bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrical modification of a composite electrode for room temperature operable polyethylene oxide-based lithium polymer batteries
Authors: Rajagopalan Balasubramaniyan , Kim Min , Kim Do Youb , Suk Jungdon , Kim Dong Wook , Kang Yongku
Published: July 2020

Lithium polymer batteries (LPBs) are considered to be the most promising alternatives to current lithium-ion batteries (LIBs), which have been known to exhibit certain safety issues. However, the relatively poor electrochemical performances of LPBs hinder their practical usage, particularly at high C-rates, moderate temperatures, and/or with high loading densities. Therefore, this study analyzes the use of a novel composite electrode for manufacturing room-temperature operable LPBs with high loading densities. Rapid decay in the rate capabilities of LPBs at high C-rates is found to be attributable to the increased electrical resistance in an electrode. To account for this, this study modified the composite electrode with various conducting fillers. Subsequently, the effect of the type and content of the conducting fillers on the performance of LPBs was systematically investigated using the composite electrode. The incorporation of the conducting fillers in the lithium iron phosphate (LFP) composite electrode was found to effectively reduce the electrical resistance and consequently improve the electrochemical performance of LPBs. Furthermore, LFP composite electrodes with a mixture of structurally different graphene (G) and carbon nanotube (CNT) (1 wt%) were observed to demonstrate synergistic effects on improving the electrochemical performance of LPBs. The results obtained in this study elucidate that the facilitated electrical conduction within a composite electrode is critically important for the performance of LPBs and the expedited diffusion of Li+.
Identifying disease-causing mutations with privacy protection
Authors: Akgün Mete , Ünal Ali Burak , Ergüner Bekir , Pfeifer Nico , Kohlbacher Oliver
Published: July 2020

Motivation

The use of genome data for diagnosis and treatment is becoming increasingly common. Researchers need access to as many genomes as possible to interpret the patient genome, to obtain some statistical patterns and to reveal disease–gene relationships. The sensitive information contained in the genome data and the high risk of re-identification increase the privacy and security concerns associated with sharing such data. In this article, we present an approach to identify disease-associated variants and genes while ensuring patient privacy. The proposed method uses secure multi-party computation to find disease-causing mutations under specific inheritance models without sacrificing the privacy of individuals. It discloses only variants or genes obtained as a result of the analysis. Thus, the vast majority of patient data can be kept private.

Results

Our prototype implementation performs analyses on thousands of genomic data in milliseconds, and the runtime scales logarithmically with the number of patients. We present the first inheritance model (recessive, dominant and compound heterozygous) based privacy-preserving analyses of genomic data to find disease-causing mutations. Furthermore, we re-implement the privacy-preserving methods (MAX, SETDIFF and INTERSECTION) proposed in a previous study. Our MAX, SETDIFF and INTERSECTION implementations are 2.5, 1122 and 341 times faster than the corresponding operations of the state-of-the-art protocol, respectively.

Availability and implementation

https://gitlab.com/DIFUTURE/privacy-preserving-genomic-diagnosis.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Caregiver Identity in Context: Consequences of Identity Threat From Siblings
Authors: Rurka Marissa , Jill Suitor J , Gilligan Megan
Published: July 2020

Objectives

Although siblings represent central members of the networks of caregivers and their parents, there has been limited attention to how siblings affect one another’s well-being during caregiving. In this article, we draw from theories of identity and stress to examine the impact that siblings have on caregivers’ psychological well-being. Specifically, we employ a mixed-methods approach to explore whether caregivers’ perceptions that their siblings are critical of the care they provide their mother are associated with higher depressive symptoms and the mechanisms underlying this association.

Methods

Using quantitative data collected from 404 caregivers nested within 231 families as part of the Within-Family Differences Study, we conduct mediation analyses to examine whether perceived sibling criticisms are associated with caregivers’ depressive symptoms (a) directly and/or (b) indirectly through sibling tension. We then analyze qualitative data collected from the same caregivers to gain insight into the processes underlying statistical associations.

Results

Quantitative analyses revealed that there was no direct relationship between perceived sibling criticisms and depressive symptoms; there was, however, an indirect relationship such that perceived sibling criticisms were associated with greater sibling tension, which in turn was associated with higher depressive symptoms. These quantitative findings were corroborated by qualitative analyses, which demonstrated that, in an effort to mitigate the negative impact of sibling criticisms, caregivers often employed strategies that may have fueled sibling tension.

