bluuebunny/crossref_metadata_2025 huggingface dataset:
Causes of Outcome Learning: a causal inference-inspired machine learning approach to disentangling common combinations of potential causes of a health outcome
Authors: Rieckmann Andreas , Dworzynski Piotr , Arras Leila , Lapuschkin Sebastian , Samek Wojciech , Arah Onyebuchi Aniweta , Rod Naja Hulvej , Ekstrøm Claus Thorn
Published: April 2022

Nearly all diseases are caused by different combinations of exposures. Yet, most epidemiological studies focus on estimating the effect of a single exposure on a health outcome. We present the Causes of Outcome Learning approach (CoOL), which seeks to discover combinations of exposures that lead to an increased risk of a specific outcome in parts of the population. The approach allows for exposures acting alone and in synergy with others. The road map of CoOL involves (i) a pre-computational phase used to define a causal model; (ii) a computational phase with three steps, namely (a) fitting a non-negative model on an additive scale, (b) decomposing risk contributions and (c) clustering individuals based on the risk contributions into subgroups; and (iii) a post-computational phase on hypothesis development, validation and triangulation using new data before eventually updating the causal model. The computational phase uses a tailored neural network for the non-negative model on an additive scale and layer-wise relevance propagation for the risk decomposition through this model. We demonstrate the approach on simulated and real-life data using the R package ‘CoOL’. The presentation focuses on binary exposures and outcomes but can also be extended to other measurement types. This approach encourages and enables researchers to identify combinations of exposures as potential causes of the health outcome of interest. Expanding our ability to discover complex causes could eventually result in more effective, targeted and informed interventions prioritized for their public health impact.
Risk factors for Ebola virus disease among household care providers, Sierra Leone, 2015
Authors: Duffy Nadezhda , Bruden Dana , Thomas Harold , Nichols Erin , Knust Barbara , Hennessy Thomas , Reichler Mary R ,   and the Household Transmission Investigative Team, Bangura James , Keimbe Charles , Jambai Amara , Morgan Oliver , Farmar Ismail , Davies Francis , Dumbuya Mohamed Sima , Kamara Hannah , Kallon Mohamed , Kpukumu Joseph , Abu Sheku , Bangura Fatmata , Bangura Saidu Rahim , Bangura Tomeh , Benya Hassan , Blango Sandi , Conteh Imurana , Conteh Peter , Jabbie Bintu , Jabbie Sheku , Kamara Luseni , Lansana Francis , Rogers Maada , Sewa Sahr Brima , Yamba Matthew , Bessler P , Washburn Faith , Ervin E , Campbell S , Chung W , Hersey S
Published: April 2022

Background

Household contacts who provide care to an Ebola virus disease (EVD) case have a 3-fold higher risk of EVD compared with contacts who do not provide care.

Methods

We enrolled persons with confirmed EVD from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index cases and contacts were interviewed, and contacts were followed for 21 days to identify secondary cases. Epidemiological data were analysed to describe household care and to identify risk factors for developing EVD.

Results

Of 838 contacts in 147 households, 156 (17%) self-reported providing care to the index case; 56 households had no care provider, 52 a single care provider and 39 multiple care providers. The median care provider age was 29 years, 68% were female and 32% were the index case’s spouse. Care providers were more likely to report physical contact, contact with body fluids or sharing clothing, bed linens or utensils with an index case, compared with non-care providers (P <0.01). EVD risk among non-care providers was greater when the number of care providers in the household increased (odds ratio: 1.61; 95% confidence interval: 1.1, 2.4). In multivariable analysis, factors associated with care provider EVD risk included no piped water access and absence of index case fever, and protective factors included age <20 years and avoiding the index case.

Conclusions

Limiting the number of care providers in a household could reduce the risk of EVD transmission to both care providers and non-care providers. Strategies to protect care providers from EVD exposure are needed.
Long-term exposure to ambient fine particulate matter (PM2.5) and associations with cardiopulmonary diseases and lung cancer in Taiwan: a nationwide longitudinal cohort study
Authors: Lo Wei-Cheng , Ho Chi-Chang , Tseng Eva , Hwang Jing-Shiang , Chan Chang-Chuan , Lin Hsien-Ho
Published: April 2022

Background

Although a number of studies have reported on the health effects of fine particulate matter (PM2.5) exposure, particularly in North American and European countries as well as China, the evidence about intermediate to high levels of PM2.5 exposures is still limited. We aimed to investigate the associations between long-term exposure to PM2.5 and risk of cardiopulmonary disease incidence in Taiwan with intermediate levels of PM2.5 exposure.

Methods

A cohort of Taiwanese adults, who participated in the 2001, 2005, 2009 and 2013 National Health Interview Surveys, was followed through 2016 to identify cardiopulmonary disease onset. Exposure to PM2.5 was estimated by incorporating a widespread monitoring network of air quality monitoring stations and microsensors. We used time-dependent Cox regression models to examine the associations between the PM2.5 exposures and health outcomes, adjusting for individual characteristics and ecological covariates. The natural cubic spline functions were used to explore the non-linear effects of the PM2.5 exposure.

