bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences at the platelet–vascular interface
Authors: Sabetta Annamaria , Lombardi Ludovica , Stefanini Lucia
Published: May 2022

Platelets are multifunctional cells that ensure the integrity of the vascular wall and modulate the immune response at the blood/vascular interface. Their pathological activation results in both thrombosis and inflammation and implicates them in the pathogenesis of vascular disease. Vascular diseases are sexually dimorphic in terms of incidence, clinical presentation, outcome, and efficacy of anti-platelet therapy. We here provide an overview of what is known about the role of platelets in the initiation and progression of vascular diseases and summarize what is known about the sex differences in platelet reactivity and in the thromboinflammatory mechanisms that drive these diseases, with a particular focus on atherosclerosis, obstructive and non-obstructive coronary artery disease, and ischemic stroke. Understanding the sex differences at the platelet–vascular interface is clinically relevant as it will enable: (1) to design new therapeutic strategies that prevent the detrimental effects of the immune-modulatory function of platelets taking sex into account, and (2) to evaluate if sex-specific anti-platelet drug regimens should be used to reduce the risk not only of thrombosis but also of vascular disease progression.
Automation software architectures in automated production systems: an industrial case study in the packaging machine industry
Authors: Neumann Eva-Maria , Vogel-Heuser Birgit , Fischer Juliane , Diehm Sebastian , Schwarz Michael , Englert Tobias
Published: May 2022

In the era of Industry 4.0, advances in production engineering are driven by modern machines and equipment, whose evolution depends primarily on software nowadays. These machines are combined in automated Production Systems (aPS), whose software is characterized by high complexity, long lifetimes, and strong coupling of mechatronic disciplines. The development of modular, flexible software architectures that adapt to company- and process-specific boundary conditions is an essential prerequisite for companies to compete globally. While there are many approaches in computer science, a clear definition of control software architecture in aPS and systematic approaches to analyze company-specific software architectures and the underlying design decisions are still missing. This gap is addressed by defining control software architecture in aPS, including architectural views to address the heterogeneity of influencing factors on control software. To enable a systematic architecture analysis, templates are defined for visualizing design decisions to derive concrete recommendations to support practitioners in improving software. An in-depth interview study in three renowned companies from packaging machinery confirmed the benefit of the proposed architecture analysis to systematically identify optimization potentials and concrete starting points for the implementation.
Can dementia become the most prevalent disease at the time of death in Germany? Projections up to the year 2060 for the five most important diseases at the time of death
Authors: Doblhammer Gabriele , Fritze Thomas , Reinke Constantin , Fink Anne
Published: May 2022

Data on the burden of disease in the last years of life are an important basis for health policy decisions and the allocation of health care resources. Since dementia is one of the most expensive diseases, we ask the question whether dementia will ever be the most common disease at the time of death in older people? While international cause-of-death statistics report the underlying cause of death, dementia patients generally die from complications or sequelae. Instead of using causes of death, we identified the five most prevalent disease categories at age 70 and older at the time of death using German health claims data from 2004 to 2007 and 2014–2017, and combined their prevalence rates with the estimated number of deaths at age 70 and older up to the year 2060. We developed two scenarios, first, to represent the impact of population aging and increasing life expectancy. Second, to additionally examine the impact of morbidity trends among those who died. We found that dementia was already the most prevalent disease at the time of death among German women aged 70 years and older in 2014–2017, while it was still in fifth place among German men. Population aging and increasing life expectancy will result in dementia ranking first among women and second among men if the morbidity profile at the time of death remains constant. Extrapolating the observed time trends into the projections, cancer will be the most prevalent disease at the time of death for both sexes. Dementia will be second for women, and third for men after IHD. In addition to projections of causes of death, we also need projections of diseases at the time of death to better prepare for the needs of people in their final stages of life.
Are gender roles associated with well-being indicators? The role of femininity, fear of negative evaluation, and regret in decision-making in a spanish sample
Authors: Villanueva-Moya Laura , Expósito Francisca
Published: May 2022

Gender roles operate as a social schema through which people learn how they must behave and make decisions; that is, socially, what women and men are expected to do is pre-established. This gender socialization is such a deep-rooted process that people may not aware of how they have been socialized, which is thus often is difficult to analyze in people's discussions of their own decision-making. On this basis, this research examines whether endorsing gender roles could be related to women’s decisions (regret), as well as the possible consequences for their well-being. Moreover, we analyzed the content of the most important decisions that people make throughout their lives. Therefore, this research aimed to understand the meaning of gender and how its internalization seems to be related to sex differences in decision-making and well-being. In a sample of the Spanish general population (N = 203; Mage = 41.70, SD = 10.93; range from 20 to 65 years old), results showed that women (vs. men) had a greater internalization of gender roles (i.e., femininity), which was associated with higher fear of negative evaluation. This, in turn, was associated with experienced regret in decision-making, which finally seemed to lead to lower well-being. Analysis of the content of decisions showed that women’s decisions were based mainly on work and family domains, whereas men’s decisions were based on work to a greater extent.
Latex-Based Paper Devices with Super Solvent Resistance for On-the-Spot Detection of Metanil Yellow in Food Samples
Authors: Ray Rohitraj , Noronha Calvin , Prabhu Anusha , Mani Naresh Kumar
Published: May 2022

