterial flagellin glycosyltransferases
Authors: Khairnar Aasawari , Sunsunwal Sonali , Babu Ponnusamy , Ramya T N C 
Published: September 2020

Abstract
Some bacterial flagellins are O-glycosylated on surface-exposed serine/threonine residues with nonulosonic acids such as pseudaminic acid, legionaminic acid and their derivatives by flagellin nonulosonic acid glycosyltransferases, also called motility-associated factors (Maf). We report here two new glycosidic linkages previously unknown in any organism, serine/threonine-O-linked N-acetylneuraminic acid (Ser/Thr-O-Neu5Ac) and serine/threonine-O-linked 3-deoxy-D-manno-octulosonic acid or keto-deoxyoctulosonate (Ser/Thr-O-KDO), both catalyzed by Geobacillus kaustophilus Maf and Clostridium botulinum Maf. We identified these novel glycosidic linkages in recombinant G. kaustophilus and C. botulinum flagellins that were coexpressed with their cognate recombinant Maf protein in Escherichia coli strains producing the appropriate nucleotide sugar glycosyl donor. Our finding that both G. kaustophilus Maf (putative flagellin sialyltransferase) and C. botulinum Maf (putative flagellin legionaminic acid transferase) catalyzed Neu5Ac and KDO transfer on to flagellin indicates that Maf glycosyltransferases display donor substrate promiscuity. Maf glycosyltransferases have the potential to radically expand the scope of neoglycopeptide synthesis and posttranslational protein engineering.
Team-based primary health care for non-communicable diseases: complexities in South India
Authors: Lall Dorothy , Engel Nora , Devadasan Narayanan , Horstman Klasien , Criel Bart 
Published: September 2020

Abstract
Chronic non-communicable diseases (NCDs), such as diabetes and cardiovascular diseases, have reached epidemic proportions worldwide. Health systems, especially those in low- and middle-income countries, such as India, struggle to deliver quality chronic care. A reorganization of healthcare service delivery is needed to strengthen care for chronic conditions. In this study, we evaluated the implementation of a package of tailored interventions to reorganize care, which were identified following a detailed analysis of gaps in delivering quality NCD care at the primary care level in India. Interventions included a redesign of the workflow at primary care clinics, a redistribution of tasks, the introduction of patient information records and the involvement of community health workers in the follow-up of patients with NCDs. An experimental case study design was chosen to study the implementation of the quality improvement measures. Three public primary care facilities in rural South India were selected. Qualitative methods were used to gain an in-depth understanding of the implementation process and outcomes of implementation. Observations, field notes and semi-structured interviews with staff at these facilities (n = 15) were thematically analysed to identify contextual factors that influenced implementation. Only one of the primary health centres implemented all components of the intervention by the end of 9 months. The main barriers to implementation were hierarchical arrangements that inhibited team-based care, the amount of time required for counselling and staff transfers. Team cohesion, additional staff and staff motivation seem to have facilitated implementation. This quality improvement research highlights the importance of building relational leadership to enable team-based care at primary care clinics in India. Redesigned organization of care and task redistribution is important solutions to deliver quality chronic care. However, implementing these will require capacity building of local primary care teams.
Diving into a Simple Anguilliform Swimmer’s Sensitivity
Authors: Battista Nicholas A 
Published: September 2020

SynopsisComputational models of aquatic locomotion range from modest individual simple swimmers in 2D to sophisticated 3D multi-swimmer models that attempt to parse collective behavioral dynamics. Each of these models contain a multitude of model input parameters to which its outputs are inherently dependent, that is, various performance metrics. In this work, the swimming performance’s sensitivity to parameters is investigated for an idealized, simple anguilliform swimming model in 2D. The swimmer considered here propagates forward by dynamically varying its body curvature, similar to motion of a Caenorhabditis elegans. The parameter sensitivities were explored with respect to the fluid scale (Reynolds number), stroke (undulation) frequency, as well as a kinematic parameter controlling the velocity and acceleration of each upstroke and downstroke. The input Reynolds number and stroke frequencies sampled were from [450, 2200] and [1, 3] Hz, respectively. In total, 5000 fluid–structure interaction simulations were performed, each with a unique parameter combination selected via a Sobol sequence, in order to conduct global sensitivity analysis. Results indicate that the swimmer’s performance is most sensitive to variations in its stroke frequency. Trends in swimming performance were discovered by projecting the performance data onto particular 2D subspaces. Pareto-like optimal fronts were identified. This work is a natural extension of the parameter explorations of the same model from Battista in 2020.
Sea-louse abundance on salmon farms in relation to parasite-control policy and climate change
Authors: Godwin Sean C , Krkosek Martin , Reynolds John D , Bateman Andrew W 
Published: September 2020

Abstract
The ectoparasitic copepods, sea lice (Lepeophtheirus salmonis and Caligus spp.), are major pests to salmon aquaculture and can also affect the health and survival of wild salmon. Policies exist to protect wild salmon by delousing farmed fish when louse abundance exceeds a threshold, but their effectiveness under future climate change is uncertain. We fitted a Bayesian model for sea-louse population dynamics and management to timeseries data of sea lice on farmed salmon in Pacific Canada and analysed the model under scenarios of warmer climates. We found that in high-temperature years, current parasite control policy becomes ineffective as sea-louse abundance is expected to increase. We simulated two alternative management scenarios and observed that both would decrease average louse counts on farms in high-temperature years relative to the current system but relied on more delousing treatments than are currently performed. We also found evidence that non-salmonids can play a role in louse transmission to farms, as increased farm colonization of Caligus clemensi occurs in April, coincident with wild herring (Clupea pallasii) spawner abundance. Our results highlight the need for careful management of sea lice on salmon farms in warmer years and the importance of policies designed to account for future environmental change.