Discussion

These findings demonstrate how identity processes, as well as the family networks in which caregiving takes place, shape the experiences and consequences of parent care.
Abuse of Dominant Position and Cease-and-Desist Agreements: Risks to Brazilian Competition Policy Arising from the Atypical Case of Petrobras’ Refineries
Authors: Cabral Mário André Machado
Published: July 2020

This paper aims to analyze how the Brazilian competition authority, Cade, deals with cease-and-desist agreements involving abuse of dominant position. The focus is a recent abuse-of-dominant-position case. Cade and the Brazilian state-owned oil and gas company, Petrobras, negotiated a cease-and-desist agreement establishing as remedy the divestment of eight out of 13 Petrobras’ refineries. The hypothesis is that the case was atypical in the light of Cade’s own case law. The paper assesses the Petrobras’ case and compares it to Cade’s case law (2012-2019) concerning cease-and-desist agreements relating to the abuse of a dominant position. The results of the study confirm the atypicality of the case. It demonstrates that the case causes risks to Brazilian competition policy. The paper is divided as follows: after an introduction, the first section discusses abuse of dominant position in Brazil, especially the cases that concluded with cease-and-desist agreements; the second section describes the case related to Petrobras’ oil refinery assets; the third section verifies whether the case may be considered atypical; the fourth section debates the legal and policy risks arising from the case; the final section contains some concluding remarks.
Impact of COVID-19 Pandemic on Laboratory Utilization
Authors: Durant Thomas J S , Peaper David R , Ferguson David , Schulz Wade L
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) was formally characterized as a pandemic on March 11, 2020. Since that time, the COVID-19 pandemic has led to unprecedented demand for healthcare resources. The purpose of this study was to identify changes in laboratory test utilization in the setting of increasing local incidence of COVID-19.

Methods

We performed a retrospective assessment of laboratory test order and specimen container utilization at a single, urban tertiary care medical center. Data were extracted from the laboratory information system database over a 10-week period, spanning the primordial inflection of COVID-19 incidence in our region. Total testing volumes were calculated during the first 2 and last 2 weeks of the observation period and used as reference points to examine the absolute and relative differences in test order volume between the prepandemic and COVID-19 surge periods.

Results

Between February 2, 2020, and April 11, 2020, there were 873 397 tests ordered and final verified. The in-house SARS-CoV-2 PCR positivity rate for admitted patients in the last week of the observation period was 30.8%. Significant increases in workload were observed in the send-out laboratory section and for COVID-19 diagnosis (PCR) and management-related testing. Otherwise, there was a net decrease in overall demand across nearly all laboratory sections. Increases in testing were noted for tests related to COVID-19 management. Viral transport media and citrated blue top containers demonstrated increases in utilization.

Conclusion

Increasing local incidence of COVID-19 had a profound impact on laboratory operations. While volume increases were seen for laboratory tests related to COVID-19 diagnostics and management, including some with limited evidence to support their use, overall testing volumes decreased substantially. During events such as COVID-19, monitoring of such patterns can help inform laboratory management, staffing, and test stewardship recommendations for managing resource and supply availability.
Clostridioides difficile Infections in Inpatient Pediatric Oncology Patients: A Cohort Study Evaluating Risk Factors and Associated Outcomes
Authors: Willis Daniel N , Huang Frederick S , Elward Alexis M , Wu Ningying , Magnusen Brianna , Dubberke Erik R , Hayashi Robert J
Published: July 2020

Background

Clostridioides difficile infection (CDI) is a significant source of morbidity in pediatric cancer patients. Few reports to date have evaluated risk factors and short-term outcomes for this population.

Methods

We retrospectively evaluated pediatric oncology admissions at St Louis Children’s Hospital from 2009 to 2018. All inpatient cases of diagnosed initial CDI were identified. We aimed to investigate the prevalence of CDI and associated risk factors, including coadmission with another patient with CDI, and to evaluate short-term outcomes including length of stay and delays in subsequent scheduled chemotherapy.

Results

Review of 6567 admissions from 952 patients revealed 109 CDI cases (11.4% of patients). Patients with leukemia or lymphoma, compared to those with solid tumors, were more likely to have CDI (odds ratio [OR], 3 [95% CI, 1.4–6.6], and 3 [95% CI, 1.3–6.8], respectively). Autologous hematopoietic stem cell transplant (HSCT) was also a risk factor (OR, 3.5 [95% CI, 1.7–7.4]). Prior antibiotic exposure independently increased the risk for CDI (OR, 3.0 [95% CI, 1.8–4.8]). Concurrent admission with another patient with CDI also significantly increased the risk (OR, 84.7 [95% CI, 10.5–681.8]). In contrast to previous reports, exposure to acid-suppressing medications decreased the risk for CDI (OR, 0.5 [95% CI, .3–.7]). CDI was associated with increased length of stay (mean difference, 8 days [95% CI, 4.6–11.4]) and prolonged delays for subsequent chemotherapy (mean difference, 1.4 days [95% CI, .1–2.7]).