The following paper presents a construct for a paper-based device which utilizes latex as the hydrophobic material for the fabrication of its hydrophobic barrier, which was deposited onto the cellulose surface either by free-hand or stenciled drawing. This method demands the least amount of expertise and time from its use, enabling a simple and rapid fabrication experience. Several properties of the hydrophobic material were characterized, such as the hydro head and penetration rate, with the aim of assessing its robustness and stability. The presented hydrophobic barriers fabricated using this approach have a barrier width of 4 mm, a coating thickness of 208 µm, and a hydrophilic resolution of 446.5 µm. This fabrication modality boasts an excellent solvent resistance with regard to the hydrophobic barrier. These devices were employed for on-the-spot detection of Metanil Yellow, a banned food adulterant often used in curcumin and pigeon peas, within successful limits of detection (LOD) of 0.5% (w/w) and 0.25% (w/w), respectively. These results indicate the great potential this fabricated hydrophobic device has in numerous paper-based applications and other closely related domains, such as diagnostics and sensing, signalling its capacity to become commonplace in both industrial and domestic settings.
Vepris onanae (Rutaceae), a new Critically Endangered cloud-forest tree species, and the endemic plant species of Bali Ngemba Forest Reserve, Bamenda Highlands Cameroon
Authors: Cheek Martin , Hatt Sebastian , Onana Jean Michel
Published: May 2022

We revise and update the records of strict and near-endemic species of the Bali Ngemba Forest Reserve, the largest known surviving patch (c. 8 km2 in area) of submontane or cloud forest in the Bamenda Highlands, Cameroon which have lost >96 % of their original forest due to human activities. Nine strict endemics, and 11 near endemics are now documented, a drop from the number recorded after the first survey in 2004, since when five of the provisionally named species have been validly published. We test the hypothesis that a further one of the provisionally named putative Bali Ngemba new species, Vepris sp. A, an 8 – 20 m tall tree from cloud forest in the 1310 – 1700 m altitudinal band, is indeed new to science. We compare it morphologically with other multicarpellate, apocarpous, trifoliolate Cameroon tree species formerly placed in the genus Oricia Pierre until they were subsumed into Vepris by Mziray (1992). These are V. trifoliolata (Engl.) Mziray and V. gabonensis (Pierre) Mziray. We conclude that Vepris sp. A is a new undescribed species here named as Vepris onanae. The new species is illustrated, mapped and its conservation status assessed as Critically Endangered using the 2012 IUCN standard due to severe fragmentation and the threats of habitat clearance from agricultural pressures at its three locations all of which remain formally unprotected. Vepris onanae appears unique among the Guineo-Congolian African oricioid species of Vepris in that it occurs in cloud forest, the other species, apart from V. renieri (G.C.C.Gilbert) Mziray of the Albertine Rift, occurring in lowland forest. It also differs in the very broad, (7.8 –) 11.3 – 18 cm wide leaflets of the flowering stems which have a 6 – 18 (– 30) mm long, narrowly triangular acumen (vs leaflets <12 cm wide, acumen absent or short) and in having both subsessile and pedicellate (pedicels 0.25 – 0.3 mm long and 1 (– 2) mm long) male flowers (vs male flower pedicels all sessile, or all c. 3 mm long). We report for the first time on stage-dependent leaf heteromorphy in Vepris and characterise a level of sexual dimorphism more advanced than usual in the genus. We highlight the importance of protecting Bali Ngemba and other forest patches in the Bamenda Highlands if species such as Vepris onanae are not soon to become extinct.
New insights in Neanderthal palaeoecology using stable oxygen isotopes preserved in small mammals as palaeoclimatic tracers in Teixoneres Cave (Moià, northeastern Iberia)
Authors: Fernández-García M. , López-García J. M. , Royer A. , Lécuyer C. , Rivals F. , Rufà A. , Blasco R. , Rosell J.
Published: May 2022