Results

A total of 62 694 adults from 353 towns were enrolled. Each 10-μg/m3 increase in 5-year average exposure to PM2.5 was associated with a 4.8% increased risk of incident ischaemic heart disease (95% CI: -3.3, 13.6), 3.9% increased risk of incident stroke (95% CI: -2.9, 11.1), 6.7% increased risk of incident diabetes (95% CI: 1.1, 12.7), 15.7% increased risk of incident lung cancer (95% CI: -0.9, 35.1) and 11.5% increased risk of incident chronic obstructive pulmonary disease (95% CI: -0.8, 25.2). The concentration-response curve showed that there was no statistical evidence of non-linearity for most of the disease outcomes except for ischaemic heart disease (P for non-linearity = 0.014).

Conclusions

Long-term exposure to intermediate levels of ambient PM2.5 was associated with cardiopulmonary health outcomes. Our study adds value to future application and national burden of disease estimation in evaluating the health co-benefits from ambient air pollution reduction policy in Asian countries.
Immunosuppressants contribute to a reduced risk of Parkinson’s disease in rheumatoid arthritis
Authors: Guo Xingzhi , Chong Li , Zhang Xin , Li Rui
Published: April 2022

Background

Observational studies have suggested a decreased risk of Parkinson’s disease (PD) in patients with rheumatoid arthritis (RA). However, the results are controversial and the biological mechanism underlying this effect remains largely unknown.

Methods

The effect sizes of five observational studies were summarized to determine the association between RA and PD. A two-step Mendelian randomization (TSMR) analysis was conducted using genome-wide association studies data sets of RA, PD and prescription of non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (IS) and glucocorticoids (GC). A multivariable MR (MVMR) was also performed to verify the impact of prescription history on PD risk.

Results

Integrated data from observational studies showed that RA was associated with a decreased risk of PD in the European population (effect size = –0.38, P = 0.004). We found that genetically predicted RA was correlated with a decreased risk of PD [odds ratio (OR) = 0.91, P = 0.007]. In the TSMR, RA patients tended to have an increased prescription of GC (OR = 1.16, P = 2.96e − 07) and IS (OR = 1.77, P = 5.58e − 64), which reduced the risk of PD (GC: OR = 0.86, P = 0.0270; IS: OR = 0.82, P = 0.0277), respectively. Further MVMR analysis demonstrated that only IS was linked to a decreased risk of PD (OR = 0.86, P = 0.004).

Conclusion

This work clarified that patients with RA had a decreased risk of PD, which was partially attributed to the use of IS in RA patients but not GC or NSAIDs.
Dynamic analysis of biodiversity, carbon storage and environmental factors of coniferous forest in Loudi City, Hunan Province
Authors: Zhou You , She Jiyun , Zhu Xiongmei
Published: April 2022

The analyzation of the dynamics of biodiversity, carbon storage and environmental factors of coniferous forest in Loudi, Hunan Province is meaningful, and the determination of the aboveground and underground carbon storage, plant diversity and environmental factors of multiple plant communities in Loudi, Hunan Province among different succession stage is of great significance to effectively clarify the distribution of plant diversity and carbon storage in coniferous forests along the succession gradient, to clarify the influence of environmental factors on carbon storage, and to quantify the relationship between carbon storage and plant diversity. This article selected the natural growth of subalpine coniferous forest in Loudi, Hunan Province from 5 to 60 years as the research objective and compared the species richness (S), plant diversity (S) and other information. The results showed that the carbon pools of aboveground and underground ecosystems of several plant communities are significantly different during vegetation restoration, and there is a functional relationship between plant diversity and carbon storage. The aboveground carbon content increased several times, and the soil organic carbon (SOC) content increased from the herbaceous community type to the mixed forest type, constituting the main carbon pool of the system (63–89%) and then decreased. The average carbon storage of the whole ecosystem was between 105 and 730 Mg C ha−1. In addition, it was also found that root biomass and litter C/N ratio had significant effects on SOC. Path analysis also showed that the C/N ratio of litter was mainly regulated by the changes of microbial population and soil invertase activity. The research of this project is of positive significance to deepen the understanding of coniferous forest biodiversity and corresponding conservation measures.
Effect of desiccation on ashcrete (HSDA)-treated soft soil used as flexible pavement foundation: zero carbon stabilizer approach
Authors: Onyelowe Kennedy C , Tome Sylvain , Ebid Ahmed M , Usungedo Thompson , Bui Van Duc , Etim Roland K , Onuoha Ifeanyi C , Attah Imoh C
Published: April 2022

