bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopant activity for highly in-situ doped polycrystalline silicon: hall, XRD, scanning capacitance microscopy (SCM) and scanning spreading resistance microscopy (SSRM)
Authors: Coq Germanicus Rosine , Lallemand Florent , Chateigner Daniel , Jouha Wadia , Moultif Niemat , Latry Olivier , Fouchet Arnaud , Murray Hugues , Bunel Catherine , Lüders Ulrike
Published: March 2021

Progressing miniaturization and the development of semiconductor integrated devices ask for advanced characterizations of the different device components with ever-increasing accuracy. Particularly in highly doped layers, a fine control of local conduction is essential to minimize access resistances and optimize integrated devices. For this, electrical Atomic Force Microscopy (AFM) are useful tools to examine the local properties at nanometric scale, for the fundamental understanding of the layer conductivity, process optimization during the device fabrication and reliability issues. By using Scanning Capacitance Microscopy (SCM) and Scanning Spreading Resistance Microscopy (SSRM), we investigate a highly in situ doped polycrystalline silicon layer, a material where the electrical transport properties are well known. This film is deposited on a oxide layer as a passivating contact. The study of the nano-MIS (SCM) and nano-Schottky (SSRM) contacts allows to determine the distribution and homogeneity of the carrier concentration (active dopants), especially by investigating the redistribution of the dopants after an annealing step used for their activation. While the chemical analysis by Secondary Ions Mass Spectroscopy (SIMS) quantifies only the dopant concentration in the polycrystalline layer, the comparison with macroscopic characterization techniques as Hall effect measurements, supported with XRD characterization, shows that careful SCM and SSRM measurements can be used to highlight the dopant activation. This analysis gives a complete investigation of the local electrical properties of the passivating contact when the parameters (applied voltages and applied forces) of the AFM nano-contacts are correctly controlled.
Disparities in Coronavirus Disease 2019 Mortality by Country of Birth in Stockholm, Sweden: A Total-Population–Based Cohort Study
Authors: Rostila Mikael , Cederström Agneta , Wallace Matthew , Brandén Maria , Malmberg Bo , Andersson Gunnar
Published: March 2021

Preliminary evidence points to higher morbidity and mortality from coronavirus disease 2019 (COVID-19) in certain racial and ethnic groups, but population-based studies using microlevel data are lacking so far. We used register-based cohort data including all adults living in Stockholm, Sweden, between January 31, 2020 (the date of the first confirmed case of COVID-19) and May 4, 2020 (n = 1,778,670) to conduct Poisson regression analyses with region/country of birth as the exposure and underlying cause of COVID-19 death as the outcome, estimating relative risks and 95% confidence intervals. Migrants from Middle Eastern countries (relative risk (RR) = 3.2, 95% confidence interval (CI): 2.6, 3.8), Africa (RR = 3.0, 95% CI: 2.2, 4.3), and non-Sweden Nordic countries (RR = 1.5, 95% CI: 1.2, 1.8) had higher mortality from COVID-19 than persons born in Sweden. Especially high mortality risks from COVID-19 were found among persons born in Somalia, Lebanon, Syria, Turkey, Iran, and Iraq. Socioeconomic status, number of working-age household members, and neighborhood population density attenuated up to half of the increased COVID-19 mortality risks among the foreign-born. Disadvantaged socioeconomic and living conditions may increase infection rates in migrants and contribute to their higher risk of COVID-19 mortality.
Schnake-Mahl and Bilal Respond to “Structural Racism and COVID-19 Mortality in the US”
Authors: Schnake-Mahl Alina S , Bilal Usama
Published: March 2021