The northeastern region of Iberia constitutes a natural pass-area for arriving populations into the peninsula and becomes a key area to understand Neanderthal resilience to changing environmental conditions experienced during Marine Isotope Stage 3 (MIS 3; 60–30 ka). Short-term but repeated occupations by Neanderthal groups occurred in Teixoneres Cave (Moià, Barcelona) in alternation with large and small carnivores during MIS3. Abundant small-mammal remains accumulated in units III and II of this fossiliferous deposit, providing local climatic and environmental information. This work focuses on the taphonomic history of small-mammal faunas, which a is clue to validate previous palaeoecological interpretations. As was observed with leporids and bird remains, raptors are considered the major source of small-mammal remains. The most likely accumulator is an opportunistic predator, the eagle owl, with very rare inputs by mammalian carnivores. In parallel, high-resolution palaeoclimatic data are provided through oxygen isotope analyses (δ18O) of rodent teeth from four subunits (IIIb to IIa), which are compared with independent methods of palaeotemperature estimations. According to air temperatures estimated from δ18O rodent teeth, cooler conditions than present day (− 1.6/ − 0.5 °C) are recorded along the sequence, but homogenous (< 1 °C). Complementary methods also explain higher rainfall than present day (+ 44/ + 682 mm). Only slight changes between units III and II show climatic instability, which could be related to palimpsests of stadial-interstadial events. Climatic stable conditions are reported from coeval isotopic and palaeodiet analyses from northeastern Iberia in agreement with the palynological records that underline how the Mediterranean area could have sustained rich ecosystems that assured the Neanderthal subsistence during the abrupt climatic pulsations of the Late Glacial.
Embracing the Complexity of our Inner Worlds: Understanding the Dynamics of Self-Compassion and Self-Criticism
Authors: Ferrari Madeleine , Ciarrochi Joseph , Yap Keong , Sahdra Baljinder , Hayes Steven C.
Published: May 2022

Objectives

Although research in self-compassion has been rapidly growing, there is still substantial controversy about its meaning and measurement. The controversy centers on Neff’s popular Self- Compassion Scale (SCS) and the argument that compassionate self-responding (CSR) and uncompassionate self-responding (UCS) are a single dimension versus the argument that they are two semi-independent, unipolar dimensions, with UCS not reflective of “true” self-compassion.

Methods

We review the evidence for both positions and conclude that the data cannot yet resolve the debate.

Results

Neither position is proven to be right or wrong. We recommend the way forward is to let go of traditional factor analytic approaches and examine self-compassionate behavior as a dynamic network of interacting processes that are influenced by context. This leads us to three classes of testable hypotheses. The link between CS and UCS will depend on the timeframe of measurement, current circumstances, and individual differences.

Conclusions

We propose a middle ground to the SCS debate; rather than supporting the single total score, 2-factor score (CSR and UCS) or the 6-factor score (the six subscales of the SCS), we argue these constructs interact dynamically, and the decision of which scoring method to use should depend on the three testable contextual hypotheses.
KLF14 targets ITGB1 to inhibit the progression of cervical cancer via the PI3K/AKT signalling pathway
Authors: Lyu Xinran , Ding Xuchao , Ye Hui , Guo Rong , Wu Minhang , Cao Lili
Published: May 2022

Our study aimed to determine whether Krüppel-like factor 14 (KLF14) inhibits the proliferation and promotes the apoptosis of cervical cancer cells through integrin β1 (ITGB1). Immunohistochemistry was performed to determine the expression of KLF14. The effect of KLF14 on the proliferation of cervical cancer cells was verified by Cell Counting Kit-8 (CCK-8) assays, colony formation assays and in vivo experiments. The effect of KLF14 on cervical cancer cell apoptosis was detected by flow cytometry. The targeting relationship between KLF14 and ITGB1 was evaluated by Western blotting and a dual-luciferase reporter assay. Moreover, Flow cytometry was performed to verify the relationship between KLF14 and ITGB1 on the apoptosis of cervical cancer cells. Additionally, Western blot analysis was performed to investigate the relationship between KLF14 and ITGB1 on the expression of downstream related molecules. As a result, the expression of KLF14 in cervical cancer tissues was lower than that in paracancerous tissues. KLF14 inhibited proliferation and promoted apoptosis in cervical cancer cells. Mechanistically, ITGB1 expression was significantly downregulated in KLF14-overexpressing cervical cancer cells. At the same time, we found that the effects of KLF14 and ITGB1 on apoptosis of cervical cancer cells could be mutually affected. KLF14 directly targeted ITGB1 to regulate its downstream PI3K/AKT signalling pathway. In summary, KLF14 inhibits the progression of cervical cancer by targeting ITGB1 via the PI3K/AKT signalling pathway.
Explaining Artificial Intelligence with Care
Authors: Szepannek Gero , Lübke Karsten
Published: May 2022

In the recent past, several popular failures of black box AI systems and regulatory requirements have increased the research interest in explainable and interpretable machine learning. Among the different available approaches of model explanation, partial dependence plots (PDP) represent one of the most famous methods for model-agnostic assessment of a feature’s effect on the model response. Although PDPs are commonly used and easy to apply they only provide a simplified view on the model and thus risk to be misleading. Relying on a model interpretation given by a PDP can be of dramatic consequences in an application area such as forensics where decisions may directly affect people’s life. For this reason in this paper the degree of model explainability is investigated on a popular real-world data set from the field of forensics: the glass identification database. By means of this example the paper aims to illustrate two important aspects of machine learning model development from the practical point of view in the context of forensics: (1) the importance of a proper process for model selection, hyperparameter tuning and validation as well as (2) the careful used of explainable artificial intelligence. For this purpose, the concept of explainability is extended to multiclass classification problems as e.g. given by the glass data.
Indifferent to difference? Understanding the unequal impacts of farming technologies among smallholders. A review
Authors: Thuijsman Eva S. , den Braber Harmen J. , Andersson Jens A. , Descheemaeker Katrien , Baudron Frédéric , López-Ridaura Santiago , Vanlauwe Bernard , Giller Ken E.
Published: May 2022