Conclusions

CDI in pediatric oncology patients significantly prolongs hospitalization and delays chemotherapy treatment plans. Interventions to control CDI will improve the care of pediatric oncology patients.
Laparoscopic treatment of idiopathic jejuno-jejunal intussusception in an adult
Authors: Lovisetto Federico , Caneparo Andrea , Zonta Sandro
Published: July 2020

Here we present the case of a 29-year-old female patient who underwent to laparoscopic reduction of idhiopatic jejuno-jenunal intussusception, a very rare cause of intestinal obstruction in adults. Laparoscopic exploration represents the best approach in adults. Unfortunately, manoeuvres of laparoscopic reduction are difficult and conversion to laparotomy is often needed.
Legal Exegesis and Historical Narrative in Luke 2:22–4
Authors: Kozitza Evangeline M
Published: July 2020

This article wrestles with critical questions often cited in relation to Luke 2:22–4, the gospel writer’s description of two legal rituals (the sacrifice to complete purification after birth, and the consecration of a firstborn son) performed by Mary and Joseph at the Temple. In contrast with previous interpretations of this text, which have tended to conclude either that Luke has been misinformed about Jewish law, or that he simply is not interested in legal precision (thus creating a purely fictive narrative motivated by theological or literary concerns), this essay argues for a more nuanced reading of Luke’s account along a broader spectrum of Second Temple and early rabbinic legal interpretation, and in light of Luke’s claims about the genre and methodology of his gospel. By positioning Luke 2:22–4 among other examples of legal exegesis in ancient Judaism, particularly those that deal with the laws Luke cites, I conclude not only that the childbirth laws in the Torah leave multiple gaps that invite later interpretive differences, but that Luke’s own halakhic reading can be contextualized by comparable readings within the diversity of Second Temple interpretation.
Vetting the optical transient candidates detected by the GWAC network using convolutional neural networks
Authors: Turpin Damien , Ganet M , Antier S , Bertin E , Xin L P , Leroy N , Wu C , Xu Y , Han X H , Cai H B , Li H L , Lu X M , Feng Q C , Wei J Y
Published: July 2020

The observation of the transient sky through a multitude of astrophysical messengers has led to several scientific breakthroughs in the last two decades, thanks to the fast evolution of the observational techniques and strategies employed by the astronomers. Now, it requires to be able to coordinate multiwavelength and multimessenger follow-up campaigns with instruments both in space and on ground jointly capable of scanning a large fraction of the sky with a high-imaging cadency and duty cycle. In the optical domain, the key challenge of the wide field-of-view telescopes covering tens to hundreds of square degrees is to deal with the detection, identification, and classification of hundreds to thousands of optical transient (OT) candidates every night in a reasonable amount of time. In the last decade, new automated tools based on machine learning approaches have been developed to perform those tasks with a low computing time and a high classification efficiency. In this paper, we present an efficient classification method using convolutional neural networks (CNNs) to discard many common types of bogus falsely detected in astrophysical images in the optical domain. We designed this tool to improve the performances of the OT detection pipeline of the Ground Wide field Angle Cameras (GWAC) telescopes, a network of robotic telescopes aiming at monitoring the OT sky down to R = 16 with a 15 s imaging cadency. We applied our trained CNN classifier on a sample of 1472 GWAC OT candidates detected by the real-time detection pipeline.
Gene Loss Predictably Drives Evolutionary Adaptation
Authors: Helsen Jana , Voordeckers Karin , Vanderwaeren Laura , Santermans Toon , Tsontaki Maria , Verstrepen Kevin J , Jelier Rob
Published: July 2020

Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism’s capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain’s genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths.
Real-Time and Conventional PCR Tools for Detection and Discrimination of Calonectria pseudonaviculata and C. henricotiae Causing Boxwood Blight
Authors: Guo Yonghong , Pooler Margaret
Published: July 2020

Calonectria pseudonaviculata and C. henricotiae are the causal agents of boxwood blight, a devastating disease of boxwood that has caused significant economic impact on the nursery and landscape industries in the U.S. and in Europe. The two species are genetically distinct and are found in different geographic areas but are difficult to distinguish based on morphology and pathogenicity. Fast, accurate, and inexpensive methods to detect and differentiate these species is critical in stopping the spread of the disease. We designed primer pairs based on available sequences of four conserved regions—calmodulin, histone H3, internal transcribed spacer, and β-tubulin—and tested their ability to differentiate the two Calonectria species. Here we report three primer pairs derived from sequence differences in the histone H3 region that can be used to specifically detect C. pseudonaviculata, C. henricotiae, or both species. Specificity of these primers was tested against nine isolates of C. pseudonaviculata, three isolates of C. henricotiae, 13 other Calonectria species, and five isolates from related genera using conventional and real-time PCR. These are the first primers available that can be used with either a multiplexed conventional PCR or SYBR-based real-time PCR to specifically detect and differentiate the two fungal species.
Assessment of Right Heart Function during Extracorporeal Therapy by Modified Thermodilution in a Porcine Model
Authors: Bachmann Kaspar F. , Zwicker Lena , Nettelbeck Kay , Casoni Daniela , Heinisch Paul Phillipp , Jenni Hansjörg , Haenggi Matthias , Berger David
Published: July 2020

Background

Veno-arterial extracorporeal membrane oxygenation therapy is a growing treatment modality for acute cardiorespiratory failure. Cardiac output monitoring during veno-arterial extracorporeal membrane oxygenation therapy remains challenging. This study aims to validate a new thermodilution technique during veno-arterial extracorporeal membrane oxygenation therapy using a pig model.