In their commentary, Zalla et al. (Am J Epidemiol. 2021;190(8):1439–1446) argue that the approach taken by the Centers for Disease Control and Prevention, comparing the proportion of coronavirus disease 2019 (COVID-19) deaths by race/ethnicity with a weighted population distribution, ignores how systemic racism structures the composition of places. While the Centers for Disease Control and Prevention have abandoned their measure, they did so because of the changing geographic distribution of COVID-19, not because the measure underestimates racial disparities. We further Zalla et al.’s argument, advocating for a relational approach to estimating COVID-19 racial inequities that integrates the reciprocal relationship between context and composition through the interaction of places and people over time. To support our argument, we present a series of figures exploring the heterogeneous relationships between places, people, and time, using publicly available, US county-level COVID-19 mortality data from February to December 2020 from Johns Hopkins University. Longitudinal and more geographically granular data that allows for disaggregation by person, place, and time will improve our estimation and understanding of inequities in COVID-19.
PTEN/AKT upregulation of TMSB10 contributes to lung cancer cell growth and predicts poor survival of the patients
Authors: Li Jie , Zhou Shaohui , Li Hongchen , Xu Yanzhao , Zhou Ning , Liu Rongfeng
Published: March 2021

PTEN/AKT signaling cascade is frequently activated in various cancers, including lung cancer. The downstream effector of this signaling cascade is poorly understood. β-Thymosin 10 (TMSB10) functions as an oncogene or tumor suppressors in cancers, whereas its significance in lung cancer remains unknown. In this study, we showed that the activation of PTEN/AKT signaling promoted the expression of TMSB10. Based on the TCGA database, TMSB10 was upregulated in lung cancer tissues and its overexpression was correlated with poor prognosis of lung cancer patients. Functional experiments demonstrated that TMSB10 knockdown suppressed, while its overexpression promoted the proliferation, growth, and migration of lung cancer cells. Apoptosis and epithelial-mesenchymal transition were also regulated by TMSB10. We therefore suggest that TMSB10 is a novel oncogene for lung cancer. Targeting TMSB10 may benefit lung cancer patients with activated PTEN/AKT signaling.
Membrane traffic related to endosome dynamics and protein secretion in filamentous fungi
Authors: Higuchi Yujiro
Published: March 2021

In eukaryotic cells, membrane-surrounded organelles are orchestrally organized spatiotemporally under environmental situations. Among such organelles, vesicular transports and membrane contacts occur to communicate each other, so-called membrane traffic. Filamentous fungal cells are highly polarized and thus membrane traffic is developed to have versatile functions. Early endosome (EE) is an endocytic organelle that dynamically exhibits constant long-range motility through the hyphal cell, which is proven to have physiological roles, such as other organelle distribution and signal transduction. Since filamentous fungal cells are also considered as cell factories, to produce valuable proteins extracellularly, molecular mechanisms of secretory pathway including protein glycosylation have been well investigated. In this review, molecular and physiological aspects of membrane traffic especially related to EE dynamics and protein secretion in filamentous fungi are summarized, and perspectives for application are also described.
Thermal adaptation of acetic acid bacteria for practical high-temperature vinegar fermentation
Authors: Matsumoto Nami , Osumi Naoki , Matsutani Minenosuke , Phathanathavorn Theerisara , Kataoka Naoya , Theeragool Gunjana , Yakushi Toshiharu , Shiraishi Yasushi , Matsushita Kazunobu
Published: March 2021

Thermotolerant microorganisms are useful for high-temperature fermentation. Several thermally adapted strains were previously obtained from Acetobacter pasteurianus in a nutrient-rich culture medium, while these adapted strains could not grow well at high temperature in the nutrient-poor practical culture medium, “rice moromi.” In this study, A. pasteurianus K-1034 originally capable of performing acetic acid fermentation in rice moromi was thermally adapted by experimental evolution using a “pseudo” rice moromi culture. The adapted strains thus obtained were confirmed to grow well in such the nutrient-poor media in flask or jar-fermentor culture up to 40 or 39 °C; the mutation sites of the strains were also determined. The high-temperature fermentation ability was also shown to be comparable with a low-nutrient adapted strain previously obtained. Using the practical fermentation system, “Acetofermenter,” acetic acid production was compared in the moromi culture; the results showed that the adapted strains efficiently perform practical vinegar production under high-temperature conditions.
Studies on analogs of DAMASCENOLIDETM: Part 4. Synthesis and odor evaluation of sulfur-containing analogs of DAMASCENOLIDETM
Authors: Miyazawa Yamato , Kawaguchi Kenji , Katsuta Ryo , Nukada Tomoo , Ishigami Ken
Published: March 2021