With many of the world’s poor engaged in agriculture, agricultural development programmes often aim to improve livelihoods through improved farming practices. Research on the impacts of agricultural technology interventions is dominated by comparisons of adopters and non-adopters. By contrast, in this literature study, we critically review how technology evaluation studies assess differentiated impacts in smallholder farming communities. We searched systematically for studies which present agricultural technology impacts disaggregated for poor and relatively better-off users (adopters). The major findings of our systematic review are as follows: (1) The number of studies that assessed impact differentiation was startlingly small: we were able to identify only 85, among which only 24 presented empirical findings. (2) These studies confirm an expected trend: absolute benefits are larger for the better-off, and large relative benefits among the poor are mostly due to meagre baseline performance. (3) Households are primarily considered as independent entities, rather than as connected with others directly or indirectly, via markets or common resource pools. (4) Explanations for impact differentiation are mainly sought in existing distributions of structural household characteristics. We collated the explanations provided in the selected studies across a nested hierarchy: the field, the farm or household, and households interacting at the farming system level. We also consider impact differentiation over time. With this, we provide a structured overview of potential drivers of differentiation, to guide future research for development towards explicitly recognizing the poor among the poor, acknowledging unequal impacts, aiming to avoid negative consequences, and mitigating them where they occur.
The carbon footprint of milk during the conversion from conventional to organic production on a dairy farm in central Germany
Authors: Gross Arthur , Bromm Tobias , Polifka Steven , Schierhorn Florian
Published: May 2022

Dairy products play an important role in human nutrition, but at the same time, the dairy sector is a major contributor to global warming. The conversion from conventional to organic milk production could reduce the carbon footprint due to the elimination of synthetic fertilizers and strong reliance on closed on-farm nutrient cycling. We present one of the first studies to comprehensively estimate the climate-change impacts of the conversion to organic production of a large-scale dairy operation in central Germany. We used detailed farm data and a carbon footprint approach based on the IPCC tier-2 methodology to estimate greenhouse gas (GHG) emissions associated with feed production, animal husbandry, and animal rearing. Our results show that the carbon footprint per kg of energy-corrected milk (ECM) decreased by 9% during the first year of conversion to organic milk production. Conversely, livestock emissions per kg ECM increased by 12% in the first conversion year due to the increase in methane emissions from enteric fermentation, but this increase was more than offset by the decrease in emissions from feed production. Emissions from internal and external feed production per kg ECM decreased by 17% and 29%, respectively. Our study helps to understand how individual emission sources change as a result of a farm’s conversion to organic production. This research is important and timely, as the European Union is pursuing ambitious goals to increase the area under organic farming, although the impact of the conversion period on GHG emissions has been insufficiently studied.
Agro-climatic profiles of summer mountain pastures in the French Alps: towards a monitoring tool to contribute to climate risk assessment
Authors: Deléglise Claire , François Hugues , Dodier Hermann , Crouzat Emilie , Samacoïts Raphaëlle , Morin Samuel , Bray Frédéric , Nettier Baptiste
Published: May 2022

Summer mountain pastures (also called alpages) are a central element for many agro-pastoral livestock systems in the alpine region, by providing the feedstock for herds during the summer transhumance. However, vegetation phenology and productivity in mountain pastures are increasingly affected by climate hazards exacerbated by climate change, such as early snow removal, late frost events, or droughts. Difficulties can then arise to match animal demand with forage resource on alpages and, in the long term, threaten the sustainable management of these highly multifunctional socio-ecological systems. To help agro-pastoral actors adapt, an essential step is to quantify the risk of impacts on the forage resource, due to an increased occurrence or intensity of climate hazards.

Exposure to climate hazards on alpages is defined locally by topographic aspects in combination with the broader influence of the regional climate. Our work therefore aimed at providing a tailored assessment of potential climate risk for the forage resource at the individual scale of each alpage in the French Alps. To this end, we developed agro-climatic indicators based on atmospheric and snow cover data accounting for geographic and topographic conditions, and applied them to a database providing unique spatially explicit information at the alpage level.

For the first time, we introduce a description of agro-climatic conditions and provide a classification of agro-climatic profiles of alpages in the French Alps, ranging from low to high potential risk for the forage resource, mainly following a North-South gradient combined with altitude. We also bring insights on the evolutions of the climate risk with climate change and discuss management implications for agro-pastoral livestock systems using alpages. We finally present a web-based visualization tool that aim at communicating agro-climatic profiles and their evolution to practitioners and at assisting decision makers in understanding climate-related risks on the alpages of the French Alps.
Respiratory muscle dysfunction in long-COVID patients
Authors: Hennigs Jan K. , Huwe Marie , Hennigs Annette , Oqueka Tim , Simon Marcel , Harbaum Lars , Körbelin Jakob , Schmiedel Stefan , Schulze zur Wiesch Julian , Addo Marylyn M. , Kluge Stefan , Klose Hans
Published: May 2022

Purpose

Symptoms often persistent for more than 4 weeks after COVID-19—now commonly referred to as ‘Long COVID’. Independent of initial disease severity or pathological pulmonary functions tests, fatigue, exertional intolerance and dyspnea are among the most common COVID-19 sequelae. We hypothesized that respiratory muscle dysfunction might be prevalent in persistently symptomatic patients after COVID-19 with self-reported exercise intolerance.