Methods

Sixteen healthy pigs were centrally cannulated for veno-arterial extracorporeal membrane oxygenation, and precision flow probes for blood flow assessment were placed on the pulmonary artery. After chest closure, cold boluses of 0.9% saline solution were injected into the extracorporeal membrane oxygenation circuit, right atrium, and right ventricle at different extracorporeal membrane oxygenation flows (4, 3, 2, 1 l/min). Rapid response thermistors in the extracorporeal membrane oxygenation circuit and pulmonary artery recorded the temperature change. After calculating catheter constants, the distributions of injection volumes passing each circuit were assessed and enabled calculation of pulmonary blood flow. Analysis of the exponential temperature decay allowed assessment of right ventricular function.

Results

Calculated blood flow correlated well with measured blood flow (r
2 = 0.74, P < 0.001). Bias was −6 ml/min [95% CI ± 48 ml/min] with clinically acceptable limits of agreement (668 ml/min [95% CI ± 166 ml/min]). Percentage error varied with extracorporeal membrane oxygenation blood flow reductions, yielding an overall percentage error of 32.1% and a percentage error of 24.3% at low extracorporeal membrane oxygenation blood flows. Right ventricular ejection fraction was 17 [14 to 20.0]%. Extracorporeal membrane oxygenation flow reductions increased end-diastolic and end-systolic volumes with reductions in pulmonary vascular resistance. Central venous pressure and right ventricular ejection fractions remained unchanged. End-diastolic and end-systolic volumes correlated highly (r
2 = 0.98, P < 0.001).

Conclusions

Adapted thermodilution allows reliable assessment of cardiac output and right ventricular behavior. During veno-arterial extracorporeal membrane oxygenation weaning, the right ventricle dilates even with stable function, possibly because of increased venous return.

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Dorsomedial Prefrontal Cortex Repetitive Transcranial Magnetic Stimulation for Tinnitus: Promising Results of a Blinded, Randomized, Sham-Controlled Study
Authors: Ciminelli Patricia , Machado Sergio , Palmeira Manoela , Coutinho Evandro Silva Freire , Sender David , Nardi Antonio Egidio
Published: July 2020

Objectives:

Tinnitus is the perception of sound in ears or head without corresponding external stimulus. Despite the great amount of literature concerning tinnitus treatment, there are still no evidence-based established treatments for curing or for effectively reducing tinnitus intensity. Sham-controlled studies revealed beneficial effects using repetitive transcranial magnetic stimulation (rTMS). Still, results show moderate, temporary improvement and high individual variability. Subcallosal area (ventral and dorsomedial prefrontal and anterior cingulate cortices) has been implicated in tinnitus pathophysiology. Our objective is to evaluate the use of bilateral, high frequency, dorsomedial prefrontal cortex (DMPFC) rTMS in treatment of chronic subjective tinnitus.

Design:

Randomized placebo-controlled, single-blinded clinical trial. Twenty sessions of bilateral, 10 Hz rTMS at 120% of resting motor threshold of extensor hallucis longus were applied over the DMPFC. Fourteen patients underwent sham rTMS and 15 were submitted to active stimulation. Tinnitus Handicap Inventory (THI), visual analog scale, and tinnitus loudness matching were obtained at baseline and on follow-up visits. The impact of intervention on outcome measures was evaluated using mixed-effects restricted maximum likelihood regression model for longitudinal data.

Results:

A difference of 11.53 points in the THI score was found, favoring the intervention group (p = 0.05). The difference for tinnitus loudness matching was of 4.46 dB also favoring the intervention group (p = 0.09).

Conclusions:

Tinnitus treatment with high frequency, bilateral, DMPFC rTMS was effective in reducing tinnitus severity measured by THI and matched tinnitus loudness when compared to sham stimulation.
Antibody–drug conjugates in breast cancer: the chemotherapy of the future?
Authors: Nicolò Eleonora , Zagami Paola , Curigliano Giuseppe
Published: July 2020

Purpose of review

Antibody–drug conjugates (ADCs) represent an interesting new class of anticancer agents, capable of exploiting the specificity of monoclonal antibodies toward cellular-antigens for a targeted release of potent cytotoxic drugs, with a potential increased activity and reduced toxicity compared with traditional chemotherapies. The aim of this article is to review the efficacy and safety of ADCs in breast cancer.

Recent findings

Following the approval of T-DM1 both in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel anti-HER2 ADCs have been investigated. Some of these compounds, such as the recently FDA-approved trastuzumab deruxtecan, have shown relevant activity in T-DM1-pretreated patients, possibly thanks to the so-called bystander effect, namely the ability to exert cytotoxic activity also against antigen-negative cells. Such feature allows to overcome the HER2 intratumoral heterogeneity in breast cancer and could explain in the preliminary activity demonstrated also in HER2-low breast cancers. However, several ADCs targeting other cancer-associated antigens than HER2 are under development, representing a promising strategy for the treatment of triple-negative tumors, exemplified by the encouraging results of sacituzumab govitecan.