The potential of using ashcrete to improve the microstructural, microspectral and shrinkage properties of expansive soils has been investigated under laboratory conditions. In addition to microstructural, three chemical modulus (TCM) and microspectral examinations, responses to linear shrinkage, volumetric shrinkage and crack width were also investigated using 30-day drying periods for expansive soil treated with ash cement. Moisture-related infrastructures such as the sub-floor of resilient pavements are prone to moisture by the rise and fall of the water table during seasonal changes. Therefore, the effect of soil improvement on soil morphology, chemical content and microspectral patterns was investigated. The soil was classified and characterized as (A-7-6) high plasticity soil and poor classification conditions. The hybrid sawdust ash (SDA) known as ashcrete, which has zero carbon footprint was obtained by activating SDA by mixing it with a reformulated activator material (a mixture of 8 M NaOH and a solution of NaSiO2 in a 1:1 ratio). The zero carbon cement was further used in percent-by-weight proportions of 3, 6, 9 and 12 for the soil improvement. X-ray fluorescence (XRF) and scanning electron microscopy (SEM) experiments were carried out to evaluate the pozzolanic resistance via the chemical composition of the oxide, TCM and the profile of the surface contour of the additives and the soil. XRF exposures revealed that the additives had lower pozzolanic resistance, which increased with the improved mixtures thus forming an improved soil mass. In addition, it showed that TCM silica moduli dominated soil stabilization with ashcrete. Scanning electron microscopy examination showed an increase in soil-ettringite and gel formation with the addition of ashcrete. Also, the microspectral studies of chemical oxide EDXRF and XRD have shown excellent results at 12 mass percent cement and soil cement, which has optimized aluminosilicate formation more than 70% and formation of calcite and quartz that has shown the potential of a zero carbon stabilization geomaterial ash cement as a good complementary binder.
Skin Tones and Polarized Politics: How Skin Color Differences Between Interviewers and Respondents Influence Survey Answers in Bolivia
Authors: Blanchard Maxime
Published: April 2022

American scholarship claims that the racial make-up of interviews influences the attitudes disclosed in public opinion surveys. It remains unclear whether such an effect travels to other cases where racial cleavages are less salient, and whether it affects all respondents. We address these gaps by using a flexible approach focusing on skin tone rather than race. Relying on survey data from Bolivia, where polarization maps onto ethnic lines, we investigate whether the skin color difference between an interviewer and a respondent influences the latter’s answers. Building on the race-of-interviewer effect and colorism literatures, this article investigates the effect of the skin color dynamic of interviews by leveraging the random interviewer-to-respondent assignment process of LAPOP surveys. The results suggest that nonresponses are more likely in cross-skin tone interviews and that respondents questioned by interviewers of lighter skin tone than them will express opinions that more closely align with the stereotypical opinions of the interviewer than if their interviewer shared their skin tone. This article contributes to the interviewer effect literature by testing the competing claims of the social distance and social acquiescence theories, along with providing an adaptation of the race-of-interviewer effect to cases that are not polarized along racial lines.
Multicentre prospective observational study on community pharmacist interventions to reduce inappropriate medications
Authors: Uchida Mayako , Suzuki Shinya , Sugawara Hideki , Suga Yukio , Nakagawa Takayuki , Takase Hisamitsu
Published: April 2022

Objectives

The status of community pharmacists’ involvement in inappropriate prescription practices among outpatients who visit community pharmacies has not been reported in Japan. Therefore, this study described community pharmacists’ interventions aimed at the discontinuation of inappropriate drugs or the reduction of drug doses.

Methods

We conducted a multicentre prospective observational study of pharmacists’ interventions on inappropriate prescriptions for outpatients during a 1-month period in September 2018. A total of 28 pharmacists from 28 community pharmacies in Japan participated in this study. We analysed cases in which pharmacists discontinued drugs or changed the doses due to drugs being inappropriate, adverse effects, duplication of pharmacological effects and drug–drug interactions.

Key findings

Community pharmacists provided interventions for 736 patients at an average of 26.2 patients per day during the study period. The pharmacists recommended that doctors discontinue inappropriate drugs or reduce the doses of regular drugs for 103 patients (13.9%). Among the 107 pharmacist recommendations to decrease inappropriate prescriptions, 83 (77.6%) were accepted, including 62 cases of discontinuation (57.9%) and 21 of drug dose reduction (19.6%). A total of 122 drugs were discontinued according to pharmacists’ recommendations. In addition, pharmacists’ intervention improved sleepiness, sedation and cognitive function.

Conclusions

This study shows the active involvement of community pharmacists in polypharmacy by discontinuing inappropriate drugs or reducing the dose of regular drugs, which may contribute to the improvement of adverse effects among outpatients.
Reach control problem for a class of convex differential inclusions on simplices
Authors: Lv Dejing , Ge Bin , Wu Mingze
Published: April 2022

This paper focuses on the reach control problem for systems expressed as a class of convex differential inclusions. The purpose is to find affine feedback for the trajectories of the systems to reach and leave an unrestricted facet of a given simplex in a finite time. It is proved that the condition for strong reachability is sufficient and necessary. The sufficient condition for weak reachability is obtained based on the solvability of the reach control problem for linear affine systems. At last, algorithms are designed and numerical examples are given to verify the validity of the results.
A sequential optimality condition for Mathematical Programs with equilibrium constraints based on a nonsmooth formulation
Authors: Helou Elias S , Santos Sandra A , Simões Lucas E A
Published: April 2022

Explicitly nonsmooth reformulations of mathematical programs with equilibrium constraints (MPEC) described by smooth functions are investigated. A sequential optimality condition ($\epsilon $-ANOC) previously developed for nonsmooth optimization problems is adapted to suit the reformulations under analysis. Relationships between $\epsilon $-ANOC and sequential optimality conditions especially crafted for MPEC are established. It is revealed that approaches developed for nonsmooth optimization improve the understanding of smooth problems with ill-conditioned geometries, which is the case for MPEC. Moreover, based on the availability of algorithms capable of generating $\epsilon $-ANOC sequences, illustrative experiments are reported in which difficult problems are successfully solved.
Special Cubic Four-Folds, K3 Surfaces, and the Franchetta Property
Authors: Fu Lie , Laterveer Robert
Published: April 2022

