bluuebunny/crossref_metadata_2025 huggingface dataset:
DUSP4 promotes the carcinogenesis of CCRCC via negative regulation of autophagic death
Authors: Zeng Xianyou , Zhu Changyan , Zhu Xianxin
Published: June 2021

DUSP4 is considered as an oncogenic gene. However, the effect of DUSP4 on the carcinogenesis of clear cell Renal cell carcinoma (CCRCC) is still unclear. In this study, DUSP4 mRNA levels were significantly increased in CCRCC tissues and cell lines. Furthermore, DUSP4 overexpression promotes the proliferation, migration, and tumorigenicity of CCRCC cells while DUSP4 silencing showed the opposite effects. Importantly, both autophagic activity (LC3 conversion rate and LC3 puncta formation) and total death level promoted by DUSP4 silencing were reversed by treatment with 3-MA in CCRCC cells. Moreover, the proliferation and migration of CCRCC cells inhibited by DUSP4 silencing were also recovered by suppression of autophagy with 3-MA. In conclusion, DUSP4 serves as an oncogenic gene in CCRCC carcinogenesis due to its inhibitory effect on autophagic death, indicating the potential value of DUSP4 in the diagnosis and treatment of CCRCC.
ENNAVIA is a novel method which employs neural networks for antiviral and anti-coronavirus activity prediction for therapeutic peptides
Authors: Timmons Patrick Brendan , Hewage Chandralal M
Published: June 2021

Viruses represent one of the greatest threats to human health, necessitating the development of new antiviral drug candidates. Antiviral peptides often possess excellent biological activity and a favourable toxicity profile, and therefore represent a promising field of novel antiviral drugs. As the quantity of sequencing data grows annually, the development of an accurate in silico method for the prediction of peptide antiviral activities is important. This study leverages advances in deep learning and cheminformatics to produce a novel sequence-based deep neural network classifier for the prediction of antiviral peptide activity. The method outperforms the existent best-in-class, with an external test accuracy of 93.9%, Matthews correlation coefficient of 0.87 and an Area Under the Curve of 0.93 on the dataset of experimentally validated peptide activities. This cutting-edge classifier is available as an online web server at https://research.timmons.eu/ennavia, facilitating in silico screening and design of peptide antiviral drugs by the wider research community.
VSS: variance-stabilized signals for sequencing-based genomic signals
Authors: Bayat Faezeh , Libbrecht Maxwell
Published: June 2021

Motivation

A sequencing-based genomic assay such as ChIP-seq outputs a real-valued signal for each position in the genome that measures the strength of activity at that position. Most genomic signals lack the property of variance stabilization. That is, a difference between 0 and 100 reads usually has a very different statistical importance from a difference between 1000 and 1100 reads. A statistical model such as a negative binomial distribution can account for this pattern, but learning these models is computationally challenging. Therefore, many applications—including imputation and segmentation and genome annotation (SAGA)—instead use Gaussian models and use a transformation such as log or inverse hyperbolic sine (asinh) to stabilize variance.

Results

We show here that existing transformations do not fully stabilize variance in genomic datasets. To solve this issue, we propose VSS, a method that produces variance-stabilized signals for sequencing-based genomic signals. VSS learns the empirical relationship between the mean and variance of a given signal dataset and produces transformed signals that normalize for this dependence. We show that VSS successfully stabilizes variance and that doing so improves downstream applications such as SAGA. VSS will eliminate the need for downstream methods to implement complex mean–variance relationship models, and will enable genomic signals to be easily understood by eye.

Availability and implementation

https://github.com/faezeh-bayat/VSS

Supplementary information

Supplementary data are available at Bioinformatics online.
Population divergence in aggregation and sheltering behaviour in surface- versus cave-adapted Asellus aquaticus (Crustacea: Isopoda)
Authors: Horváth Gergely , Sztruhala Sára Sarolta , Balázs Gergely , Herczeg Gábor
Published: June 2021

Aggregation (gathering together) and sheltering (hiding in cover) are basic behaviours that can reduce the risk of predation. However, both behaviours have costs, such as increased competition over resources and high prevalence of contact-spread parasites (aggregation) or lost opportunities for foraging and mating (sheltering). Therefore, variation in these behaviours is expected between populations with varying levels of predation risk. We compared aggregation and sheltering in surface- (various predators) and cave-adapted (no predator) populations of the isopod Asellus aquaticus in a common garden experiment. Given that the cave environment is constantly dark, we also tested for population variation in light-induced behavioural plasticity. Variation in sheltering was explained by habitat type: cave individuals sheltered less than surface individuals. We found high between-population variation in aggregation with or without shelters and their light-induced plasticity, which was not explained by habitat type. Cave individuals decreased (habituation) whereas surface individuals increased sheltering with time (sensitization). We suggest that population variation in sheltering is driven by predation, whereas variation in aggregation must be driven by other, unaccounted environmental factors, in a similar manner to light-induced behavioural plasticity. Based on habituation/sensitization patterns, we suggest that predation-adapted populations are more sensitive to disturbance related to routine laboratory procedures.
Low CLOCK and CRY2 in 2nd trimester human maternal blood and risk of preterm birth: a nested case-control study†
Authors: Zhou Guoli , Duong Thu V , Kasten Eric P , Hoffmann Hanne M
Published: June 2021

