bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetition of Key Words During Phun Week Activities Increases Correct Answers in a Population of Junior Students in Puerto Rico
Authors: Martínez‐Orengo Neysha , Marrero‐Criado Marangelie , Ramos Sugeily , Cora Evelyn , Santiago Cariluz , Appleyard Caroline , Chompre Gladys 
Published: June 2021

Puerto Rico Physiological Society has been conducting PhUn Week activities in schools located in the south of the Island. This year junior students received talks and participated in hands‐on activities related to several topics in physiology.AimThe main was to provide information on basic physiological concepts, what scientists do, and how to pursue a scientific career. We hypothesized that combining conventional talks with hands‐on activities emphasizing key words will increase the students' attention and retention, leading to correct answers on a written evaluation.MethodsStudents from eleventh grade (22 males and 8 females) were given a pre‐test which consisted of 5 multiple choice questions related to cardiovascular, respiratory, nervous, and gastrointestinal systems. Oral presentations were given followed by hands‐on activities using repetition of key words during each activity. A post‐test was given to measure learning outcomes.ResultsIn the pre‐test, 59.3% of the overall questions were answered correctly, and this increased to 98.7% in the post‐test. Repetition during the talks and hands‐on activities increases the selection of correct answers in the written evaluation.ConclusionsWe were able to call the students attention by sharing our personal experiences as scientists and explaining physiology via a variety of assessments, which includes the repetition of key words in each activity. This outreach endeavor provides the student with alternative ways of learning physiology and a better understanding of a career in the sciences.
Efficacy and Safety of Intraventricular Antibiotic Administration
Authors: Llave Nathaniel , Young Nicholas , Abernathy Casey , Reinert Justin P. 
Published: June 2021

Abstract
The administration of antibiotics via intraventricular administration for treatment of central nervous system infections is an understudied topic that lacks data for specific patient outcomes regarding dosing and adverse events. A comprehensive review of the literature was performed on PubMed, MEDLINE, Scopus, and CINAHL using the following terminology: “intraventricular” OR “intraventricular drug administration” AND “antibiotic” OR “antimicrobial” AND “infection” AND “CNS” NOT “Intrathecal.” Studies that described adult human patients who received an antibiotic via intraventricular administration with complete dosing, efficacy, and safety data were included. A total of 8 studies met inclusion and were used in this review and detailed the use of antibiotics targeting resistant Gram-positive and Gram-negative bacteria. Minimal adverse effects were reported, although the determination of appropriate dosing and markers of efficacy remains elusive due to the common concomitant administration of intravenous antibiotics. Further clinical evaluation is necessary.
Topical Therapy Failure in Chronic Suppurative Otitis Media is Due to Persister Cells in Biofilms
Authors: Santa Maria Peter L. , Kaufman Adam C. , Bacacao Brian , Thai Anthony , Chen Xiaohua , Xia Anping , Cao Zhixin , Fouad Ayman , Bekale Laurent A. 
Published: June 2021

Objective:
Chronic suppurative otitis media (CSOM) is characterized by a chronically draining middle ear. CSOM is typically treated with multiple courses of antibiotics or antiseptics which are successful in achieving quiescence; however, the disease is prone to relapse. Understanding why these treatment failures occur is essential.

Study Design:
The minimum inhibitory concentration (MIC), minimal biofilm eradication concentration, and the inhibitory zone were determined for ototopicals and ofloxacin for the laboratory strains and CSOM-derived isolates. The percentage of persister cells and bacterial biofilm formation were measured. Disease eradication was tested in a validated in-vivo model of CSOM after treatment with ofloxacin.

Setting:
Microbiology Laboratory.

Methods:
Basic science experiments were performed to measure the effectiveness of a number of compounds against CSOM bacteria in a number of distinct settings.

Results:
The minimal biofilm eradication concentration is higher than is physiologically achievable with commercial preparations, except for povo-iodine. Clincial isolates of CSOM have equivalent biofilm-forming ability but increased proportions of persister cells. Ofloxacin can convert to inactive disease temporarily but fails to eradicate disease in an in-vivo model.

Conclusions:
Higher percentages of persister cells in clinical CSOM isolates are associated with resistance to ototopicals. Current ototopicals, except povo-iodine, have limited clinical effectiveness; however, it is unknown what the maximum achievable concentration is and there are ototoxicity concerns. Fluoroquinolones, while successful in producing inactive disease in the short term, have the potential to encourage antimicrobial resistance and disease recalcitrance and do not achieve a permanent remission. Given these limitations, clinicians should consider surgery earlier or use of clinically safe concentrations of povo-iodine earlier into the treatment algorithm.
Outcomes of Initial Observation Versus Upfront Microsurgical Resection for Small to Medium-sized Vestibular Schwannomas
Authors: Patro Ankita , Totten Douglas J. , Sherry Alexander D. , Manzoor Nauman F. , Cass Nathan D. , Tawfik Kareem , Bennett Marc L. , O’Malley Matthew R. , Haynes David S. , Perkins Elizabeth L. 
Published: June 2021

Objective:
To assess postoperative outcomes and predictive factors of patients observed prior to microsurgery and those undergoing upfront resection for small and medium-sized VS.