Methods

In a small cross-sectional pilot study (n = 67) of mild-to-moderate (nonhospitalized) and moderate-to-critical convalescent (formerly hospitalized) patients presenting to our outpatient clinic approx. 5 months after acute infection, we measured neuroventilatory activity P0.1, inspiratory muscle strength (PImax) and total respiratory muscle strain (P0.1/PImax) in addition to standard pulmonary functions tests, capillary blood gas analysis, 6 min walking tests and functional questionnaires.

Results

Pathological P0.1/PImax was found in 88% of symptomatic patients. Mean PImax was reduced in hospitalized patients, but reduced PImax was also found in 65% of nonhospitalized patients. Mean P0.1 was pathologically increased in both groups. Increased P0.1 was associated with exercise-induced deoxygenation, impaired exercise tolerance, decreased activity and productivity and worse Post-COVID-19 functional status scale. Pathological changes in P0.1, PImax or P0.1/PImax were not associated with pre-existing conditions.

Conclusions

Our findings point towards respiratory muscle dysfunction as a novel aspect of COVID-19 sequelae. Thus, we strongly advocate for systematic respiratory muscle testing during the diagnostic workup of persistently symptomatic, convalescent COVID-19 patients.
The cutoff phenomenon for the stochastic heat and wave equation subject to small Lévy noise
Authors: Barrera Gerardo , Högele Michael A. , Pardo Juan Carlos
Published: May 2022

This article generalizes the small noise cutoff phenomenon obtained recently by Barrera, Högele and Pardo (JSP2021) to the mild solutions of the stochastic heat equation and the damped stochastic wave equation over a bounded domain subject to additive and multiplicative Wiener and Lévy noises in the Wasserstein distance. The methods rely on the explicit knowledge of the respective eigensystem of the stochastic heat and wave operator and the explicit representation of the multiplicative stochastic solution flows in terms of stochastic exponentials.
Updates in the Pharmacologic Prophylaxis and Treatment of Invasive Candidiasis in the Pediatric and Neonatal Intensive Care Units
Authors: Fly James Hunter , Kapoor Seerat , Bobo Kelly , Stultz Jeremy S.
Published: May 2022

Purpose of review

The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).

Recent findings

Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United States Food and Drug Administration (FDA) for use in infants < 4 months of age. Prophylactic strategies in the PICU could include zinc and vitamin D. Anidulafungin has recent non-comparative data supporting use in pediatric patients older than 1 month of age and also has a recent FDA approval for use in children 1 month of age and older.

Fluconazole prophylaxis remains a reasonable strategy in select NICU patients, although further analyses of resistance and the optimal dosage regimen are needed. Echinocandins are potential therapeutic options for non-meningitis or urinary tract infections in both the neonatal and pediatric population.
Role of diagnostic stewardship in reducing healthcare facility-onset Clostridioides difficile infections
Authors: Shallal Anita , Cherabuddi Medha , Podsiad Lance , Gortat Christopher , Shanahan Clare , Kirkpatrick Jessica , Chami Eman , Schuldt Stephanie , Holsey Tarlisha , Levesque Martin , Alangaden George , Suleyman Geehan
Published: May 2022

Background:Clostridioides difficile infection (CDI) is the most common healthcare-associated infection (HAI) in the United States. Healthcare facility-onset (HO) CDI reporting is a laboratory-identified (LabID) event and does not rely on symptoms. Inappropriate testing can lead to overdiagnosis in patients who are colonized, especially in those receiving promotility agents. Approximately 45% of HO-CDI cases at our institution occurred in the setting of laxative use in 2019. We assessed the effectiveness of an electronic medical record (EMR) “hard stop” in reducing inappropriate CDI testing and its impact on HO-CDI rates. Methods: We conducted a pre–post quasi-experimental retrospective study comparing test order rates per 1,000 patient days, CDI rate per 1,000 patient days, and standardized infection ratio (SIR) in the preintervention period (January 2018–December 2019) to the intervention period (April 2020–September 2021), at a 5-hospital healthcare system in southeastern Michigan. In February 2020, we implemented a hard stop in Epic that was triggered >3 days after admission for the following criteria: patients <1 year of age; repeated testing within 7 days, and receipt of promotility agents within 48 hours. After discontinuing the promotility agents for at least 48 hours, providers were allowed to place an order if diarrhea persisted. The medical director of infection prevention and control or designee had the ability to override the hard stop when deemed necessary after reviewing the case upon provider request. All orders expired after 24 hours if a specimen was not collected. We retrospectively reviewed the number of overrides after the intervention to determine the positivity rate. Results: Our CDI rates per 1,000 patient days were 3.21 in the preintervention period and 1.48 in the postintervention period, a 54% reduction (Fig. 1). The test order rates were 119.4 in the preintervention period and 87.7 in the postintervention period, a 26.5% reduction (Fig. 2). The SIR decreased from 0.542 in the preintervention period to 0.361 in the postintervention period, a 33% reduction (95% CI, 0.54–0.82; P = .0001). After the intervention, 299 patients had an override. Of these, samples from 218 patients (72.9%) were negative, 50 orders (16.7%) were cancelled, and 28 samples (9%) were positive. Conclusions: Diagnostic stewardship, utilizing an electronic hard stop, was effective in reducing inappropriate C. difficile testing in the setting of promotility agents without delaying diagnosis of HO-CDI. This strategy combined with standard best practices can significantly reduce HO-CDI rates.

