bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Prescribing of Antibiotics and Drugs Investigated for Coronavirus Disease 2019 (COVID-19) Treatment in US Nursing Home Residents During the COVID-19 Pandemic
Authors: Gouin Katryna A , Creasy Stephen , Beckerson Mary , Wdowicki Martha , Hicks Lauri A , Lind Jennifer N , Geller Andrew I , Budnitz Daniel S , Kabbani Sarah 
Published: March 2021

Abstract

Background
Trends in prescribing for nursing home (NH) residents, which may have been influenced by the coronavirus disease 2019 (COVID-19) pandemic, have not been characterized.

Methods
Long-term care pharmacy data from 1944 US NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1000 residents serviced was calculated from January to October and compared as relative percent change from 2019 to 2020.

Results
In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval [CI]: 5.87, 7.48) and azithromycin (+150%, 95% CI: 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI: 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI: .55, .73) and 303% higher in July (95% CI: 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (−5%, 95% CI: .94, .97) through October (−4%, 95% CI: .94, .97) in 2020 compared to 2019.

Conclusions
During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety.
Evaluating the Long-term Efficacy of Coronavirus Disease 2019 (COVID-19) Vaccines
Authors: Lin Dan-Yu , Zeng Donglin , Gilbert Peter B 
Published: March 2021

AbstractLarge-scale deployment of safe and durably effective vaccines can curtail the coronavirus disease-2019 (COVID-19) pandemic. However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about 2 months, and thus does not pertain to long-term efficacy. To evaluate the duration of protection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the performance of blinded and unblinded crossover designs in estimating long-term VE.
Impact of the Coronavirus Disease 2019 (COVID-19) Vaccine on Asymptomatic Infection Among Patients Undergoing Preprocedural COVID-19 Molecular Screening
Authors: Tande Aaron J , Pollock Benjamin D , Shah Nilay D , Farrugia Gianrico , Virk Abinash , Swift Melanie , Breeher Laura , Binnicker Matthew , Berbari Elie F 
Published: March 2021

Abstract

Background
Several vaccines are now available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. Vaccine impact on asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is largely unknown.

Methods
We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39 156) within a large US healthcare system who underwent 48 333 preprocedural SARS-CoV-2 molecular screening tests between 17 December 2020 and 8 February 2021. The primary exposure of interest was vaccination with ≥1 dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk (RR) of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received ≥1 dose of vaccine compared with persons who had not received vaccine during the same time period. RR was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs nonlocal), healthcare system regions, and repeated screenings among patients using mixed-effects log-binomial regression.

Results
Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3006 tests and 1436 (3.2%) of 45 327 tests performed on vaccinated and unvaccinated patients, respectively (RR, .44; 95% CI, .33–.60; P &lt; .0001). Compared with unvaccinated patients, risk of asymptomatic SARS-CoV-2 infection was lower among those &gt;10 days after the first dose (RR, .21; 95% CI, .12–.37; P &lt; .0001) and &gt;0 days after the second dose (RR, .20; 95% CI, .09–.44; P &lt; .0001) in the adjusted analysis.

Conclusions
COVID-19 vaccination with an mRNA-based vaccine showed a significant association with reduced risk of asymptomatic SARS-CoV-2 infection as measured during preprocedural molecular screening. Results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.
Effectiveness of 3 Versus 6 ft of Physical Distancing for Controlling Spread of Coronavirus Disease 2019 Among Primary and Secondary Students and Staff: A Retrospective, Statewide Cohort Study
Authors: van den Berg Polly , Schechter-Perkins Elissa M , Jack Rebecca S , Epshtein Isabella , Nelson Richard , Oster Emily , Branch-Elliman Westyn 
Published: March 2021

Abstract

Background
National and international guidelines differ about the optimal physical distancing between students for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission; studies directly comparing the impact of ≥3 versus ≥6 ft of physical distancing policies in school settings are lacking. Thus, our objective was to compare incident cases of SARS-CoV-2 in students and staff in Massachusetts public schools among districts with different physical distancing requirements. State guidance mandates masking for all school staff and for students in grades 2 and higher; the majority of districts required universal masking.

Methods
Community incidence rates of SARS-CoV-2, SARS-CoV-2 cases among students in grades K-12 and staff participating in-person learning, and district infection control plans were linked. Incidence rate ratios (IRRs) for students and staff members in traditional public school districts with ≥3 versus ≥6 ft of physical distancing were estimated using log-binomial regression; models adjusted for community incidence are also reported.

Results
Among 251 eligible school districts, 537 336 students and 99 390 staff attended in-person instruction during the 16-week study period, representing 6 400 175 student learning weeks and 1 342 574 staff learning weeks. Student case rates were similar in the 242 districts with ≥3 versus ≥6 ft of physical distancing between students (IRR, 0.891; 95% confidence interval, .594–1.335); results were similar after adjustment for community incidence (adjusted IRR, 0.904; .616–1.325). Cases among school staff in districts with ≥3 versus ≥6 ft of physical distancing were also similar (IRR, 1.015, 95% confidence interval, .754–1.365).