Study design:
Retrospective cohort.

Setting:
Tertiary referral center.

Patients:
VS patients who had microsurgery from 2003 to 2018 for tumors up to 2.5 cm.

Main outcome measures:
Postoperative outcomes including facial nerve function and interventions, complications, extent of resection, and salvage therapy.

Results:
Of 220 patients, 120 were initially observed, and 100 pursued upfront microsurgery. There was no significant association between initial observation and upfront microsurgery for postoperative facial nerve function at 2 to 3 weeks (p = 0.18) or 12 months (p = 0.5), facial nerve intervention (p = 0.5), major/minor complications (p = 0.48/0.63), recurrence (p = 0.8), subtotal resection (p = 0.6), or salvage therapy (p = 0.9). Time from initial consultation to surgery did not significantly impact outcomes. Intrameatal tumors were more likely to be observed (odds ratios [OR] 2.93; 95% CI 1.53–5.63; p = 0.001). Patients with larger tumor volume (OR 0.52; 95% CI 0.37–0.72; p < 0.0001), brainstem compression (OR 0.28; 95% CI 0.09–0.91; p = 0.03), or higher PTA were less likely to undergo observation (OR 0.99; 95% CI 0.97–0.997; p = 0.02). On multivariable analysis, predictive factors for observation were smaller tumor volume (OR 0.53; 95% CI 0.38–0.75; p < 0.001), lower PTA (OR 0.99; 95% CI 0.98–0.999; p = 0.04), and diabetes (OR 2.54; 95% CI 0.95–6.83; p = 0.06).

Conclusions:
Patients with worse hearing, larger tumor volume, and brainstem compression were more likely to pursue upfront microsurgery. A watchful waiting period does not appear to worsen outcomes and can be considered for patients with better hearing and smaller tumors without brainstem compression.
Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms
Authors: Zhong Wen , Altay Ozlem , Arif Muhammad , Edfors Fredrik , Mardinoglu Adil , Uhlén Mathias , Fagerberg Linn 
Published: June 2021

SUMMARYCOVID-19 has caused millions of deaths globally, yet the cellular mechanisms underlying the various effects of the disease remain poorly understood. Recently, a new analytical platform for comprehensive analysis of plasma protein profiles using proximity extension assays combined with next generation sequencing has been developed. Here, we describe the analysis of the plasma profiles of COVID-19 patients with mild and moderate symptoms by comparing the protein levels in newly diagnosed patients with the plasma profiles in the same individuals after recovery 14 days later. The study has identified more than 200 proteins that are significantly elevated at infection and many of these are related to cytokine response and other immune-related functions. In addition, several other proteins are shown to be elevated, including SCARB2, a host cell receptor protein involved in virus entry. A comparison with the plasma protein response in patients with severe symptoms shows a highly similar pattern, but with some interesting differences. In conclusion, the results will facilitate further studies to understand the molecular mechanism of the immune-related response of the SARS-CoV-2 virus.
Self-collection and pooling of samples as resources-saving strategies for RT-PCR-based SARS-CoV-2 surveillance, the example of travelers in French Polynesia
Authors: Aubry Maite , Teiti Iotefa , Teissier Anita , Richard Vaea , Mariteragi-Helle Teheipuaura , Chung Kiyojiken , Deen Farah , Paoaafaite Tuterarii , Cao-Lormeau Van-Mai 
Published: June 2021