Previous studies have observed an association between maternal circadian rhythm disruption and preterm birth (PTB). However, the underlying molecular mechanisms and the potential of circadian clock genes to serve as predictors of PTB remain unexplored. We examined the association of 10 core circadian transcripts in maternal blood with spontaneous PTB (sPTB) vs term births using a nested case-control study design. We used a public gene expression dataset (GSE59491), which was nested within the All Our Babies (AOB) study cohort in Canada. Maternal blood was sampled in Trimesters 2–3 from women with sPTB (n = 51) and term births (n = 106), matched for five demographic variables. In 2nd trimester maternal blood, only CLOCK and CRY2 transcripts were significantly lower in sPTB vs term (P = 0.02–0.03, false discovery rate (FDR) < 0.20). A change of PER3 mRNA from trimesters 2–3 was significantly associated with sPTB (decline in sPTB, P = 0.02, FDR < 0.20). When CLOCK and CRY2 were modeled together in 2nd trimester blood, the odds of being in the low level of both circadian gene transcripts was greater in sPTB vs term (OR = 4.86, 95%CI = (1.75,13.51), P < 0.01). Using GSVA and Pearson correlation, we identified 98 common pathways that were negatively or positively correlated with CLOCK and CRY2 expression (all P < 0.05, FDR < 0.10). The top three identified pathways were amyotrophic lateral sclerosis, degradation of extracellular matrix, and inwardly rectifying potassium channels. These three processes have previously been shown to be involved in neuron death, parturition, and uterine excitability during pregnancy, respectively.
Antimicrobial Resistance Trends in Urine Escherichia coli Isolates From Adult and Adolescent Females in the United States From 2011 to 2019: Rising ESBL Strains and Impact on Patient Management
Authors: Kaye Keith S , Gupta Vikas , Mulgirigama Aruni , Joshi Ashish V , Scangarella-Oman Nicole E , Yu Kalvin , Ye Gang , Mitrani-Gold Fanny S
Published: June 2021

Background

Uncomplicated urinary tract infection (uUTI) is predominantly caused by Escherichia coli, which has increasing antimicrobial resistance (AMR) at the United States (US)-community level. As uUTI is often treated empirically, assessing AMR is challenging, and there are limited contemporary data characterizing period prevalence in the US.

Methods

This was a retrospective study of AMR using Becton, Dickinson and Company Insights Research Database (Franklin Lakes, New Jersey, US) data collected 2011–2019. Thirty-day, nonduplicate Escherichia coli urine isolates from US female outpatients (aged ≥12 years) were included. Isolates were evaluated for nonsusceptibility (intermediate/resistant) to trimethoprim-sulfamethoxazole, fluoroquinolones, or nitrofurantoin, and assessed for extended-spectrum β-lactamase production (ESBL+) and for ≥2 or ≥3 drug-resistance phenotypes. Generalized estimating equations were used to model AMR trends over time and by US census region.

Results

Among 1 513 882 E. coli isolates, the overall prevalence of isolates nonsusceptible to trimethoprim-sulfamethoxazole, fluoroquinolones, and nitrofurantoin was 25.4%, 21.1%, and 3.8%, respectively. Among the isolates, 6.4% were ESBL+, 14.4% had ≥2 drug-resistance phenotypes, and 3.8% had ≥3. Modeling demonstrated a relative average yearly increase of 7.7% (95% confidence interval [CI], 7.2–8.2%) for ESBL+ isolates and 2.7% (95% CI, 2.2–3.2%) for ≥3 drug-phenotypes (both P < .0001). Modeling also demonstrated significant variation in AMR prevalence between US census regions (P < .001).

Conclusions

Period prevalence of AMR among US outpatient urine-isolated E. coli was high, and for multidrug-resistance phenotypes increased during the study period with significant variation between census regions. Knowledge of regional AMR rates helps inform empiric treatment of community-onset uUTI and highlights the AMR burden to physicians.
Safety and Effectiveness of Intravenous Artesunate for Treatment of Severe Malaria in the United States—April 2019 Through December 2020
Authors: Abanyie Francisca , Acharya Sushama D , Leavy Isabelle , Bowe Meara , Tan Kathrine R
Published: June 2021

Background

Severe malaria can be deadly and requires treatment with intravenous artesunate (IVAS). The Centers for Disease Control and Prevention provided IVAS starting 1 April 2019 for all patients with severe malaria in the United States. This study describes the safety and effectiveness of IVAS in these patients.