DAMASCENOLIDETM [1, 4-(4-methylpent-3-en-1-yl)furan-2(5H)-one], which is isolated from damask rose, is a useful aroma compound with a citrus-like odor. We have previously reported on the synthesis and odor properties of 34 analogs of 1 as part of our new aroma compound development project. In order to develop better aroma compounds and to gather more information on structure–odor relationships, 6 novel sulfur-containing analogs of 1 were synthesized. Odor evaluation revealed that their odors differed significantly from those of the corresponding sulfur-free compounds. The introduction of a sulfur atom does not necessarily result in a sulfur-like odor. In particular, the 2(5H)-thiophenone analogs gave waxy, oily, and lactone-like odors that are uncharacteristic of sulfur-containing compounds. In many synthesized analogs, the introduction of a sulfur atom led to an increase in odor intensity, as expected.
Mortality prediction by bispectral electroencephalography among 502 patients: its role in dementia
Authors: Saito Taku , Malicoat Johnny R , Leyden Lydia R , Williams Jessica C , Jellison Sydney S , Long Hailey , Hellman Mandy M , Crutchley Kaitlyn J , Anderson Zoe-Ella E M , Lo Duachee , Modukuri Manisha V , Schacher Cassidy J , Yoshino Aihide , Toda Hiroyuki , Shinozaki Eri , Cho Hyunkeun R , Lee Sangil , Shinozaki Gen
Published: March 2021

Complications of delirium and dementia increase mortality; however, it is difficult to diagnose delirium accurately, especially among dementia patients. The bispectral electroencephalography score can detect delirium and predict mortality in elderly patients. We aimed to develop an efficient and reliable bispectral electroencephalography device for high-throughput screening. We also hypothesized that bispectral electroencephalography score can predict mortality among dementia patients. A prospective cohort study was conducted between January 2016 and December 2018 to measure bispectral electroencephalography from elderly patients and correlate with outcomes. A total of 502 elderly (55 years old or older) patients with and without dementia were enrolled. For a replication of the utility of bispectral electroencephalography, mortalities between bispectral electroencephalography-positive and bispectral electroencephalography-negative group were compared. In addition, patients with and without dementia status were added to examine the utility of bispectral electroencephalography among dementia patients. The mortality within 180 days in the bispectral electroencephalography-positive group was higher than that of the bispectral electroencephalography-negative group in both the replication and the total cohorts. Mortality of those in the bispectral electroencephalography-positive group showed a dose-dependent increase in both cohorts. When the dementia patients showed bispectral electroencephalography positive, their mortality was significantly higher than those with dementia but who were bispectral electroencephalography-negative. Mortality within 30 days in the bispectral electroencephalography-positive group was significantly higher than that of the bispectral electroencephalography-negative group. The utility of the bispectral electroencephalography to predict mortality among large sample of 502 elderly patients was shown. The bispectral electroencephalography score can predict mortality among elderly patients in general, and even among dementia patients, as soon as 30 days.
The syndrome of transient epileptic amnesia: a combined series of 115 cases and literature review
Authors: Baker John , Savage Sharon , Milton Fraser , Butler Christopher , Kapur Narinder , Hodges John , Zeman Adam
Published: March 2021