ADCs are innovative and effective therapeutic drugs in breast cancer. Research efforts are ongoing to identify novel targets and combination with other treatment modalities, particularly with immunotherapy, to further improve patients’ outcomes.
“I Shall Live and Not Die”
Authors: Kerr Jelani , Harris Lesley , Glass Elizabeth , Golden Tasha , Crawford Timothy
Published: July 2020

Remediating racial/ethnic HIV inequities necessitates addressing HIV-related stigma. Arts- and media-based approaches demonstrate potential for effective knowledge translation and HIV-related stigma reduction. This study employs 5 monologues portraying lived experiences of older African Americans living with HIV to do this. Monologues were developed on the basis of qualitative research, actors performed them for live and online audiences, and surveys were distributed to gauge their potential for raising awareness about HIV-related stressors, reducing HIV-related stigma, and entertainment value. Monologues may also foster HIV testing. More scholarship should integrate arts-based knowledge translation with HIV education. Future efforts should focus on scaling this approach.
Longitudinal Cytokine Profiling Identifies GRO‐α and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia
Authors: Øbro Nina F. , Grinfeld Jacob , Belmonte Miriam , Irvine Melissa , Shepherd Mairi S. , Rao Tata Nageswara , Karow Axel , Riedel Lisa M. , Harris Oliva B. , Baxter E. Joanna , Nangalia Jyoti , Godfrey Anna , Harrison Claire N. , Li Juan , Skoda Radek C. , Campbell Peter J. , Green Anthony R. , Kent David G.
Published: July 2020

Supplemental Digital Content is available in the text
The Emerging Role of Convalescent Plasma in the Treatment of COVID‐19
Authors: Psaltopoulou Theodora , Sergentanis Theodoros N. , Pappa Vasiliki , Politou Marianna , Terpos Evangelos , Tsiodras Sotirios , Pavlakis George N. , Dimopoulos Meletios A.
Published: July 2020

Various agents are currently under evaluation as potential treatments in the fight against coronavirus disease 2019 (COVID‐19). Plasma from patients that have overcome COVID‐19 infection, referred to as convalescent plasma, is a treatment option with considerable background in viral diseases such as Spanish influenza, H1N1, Ebola, Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS). Although convalescent plasma has historically proven beneficial in the treatment of some viral diseases, its use is still explorative in the context of COVID‐19. To date, preliminary evidence from case series is favorable as significant clinical, biochemical improvement and hospital discharge have been reported. A detailed overview of randomized as well non‐randomized trials of treatment with convalescent plasma, which have been registered worldwide, is provided in this review. Based on these studies, data from thousands of patients is anticipated in the near future. Convalescent plasma seems to be a safe option, but potential risks such as transfusion‐related acute lung injury and antibody‐dependent enhancement are discussed. Authorities including the Food and Drug Administration (FDA), and scientific associations such as the International Society of Blood Transfusion (ISBT) and the European Blood Alliance (EBA), have provided guidance into the selection criteria for donors and recipients. A debatable, pivotal issue pertains to the optimal timing of convalescent plasma transfusion. This treatment should be administered as early as possible to maximize efficacy, but at the same time be reserved for severe cases. Emerging risk stratification algorithms integrating clinical and biochemical markers to trace the cases at risk of significant deterioration can prove valuable in this direction.
A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants
Authors: Platt Heather L. , Greenberg David , Tapiero Bruce , Clifford Robert A. , Klein Nicola P. , Hurley David C. , Shekar Tulin , Li Jianing , Hurtado Kim , Su Shu-Chih , Nolan Katrina M. , Acosta Camilo J. , McFetridge Richard D. , Bickham Kara , Musey Luwy K. ,   for the V114-008 Study Group
Published: July 2020

Background:

Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of 2 clinical lots of V114 (investigational 15-valent pneumococcal vaccine: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F*, 23F, 33F*) to 13-valent pneumococcal conjugate vaccine (PCV13) in healthy infants (*serotypes unique to V114).

Methods:

Healthy infants 6–12 weeks old were randomized to receive a 4-dose regimen of V114 Lot 1, V114 Lot 2 or PCV13 at 2, 4, 6 and 12–15 months old. Adverse events were evaluated after each dose. Primary immunogenicity endpoint was to demonstrate noninferiority of V114 Lot 1 and V114 Lot 2 relative to PCV13 based on proportion of infants achieving serotype-specific IgG concentration ≥0.35 µg/mL for 13 serotypes shared with PCV13 at 1 month postdose 3 (PD3). Serotype-specific IgG geometric mean concentrations (GMCs) for all 15 V114 serotypes were measured at PD3, predose 4 and 1 month postdose 4 (PD4).

Results:

Overall, 1044 of 1051 randomized infants received ≥1 dose of vaccine (V114 Lot 1 [n = 350], V114 Lot 2 [n = 347] or PCV13 [n = 347]). Adverse events were generally comparable across groups. At PD3, both V114 lots met noninferiority criteria for all 13 serotypes shared with PCV13. IgG GMCs were comparable among V114 and PCV13 recipients at PD3 and PD4. Serotype 3 responses were higher following receipt of V114 than PCV13. Both V114 lots induced higher GMCs than PCV13 to the 2 unique V114 serotypes.