Methods

Patients meeting criteria for severe malaria April 2019–December 2020 who received IVAS were included. Demographic, clinical, laboratory, adverse event, and outcome information were collected. Clinical presentation, time to reach 1% and 0% parasitemia, adverse events, and death were described using proportions, medians, interquartile range (IQR), and tests of significance for differences in proportions.

Results

Of 280 patients included, the majority were male (61.4%), Black (75.0%), with a median age of 35 years (IQR: 15.8–53.9). Most had Plasmodium falciparum (83.6%) with median parasitemia of 8.0% (IQR: 4.6–13.2). Of 170 patients with information, 159 (93.5%) reached ≤1% parasitemia by the third IVAS dose with a median time of 17.6 hours (IQR: 10.8–28.8), and 0% parasitemia in a median of 37.2 hours (IQR 27.2–55.2). Patients with parasite densities >10% and those requiring adjunct therapy had significantly higher parasite clearance times. Adverse events associated with IVAS were reported in 4.8% (n = 13 of 271). Eight patients had post-artesunate delayed hemolysis that resolved. There were 5 (1.8%) deaths, all attributable to severe malaria.

Conclusions

IVAS is a safe and effective drug for the treatment of severe malaria in the United States; timely administration can be lifesaving.
China–US Strategic Competition and the Descent of a Porous Curtain
Authors: Zhang Jue , Xu Jin
Published: June 2021

Since the onset of the Coronavirus Disease 2019(COVID-19) global pandemic, Sino–US strategic rivalry has dramatically heightened to a pitch where there is a mounting discussion over whether or not China and the United States have embarked on a “new Cold War.” There are three main views in this regard. The first is that China and the United States have indeed entered a new Cold War; the second is that China and the United States are heading for a new Cold War; and the third is that China and the United States will not descend into a new Cold War. Different views reflect different scholarly understandings of the essential properties of the Cold War concept. Fundamentally, the two core features of the Cold War were ideological confrontation and proxy war. Considering that current US–China strategic competition is in the technological rather than ideological domain, and that neither side has instigated any proxy war; however, the phrase “new Cold War” is inappropriate; that of “Porous Curtain” is more apt. The ever-narrowing power gap between China and the United States has undoubtedly prompted the US government’s adoption of a policy of blockade and containment to curb China’s rising power. However, the deep integration of the international system and historical inertia of US–China interaction preclude the US’s complete isolation from China. This has resulted in bilateral relations of a more porous nature. Although the future may not be promising, competition does not necessarily lead to conflict. For this reason, managing the bilateral competitive relationship and striving towards coexistence under competition should be the key task of both countries.
Emotions in Deaf and Hard-of-Hearing and Typically Hearing Children
Authors: Tsou Yung-Ting , Li Boya , Eichengreen Adva , Frijns Johan H M , Rieffe Carolien
Published: June 2021

For deaf and hard-of-hearing (DHH) children living in an environment where their access to linguistic input and social interactions is compromised, learning emotions could be difficult, which may further affect social functioning. To understand the role of emotion in DHH children’s social life, this study investigated emotional functioning (i.e., emotion recognition, empathy, emotion expression), and its relation with social functioning (i.e., social competence and externalizing behaviors), in 55 DHH children and 74 children with typical hearing (aged 3–10 years; Mage = 6.04). Parental reports on children’s emotional and social functioning and factors related to DHH children’s hearing were collected. Results showed similar levels of emotional and social functioning in children with and without hearing loss. Use of auditory intervention and speech perception did not correlate with any measures in DHH children. In both groups, higher levels of empathy related to higher social competence and fewer externalizing behaviors; emotion recognition and positive emotion expression were unrelated to either aspect of social functioning. Higher levels of negative emotion expression related to lower social competence in both groups, but to more externalizing behaviors in DHH children only. DHH children in less linguistically accessible environments may not have adequate knowledge for appropriately expressing negative emotions socially.
Association of autoimmune diseases with cardiomyopathy: a nationwide follow-up study from Sweden
Authors: Li Xinjun , Sundquist Jan , Nymberg Veronica , Sundquist Kristina
Published: June 2021

Aims

Certain autoimmune diseases (ADs), such as Crohn’s disease and celiac diseases, have been linked to acute cardiovascular disorders. We examined whether there is an association between 43 different ADs and risk of subsequent hospitalization and mortality of cardiomyopathy in a nationwide follow-up study in Sweden.

Methods and results

All individuals in Sweden hospitalized with a main diagnosis of an AD (n = 955 410) without previous or coexisting cardiomyopathy, between 1 January 1987 and 31 December 2018, were followed for hospitalization or mortality of cardiomyopathy. The reference population was the total population of Sweden. Standardized incidence ratios (SIRs) for cardiomyopathy were calculated. Overall risk of cardiomyopathy during the first year after hospitalization for an AD was 3.63 [99% confidence interval (CI) 3.29–4.00]. A total of 21 of the 43 ADs studied were associated with an increased risk of cardiomyopathy during the first year after hospitalization. The overall risk of cardiomyopathy decreased over time, from 1.18 (99% CI 1.12–1.25) after 1+ year to 1.07 (99% CI 0.96–1.19) after 5+ years. Females generally had higher SIRs than males. The ADs for which the SIRs of cardiomyopathy were highest after 1 year of hospitalization included Crohn’s disease (1.92), rheumatoid arthritis (1.57), sarcoidosis (1.48), and psoriasis (1.31).