O’Grady conjectured that the Chow group of 0-cycles of the generic fiber of the universal family over the moduli space of polarized K3 surfaces of genus $g$ is cyclic. This so-called generalized Franchetta conjecture has been solved only for low genera where there is a Mukai model (precisely, when $g\leq 10$ and $g=12, 13, 16, 18, 20$), by the work of Pavic–Shen–Yin. In this paper, as a non-commutative analogue, we study the Franchetta property for families of special cubic four-folds (in the sense of Hassett) and relate it to O’Grady’s conjecture for K3 surfaces. Most notably, by using special cubic four-folds of discriminant 26, we prove O’Grady’s generalized Franchetta conjecture for $g=14$, providing the first evidence beyond Mukai models.
Rigidity of Lagrangian embeddings into symplectic tori and K3 surfaces
Authors: Entov Michael , Verbitsky Misha
Published: April 2022

A Kähler-type form is a symplectic form compatible with an integrable complex structure. Let $M$ be either a torus or a K3-surface equipped with a Kähler-type form. We show that the homology class of any Maslov-zero Lagrangian torus in $M$ has to be nonzero and primitive. This extends previous results of Abouzaid and Smith (for tori) and Sheridan and Smith (for K3-surfaces) who proved it for particular Kähler-type forms on $M$. In the K3 case, our proof uses dynamical properties of the action of the diffeomorphism group of $M$ on the space of the Kähler-type forms. These properties are obtained using Shah’s arithmetic version of Ratner’s orbit closure theorem.
Set Partitions, Fermions, and Skein Relations
Authors: Kim Jesse , Rhoades Brendon
Published: April 2022

Let $\Theta _n = (\theta _1, \dots , \theta _n)$ and $\Xi _n = (\xi _1, \dots , \xi _n)$ be two lists of $n$ variables, and consider the diagonal action of ${{\mathfrak {S}}}_n$ on the exterior algebra $\wedge \{ \Theta _n, \Xi _n \}$ generated by these variables. Jongwon Kim and the 2nd author defined and studied the fermionic diagonal coinvariant ring$FDR_n$ obtained from $\wedge \{ \Theta _n, \Xi _n \}$ by modding out by the ideal generated by the ${{\mathfrak {S}}}_n$-invariants with vanishing constant term. On the other hand, the 2nd author described an action of ${{\mathfrak {S}}}_n$ on the vector space with basis given by noncrossing set partitions of $\{1,\dots ,n\}$ using a novel family of skein relations that resolve crossings in set partitions. We give an isomorphism between a natural Catalan-dimensional submodule of $FDR_n$ and the skein representation. To do this, we show that set partition skein relations arise naturally in the context of exterior algebras. Our approach yields an ${{\mathfrak {S}}}_n$-equivariant way to resolve crossings in set partitions. We use fermions to clarify, sharpen, and extend the theory of set partition crossing resolution.
Mortality Associated With Respiratory Syncytial Virus, Bronchiolitis, and Influenza Among Infants in the United States: A Birth Cohort Study From 1999 to 2018
Authors: Reichert Heidi , Suh Mina , Jiang Xiaohui , Movva Naimisha , Bylsma Lauren C , Fryzek Jon P , Nelson Christopher B
Published: April 2022

Background

Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood.

Methods

From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants <1 year using linked birth/death datasets from the National Vital Statistics System. Mortality was described overall and by infant birth and death characteristics. Bronchiolitis was included as the plausible upper limit of RSV, while influenza served as a comparator.

Results

Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4–7.5), 19.8 (95% CI, 18.9–20.8), and 6.2 (95% CI, 5.7–6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among <29 weeks’ gestational age infants (103.5; 95% CI, 81.8–129.1), American Indian/Alaskan Native (20.3; 95% CI, 11.6–33.0), and Medicaid-insured (7.3; 95% CI, 5.9–8.9). However, RSV mortality burden was greatest in full-term (53.7%), white (44.9%), and Medicaid-insured (61.7%) infants. Deaths outside the inpatient setting were 21% and 54% for RSV and bronchiolitis; more Medicaid- (58%) and other/unknown-insured (69%) infants with bronchiolitis died outside of the inpatient setting, compared to privately insured infants (48%) (P = .0327).