Conclusions:

Immunogenicity of both V114 lots was noninferior to PCV13 for all 13 shared serotypes between the 2 vaccines and displayed comparable safety and tolerability profiles to PCV13.
Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis
Authors: Bradley John S. , Arrieta Antonio C. , Digtyar Valeri A. , Popejoy Myra W. , Grandhi Anjana , Bokesch Paula , Hershberger Ellie , Dorr Mary Beth , Tan Christopher M. , Murata Yoshihiko , Wolf Dominik J. , Bensaci Mekki
Published: July 2020

Background:

We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO).

Methods:

Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1–17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14–42 days total). Primary endpoint: protocol-defined clinical improvement by Day 5 in the modified intention-to-treat (MITT) population (confirmed AHO, ≥1 dose of study treatment); differences between study arms were evaluated using a prespecified 15% noninferiority margin for daptomycin.

Results:

Seventy-three patients per arm received treatment. Pathogens were isolated from 62% of patients (83% methicillin-susceptible Staphylococcus aureus, 9% methicillin-resistant S. aureus [MRSA]). Clinical improvement by Day 5 was observed in 55/71 (78%) daptomycin- and 58/70 (83%) comparator-treated MITT patients (95% confidence interval [CI]: −19.4, 7.4). This difference was not statistically significant; however, daptomycin did not meet the prespecified 15% noninferiority margin, since the lower bound of the 95% CI extended below 15%. Overall, 82% of daptomycin and 87% of comparator patients achieved clinical cure at the test-of-cure visit (secondary endpoint). More comparator patients had treatment-emergent (63% vs. 46%) and treatment-related (18% vs. 7%) adverse events.

Conclusions:

Differences between daptomycin and comparator for the primary endpoint were not statistically significant; however, prespecified noninferiority criteria for daptomycin were not met. With insufficient cases of confirmed MRSA, we could not evaluate daptomycin for MRSA AHO. Our nonvalidated protocol design yields valuable information for implementing future trials in AHO (ClinicalTrials.gov NCT01922011).
A transcriptional toolbox for exploring peripheral neuroimmune interactions
Authors: Liang Zhi , Hore Zoe , Harley Peter , Uchenna Stanley Federico , Michrowska Aleksandra , Dahiya Monica , La Russa Federica , Jager Sara E. , Villa-Hernandez Sara , Denk Franziska
Published: July 2020

Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies, and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type-specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3 1/2 months after the initial injury. This raises the question of whether the commonly used categorisation of pain into “inflammatory” and “neuropathic” is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq data sets on neurons, macrophages, and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data mining of peripheral neuroimmune interactions. http://rna-seq-browser.herokuapp.com/
Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility
Authors: Power Andrea , Brown Christopher Andrew , Sivan Manoj , Lenton Ann , Rainey Timothy , El-Deredy Wael , Jones Anthony Kenneth Peter , Watson Alison
Published: July 2020

It is unclear whether a diagnosis of chronic pain is associated with an increase or decrease in the placebo response. The aim of this study was to use an experimental placebo conditioning paradigm to test whether expectancy for pain relief impacts on acute pain perception in individuals with a chronic pain diagnosis of osteoarthritis (OA) or fibromyalgia (FM), compared to healthy individuals (HIs). An inert cream was applied to the dominant forearm of participants (60 OA, 79 FM, and 98 HI), randomly assigned to either a placebo or control group. In both groups, an inactive cream was applied to the dominant forearm. The placebo group was told this may or may not be a local anaesthetic cream, whereas the control group was told the cream was inactive. Laser pain was delivered, and numerical pain intensity ratings collected before, during, and after cream application, along with expectation of pain relief and anxiety. The procedure was repeated 2 weeks later to assess reproducibility. There was a significant reduction in pain in the placebo group, independent of clinical diagnosis. Diagnostic groups (OA, FM, and HI) did not differ in their magnitude of placebo analgesia or expectancy of pain relief. The results were similar in the repeat session. The results demonstrate that individuals with chronic pain respond to experimental placebo analgesia in a similar and reproducible manner as HIs, despite higher levels of psychological comorbidity. This has implications for using placebo analgesia in the treatment of chronic pain.
Quantitative differences in neuronal subpopulations between mouse and human dorsal root ganglia demonstrated with RNAscope in situ hybridization
Authors: Shiers Stephanie , Klein Rebecca M. , Price Theodore J.
Published: July 2020