Conclusion

Most ADs are associated with an increased risk of cardiomyopathy, particularly in the first year after hospital admission. Our findings show that many hospitalized ADs are tightly linked to cardiomyopathy but the mechanisms need to be further evaluated.
The Stanford experience of heart transplantation over five decades
Authors: Zhu Yuanjia , Lingala Bharathi , Baiocchi Michael , Toro Arana Veronica , Williams Kiah M , Shudo Yasuhiro , Oyer Philip E , Woo Y Joseph
Published: June 2021

Aims 

Since 1968, heart transplantation has become the definitive treatment for patients with end-stage heart failure. We aimed to summarize our experience in heart transplantation at Stanford University since the first transplantation performed over 50 years ago.

Methods and results 

From 6 January 1968 to 30 November 2020, 2671 patients presented to Stanford University for heart transplantation, of which 1958 were adult heart transplantations. Descriptive analyses were performed for patients in 1968–95 (n = 639). Stabilized inverse probability weighting was applied to compare patients in 1996–2006 (n = 356) vs. 2007–19 (n = 515). Follow-up data were updated through 2020. The primary endpoint was all-cause mortality. Prior to weighting, recipients in 2007–19 vs. those in 1996–2006 were older and had heavier burden of chronic diseases. After the application of stabilized inverse probability weighting, the distance organ travelled increased from 84.2 ± 111.1 miles to 159.3 ± 169.9 miles from 1996–2006 to 2007–19. Total allograft ischaemia time also increased over time (199.6 ± 52.7 vs. 225.3 ± 50.0 min). Patients in 2007–19 showed superior survival than those in 1996–2006 with a median survival of 12.1 vs. 11.1 years.

Conclusion 

In this half-century retrospective descriptive study from one of the largest heart transplant programmes in the USA, long-term survival after heart transplantation has improved over time despite increased recipient and donor age, worsening comorbidities, increased technical complexity, and prolonged total allograft ischaemia time. Further investigation is warranted to delineate factors associated with the excellent outcomes observed in this study.
LDL cholesterol levels and in-hospital bleeding in patients on high-intensity antithrombotic therapy: findings from the CCC-ACS project
Authors: Yang Qing , Sun Dongdong , Pei Chongzhe , Zeng Yuhong , Wang Zhuoqun , Li Ziping , Hao Yongchen , Song Xiwen , Li Yongle , Liu Gang , Tang Yida , Smith Sidney C , Han Yaling , Huo Yong , Ge Junbo , Ma Changsheng , Fonarow Gregg C , Morgan Louise , Liu Jing , Liu Jun , Zhou Mengge , Zhao Dong , Zhou Yujie , Zhou Xin ,   the CCC-ACS Investigators
Published: June 2021

Aims 

Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose–response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients.

Methods and results 

Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose–response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21–1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels.

Conclusions 

In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted.

Trial registration

ClinicalTrials.gov Identifier: NCT02306616
Water saturation variation in a fire-heated limestone gallery monitored by ERT
Authors: Verdet Cécile , Salmon Fabien , Sirieix Colette , Lacanette Delphine
Published: June 2021

Water migration within the rock mass during a fire has not yet been studied. Here, an innovative high-resolution micro-ERT method is developed at a centimetric scale to measure this phenomenon. The method is two-step based: first, a correction of the electrode effect, and second, the correction of resistivity for rapid variations in temperature with high values. Water migration is successfully described within the wall of an underground limestone quarry with three phases: from fire ignition to 36 min, the surface dries to a 3-cm depth and a higher saturated layer forms deeper than 0.10 m; from 36 min to 46 min (fire supply stops), the rock dries out and water migrates from deeper parts of the rock wall, deeper than 20 cm, towards the surface; finally, after fire extinction, the water migrates through a readjustment phase until it returns to its initial state.
Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL
Authors: Justice Anne E , Young Kristin , Gogarten Stephanie M , Sofer Tamar , Graff Misa , Love Shelly Ann M , Wang Yujie , Klimentidis Yann C , Cruz Miguel , Guo Xiuqing , Hartwig Fernando , Petty Lauren , Yao Jie , Allison Matthew A , Below Jennifer E , Buchanan Thomas A , Chen Yii-Der Ida , Goodarzi Mark O , Hanis Craig , Highland Heather M , Hsueh Willa A , Ipp Eli , Parra Esteban , Palmas Walter , Raffel Leslie J , Rotter Jerome I , Tan Jingyi , Taylor Kent D , Valladares Adan , Xiang Anny H , Sánchez-Johnsen Lisa , Isasi Carmen R , North Kari E
Published: June 2021

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10−6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10−8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.
Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women
Authors: Schwarz Tino F , Johnson Casey , Grigat Christine , Apter Dan , Csonka Peter , Lindblad Niklas , Nguyen Thi Lien-Anh , Gao Feng F , Qian Hui , Tullio Antonella N , Dieussaert Ilse , Picciolato Marta , Henry Ouzama
Published: June 2021

Background

Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life.