AbstractIn French Polynesia, the first case of SARS-CoV-2 infection was detected on March 10th, 2020, in a resident returning from France. Between March 28th and July 14th, international air traffic was interrupted and local transmission of SARS-CoV-2 was brought under control, with only 62 cases recorded. The main challenge for reopening the air border without requiring travelers to quarantine on arrival was to limit the risk of re-introducing SARS-CoV-2. Specific measures were implemented, including the obligation for all travelers to have a negative RT-PCR test for SARS-CoV-2 carried out within 3 days before departure, and to perform another RT-PCR testing 4 days after arrival. Because of limitation in available medical staff, travelers were provided a kit allowing self-collection of oral and nasal swabs. In addition to increase our testing capacity, self-collected samples from up to 10 travelers were pooled before RNA extraction and RT-PCR testing. When a pool tested positive, RNA extraction and RT-PCR were performed on each individual sample. We report here the results of COVID-19 surveillance (COV-CHECK PORINETIA) conducted between July 15th, 2020, and February 15th, 2021, in travelers using self-collection and pooling approaches. We tested 5,982 pools comprising 59,490 individual samples, and detected 273 (0.46%) travelers positive for SARS-CoV-2. A mean difference of 1.17 Ct (CI 95% 0.93 – 1.41) was found between positive individual samples and pools (N=50), probably related to the volume of samples used for RNA extraction (200 µL versus 50 µL, respectively). Retrospective testing of positive samples self-collected from October 20th, 2020, using variants-specific amplification kit and spike gene sequencing, found at least 6 residents infected by the B1.1.7 UK variant. Self-collection and pooling approaches allowed large-scale screening for SARS-CoV-2 using less human, material and financial resources. Moreover, this strategy allowed detecting the introduction of SARS-CoV-2 variants in French Polynesia.
Clinical Pharmacy Services Provided in Public Sector Hospitals in Nigeria: A National Survey
Authors: Udoh Arit , Akpan Mary , Ibrahim Umar Idris , Lawal Basira Kankia , Labaran Kamilu Sarki , Ndem Ekpedeme , Amorha Kosisochi , Matuluko Ayodeji , Tikare Olubukola , Ohabunwa Unoma , Kpokiri Eneyi 
Published: June 2021

ABSTRACTBackgroundStudies show that clinical pharmacy services are effective in optimizing medicines use and patients’ outcomes. This study aimed to determine the clinical pharmacy services provided in public sector hospitals in Nigeria.MethodsThis was an online survey of 296 primary, secondary and tertiary care hospitals sampled purposively across the 36 States and Federal Capital Territory in Nigeria. Data analysis was conducted descriptively, and via Chi-square test and multivariate analysis of variance (MANOVA).Key findingsResponses were obtained from 272 hospitals in the country with a survey completion rate of 88%. This included 55 tertiary, 72 secondary, and 145 primary healthcare centres (PHCs). Pharmacists provided pharmaceutical care services in all the tertiary care hospitals, 94% of the secondary, and in only 6% of the PHCs surveyed. The composition of the pharmacy department per level of care was similar across the six geopolitical regions (V = 0.383, F = 1.453, P = 0.06) with more pharmacy staff employed in the tertiary care hospitals compared to the secondary care facilities. The majority (≥75%) of the tertiary and secondary care hospitals provided medicines information, patient education and counselling, alongside in- and outpatient dispensing services. However, fewer than 30% reported routine pharmacists’ involvement in multidisciplinary ward rounds, medication chart review, therapeutic guidelines development, antibiotic stewardship programmes, and drug therapy monitoring. Pharmacists routinely provided medication error reporting services in only about half of the hospitals in the sample, and this was not associated with the level of care (p > 0.05).ConclusionsThe findings of this study demonstrate disparity in clinical pharmacy service availability across the various levels of care in Nigeria. It also highlights the need to scale up and prioritize their integration within the primary care sector.
Emergence of border-ownership by large-scale consistency and long-range interactions: Neuro-computational model to reflect global configurations
Authors: Kogo Naoki , Froyen Vicky 
Published: June 2021

AbstractThe visual system performs remarkably well to perceive depth order of surfaces without stereo disparity, indicating the importance of figure-ground organization based on pictorial cues. To understand how figure-ground organization emerges, it is essential to investigate how the global configuration of an image is reflected. In the past, many neuro- computational models developed to reproduce figure-ground organization implemented algorithms to give a bias to convex areas. However, in certain conditions, a convex area can be perceived as a hole and a non-convex area as figural. This occurs when the surface properties of the convex area are consistent with the background and, hence, are grouped together in our perception. We argue that large-scale consistency of surface properties is reflected in the border-ownership computation. We developed a model, called DISC2, that first analyzes relationships between two border-ownership signals of all possible combinations in the image. It then enhances signals if they satisfy the following conditions: 1. the two signals fit to a convex configuration, and 2. the surface properties at the locations of the two signals are consistent. The strength of the enhancement decays with distance between the signals. The model gives extremely robust responses to various images with complexities both in shape and depth order. Furthermore, we developed an advanced version of the model (“augmented model”) where the global computation above interacts with local computation of curvilinearity, which further enhanced the robust nature of the model. The results suggest the involvement of similar computational processes in the brain for figure-ground organization.
Comparative performance of between-population vaccine allocation strategies with applications for emerging pandemics
Authors: Joshi Keya , Rumpler Eva , Kennedy-Shaffer Lee , Bosan Rafia , Lipsitch Marc 
Published: June 2021