Conclusions

These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.
Breakthrough Gastrointestinal COVID-19 and Intrahost Evolution Consequent to Combination Monoclonal Antibody Prophylaxis
Authors: Beddingfield Brandon J , Rowe Lori A , Russell-Lodrigue Kasi E , Doyle-Meyers Lara A , Golden Nadia , Spencer Skye , Chirichella Nicole , Blair Robert V , Maness Nicholas J , Roy Chad J
Published: April 2022

Breakthrough gastrointestinal COVID-19 was observed after experimental SARS-CoV-2 upper mucosal infection in a rhesus macaque undergoing low-dose monoclonal antibody prophylaxis. High levels of viral RNA were detected in intestinal sites contrasting with minimal viral replication in upper respiratory mucosa. Sequencing of virus recovered from tissue in 3 gastrointestinal sites and rectal swab revealed loss of furin cleavage site deletions present in the inoculating virus stock and 2 amino acid changes in spike that were detected in 2 colon sites but not elsewhere, suggesting compartmentalized replication and intestinal viral evolution. This suggests suboptimal antiviral therapies promote viral sequestration in these anatomies.
Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review
Authors: Chen Chen , Haupert Spencer R , Zimmermann Lauren , Shi Xu , Fritsche Lars G , Mukherjee Bhramar
Published: April 2022

Background

This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis.

Methods

PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection.

Results

Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39–.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44–.63) and 0.34 (95% CI, .25–.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37–.65), Europe (0.44; 95% CI, .32–.56), and United States of America (0.31; 95% CI, .21–.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26–.49), 0.25 (95% CI, .15–.38), 0.32 (95% CI, .14–.57), and 0.49 (95% CI, .40–.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17–.30), followed by memory problems (0.14; 95% CI, .10–.19).

Conclusions

This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system.
Impact of Preexisting Anti–Adenovirus 26 Humoral Immunity on Immunogenicity of the Ad26.COV2.S Coronavirus Disease 2019 Vaccine
Authors: Le Gars Mathieu , Sadoff Jerald , Struyf Frank , Heerwegh Dirk , Truyers Carla , Hendriks Jenny , Gray Glenda , Grinsztejn Beatriz , Goepfert Paul A , Schuitemaker Hanneke , Douoguih Macaya
Published: April 2022

This secondary analysis of the phase 3 ENSEMBLE trial (NCT04505722) assessed the impact of preexisting humoral immunity to adenovirus 26 (Ad26) on the immunogenicity of Ad26.COV2.S-elicited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibody levels in 380 participants in Brazil, South Africa, and the United States. Among those vaccinated in Brazil and South Africa, 31% and 66%, respectively, had prevaccination serum-neutralizing activity against Ad26, with little preexisting immunity detected in the United States. Vaccine recipients in each country had similar postvaccination spike (S) protein–binding antibody levels, indicating that baseline immunity to Ad26 has no clear impact on vaccine-induced immune responses.
SARS-CoV-2 Infection Causes Hyperglycemia in Cats
Authors: Zhang Yufei , Gao Jindong , Huang Kun , Zhao Ya , Hui Xianfeng , Wang Ting , Hu Changmin , Sun Xiaomei , Yang Ying , Wu Chao , Chen Xi , Zou Zhong , Zhao Lian zong , Jin Meilin
Published: April 2022

Isolated reports of new-onset diabetes in patients with coronavirus disease 2019 (COVID-19) have led researchers to hypothesize that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human exocrine and endocrine pancreatic cells ex vivo and in vivo. However, existing research lacks experimental evidence indicating that SARS-CoV-2 can infect pancreatic tissue. Here, we found that cats infected with a high dose of SARS-CoV-2 exhibited hyperglycemia. We also detected SARS-CoV-2 RNA in pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in islet cells. SARS-CoV-2 NP and spike proteins were primarily detected in glucagon-positive cells, and most glucagon-positive cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that blood glucose levels of immunized cats did not increase postchallenge. Our data indicate cat pancreas as a SARS-CoV-2 target and suggest that the infection of glucagon-positive cells could contribute to the metabolic dysregulation observed in SARS-CoV-2–infected cats.
A Recombinant Alpha-Like Protein Subunit Vaccine (GBS-NN) Provides Protection in Murine Models of Group B Streptococcus Infection
Authors: Brokaw Alyssa , Nguyen Shayla , Quach Phoenicia , Orvis Austyn , Furuta Anna , Johansson-Lindbom Bengt , Fischer Per B , Rajagopal Lakshmi
Published: April 2022

Background

Group B Streptococcus (GBS) transmission during pregnancy causes preterm labor, stillbirths, fetal injury, or neonatal infections. Rates of adult infections are also rising. The GBS-NN vaccine, engineered by fusing N-terminal domains of GBS Alpha C and Rib proteins, is safe in healthy, nonpregnant women, but further assessment is needed for use during pregnancy. Here, we tested GBS-NN vaccine efficacy using mouse models that recapitulate human GBS infection outcomes.

Methods

Following administration of GBS-NN vaccine or adjuvant, antibody profiles were compared by ELISA. Vaccine efficacy was examined by comparing infection outcomes in GBS-NN vaccinated versus adjuvant controls during systemic and pregnancy-associated infections, and during intranasal infection of neonatal mice following maternal vaccination.

Results

Vaccinated mice had higher GBS-NN–specific IgG titers versus controls. These antibodies bound alpha C and Rib on GBS clinical isolates. Fewer GBS were recovered from systemically challenged vaccinated mice versus controls. Although vaccination did not eliminate GBS during ascending infection in pregnancy, vaccinated dams experienced fewer in utero fetal deaths. Additionally, maternal vaccination prolonged neonatal survival following intranasal GBS challenge.