Funding: None

Disclosures: None
Relevance of RSV in hospitalized adults and the need for continued testing
Authors: Miller Katherine , Monto Arnold , Talbot H. Keipp , Gaglani Manjusha , McNeal Tresa , Silveira Fernanda , Zimmerman Richard , Middleton Donald , Ghamande Shekhar , Murthy Kempapura , Kim Lindsay , Ferdinands Jill , Patel Manish , Martin Emily
Published: May 2022

Background: RSV is underrecognized in hospitalized adults. A better understanding of RSV in this population could help prioritize targeted viral-testing resources. Hospitalization and in-hospital outcomes are widely accepted as markers of clinical severity with respect to acute respiratory illness (ARI). We compared characteristics and clinical outcomes between adults hospitalized with ARI from October 2016 through May 2019. Methods: All hospitalized adults (≥ 18 years) who met a standardized case definition of ARI were prospectively enrolled across 3 respiratory seasons from 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Demographic data were collected during enrollment interviews, and electronic medical records (EMRs) were reviewed to extract comorbidity data. Throat and nasal swabs collected at enrollment were tested for ARI pathogens using real-time PCR assays at respective HAIVEN research laboratory sites. Characteristics and clinical outcomes of participants were compared using χ2 or nonparametric tests where appropriate. Multivariable logistic regression models were used to test associations between infection status, characteristics, and clinical outcomes, adjusting for age, sex, race, Charlson comorbidity index (CCI), body mass index (BMI), site, season, and days to admission. Results: In total, 10,311 adults were included, 22.3% (n = 2,300) were aged 18–49 years, 33.2% (n = 3,423) were aged 50–64 years, and 44.5% (n = 4,588) were aged ≥65 years. Moreover, 6% of adults tested positive for RSV (n = 622), 18.8% positive for influenza (n = 1,940), and 75.1% negative for both (n = 7,749). Obesity and age ≥65 years were significantly associated with RSV detection when compared with participants negative for both RSV and influenza. Patients aged 18–49 years and ≥65 years with RSV had significantly higher median CCI scores compared to patients with influenza (Fig. 1.). The proportion of adults with CHF or COPD was significantly (p-value Conclusions: Severe RSV illness may differ from severe influenza illness, and those infected with RSV may have different characteristics than those infected with influenza. Hospitalized adults with RSV infection were more likely to have underlying cardiopulmonary comorbidities and higher CCI scores as well as experience an extended length of hospital stay and need for mechanical ventilation. These data highlight the importance of retaining testing for RSV in older adults hospitalized with ARI.

Funding: None

Disclosures: None
Effect of COVID-19 vaccination on transmission among healthcare workers in South Korea
Authors: Kim Jiyun , Jung Jiwon , Namgung Songhee , Jung Jihye , Kim Sun Kyung , Lim Young-ju , Kim Eun Ok , Kim Sung-Han
Published: May 2022

Background: SARS-CoV-2 infection of healthcare workers (HCWs) occasionally occurs via acquisition from their colleagues. Data regarding the infection rates of HCWs with close contact and non–close contacts of HCWs are limited. In addition, the protective effect of COVID-19 vaccination against transmission between HCWs is unknown. We evaluated the infection rates of HCWs with close contact and non–close contact of infected HCWs and the effect of COVID-19 vaccination on transmission among HCWs in a tertiary-care hospital in South Korea. Methods: This study was performed in a tertiary-care hospital in Korea. We analyzed the COVID-19 cases and contacts among HCWs from January to December 2021. We reviewed the vaccination status of confirmed and exposed HCWs, the type of vaccination, and the infection rate according to the contact. We performed subgroup analyses in individuals who had been diagnosed since July 2021 when the δ (delta) variant became the dominant strain in South Korea. Transmission was defined based on their spatiotemporal epidemiologic association. Results: During the study period, 173 HCWs had COVID-19, and 2,693 HCWs were exposed to them. Among them, 18 (1.52%) of 1,186 close contacts and 13 (0.86%) of 1,507 non–close contacts had a positive SARS-CoV-2 test (P = .11). When the index cases had been fully vaccinated, the infection rate of close contacts was 0.85% (7 of 820), whereas the infection rate of close contacts was 3.01% (11 of 366) when the index had not been fully vaccinated (P = .005). However, the infection rate of non–close contacts was not different according to the vaccination status of index (0.83% vs 0.89%; P = .90). During the period of δ (delta) variant being dominant, the infection rate of close contacts was significantly lower when the index case had been fully vaccinated index than in cases with a non–fully vaccinated index case (0.85% vs 5.88%; P < .001). Conclusions: Transmission to colleagues was significantly lower from vaccinated HCWs than from nonvaccinated HCWs, and this finding was more significant in the era of the δ (delta) variant. Our findings support the importance of vaccination in HCWs.