The term transient epileptic amnesia was coined in 1990 to describe a form of epilepsy causing predominantly amnestic seizures which could be confused with episodes of Transient Global Amnesia. Subsequent descriptions have highlighted its association with ‘atypical’ forms of memory disturbance including accelerated long-term forgetting, disproportionate autobiographical amnesia and topographical amnesia. However, this highly treatment-responsive condition remains under-recognized and undertreated. We describe the clinical and neuropsychological features in 65 consecutive cases of transient epileptic amnesia referred to our study, comparing these to our previous cohort of 50 patients and to those reported in 102 literature cases described since our 2008 review. Findings in our two cohorts are substantially consistent: The onset of transient epileptic amnesia occurs at an average age of 62 years, giving rise to amnestic episodes at a frequency of around 1/month, typically lasting 15–30 min and often occurring on waking. Amnesia is the only manifestation of epilepsy in 24% of patients; olfactory hallucinations occur in 43%, motor automatisms in 41%, brief unresponsiveness in 39%. The majority of patients describe at least one of the atypical forms of memory disturbance mentioned above; easily provoked tearfulness is a common accompanying feature. There is a male predominance (85:30). Epileptiform changes were present in 35% of cases, while suspected causative magnetic resonance imaging abnormalities were detected in only 5%. Seizures ceased with anticonvulsant treatment in 93% of cases. Some clinical features were detected more commonly in the second series than the first, probably as a result of heightened awareness. Neuropsychological testing and comparison to two age and IQ-matched control groups (n = 24 and 22) revealed consistent findings across the two cohorts, namely elevated mean IQ, preserved executive function, mild impairment at the group level on standard measures of memory, with additional evidence for accelerated long-term forgetting and autobiographical amnesia, particularly affecting episodic recollection. Review of the literature cases revealed broadly consistent features except that topographical amnesia, olfactory hallucinations and emotionality have been reported rarely to date by other researchers. We conclude that transient epileptic amnesia is a distinctive syndrome of late-onset limbic epilepsy of unknown cause, typically occurring in late middle age. It is an important, treatable cause of memory loss in older people, often mistaken for dementia, cerebrovascular disease and functional amnesia. Its aetiology, the monthly occurrence of seizures in some patients and the mechanisms and interrelationships of the interictal features—amnestic and affective—all warrant further study.
Distribution of the Noradrenaline Innervation and Adrenoceptors in the Macaque Monkey Thalamus
Authors: Pérez-Santos Isabel , Palomero-Gallagher Nicola , Zilles Karl , Cavada Carmen
Published: March 2021

Noradrenaline (NA) in the thalamus has important roles in physiological, pharmacological, and pathological neuromodulation. In this work, a complete characterization of NA axons and Alpha adrenoceptors distributions is provided.

NA axons, revealed by immunohistochemistry against the synthesizing enzyme and the NA transporter, are present in all thalamic nuclei. The most densely innervated ones are the midline nuclei, intralaminar nuclei (paracentral and parafascicular), and the medial sector of the mediodorsal nucleus (MDm). The ventral motor nuclei and most somatosensory relay nuclei receive a moderate NA innervation. The pulvinar complex receives a heterogeneous innervation. The lateral geniculate nucleus (GL) has the lowest NA innervation.

Alpha adrenoceptors were analyzed by in vitro quantitative autoradiography. Alpha-1 receptor densities are higher than Alpha-2 densities. Overall, axonal densities and Alpha adrenoceptor densities coincide; although some mismatches were identified. The nuclei with the highest Alpha-1 values are MDm, the parvocellular part of the ventral posterior medial nucleus, medial pulvinar, and midline nuclei. The nucleus with the lowest Alpha-1 receptor density is GL. Alpha-2 receptor densities are highest in the lateral dorsal, centromedian, medial and inferior pulvinar, and midline nuclei.

These results suggest a role for NA in modulating thalamic involvement in consciousness, limbic, cognitive, and executive functions.
Scent Marks Signal Species, Sex, and Reproductive Status in Tamarins (Saguinusspp., Neotropical Primates)
Authors: Poirier Alice C , Waterhouse John S , Dunn Jacob C , Smith Andrew C
Published: March 2021