Conclusions

These findings demonstrate GBS-NN vaccine efficacy in murine systemic and perinatal GBS infections and suggest that maternal vaccination facilitates the transfer of protective antibodies to neonates.
Buying influence? Rotating leadership in ASEAN and allocation of Chinese foreign aid
Authors: Lim Taegyun , Kim Sung Eun
Published: April 2022

China has expanded its economic footprint in Southeast Asian countries by providing a growing amount of development finance to the region. We examine the allocation of Chinese foreign aid toward Southeast Asian countries exploiting the exogenous variation of rotating leadership within Association of Southeast Asian Nation (ASEAN). As the ASEAN Chair possesses the agenda-setting power and represents the organization, China strategically allocates more development aid to the ASEAN Chair to augment its influence in the region. Our analysis of Chinese aid allocation between 2000 and 2017 finds that taking the leadership position at ASEAN appears to be significantly associated with an increase of official development aid flows from China, while other commercial flows are only weakly associated with the leadership position. Our findings underscore the importance of considering the regional context in examining foreign aid allocation and show that a donor can target a regional organization to exert its political influence in the region.
Solidarity through Cynicism? The Influence of Russian Conspiracy Narratives Abroad
Authors: Radnitz Scott
Published: April 2022

As conspiracy theories have become a popular form of political discourse worldwide, states have promoted conspiratorial ideas to advance their foreign policy goals. Yet, despite recent attention to the spread of propaganda abroad, scholars have not addressed whether and how conspiracy theories spread across borders. This study assesses this question in the post-Soviet region, by examining the relationship between exposure to Russian state propaganda and belief in conspiracy theories in two countries that border the Russian Federation. Analyzing data from an original survey of Georgia and Kazakhstan indicates that exposure to Russian propaganda through television, social media, or websites has minimal effects on respondents’ endorsement of conspiracy theories. Respondents in Kazakhstan, and especially ethnic Russians, are likely to endorse pro-Russian conspiracy claims that are frequently propagated, owing to preexisting affinities. Yet the most consistent predictor of conspiracy beliefs is alienation from the political system, which occurs independent of foreign media consumption. The findings cast doubt on the ability of states to shape the attitudes of citizens abroad through the media and shine light on the domestic political factors underlying belief in conspiracy theories.
Start with the Human, Technology Comes Later: Values for the Digital Transformation of Peacekeeping
Authors: Hall Lynne , Paracha Samiullah , Hagan-Green Gillian
Published: April 2022

As the United Nations inevitably embarks on the digital transformation of peacekeeping, it raises key questions—‘technology’ or ‘human’ first. This paper argues that narrowly focusing on technical solutions may move this world body closer to a modern infrastructure, but misses it opportunities for bigger, more impactful peacekeeping process improvement. Whereas, starting with ‘humans’ or peacekeepers, their goals and pain points and the context of their interactions, means that solutions are targeting meaningful outcomes, not just new software. Using the value sensitive design approach to technology design, the paper extends its application to peacekeeping by integrating human values and the values instantiated in existing or imagined technical designs. These values were distilled out of a mixed methods study carried out at a peace mission deployed in Africa. Analysis identified four horizontal themes (positive UX, integration, connectivity and privacy) across three use contexts (workplace productivity, personal physical safety and well-being). Core values were being safe, family connection, doing work well and being cared for by their organization. Such human-centred technological interventions will enhance the needed capabilities for the peacekeeping forces to win when they need to and to safely enforce lasting peace in a dominant but non-violent fashion where possible.
Playing With Embodied Social Interaction: A Thematic Review of Experiments on Social Aspects in Gameful Virtual Reality
Authors: Bujić Mila , Macey Anna-Leena , Järvelä Simo , Hamari Juho
Published: April 2022

Recently, there has been a burgeoning of immersive virtual reality (VR) applications in a variety of shapes, including gameful social VR. Despite a longstanding tradition of studying social factors in gameful computing, this perspective in the specific experiences of VR is only gaining traction. This highly multidisciplinary area of interest is immensely complex with potential consequences on individuals and social groups alike. To aid in constituting and systematizing this area of research from the early days, this paper explores 14 state-of-art publications on experimental research of social aspects in gameful VR. These were analysed predominantly based on the included manipulations and the studied outcomes resulting in the extraction of five and seven thematic wholes, respectively. Finally, based on the findings, four broad avenues to consider were emphasized as suggested paths for a comprehensive future of embodied gameful social VR application and research across a variety of disciplines.
Musical works, types and modal flexibility reconsidered
Authors: Puy Nemesio García-Carril
Published: April 2022

Guy Rohrbaugh and Allan Hazlett have provided two arguments against the thesis that musical works are types. In short, they assume that, according to our modal talk and intuitions, musical works are modally flexible entities; since types are modally inflexible entities, musical works are not types. I argue that Rohrbaugh’s and Hazlett’s arguments fail and that the type/token theorist can preserve the truth of our modal claims and intuitions even if types are modally inflexible entities. First, I consider two alternatives for the type/token theorist proposed in recent literature about the topic: the created types’ solution and the created abstract objects’ solution. I argue that none of them is attractive for the type/token theorist because they do not preserve the theoretical advantages of type/token theories to explain musical works’ repeatable nature. Then, I focus on the arguments’ common premise that musical works are modally flexible entities. A deeper analysis of musical practice will show that this premise is not true: our modal claims do not imply that musical works could have had different intrinsic but, instead, extrinsic properties. Finally, I show how the nested types theory may offer a satisfactory explanation of this fact and how it captures the truth of our modal talk about musical works.
Mormon-ish: Negotiating Religious Ambivalence Online
Authors: Tobey Kristen
Published: April 2022