Funding: None

Disclosures: None
Outpatient antibiotic prescribing during the COVID-19 pandemic–United States, January 2019–October 2021
Authors: Bizune Destani , Tsay Sharon , Kabbani Sarah , Hicks Lauri
Published: May 2022

Background: Improving antibiotic use is a key strategy to combat antimicrobial resistance. Here, we have described national outpatient antibiotic prescribing trends during the COVID-19 pandemic. We compared the monthly numbers of prescriptions in 2020–2021 to those from 2019 to describe the impact of the pandemic and to highlight areas for improvement. Methods: We used the IQVIA National Prescription Audit (NPA) data set to identify all antibiotic prescriptions dispensed from US retail pharmacies during January 2019–October 2021. We calculated the percentage change in volume of prescriptions for each month during the pandemic (beginning in March 2020) compared to the baseline (defined as the corresponding month in 2019). Data were characterized by patient age group (0–19 years, 20–64 years, ≥65 years) and antibiotic class and drug, including azithromycin. Results: Antibiotic prescriptions were lower than baseline during March 2020–June 2021. The greatest decrease in antibiotic prescribing volume occurred in May 2020 (40.0% lower than May 2019) (Fig. 1), with the greatest decreases among children 0–19 years of age. However, prescribing was similar to baseline levels in July–August 2021 (Fig. 1). Specifically, azithromycin prescribing exceeded the 2019 baseline by 11.0% in July and further to a 34.5% increase in August 2021 (Fig. 2). Increases in azithromycin prescribing in August 2021 were observed across all age groups: 20–64 years (46.9% above baseline), ≥65 years (25.3% above baseline), and children 0–19 years (7.8% above baseline). Conclusions: Antibiotic prescribing volume was lower during 2020 and the first half of 2021 compared to the corresponding months in 2019. Decreases in outpatient antibiotic prescriptions during the pandemic likely reflect decreased utilization of outpatient healthcare and decreased transmission of non–COVID-19 infections secondary to nonpharmaceutical interventions (eg, masking, social distancing, school closures). However, outpatient antibiotic prescribing levels in general, and azithromycin prescribing in particular, approached or exceeded prepandemic levels in July and August 2021. Ongoing surveillance and sustained outpatient antibiotic stewardship efforts are needed to optimize antibiotic use during the COVID-19 pandemic and beyond.

Funding: None

Disclosures: None
Work system barriers to & resilience strategies for COVID-19 PPE use in the emergency department: A qualitative interview study
Authors: Daodu Oluseyi , Gurses Ayse , Osei Patience , Nosakhare Esosa , Perry Shawna , Sultan Marium , Prabhu Nivedha , Peterson Susan , MacIntyre Emma , Vo Khue , Yuan Lauren , Benishek Lauren , Li Jessica
Published: May 2022

Background: Emergency departments (EDs) are complex, sociotechnical, high-paced, safety-critical work systems that have been disproportionately affected by the COVID-19 pandemic. Despite training, consistent compliance with recommended PPE use during COVID-19 pandemic has been challenging. Healthcare workers (HCWs) have had adapt to overcome these challenges to ensure their own safety and patient safety. We sought to identify barriers in the work system that impede the recommended COVID-19 PPE use in EDs. Methods: We conducted semistructured, in-depth interviews over ZoomTM from August 2020–May 2021 with 45 HCWs from the ED (ie, physicians, nurses, ancillary support staff, etc) affiliated with a large, tertiary-care, academic medical center. These audio-recorded interviews were transcribed and analyzed using a hybrid (inductive and deductive) qualitative coding approach in NVivo software. The deductive portion was guided by the SEIPS work system model, a well-known human-factors conceptual framework. Results: We identified multiple work-system factors in the ED that impede compliance with the recommended COVID-19 PPE use. In addition, ED HCWs have reported making a variety of adaptations or developing strategies to overcome these barriers. Some of these adaptations were made to the PPE physically (eg, trimming portions of PPE), and others were related to the tasks and/or processes associated with PPE, such as filming their own training video demonstrating PPE donning and doffing techniques, and environment services staff checking a patient’s status with nurses prior to entering the patient’s room when there was no COVID-19 signage on the door. Conclusions: Consistent compliance with COVID-19 PPE use in ED clinical practice is challenging and can be negatively affected by a variety of work system factors. Resilience strategies developed by HCWs can provide critical information with regards to HCW needs and potential directions for innovation. Future efforts should focus on not only changing individual HCW behavior through training but also on improving the PPE and ED work system design.