Conclusions
Lower physical distancing requirements can be adopted in school settings with masking mandates without negatively affecting student or staff safety.
Risk of developing pneumonia associated with clinically diagnosed hypothyroidism: a nationwide population-based cohort study
Authors: Huang Huei-Kai , Wang Jen-Hung , Kao Sheng-Lun 
Published: March 2021

Abstract

Background
Hypothyroidism has a detrimental effect on the immune system, which may predispose patients to infection. However, evidence about the risk of developing either community- or hospital-acquired pneumonia in patients with hypothyroidism is scarce.

Objective
To evaluate the association between hypothyroidism and the risk of developing pneumonia.

Methods
This was a retrospective population-based cohort study from Taiwan’s National Health Insurance Research Database. After 1:1 propensity score matching, 9749 patients (age ≥20 years) newly diagnosed with hypothyroidism between 2001 and 2014 and 9749 patients without hypothyroidism or other thyroid diseases were included in the hypothyroidism and non-hypothyroidism cohorts, respectively, and followed up until 2015. The development of pneumonia was defined as the primary outcome. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) of developing pneumonia between hypothyroidism and non-hypothyroidism cohorts after adjusting for age, sex and baseline comorbidities. To evaluate whether thyroxine replacement therapy (TRT) modified the risk for pneumonia, we divided patients with hypothyroidism into subgroups: patients who received TRT and those who did not.

Results
Hypothyroidism was associated with a higher risk of pneumonia [adjusted HR (aHR) 1.38, 95% confidence interval (CI) 1.29–1.49, P &lt; 0.001]. Patients with hypothyroidism who received TRT had a lower risk of pneumonia than patients who did not (aHR 0.85, 95% CI 0.76–0.93, P = 0.001). Similar results were obtained in the age- and sex-stratified analyses.

Conclusions
Clinically diagnosed hypothyroidism was independently associated with the risk of pneumonia. In patients with hypothyroidism, TRT was associated with a lower risk of pneumonia.
Evolutionary Contribution of Duplicated Genes to Genome Evolution in the Ginseng Species Complex
Authors: Li Ming-Rui , Ding Ning , Lu Tianyuan , Zhao Jing , Wang Zhen-Hui , Jiang Peng , Liu Si-Tong , Wang Xin-Feng , Liu Bao , Li Lin-Feng 
Published: March 2021

Abstract
Genes duplicated by whole genome duplication (WGD) and small-scale duplication (SSD) have played important roles in adaptive evolution of all flowering plants. However, it still remains underinvestigated how the distinct models of duplication events and their contending evolutionary patterns have shaped the genome and epigenomes of extant plant species. In this study, we investigated the contribution of the WGD- and SSD-derived duplicate genes to the genome evolution of one diploid and three closely related allotetraploid Panax species based on genome, methylome, and proteome data sets. Our genome-wide comparative analyses revealed that although the ginseng species complex was recently diverged, they have evolved distinct overall patterns of nucleotide variation, cytosine methylation, and protein-level expression. In particular, genetic and epigenetic asymmetries observed in the recent WGD-derived genes are largely consistent across the ginseng species complex. In addition, our results revealed that gene duplicates generated by ancient WGD and SSD mechanisms exhibited distinct evolutionary patterns. We found the ancient WGD-derived genes (i.e., ancient collinear gene) are genetically more conserved and hypomethylated at the cytosine sites. In contrast, some of the SSD-derived genes (i.e., dispersal duplicated gene) showed hypermethylation and high variance in nucleotide variation pattern. Functional enrichment analyses of the duplicated genes indicated that adaptation-related traits (i.e., photosynthesis) created during the distant ancient WGDs are further strengthened by both the more recent WGD and SSD. Together, our findings suggest that different types of duplicated genes may have played distinct but relaying evolutionary roles in the polyploidization and speciation processes in the ginseng species complex.
Electronic cigarettes and public health awareness: a cross-sectional analysis of Google search inquiries
Authors: Lester Drew , Torgerson Trevor , Eyabi Jorgen , Wayant Cole , Vassar Matt 
Published: March 2021