Next-generation transcriptomics in combination with imaging-based approaches have emerged as powerful tools for the characterization of dorsal root ganglion (DRG) neuronal subpopulations. The mouse DRG has been well characterized by many independently conducted studies with convergent findings, but few studies have directly compared expression of population markers between mouse and human. This is important because of our increasing reliance on the mouse as a preclinical model for translational studies. Although calcitonin gene-related peptide (CGRP) and P2X purinergic ion channel type 3 receptor (P2X3R) have been used to define peptidergic and nonpeptidergic nociceptor subpopulations, respectively, in mouse DRG, these populations may be different in other species. To directly test this, as well as a host of other markers, we used multiplex RNAscope in situ hybridization to elucidate the distribution of a multitude of unique and classic neuronal mRNAs in peptidergic (CGRP-expressing) and nonpeptidergic (P2X3R-expressing) nociceptor subpopulations in mouse and human DRG. We found a large overlapping CGRP and P2X3R neuronal subpopulation in human, lumbar DRG that was not present in mouse. We also found differential expression in a variety of mRNAs for transient receptor potential channels, cholinergic receptors, potassium channels, sodium channels, and other markers/targets. These data offer insights into the spatial and functional organization of neuronal cell subpopulations in the rodent and human DRG and support the idea that sensory system organizational principles are likely different between both species.
Does Midlife Forgetfulness Influence Positive and Negative Aspects of Social Relations at Work?
Authors: Ishtiak-Ahmed Kazi , Hansen Åse Marie , Mortensen Erik Lykke , Garde Anne Helene , Grynderup Matias Brødsgaard , Gyntelberg Finn , Islamoska Sabrina , Lund Rikke , Phung Thien Kieu Thi , Waldemar Gunhild , Nabe-Nielsen Kirsten
Published: July 2020

Objectives:

We investigated whether midlife forgetfulness was prospectively associated with changes in social relations at work (SRW) among occupationally active individuals in Denmark.

Methods:

We analyzed data of 2339 men and women participating in the first (1990) and second (1995) survey of the Danish Work Environment Cohort Study, responding to questions on working environment, SRW, and forgetfulness. We used multiple linear regression analysis while adjusting for potential confounders.

Results:

At baseline (1990), 517 (22.1%) study participants were categorized as forgetful. Forgetfulness was prospectively associated with a decline in one of the investigated items reflecting a negative aspect of SRW (experiencing teasing, regression coefficient = 0.07, 95% CI: 0.03 to 0.11), while no association was observed with positive aspects of SRW.

Conclusions:

Our findings did not support the hypothesis that memory problems such as midlife forgetfulness negatively affect SRW.
Medullary Pancreatic Carcinoma Due to Somatic POLE Mutation
Authors: Kryklyva Valentyna , ter Linden Esther , Kroeze Leonie I. , de Voer Richarda M. , van der Kolk B. Marion , Stommel Martijn W.J. , Hermans John J. , Luchini Claudio , Wood Laura D. , Hruban Ralph H. , Nagtegaal Iris D. , Ligtenberg Marjolijn J.L. , Brosens Lodewijk A.A.
Published: July 2020

Medullary pancreatic carcinoma (MPC) is a rare histological variant of pancreatic ductal adenocarcinoma (PDAC). Because of its rarity, data on the molecular background of MPC are limited. Previous studies have shown that a subset of MPCs is microsatellite instable due to mismatch repair deficiency. Here, we present a unique case of a female patient in her 60s who is a long-term survivor after surgery for pancreatic cancer. The patient had a microsatellite stable MPC with a somatic mutation of the polymerase epsilon gene (POLE). Both microsatellite instable and POLE-mutated cancers are usually associated with high tumor mutational burden and antigen load, resulting in a prominent antitumor immune response and overall better survival. The current case illustrates that, in addition to mismatch repair deficiency, MPC can develop because of a somatic POLE mutation, resulting in a tumor with a high tumor mutational burden and leading to a better prognosis compared with conventional PDAC. This new finding may have important implications in the management of patients with MPC and calls for further studies on the role of POLE in PDAC.
Improving Mental Health Communication From the Pediatric Emergency Department to Primary Care
Authors: Esposito Jeremy M. , Fein Joel A. , Marshall Jason , Mitchell Christine , Aredas Brenna , Zorc Joseph J.
Published: July 2020

Objectives

Suicide is a leading cause of adolescent death, and emergency department (ED) visits are recognized as an opportunity to identify at-risk youth. For patients screening positive for mental health concerns, we implemented a quality improvement initiative to enhance documentation of results and interventions in the ED, increase communication between the ED and primary care providers (PCPs), and increase PCP follow-up.

Methods

Interventions included education, feedback, and an alert in our electronic health record. Completion of a Behavioral Health Screen (BHS-ED) initiates an alert that reminds ED providers how to document and communicate results and needed follow-up to the PCP. We reviewed a random monthly sample of ED charts for adolescents 14 to 19 years old presenting with nonpsychiatric complaints who screened positive for severe depression or suicidality. Outcome measures included documentation of BHS-ED results in the ED note, communication of positive results to the PCP, PCP follow-up of results, and ED return visits.

Results

Documentation of BHS-ED results increased from 73% at baseline to 88% of patients after the intervention. For patients discharged from the ED with nonpsychiatric chief complaints, communication to PCPs increased from 1% at baseline to 40% during the final 3 months of the study. When PCP communication occurred, 67% of in-network PCPs followed up with patients versus 5% when no communication took place from the ED.

Conclusions

A multifaceted intervention including education and an electronic health record alert improved ED documentation, communication, and PCP follow-up of issues identified during ED-based mental health screens.
Survey of Current Institutional Practices in the Use of High-Flow Nasal Cannula for Pediatric Patients
Authors: Cheng Amy Y. , Simon Harold K. , Miller Judson , Wetzel Martha , Zmitrovich April , Hebbar Kiran B.
Published: July 2020

Objectives

High-flow nasal cannula (HFNC) is an oxygen delivery device that provides heated humidified air with higher flow rates. The purpose of this survey is to look at institutional practice patterns of HFNC initiation, weaning, and disposition for pediatric patients across the United States.