Funding: US CDC

Disclosures: The authors gratefully acknowledge the US CDC for funding this work. This material is based upon work supported by the Naval Sea Systems Command (under contract no. N00024-13-D-6400, task order NH076). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the Naval Sea Systems Command (NAVSEA) or the US CDC.
Effecting the culture: Impact of changing urinalysis with reflex culture criteria on culture rates and outcomes
Authors: Penney Jessica , Rodday Angie , Sebastiani Paola , Snydman David , Doron Shira
Published: May 2022

Background: Urinalysis and urine culture are frequently ordered diagnostic tests among hospitalized patients, often for nonspecific symptoms. Diagnostic testing stewardship with urinalysis with reflex culture (UARC) is a practice shown to reduce institutional culture rates by selecting patients who are more likely to have a true infection. Optimal reflex criteria are not well established, and downstream effects, such as antibiotic use, have not been well studied. Methods: We compared outcomes in the preimplementation period (December 2018 – October 2019) and postintervention period (November 2019–October 2020) at an academic medical center. The intervention was changing the UARC reflex criteria. The primary outcomes were urine-culture rate per 1,000 patient days, urine-culture positivity, antibiotic prescription for suspected urinary tract infection (UTI) and catheter-associated urinary tract infection (CAUTI) rate per 1,000 Foley catheter days. Analysis was performed using interrupted time-series negative binomial regression or Poisson regression where appropriate. Results: We detected a significant decrease in the rate of cultures performed (32.5 cultures per 1,000 patient days before the intervention vs 8.6 cultures per 1,000 patient days after the intervention; P = 0.10). Fig. 1 summarizes these results graphically. In an adverse events analysis, of 646 patients in the postintervention period, 130 patients were reviewed for the outcome of sepsis secondary to a urinary tract infection, with only 1 patient meeting criteria for this diagnosis. Conclusions: Changing the UARC reflex criteria resulted in the expected decrease in rate of cultures performed with increase in culture positivity, and the stricter criteria appeared to more effectively identify true UTIs. Minimal adverse events were associated with the UARC criteria change, demonstrating that these criteria are also safe. We detected a significant change in antibiotic prescriptions, but much of the decrease occurred during the preintervention period, which likely reflected educational and stewardship interventions performed at that time. Although the intervention affected culture performance, which does decrease institutional costs, continued provider education is needed to influence clinical outcomes.

Funding: None

Disclosures: None
B-Cell-Directed Therapies: A New Era in Multiple Sclerosis Treatment
Authors: Kanatas Panagiotis , Stouras Ioannis , Stefanis Leonidas , Stathopoulos Panos
Published: May 2022

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that often progresses to severe disability. Previous studies have highlighted the role of T cells in disease pathophysiology; however, the success of B-cell-targeted therapies has led to an increased interest in how B cells contribute to disease immunopathology. In this review, we summarize evidence of B-cell involvement in MS disease mechanisms, starting with pathology and moving on to review aspects of B cell immunobiology potentially relevant to MS. We describe current theories of critical B cell contributions to the inflammatory CNS milieu in MS, namely (i) production of autoantibodies, (ii) antigen presentation, (iii) production of proinflammatory cytokines (bystander activation), and (iv) EBV involvement. In the second part of the review, we summarize medications that have targeted B cells in patients with MS and their current position in the therapeutic armamentarium based on clinical trials and real-world data. Covered therapeutic strategies include the targeting of surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) and CD19 (inebilizumab), and molecules necessary for B-cell activation such as B cell activating factor (BAFF) (belimumab) and Bruton’s Tyrosine Kinase (BTK) (evobrutinib). We finally discuss the use of B-cell-targeted therapeutics in pregnancy.
Distinguishing subaerial and submarine calving with underwater noise
Authors: Glowacki Oskar
Published: May 2022

Iceberg calving is one of the major mechanisms of ice loss from tidewater glaciers and ice sheets, but obtaining accurate estimates of ice discharge that are both continuous and accurate is a challenging task. Recent results have demonstrated the effective application of passive cryoacoustics – the use of naturally generated sounds to study the cryosphere – to quantify subaerial calving fluxes. However, little is known about the acoustic signatures of submarine calving. This study investigates the underwater noise from 656 subaerial and 162 submarine calving events observed at Hansbreen, Svalbard in the summers of 2016 and 2017. Statistical analysis of the acoustic signal shows that the normalized power of the calving noise is log-normally distributed regardless of the calving mode. However, submarine events can be distinguished from subaerial events by using the shape parameter of the log-normal distribution paired with the calving signal duration. The newly developed classification model may potentially be used for two purposes: (1) to study potential causal relationships between these two calving modes and (2) to separate calving fluxes into subaerial and submarine components. The latter will also require knowledge of the relationship between ice mass and sound spectral level for submarine calving events.