Methods

In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo.

Results

Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%–53.2%) versus placebo (0%–15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one.

Conclusions

The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women.

Clinical Trials Registration

NCT03674177.
Hospitalization Rates and Direct Medical Costs for Fever in a Pediatric Cohort in South India
Authors: Srinivasan Manikandan , Sindhu Kulandaipalayam Natarajan , Nag Atrayee , Karthikeyan Arun S , Ramasamy Ranjith Kumar , Murugesan Malathi , Kumar Dilesh , Ganesan Santhosh Kumar , Rose Winsley , Kang Gagandeep , John Jacob
Published: June 2021

Background

Primary data on causes and costs of hospitalization are necessary for costing and cost-effectiveness analysis. Data on incidence and causes of hospitalization and consequent expenses among Indian children are limited.

Methods

A cohort of 6000 children aged 0.5–15 years residing in urban Vellore was followed for 3 years, under the Vellore Typhoid Study, 2016–2017, and later under the Surveillance for Enteric Fever project, 2017–2019. Data on hospitalization events and associated antibiotic use, and direct medical costs for fever-related hospitalization of study children were obtained from caregivers through weekly follow-up by study field workers.

Results

The incidence of hospitalization was 33 per 1000 child-years of observation. Children aged 0.5–5 years had the highest incidence of hospitalization. The top 5 infectious causes for hospitalization were acute undifferentiated fevers, respiratory tract infections, acute gastroenteritis, enteric fever, and dengue. The overall median cost of hospitalization for fever was 4243 (interquartile range, 2502–7215) Indian rupees (INR). An episode of dengue had a median cost of 5627 INR, followed by acute undifferentiated fevers and enteric fever with median costs of 3860 and 3507 INR, respectively.

Conclusions

Hospitalization for fever is common in young children and impacts household finances in low-income Indian households.
Immunotyping Provides Equivalent Results to Immunofixation in a Population with a High Prevalence of Monoclonal Gammopathies
Authors: Thoren Katie L , McCash Samuel I , Murata Kazunori
Published: June 2021

Background

Serum immunofixation (IF) is a common laboratory test used to diagnose and monitor patients with monoclonal gammopathies. Similarly, immunotyping (IT) by capillary electrophoresis can confirm the presence of a monoclonal protein (M-protein) and determine its isotype. The goal of this study was to compare the ability of IT and IF to detect M-proteins.

Methods

IT and IF results for 1000 waste clinical serum samples were obtained. All results were interpreted blindly by reviewers who were experienced in each technique. Results were compared by band. Results were also compared to patient history to determine if the original clone was present. We determined the sensitivity of IT and IF alone and in combination with additional tests. Finally, we evaluated the impact of reviewer training on the sensitivity of IT.

Results

IT and IF were concordant in 721/773 (93%) samples with a history of an intact M-protein and in 143/172 (83%) samples with a history of a free light chain (FLC) M-protein. IF was significantly more sensitive than IT for the detection of FLC M-proteins (P < 0.0001). However, IF was not more sensitive than IT for detection of intact M-proteins (P = 0.1272) or when each test was combined with the FLC ratio or urine immunofixation (P = 0.2812 and P = 0.6171, respectively). Finally, after training, inexperienced reviewers improved their IT sensitivity by 19%.

Conclusion

IT provides equivalent results to IF for the detection of monoclonal proteins. Training and experience are critical to the accurate interpretation of IT.
Rapid and Safe Detection of SARS-CoV-2 and Influenza Virus RNA Using Onsite Quantitative PCR Diagnostic Testing From Clinical Specimens Collected in Molecular Transport Medium
Authors: Daum Luke T , Fischer Gerald W
Published: June 2021

Background

The ability to rapidly detect severe accurate respiratory syndrome coronavirus virus-2 (SARS-CoV-2) and influenza virus infection is vital for patient care due to overlap in clinical symptoms. Roche’s cobas® Liat® SARS-CoV-2 & Influenza A/B Nucleic Acid Test used on the cobas Liat was granted approval under the Food and Drug’s Emergency Use Authorization for nasopharyngeal (NP) and nasal swabs collected in viral/universal transport medium (VTM/UTM). However, there is a critical need for media that inactivates the virus, especially when specimens are collected in decentralized settings. This study aimed to investigate the use of PrimeStore Molecular Transport Medium® (PS-MTM®), designed to inactivate/kill and stabilize RNA/DNA for ambient transport and preprocessing of collected samples.