Abstract
The number of American adults who use electronic nicotine delivery systems (ENDS) increased by 3 million people in 2018, up 38.3% from 8.1 to 11.2 million. Search data for ENDS were analyzed against relevant traits including state longitude, tobacco tax rate and national tobacco program funding. Searches increased 88% (95% CI, 70–100) over the last 5 years and peaked on 8 September 2019, after the CDC issued a warning about the link between ENDS and high-profile lung damage cases. Searches aimed at buying ENDS subsequently dropped 25% (95% CI, 20.1–29.6), while health-related ENDS searches spiked to their all-time high, increasing 22% (95% CI, −6 to 55) compared with the first half of 2019. ENDS searches are now more concentrated than 5 years ago, reversing the trend of the early 2010s, likely because certain states have passed laws to curb the use of ENDS. The public prefers searching for ‘vaping’ over ‘e-cigarette’ in a phenomenon similar to ‘high fructose corn syrup’ versus ‘sugar’. Consequently, public policy discussions and public education campaigns need to use ‘vaping’ terms, and more states should enact policies that are strongly associated with lower ENDS usage, many of which we identify.
The Lion, the Children and the Bookcase
Authors: Reynolds Margaret 
Published: March 2021

Abstract
‘The Lion, the Children and the Bookcase’, Margaret Reynolds C.S. Lewis’s The Lion, the Witch and the Wardrobe and Anne Frank’s diary, or The Diary of a Young Girl, were published in 1950 and 1947 respectively. Frank’s document is a testament to history. Lewis’s story is usually read as a fantasy or Christian allegory. But both books deal with the experience of racial hatred, betrayal, displacement, alienation, loss of identity and the damage inflicted on adults and on children. This article examines the connections, metaphorical and real, that link Frank’s statement of witness to Lewis’s reinterpretation of the effects of the 1939–45 war.
Short-run effects of poverty on asthma, ear infections and health service use: analysis of the Longitudinal Study of Australian Children
Authors: Bentley Rebecca , Simons Koen , Kvalsvig Amanda , Milne Barry , Blakely Tony 
Published: March 2021

Abstract

Background
Many studies have reported an inferred causal association of income poverty with physical health among children; but making causal inference is challenging due to multiple potential sources of systematic error. We quantified the short-run effect of changes in household poverty status on children’s health (asthma and ear infections) and service use (visits to the doctor and parent-reported hospital admissions), using a national longitudinal study of Australian children, with particular attention to potential residual confounding and selection bias due to study attrition.

Methods
We use four modelling approaches differing in their capacity to reduce residual confounding (generalized linear, random effects (RE), hybrid and fixed effects (FE) regression modelling) to model the effect of income poverty (&lt;60% of median income) on health for 10 090 children surveyed every 2nd year since 2004. For each method, we simulate the potential impact of selection bias arising due to attrition related to children’s health status.

Results
Of the 10 090 children included, 20% were in families in poverty at survey baseline (2004). Across subsequent years, ∼25% experienced intermittent and &lt;2% persistent poverty. No substantial associations between poverty and child physical health and service use were observed in the FE models least prone to residual confounding [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.81–1.10 for wheeze], in contrast to RE models that were positive (consistent with previous studies). Selection bias causing null findings was unlikely.

Conclusions
While poverty has deleterious causal effects on children’s socio-behavioural and educational outcomes, we find little evidence of a short-run causal effect of poverty on asthma, ear infections and health service use in Australia.
Emergence of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, carrying a novel mcr-1.19 variant cultured from egg in China
Authors: Hu Yujie , Fanning Séamus , Nguyen Scott V , Wang Wei , Liu Chang , Cui Xinnan , Dong Yinping , Gan Xin , Xu Jin , Li Fengqin 
Published: March 2021

Abstract

Objectives
This study aimed to characterize the genomic features of a Salmonella enterica serovar Typhimurium ST34 isolate, CFSA629, which carried a novel mcr-1 variant, designated as mcr-1.19, mapped to an ESBL-encoding IncHI2 plasmid.

Methods
Antimicrobial susceptibility assays as well as WGS were carried out on isolate CFSA629. The complete closed genome was obtained and then explored to obtain genomic features. Plasmid sequence comparison was performed for pCFSA629 with similar plasmids and the mcr-1 genetic environment was analysed.

Results
S. Typhimurium ST34 CFSA629 expressed an MDR phenotype to six classes of compound and consisted of a single circular chromosome and one plasmid. It possessed 11 resistance genes including 2 ESBL genes that mapped to the chromosome and the plasmid; an IS26-flanked composite-like transposon was identified. A novel mcr-1 variant (mcr-1.19) was identified, which had a unique SNP (G1534A) that gave rise to a novel MCR-1 protein containing a Val512Ile amino acid substitution. Plasmid pCFSA629 possessed a conjugative plasmid transfer gene cluster as well as an antimicrobial resistance-encoding gene cluster-containing region that contained two IS26 composite-like transposonal modules, but was devoid of any plasmid-mediated quinolone resistance genes. The background of mcr-1.19 consisted of an ISApl1-mcr-1-PAP2-ter module.