Olfactory communication is an important mediator of social interactions in mammals, thought to provide information about an individual’s identity and current social, reproductive, and health status. In comparison with other taxa such as carnivores and rodents, few studies have examined primate olfactory communication. Tamarins (Callitrichidae) conspicuously deposit odorous secretions, produced by specialized scent glands, in their environment. In this study, we combined behavioral and chemical data on captive cotton-top tamarins, Saguinus oedipus, and bearded emperor tamarins, S. imperator subgrisescens, to examine the role of olfactory communication in the advertisement of species, sex, and reproductive status. We observed no difference in scent-marking behavior between species; however, females marked more frequently than males, and reproductive individuals more than non-reproductive ones. In addition, tamarins predominantly used their anogenital gland when scent-marking, followed by the suprapubic gland. We collected swabs of naturally deposited tamarin anogenital scent marks, and analyzed these samples using headspace gas chromatography-mass spectrometry. Despite a limited sample size, we established differences in tamarin anogenital mark chemical composition between species, sex and reproductive status, and identified 41 compounds. The compounds identified, many of which have been reported in previous work on mammalian semiochemistry, form targets for future bioassay studies to identify semiochemicals. Our non-invasive method for collecting deposited scent marks makes it a promising method for the study of olfactory communication in scent-marking animal species, applicable to field settings and for the study of elusive animals.
Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From Asymptomatic and Presymptomatic Individuals in Healthcare Settings Despite Medical Masks and Eye Protection
Authors: Klompas Michael , Baker Meghan A , Griesbach Diane , Tucker Robert , Gallagher Glen R , Lang Andrew S , Fink Timelia , Cumming Melissa , Smole Sandra , Madoff Lawrence C , Rhee Chanu
Published: March 2021

We describe 3 instances of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission despite medical masks and eye protection, including transmission despite the source person being masked, transmission despite the exposed person being masked, and transmission despite both parties being masked. Whole genome sequencing confirmed perfect homology between source and exposed persons’ viruses in all cases.
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

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

Large-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

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 < .0001). Compared with unvaccinated patients, risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after the first dose (RR, .21; 95% CI, .12–.37; P < .0001) and >0 days after the second dose (RR, .20; 95% CI, .09–.44; P < .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

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

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 < 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

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

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

‘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

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 (<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 <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

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

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

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
A9 DORSAL ROOT GANGLIA NEURONAL RESPONSES AND SUBSTANCE P PRODUCTION ARE HIGHER IN MALE MICE
Authors: Pujo J , De Palma G , Lu J , Collins S M , Bercik P
Published: March 2021

Background

Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Sex also appears to play a key role in visceral sensitivity, as women report more abdominal pain than men. Thus, both gut bacteria and sex are important in the regulation of gut nociception, but the underlying mechanisms remain poorly understood.

Aims

To investigate the role of gut microbiota and sex in abdominal pain.

Methods

We used primary cultures of sensory neurons from dorsal root ganglia (DRG) of female and male conventionally raised (SPF) or germ-free (GF) mice (7–18 weeks old). To study the visceral afferent activity in vitro, calcium mobilization in DRG sensory neurons was measured by inverted fluorescence microscope using a fluorescent calcium probe Fluo-4 (1mM). Two parameters were considered i) the percentage of responding neurons ii) the intensity of the neuronal response. First, DRG sensory neurons were stimulated by a TRPV1 agonist capsaicin (12.5nM, 125nM and 1.25µM) or by a mixture of G-protein coupled receptors agonist (GPCR: bradykinin, histamine and serotonin; 1µM, 10µM and 100µM). We next measured the neuronal production of substance P and calcitonin gene-related peptide (CGRP), two neuropeptides associated with nociception, in response to capsaicin (1.25µM) or GPCR agonists (100µM) by ELISA and EIA, respectively.

Results

The percentage of neurons responding to capsaicin and GPCR agonists was similar in male and female SPF and GF mice. However, the intensity of the neuronal response was higher in SPF male compared to SPF female in response to capsaicin (125nM: p=0.0336; 1.25µM: p=0.033) but not to GPCR agonists. Neuronal activation was similar in GF and SPF mice of both sexes after administration of capsaicin or GPCR agonists. Furthermore, substance P and CGRP production by sensory neurons induced by capsaicin or GPCR agonists was similar in SPF and GF mice, regardless of sex. However, while the response to capsaicin was similar, the GPCR agonists-induced production of substance P was higher in SPF male mice compared to SPF females (p=0.003). The GPCR agonists-induced production of CGRP was similar in SPF male and female mice.

Conclusions

Our data suggest that at the level of DRG neurons, the absence of gut microbiota does not predispose to visceral hypersensitivity. The intensity of DRG neuronal responses to capsaicin and the GPCR agonists-induced production of substance P are higher in male compared to female mice, in contrast to previously published studies in various models of acute and chronic pain. Further studies are thus needed to investigate the role of sex in visceral sensitivity.

Funding Agencies

CIHR