Methods

A limit of detection (LOD) using serially diluted SARS-CoV-2 RNA in PS-MTM and routine UTM was established using standard quantitative PCR (qPCR). Additionally, a clinical panel of NP and oral swabs collected in PS-MTM during the 2020 coronavirus disease 2019 pandemic were evaluated on the cobas Liat and compared to “gold standard” qPCR on an ABI-7500 instrument.

Results

SARS-CoV-2 RNA LOD using standard qPCR was equivalent on the cobas Liat instrument. cobas Liat detection from oral/NP swabs in PS-MTM media exhibited equivalent positive percent agreement (100%) and negative percent agreement (96.4%).

Conclusion

PS-MTM and the Roche cobas Liat are compatible and complimentary devices for respiratory specimen collection and rapid disease detection, respectively. PS-MTM is equivalent to standard VTM/UTM with the added benefit of safe, noninfectious sample processing for near-patient testing.
Operationalizing and analyzing 2-step gender identity questions: Methodological and ethical considerations
Authors: Kidd Kacie M , Sequeira Gina M , Rothenberger Scott D , Paglisotti Taylor , Kristjansson Alfgeir , Schweiberger Kelsey , Miller Elizabeth , Coulter Robert W S
Published: June 2021

Objective

Two-step questions to assess gender identity are recommended for optimizing care delivery for gender-diverse individuals. As gender identity fields are increasingly integrated into electronic health records, guidance is needed on how to analyze these data. The goal of this study was to assess potential approaches for analyzing 2-step gender identity questions and the impact of each on suicidal ideation.

Materials and Methods

A regional Youth Risk Behavior Survey in one Northeastern school district used a 2-step question to assess gender identity. Three gender measurement strategies (GMSs) were used to operationalize gender identity, (1) combining all gender-diverse youth (GDY) into one category, (2) grouping GDY based on sex assigned at birth, and (3) categorizing GDY based on binary and nonbinary identities. Mixed-effects logistic regression was used to compare odds of suicidal ideation between gender identity categories for each GMS.

Results

Of the 3010 participants, 8.3% were GDY. Subcategories of GDY had significantly higher odds (odds ratio range, 1.6-2.9) of suicidal ideation than cisgender girls regardless of GMS, while every category of GDY had significantly higher odds (odds ratio range, 2.1-5.0) of suicidal ideation than cisgender boys.

Conclusions

The field of clinical informatics has an opportunity to incorporate inclusive items like the 2-step gender identity question into electronic health records to optimize care and strengthen clinical research. Analysis of the 2-step gender identity question impacts study results and interpretation. Attention to how data about GDY are captured will support for more nuanced, tailored analyses that better reflect unique experiences within this population.
Electronic Cigarette-Related Injuries Presenting to Five Large Burn Centers, 2015–2019
Authors: Flores Carmen E , Chestovich Paul J , Saquib Syed , Carroll Joseph , Al-Hamad Mariam , Foster Kevin N , Delapena Samantha , Richey Karen , Lallemand Michael , Dennis Bradley M , Palmieri Tina L , Romanowski Kathleen , Godat Laura , Lee Jeanne
Published: June 2021

Electronic cigarettes are advertised as safer alternatives to traditional cigarettes yet cause serious injury. U.S. burn centers have witnessed a rise in both inpatient and outpatient visits to treat thermal injuries related to their use. A multicenter retrospective chart review of American Burn Association burn registry data from five large burn centers was performed from January 2015 to July 2019 to identify patients with electronic cigarette-related injuries. A total of 127 patients were identified. Most sustained less than 10% total body surface area burns (mean 3.8%). Sixty-six percent sustained second-degree burns. Most patients (78%) were injured while using their device. Eighteen percent of patients reported spontaneous device combustion. Two patients were injured while changing their device battery, and two were injured modifying their device. Three percent were injured by secondhand mechanism. Burn injury was the most common injury pattern (100%), followed by blast injury (3.93%). Flame burns were the most common (70%) type of thermal injury; however, most patients sustained a combination-type injury secondary to multiple burn mechanisms. The most injured body region was the extremities. Silver sulfadiazine was the most common agent used in the initial management of thermal injuries. Sixty-three percent of patients did not require surgery. Of the 36% requiring surgery, 43.4% required skin grafting. Multiple surgeries were uncommon. Our data recognize electronic cigarette use as a public health problem with the potential to cause thermal injury and secondary trauma. Most patients are treated on an inpatient basis although most patients treated on an outpatient basis have good outcomes.
Comparison of Pollen Grain Treatments Without Mechanical Fracturation Prior to Protein Quantification
Authors: Westreich Lila R , Tobin Patrick C
Published: June 2021