2AbstractVaccine allocation decisions during emerging pandemics have proven to be challenging due to competing ethical, practical, and political considerations. Complicating decision making, policy makers need to consider vaccine allocation strategies that balance needs both within and between populations. Due to limited vaccine stockpiles, vaccine doses should be allocated in locations where their impact will be maximized. Using a susceptible-exposed-infectious-recovered (SEIR) model we examine optimal vaccine allocation decisions across two populations considering the impact of population size, underlying immunity, continuous vaccine roll-out, heterogeneous population risk structure, and differences in disease transmissibility. We find that in the context of an emerging pathogen where many epidemiologic characteristics might not be known, equal vaccine allocation between populations performs optimally in most scenarios. In the specific case considering heterogeneous population risk structure, first targeting individuals at higher risk of transmission or death due to infection leads to equal resource allocation across populations.
Rural prioritization may increase the impact of COVID-19 vaccines in Sub-Saharan Africa due to ongoing internal migration: A modeling study
Authors: Selvaraj Prashanth , Wagner Bradley G. , Chao Dennis L. , Jackson Maïna L’Azou , Breugelmans J. Gabrielle , Jackson Nicholas , Chang Stewart T. 
Published: June 2021

AbstractHow COVID-19 vaccine is distributed within low- and middle-income countries has received little attention outside of equity or logistical concerns but may ultimately affect campaign impact in terms of infections, severe cases, or deaths averted. In this study we examined whether subnational (urban-rural) prioritization may affect the cumulative two-year impact on disease transmission and burden of a vaccination campaign using an agent-based model of COVID-19 in a representative Sub-Saharan Africa country setting. We simulated a range of vaccination strategies that differed by urban-rural prioritization, age group prioritization, timing of introduction, and final coverage level. Urban prioritization averted more infections in only a narrow set of scenarios, when internal migration rates were low and vaccination was started by day 30 of an outbreak. Rural prioritization was the optimal strategy for all other scenarios, e.g., with higher internal migration rates or later start dates, due to the presence of a large immunological naive rural population. Among other factors, timing of the vaccination campaign was important to determining maximum impact, and delays as short as 30 days prevented larger campaigns from having the same impact as smaller campaigns that began earlier. The optimal age group for prioritization depended on choice of metric, as prioritizing older adults consistently averted more deaths across all of the scenarios. While guidelines exist for these latter factors, urban-rural allocation is an orthogonal factor that we predict to affect impact and warrants consideration as countries plan the scale-up of their vaccination campaigns.
Mild cognitive impairment is not a valid concept and should be replaced by a more restrictive, biologically validated class, named Mild Cognitive Dysfunctions (MCD): a nomothetic network approach
Authors: Maes Michael , Tangwongchai Sookjaroen 
Published: June 2021

AbstractBackgroundNo studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD).AimsTo clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients.MethodsIn 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension.ResultsClustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.ConclusionsPetersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.
Selectively expressing SARS-CoV-2 Spike protein S1 subunit in cardiomyocytes induces cardiac hypertrophy in mice
Authors: Negron Steven G. , Kessinger Chase W. , Xu Bing , Pu William T. , Lin Zhiqiang 
Published: June 2021

AbstractCardiac injury is common in hospitalized COVID-19 patients and portends poorer prognosis and higher mortality. To better understand how SARS-CoV-2 (CoV-2) damages the heart, it is critical to elucidate the biology of CoV-2 encoded proteins, each of which may play multiple pathological roles. For example, CoV-2 Spike glycoprotein (CoV-2-S) not only engages ACE2 to mediate virus infection, but also directly impairs endothelial function and can trigger innate immune responses in cultured murine macrophages. Here we tested the hypothesis that CoV-2-S damages the heart by activating cardiomyocyte (CM) innate immune responses. HCoV-NL63 is another human coronavirus with a Spike protein (NL63-S) that also engages ACE2 for virus entry but is known to only cause moderate respiratory symptoms. We found that CoV-2-S and not NL63-S interacted with Toll-like receptor 4 (TLR4), a crucial pattern recognition receptor that responsible for detecting pathogen and initiating innate immune responses. Our data show that the S1 subunit of CoV-2-S (CoV-2-S1) interacts with the extracellular leucine rich repeats-containing domain of TLR4 and activates NF-kB. To investigate the possible pathological role of CoV-2-S1 in the heart, we generated a construct that expresses membrane-localized CoV-2-S1 (S1-TM). AAV9-mediated, selective expression of the S1-TM in CMs caused heart dysfunction, induced hypertrophic remodeling, and elicited cardiac inflammation. Since CoV-2-S does not interact with murine ACE2, our study presents a novel ACE2-independent pathological role of CoV-2-S, and suggests that the circulating CoV-2-S1 is a TLR4-recognizable alarmin that may harm the CMs by triggering their innate immune responses.