Conclusions
We report on an MDR S. Typhimurium ST34 CFSA629 isolate cultured from egg in China, harbouring an mcr-1.19 variant mapped to an IncHI2 plasmid. This highlights the importance of surveillance to mitigate dissemination of mcr-encoding genes among foodborne Salmonella. Improved surveillance is important for tackling the dissemination of mcr genes among foodborne Salmonella around the world.
Utilizing health information technology in the treatment and management of patients during the COVID-19 pandemic: Lessons from international case study sites
Authors: Malden Stephen , Heeney Catherine , Bates David W , Sheikh Aziz 
Published: March 2021

Abstract

Objective
The study sought to develop an in-depth understanding of how hospitals with a long history of health information technology (HIT) use have responded to the COVID-19 (coronavirus disease 2019) pandemic from an HIT perspective.

Materials and Methods
We undertook interviews with 44 healthcare professionals with a background in informatics from 6 hospitals internationally. Interviews were informed by a topic guide and were conducted via videoconferencing software. Thematic analysis was employed to develop a coding framework and identify emerging themes.

Results
Three themes and 6 subthemes were identified. HITs were employed to manage time and resources during a surge in patient numbers through fast-tracked governance procedures, and the creation of real-time bed capacity tracking within electronic health records. Improving the integration of different hospital systems was identified as important across sites. The use of hard-stop alerts and order sets were perceived as being effective at helping to respond to potential medication shortages and selecting available drug treatments. Utilizing information from multiple data sources to develop alerts facilitated treatment. Finally, the upscaling/optimization of telehealth and remote working capabilities was used to reduce the risk of nosocomial infection within hospitals.

Discussion
A number of the HIT-related changes implemented at these sites were perceived to have facilitated more effective patient treatment and management of resources. Informaticians generally felt more valued by hospital management as a result.

Conclusions
Improving integration between data systems, utilizing specialized alerts, and expanding telehealth represent strategies that hospitals should consider when using HIT for delivering hospital care in the context of the COVID-19 pandemic.
A4 THE CIRCADIAN TIMING OF INFLAMMATORY BOWEL DISEASE
Authors: Taleb Z , Stokes K , Wang H , Collins S M , Khan W I , Karpowicz P 
Published: March 2021

Abstract

Background
The circadian clock is a highly conserved molecular pacemaker found in nearly every cell of the body. It consists of the genes BMAL1 and CLOCK that positively regulate CRY and PER, their negative regulators, resulting in a transcription/translation feedback loop that has a 24 hour cycle. This core clock mechanism drives the rhythmic expression of over 40% of the genome in a tissue-specific manner and therefore imposes 24 hour rhythms on many physiological processes. Shift work, which causes disruptions to the natural 24 hour physiological rhythms, has been shown to lead to an increased incidence of inflammatory bowel disease (IBD).

Aims
This study aims to characterize daily rhythms in inflammation and regeneration of the colon upon induction of acute colitis. We also aim to investigate the intestinal epithelial-specific effects of circadian clock disruption on overall disease progression. We hypothesize that the absence of a functional circadian clock eliminates proliferation rhythms of intestinal epithelial cells and disrupts the rhythms of inflammatory cytokines, thereby increasing the pathogenesis of IBD.

Methods
We tested the role of the clock in IBD using BMAL1+/+ (wild type) and BMAL1-/- (null mutant) mice. We also investigated the effects of the circadian clock specific to intestinal epithelial tissue using Vil+/+;BMAL1flox/flox (control) and VilCre/+;BMAL1flox/flox (conditional intestinal epithelial mutant) mice. Dextran Sulfate Sodium (DSS) was applied to induce acute colitis.

Results
We observed significantly decreased survival of BMAL1 circadian clock mutant mice when given colitis. A histology analysis indicates increased lesioning and overall inflammation in BMAL1-/- colon tissue. Disease activity and cytokine analyses reveal time-dependent severity in inflammatory response that is worse in BMAL1-/- mice. To test the circadian rhythms in intestinal regeneration of mice with IBD, we performed a 24 hour analysis comparing epithelial cell proliferation and cell death in colon tissue. We observed rhythmic expression of phosphor-histone H3 (a mitosis marker) in wild type mice which is eliminated in the BMAL1-/- lacking a circadian clock. Cell death which was measured by caspase 3 did not exhibit any differences between genotypes. Based on these results, we conclude that the loss of clock function leads to impaired regeneration during IBD, in part due to decreased and arrhythmic cell proliferation. Preliminary results in our VilCre/+;BMAL1flox/flox conditional intestinal epithelial mutant mice indicate that some of these effects may be epithelial-specific.

Conclusions
Our results support a critical role of the circadian clock in inflammatory bowel disease development. These data highlight that the circadian clock affects the regenerative abilities of intestinal epithelial cells.

Funding Agencies
CIHRChron’s and Colitis Canada, Ontario, University of Windsor