Reporting on responses from a survey of disaffected Mormons who utilize internet resources to manage feelings of distance from the Church of Jesus Christ of Latter-day Saints, this article explores the production of religious ambivalence online, arguing that ambivalence is not a default position for those too passive or afraid to leave, nor is it a failure of decisiveness or commitment. Rather, it is a produced religious mode that depends on robust socialization mechanisms to result in a strong sense of personal and collective identity. The online context enables, and indeed requires, an operationalization of religious ambivalence as both a socialization mechanism and a socialization outcome. Site users participate in a process of affective encapsulation, which both echoes and reshapes familiar Church of Jesus Christ of Latter-day Saints tropes and practices and allows them to fashion a new understanding of Mormon identity with uncertainty at its center.
Antimicrobial peptide WAM-1: a promising antibacterial and anti-inflammatory drug against carbapenem-resistant Klebsiella pneumoniae
Authors: Zhang Xiaodong , Shi Shiyi , Yao Zhuocheng , Zheng Xiangkuo , Li Wangyang , Zhang Ying , Wang Lingbo , Cao Jianming , Zhou Tieli
Published: April 2022

Background

The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a threat to public health. Antimicrobial peptides provide a new treatment option for CRKP infections.

Objectives

We studied antibacterial activities of WAM-1 against CRKP in vitro and in vivo and explored its possible mechanism. We verified safety and factors affecting antibacterial effect. Furthermore, anti-inflammatory effects were investigated.

Methods

We selected eight CRKP and eight carbapenem-susceptible K. pneumoniae to explore the antibacterial activity of WAM-1 by broth microdilution (BMD). The possible mechanism was investigated by alkaline phosphatase leakage and propidium iodide (PI). We evaluated safety of WAM-1 by cytotoxicity and haemolysis and effects of temperature and serum on the antibacterial activity. We investigated in vivo efficacy of WAM-1 by the Galleria mellonella infection model. We investigated the effect of WAM-1 on TNF-α.

Results

BMD showed that WAM-1 had a good antibacterial effect with MICs of 2–4 mg/L and MBCs of 4–8 mg/L. RT–qPCR showed that WAM-1 could inhibit the expression of TNF-α. The cytotoxicity and haemolysis test proved that WAM-1 had certain potential application in vivo. Alkaline phosphatase leakage and PI fluorescence showed that WAM-1 was highly likely to exert an antibacterial effect by destroying bacterial membrane. The G. mellonella infection model suggested that WAM-1 may have a good therapeutic effect in vivo. Temperature had little effect on the activity of WAM-1. Serum, however, reduced WAM-1 activity.

Conclusions

WAM-1 has good antibacterial effect and potential anti-inflammatory effect on infection caused by CRKP.
Estimating the impact of cefuroxime versus cefazolin and amoxicillin/clavulanate use on future collateral resistance: a retrospective comparison
Authors: Chowers Michal , Zehavi Tamir , Gottesman Bat Sheva , Baraz Avi , Nevo Daniel , Obolski Uri
Published: April 2022

Background

Quantitative estimates of collateral resistance induced by antibiotic use are scarce.

Objectives

To estimate the effects of treatment with amoxicillin/clavulanate or cefazolin, compared with cefuroxime, on future resistance to ceftazidime among hospitalized patients.

Methods

A retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016–19 was conducted. Patients were restricted to those treated with amoxicillin/clavulanate, cefazolin or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. Matching was performed using exact, Mahalanobis and propensity score matching. Each patient in the amoxicillin/clavulanate and cefazolin groups was matched to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and the g-formula (standardization) were used to estimate the OR, risk difference (RD) and number needed to harm (NNH).

Results

Cefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin; the marginal OR was 1.76 (95% CI = 1.16–2.83) compared with amoxicillin/clavulanate and 1.98 (95% CI = 1.41–2.8) compared with cefazolin and the RD was 0.118 (95% CI = 0.031–0.215) compared with amoxicillin/clavulanate and 0.131 (95% CI = 0.058–0.197) compared with cefazolin. We also estimated the NNH; replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime resistance in 1 more patient for every 8.5 (95% CI = 4.66–32.14) or 7.6 (95% CI = 5.1–17.3) patients re-hospitalized in the following year, respectively.

Conclusions

Our results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.
Determination of plasma protein binding of dalbavancin
Authors: Turner Nicholas A , Xu Allan , Zaharoff Smitha , Holland Thomas L , Lodise Thomas P
Published: April 2022

Objectives

Dalbavancin is a lipoglycopeptide with a long half-life, making it a promising treatment for infections requiring prolonged therapy, such as complicated Staphylococcus aureus bacteraemia. Free drug concentration is a critical consideration with prolonged treatment, since free concentration–time profiles may best correlate with therapeutic effect. In support of future clinical trials, we aimed to develop a reliable and reproducible assay for measuring free dalbavancin concentrations.