Methods

Survey was sent via electronic listservs to pediatric physicians in emergency medicine, hospital medicine, critical care, and urgent care. The questionnaire was divided into demographics and HFNC practices (initiation, management, and weaning). One response per institution was included in the analysis.

Results

Two hundred twenty-four responses were included in the analysis, composed of 40% pediatric emergency medicine physicians, 46% pediatric hospitalists, 13% pediatric intensive care unit (PICU) physicians, and 1% pediatric urgent care physicians. Ninety-eight percent of the participants have HFNC at their institution. Thirty-seven percent of the respondents had a formal guideline for HFNC initiation. Nearly all guideline and nonguideline institutions report HFNC use in bronchiolitis. Guideline cohort is more likely to have exclusion criteria for HFNC (42% in the guideline cohort vs 17% in the nonguideline cohort; P < 0.001) and less frequently mandates PICU admissions once on HFNC (11% in the guideline cohort vs 56% in the nonguideline cohort; P < 0.001). Forty-six percent of guideline cohort had an objective scoring system to help determine the need for HFNC, and 73% had a weaning guideline.

Conclusions

Although there is general agreement to use HFNC in bronchiolitis, great practice variation remains in the initiation, management, and weaning of HFNC across the United States. There is also a discordance on PICU use when a patient is using HFNC.
Sexual Behaviors After PrEP Discontinuation Among HIV Serodiscordant Couples in Kenya and Uganda
Authors: Stalter Randy , Mugwanya Kenneth , Thomas Katherine , Donnell Deborah , Mujugira Andrew , Ngure Kenneth , Celum Connie , Kidoguchi Lara , Bukusi Elizabeth , Baeten Jared , Heffron Renee ,   for the Partners Demonstration Project Team
Published: July 2020

Background:

A strategy of pre-exposure prophylaxis (PrEP) transitioning to treatment as prevention is highly efficacious and cost effective for prevention of HIV transmission within HIV serodiscordant couples. We assessed whether couples who adopted this strategy experienced changes in sexual behaviors after HIV-negative partners discontinued PrEP and transitioned to rely primarily on their partner's adherence to antiretroviral therapy (ART) for prevention.

Setting:

Kenya and Uganda.

Methods:

Data are from the Partners Demonstration Project, a prospective, open-label evaluation of PrEP and ART use for HIV prevention. Using zero-inflated negative binomial models, we assessed changes in the level (ie, intercept) and trend over time (ie, slope) in total and condomless sex acts reported after PrEP discontinuation by HIV-negative partners. We conducted subgroup analyses based on HIV-negative partners' age and sex.

Results:

We included 567 couples where the HIV-negative partner discontinued PrEP because of their partner with HIV using ART for ≥6 months. HIV-negative partners were women in 32.6% of couples and had a median age of 30 years. We observed no change in the level or trend over time in total sex acts [level adjusted rate ratio (aRR) = 0.95, 95% confidence interval (CI): 0.87 to 1.04; trend aRR = 1.00, 95% CI: 0.99 to 1.01] or condomless sex acts (level aRR = 0.97, 95% CI: 0.81 to 1.17; trend aRR = 1.00, 95% CI: 0.98 to 1.03) reported after PrEP discontinuation versus prediscontinuation. No significant changes in behaviors were observed in age and sex subgroups.

Conclusions:

PrEP discontinuation seems to result in no significant changes in couples' sexual behaviors. These data further support a strategy of time-limited PrEP use by serodiscordant couples.
Prospective Evaluation of Outpatient Flexible Sigmoidoscopy in Patients With Deep Infiltrating Endometriosis
Authors: Celentano Valerio , Di Donato Nadine , Buccomino Giusy E. , Candy Katie , Solomon Lemke , Ihezue Chukwumobi , Berry Janet , Tsepov Denis
Published: July 2020

Introduction:

To study patients’ acceptability of an outpatient flexible sigmoidoscopy (FS) protocol and to assess the diagnostic value of endoscopic assessment in patients with deep endometriosis (DE).

Methods:

All patients with DE and suspected bowel involvement diagnosed were reviewed in the colorectal outpatient clinic before elective surgery following multidisciplinary team meeting discussion. Patients were consented for having the FS performed at the same time of the clinical consultation. Primary outcome was diagnostic value of the FS.

Results:

Sixty patients were included. Fifty-eight (96.7%) patients consented for the outpatient FS, demonstrating a high rate of patients’ acceptability. The sigmoidoscopy demonstrated no abnormalities in 48 patients (82.7%), diverticulosis in 5 patients (8.6%), polyps in 2 patients (3.4%) and mucosal endometriosis in 1 patient only (1.7%).

Conclusions:

Outpatient FS during the preoperative consultation with the colorectal surgeon is feasible in patients with DE affecting the bowel with a high rate of patients’ acceptability but limited additional diagnostic value.