Protein and amino acids in pollen are important nutritional components for larval development in several insect species, especially in Apoidea. The Bradford assay is a widely used method to measure relative protein content of pollen, which can shed light on pollen quality and consequences to fitness. Prior to using the Bradford assay, protein must be released from pollen grains, often using a mixture of chemical and mechanical fracturation methods. In this study, we tested the efficacy of protein extraction without using mechanical fracturation. We used pollen collected by the solitary bee Osmia lignaria Say to compare two known buffers associated with pollen protein analysis: phosphate-buffered saline and sodium hydroxide, and deionized water, and with different pollen weights from which we quantified protein using the Bradford assay. While all buffers and deionized water were useful in releasing protein from pollen grains collected by O. lignaria, the use of sodium hydroxide resulted in significantly higher protein quantification across all pollen weights. This methodological study can inform future studies of pollen nutrition in pollen-foraging species.
A recursion theoretic foundation of computation over real numbers
Authors: Ng Keng Meng , R Tavana Nazanin , Yang Yue
Published: June 2021

We define a class of computable functions over real numbers using functional schemes similar to the class of primitive and partial recursive functions defined by Gödel (1931, 1934) and Kleene (1936, Math. Ann., 112, 727–742). We show that this class of functions can also be characterized by MS-machines, which are Turing machine-like devices. The proof of the characterization gives a normal form theorem in the style of Kleene (1936, Math. Ann., 112, 727–742). Furthermore, this characterization is a natural combination of two most influential theories of computation over real numbers, namely the type-two theory of effectivity (see, e.g. Weihrauch (2000, Springer)) and the Blum–Shub–Smale (1989, Bull. Amer. Math. Soc. (N.S.), 21, 1–46) model of computation. Under this notion of computability, the recursive (or computable) subsets of real numbers are exactly effective $\varDelta ^0_2$ sets.
Effects of Left Ventricular Versus Traditional Chest Compressions in a Traumatic Pulseless Electrical Activity Model
Authors: Anderson Kenton L , Evans Jacqueline C , Castaneda Maria G , Boudreau Susan M , Maddry Joseph K , Morgan Jeffrey D
Published: June 2021

Background

Prehospital cardiopulmonary resuscitation has commonly been considered ineffective in traumatic cardiopulmonary arrest because traditional chest compressions do not produce substantial cardiac output. However, recent evidence suggests that chest compressions located over the left ventricle (LV) produce greater hemodynamics when compared to traditional compressions. We hypothesized that chest compressions located directly over the LV would result in an increase in return of spontaneous circulation (ROSC) and hemodynamic variables, when compared to traditional chest compressions, in a swine model of traumatic pulseless electrical activity (PEA).

Methods

Transthoracic echocardiography was used to mark the location of the aortic root (traditional compressions) and the center of the LV on animals (n = 34) that were randomized to receive chest compressions in one of the two locations. Animals were hemorrhaged to mean arterial pressure <20 to simulate traumatic PEA. After 5 minutes of PEA, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 minutes followed by advanced life support for an additional 10 minutes. Hemodynamic variables were averaged over the final 2 minutes of BLS and advanced life support periods.

Results

Six of the LV group (35%) achieved ROSC compared to eight of the traditional group (47%) (P = .73). There was an increase in aortic systolic blood pressure (P < .01), right atrial systolic blood pressure (P < .01), and right atrial diastolic blood pressure (P = .02) at the end of BLS in the LV group compared to the traditional group.

Conclusions

In our swine model of traumatic PEA, chest compressions performed directly over the LV improved blood pressures during BLS but not ROSC.
Oversight May Reduce Military Health System Leakage: Preventing Inappropriate Interhospital Transfers
Authors: Gragg James , Hudson Ian , Hannick Vanessa , Davis Philip , Mitchell Christopher , Ingram Joan , Hall Brian , Malish Richard
Published: June 2021

Introduction

The Military Health System (MHS) offers an example of a socialized healthcare model, operating within a larger “purchased care” civilian healthcare market. This arrangement has facilitated a trend wherein MHS clinicians often transfer moderate-to-complex patients to surrounding civilian hospitals, despite having the capability to care for such patients in-house. In an effort to stem this behavior, two initiatives were introduced at Carl R Darnall Army Medical Center (CRDAMC): A Transfer Policy Statement and Transfer Rounds. The Transfer Policy Statement emphasized that patients ought to be transferred only for capability gaps within the hospital. Transfer Rounds were then used to review the care received by each transferred patient and assess if that care could have been delivered internally. The purpose of this study is to assess the effect of these initiatives on reducing transfers from our hospital.

Materials and Methods

We performed a retrospective chart review from July 2019 through June 2020 to identify the number of total emergency department (ED) transfers, subcategorized as either transfers we had the capability to care for or transfers we did not have the capability to care for. The Transfer Policy Statement was published in August 2019, and Transfer Rounds were instituted in November 2019. We hypothesized that the two interventions would decrease the number of monthly inappropriate transfers. This was assessed by analyzing the proportion of inappropriate to appropriate patient transfers via Cochran and Armitage using SAS 9.4 (SAS Institute, Cary, NC). The projected received an Exemption Determination from the CRDAMC’s Human Research Protections Office. The Defense Health Agency approved the data-sharing agreement.