Methods

The ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200 mg/L) in duplicate. Centrifuge tubes and pipette tips were treated for 24 h before use with Tween 80 to assess adsorption. Dalbavancin concentrations were analysed from the plasma samples (total) and middle layer samples (free) by LC/MS/MS with isotopically labelled internal standard. Warfarin served as a positive control with known high protein binding.

Results

Measurement of free dalbavancin was sensitive to adsorption onto plastic. Treatment of tubes and pipette tips with ≥2% Tween 80 effectively prevented drug loss during protein binding experiments. By the ultracentrifugation method, dalbavancin’s protein binding was estimated to be approximately 99%.

Conclusions

Dalbavancin has very high protein binding. Given dalbavancin’s high protein binding, accurate measurement of free dalbavancin concentrations should be a key consideration in future exposure–response studies, especially clinical trials. Future investigations should confirm if the active fraction is best predicted by the free or total fraction.
Drug resistance and genetic transmission characteristics of HIV-1 CRF59_01B in infected patients in Guangdong Province, China
Authors: Lan Yun , Li Feng , Li Linghua , Deng Xizi , Li Liya , Li Junbin , Cai Xiaoli , Ling Xuemei , Hu Fengyu
Published: April 2022

Objectives

To comprehensively analyse the prevalence of drug resistance and the transmission characteristics of CRF59_01B strains in infected patients in Guangdong, China.

Methods

CRF59_01B-infected individuals were recruited, and the HIV-1 pol region was amplified. Drug resistance-associated mutations (DRMs) and antiretroviral susceptibility were examined using the Stanford University HIV Drug Resistance Database to analyse pretreatment drug resistance (PDR) and acquired drug resistance (ADR). Genetic transmission networks were extracted from the maximum likelihood phylogenetic tree with Cluster Picker and visualized with Cytoscape.

Results

Two hundred and twenty-five CRF59_01B-infected individuals, comprising 35 ART-experienced and 190 ART-naive individuals, were recruited. No patients harboured PI DRMs, 5.33% (12/225) of the patients harboured NRTI DRMs and 11.11% (25/225) of the patients harboured NNRTI DRMs. The overall prevalence of strains with ADR was 51.43% (18/35), while the prevalence of strains with PDR was 2.63% (5/190). A total of 20 transmission networks, involving 25.78% (58/225) database-derived sequences, were identified. The networks ranged in size from 2 to 10 individuals, of which most (55.00%, 11/20) were made up of two individuals. Among the 225 study subjects, 9.78% (22/225) had 1 link and 16.00% (36/225) had ≥2 links.

Conclusions

The overall prevalence of CRF59_01B strains with ADR among the ART-experienced patients was high. Although the overall prevalence of CRF59_01B strains with PDR among the ART-naive patients was low, it is necessary to remain vigilant regarding some important DRMs.
Antimicrobial resistance genes aph(3′)-III, erm(B), sul2 and tet(W) abundance in animal faeces, meat, production environments and human faeces in Europe
Authors: Yang Dongsheng , Heederik Dick J J , Scherpenisse Peter , Van Gompel Liese , Luiken Roosmarijn E C , Wadepohl Katharina , Skarżyńska Magdalena , Van Heijnsbergen Eri , Wouters Inge M , Greve Gerdit D , Jongerius-Gortemaker Betty G M , Tersteeg-Zijderveld Monique , Portengen Lützen , Juraschek Katharina , Fischer Jennie , Zając Magdalena , Wasyl Dariusz , Wagenaar Jaap A , Mevius Dik J , Smit Lidwien A M , Schmitt Heike
Published: April 2022

Background

Real-time quantitative PCR (qPCR) is an affordable method to quantify antimicrobial resistance gene (ARG) targets, allowing comparisons of ARG abundance along animal production chains.

Objectives

We present a comparison of ARG abundance across various animal species, production environments and humans in Europe. AMR variation sources were quantified. The correlation of ARG abundance between qPCR data and previously published metagenomic data was assessed.

Methods

A cross-sectional study was conducted in nine European countries, comprising 9572 samples. qPCR was used to quantify abundance of ARGs [aph(3′)-III, erm(B), sul2, tet(W)] and 16S rRNA. Variance component analysis was conducted to explore AMR variation sources. Spearman’s rank correlation of ARG abundance values was evaluated between pooled qPCR data and earlier published pooled metagenomic data.

Results

ARG abundance varied strongly among animal species, environments and humans. This variation was dominated by between-farm variation (pigs) or within-farm variation (broilers, veal calves and turkeys). A decrease in ARG abundance along pig and broiler production chains (‘farm to fork’) was observed. ARG abundance was higher in farmers than in slaughterhouse workers, and lowest in control subjects. ARG abundance showed a high correlation (Spearman’s ρ > 0.7) between qPCR data and metagenomic data of pooled samples.

Conclusions

qPCR analysis is a valuable tool to assess ARG abundance in a large collection of livestock-associated samples. The between-country and between-farm variation of ARG abundance could partially be explained by antimicrobial use and farm biosecurity levels. ARG abundance in human faeces was related to livestock antimicrobial resistance exposure.