Results

Over the study period, a total of 706 transfers met the criteria for analysis. The monthly median for total ED transfers was 64.5 (Interquartile Range (IQR) 45-74); appropriate transfers averaged 29.5 (median, IQR 24.5-36) and inappropriate 25.5 (median, IQR 9-41.5). A statistically significant downward trend in the fraction of inappropriate transfers was demonstrated by Cochran and Armitage (P < .0001).

Conclusion

Our analysis supports the hypothesis that implementing a Transfer Policy and Transfer Rounds can significantly reduce the amount of MHS Leakage—that is the number of transferred patients that the MHS could have equally cared for. The effects of reduced patient transfers have many implications for the MHS: patients experience improved continuity of care by remaining in the same hospital system; clinicians maintain and extend their scope of practice by treating more complex patients; and patient flow and ED wait times are reduced by eliminating the transfer process. The financial implications of reduced MHS Leakage were not directly evaluated by our study, however may be assessed in future study.
Effect of Arrival Quarantine on Subsequent COVID-19 Testing in a Cohort of Military Basic Trainees
Authors: Marcus Joseph E , Frankel Dianne N , Pawlak Mary T , Casey Theresa M , Enriquez Erin , Yun Heather C
Published: June 2021

Introduction

Basic Military Training at Joint Base San Antonio-Lackland implemented several sequential non-pharmaceutical interventions in response to coronavirus disease-2019 (COVID-19). One measure, arrival quarantine, has not been studied as a modern military disease prevention strategy. This study aimed to determine the effect of a 14-day arrival quarantine on symptomatic COVID-19 testing.

Material and Methods

A retrospective cohort study compared symptomatic COVID-19 testing among all trainees who entered Basic Military Training between March 17, 2020, and April 17, 2020, before the implementation of universal arrival COVID-19 testing, during their first 2 weeks in arrival quarantine compared to the rest of their training. Furthermore, symptomatic COVID-19 testing in the last 5 weeks of training in those who completed arrival quarantine was compared to testing in the last 5 weeks for trainees who arrived between February 16, 2020, and March 16, 2020, and did not undergo arrival quarantine. Nominal variables were compared by chi-square test, and continuous variables were compared by Mann–Whitney U test. This study was approved as a public health surveillance project by the 59th Medical Wing Institutional Review Board.

Results

Five thousand five hundred and seventy-six trainees started training between February 16, 2020, and April 17, 2020, with 2,573 trainees undergoing an arrival quarantine compared to 3,003 trainees who did not. Trainees who underwent arrival quarantine had higher rates of COVID-19 testing while in arrival quarantine (10.5 tests per 1,000 trainee-weeks vs. 2.3, P ≤ .001) and higher rates of concomitant influenza testing (74% vs. 38%, P = .001) compared to after they completed quarantine. Trainees that completed quarantine had less symptomatic COVID-19 testing after day 14 of training (2.3 tests per 1,000 trainee-weeks vs. 14.3, P ≤ .001) and influenza testing (38% vs. 74%, P = .001) compared to trainees that did not undergo arrival quarantine.

Conclusion

Arrival quarantine appears to be an effective non-pharmaceutical intervention associated with fewer symptomatic COVID-19 tests, especially after completion of quarantine.
Peculiar orbits and asymmetries in extreme trans-Neptunian space
Authors: de la Fuente Marcos C , de la Fuente Marcos R
Published: June 2021

It is still an open question how the Solar system is structured beyond 100 au from the Sun. Our understanding of this vast region remains very limited and only recently we have become aware of the existence there of a group of enigmatic bodies known as the extreme trans-Neptunian objects (ETNOs) that have large orbits with perihelia beyond the orbit of Neptune. Four ETNOs – Sedna, Leleakuhonua, 2012 VP113, and 2013 SY99 – have perihelia beyond 50 au. The study of the ETNOs may provide much needed information on how this remote region is organized. Here, we apply machine-learning techniques to the sample of 40 known ETNOs to identify statistically significant clusters that may signal the presence of true dynamical groupings and study the distribution of the mutual nodal distances of the known ETNOs that measure how close two orbits can get to each other. Machine-learning techniques show that the known ETNOs may belong to four different populations. Results from the analysis of the distribution of nodal distances show that 41 per cent of the known ETNOs have at least one mutual nodal distance smaller than 1.45 au (first percentile of the distribution), perhaps hinting at past interactions. In this context, the peculiar pair of ETNOs made of 505478 (2013 UT15) and 2016 SG58 has a mutual ascending nodal distance of 1.35 at 339 au from the Sun. In addition, the known ETNOs exhibit a highly statistically significant asymmetry between the distributions of object pairs with small ascending and descending nodal distances that might be indicative of a response to external perturbations.