bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Transcriptomics of Nematodes Identifies Sperm Cells as a Source of Genomic Novelty and Rapid Evolution
Authors: Rödelsperger Christian , Ebbing Annabel , Sharma Devansh Raj , Okumura Misako , Sommer Ralf J , Korswagen Hendrik C 
Published: August 2020

AbstractDivergence of gene function and expression during development can give rise to phenotypic differences at the level of cells, tissues, organs, and ultimately whole organisms. To gain insights into the evolution of gene expression and novel genes at spatial resolution, we compared the spatially resolved transcriptomes of two distantly related nematodes, Caenorhabditis elegans and Pristionchus pacificus, that diverged 60–90 Ma. The spatial transcriptomes of adult worms show little evidence for strong conservation at the level of single genes. Instead, regional expression is largely driven by recent duplication and emergence of novel genes. Estimation of gene ages across anatomical structures revealed an enrichment of novel genes in sperm-related regions. This provides first evidence in nematodes for the “out of testis” hypothesis that has been previously postulated based on studies in Drosophila and mammals. “Out of testis” genes represent a mix of products of pervasive transcription as well as fast evolving members of ancient gene families. Strikingly, numerous novel genes have known functions during meiosis in Caenorhabditis elegans indicating that even universal processes such as meiosis may be targets of rapid evolution. Our study highlights the importance of novel genes in generating phenotypic diversity and explicitly characterizes gene origination in sperm-related regions. Furthermore, it proposes new functions for previously uncharacterized genes and establishes the spatial transcriptome of Pristionchus pacificus as a catalog for future studies on the evolution of gene expression and function.
Frequent DNA methylation changes in cancerous and noncancerous lung tissues from smokers with non-small cell lung cancer
Authors: Daniunaite Kristina , Sestokaite Agne , Kubiliute Raimonda , Stuopelyte Kristina , Kettunen Eeva , Husgafvel-Pursiainen Kirsti , Jarmalaite Sonata 
Published: August 2020

AbstractCancer deaths account for nearly 10 million deaths worldwide each year, with lung cancer (LCa) as the leading cause of cancer-related death. Smoking is one of the major LCa risk factors, and tobacco-related carcinogens are potent mutagens and epi-mutagens. In the present study, we aimed to analyse smoking-related epigenetic changes in lung tissues from LCa cases. The study cohort consisted of paired LCa and noncancerous lung tissues (NLT) from 104 patients, 90 of whom were smokers or ex-smokers (i.e. ever smokers) at the time of diagnosis. DNA methylation status of tumour suppressor genes DAPK1, MGMT, p16, RASSF1 and RARB was screened by means of methylation-specific PCR (MSP) and further analysed quantitatively by pyrosequencing. Methylation of at least one gene was detected in 59% (61 of 104) of LCa samples and in 39% (41 of 104) of NLT. DAPK1 and RASSF1 were more frequently methylated in LCa than in NLT (P = 0.022 and P = 0.041, respectively). The levels of DNA methylation were higher in LCa than NLT at most of the analysed CpG positions. More frequent methylation of at least one gene was observed in LCa samples of ever smokers (63%, 57 of 90) as compared with never smokers (36%, 5 of 14; P = 0.019). In the ever smokers group, methylation of the genes also occurred in NLT, but was rare or absent in the samples of never smokers. Among the current smokers, RASSF1 methylation in LCa showed association with the number of cigarettes smoked per day (P = 0.017), whereas in NLT it was positively associated with the duration of smoking (P = 0.039). Similarly, p16 methylation in LCa of current smokers correlated with the larger number of cigarettes smoked per day (P = 0.047). Overall, DNA methylation changes were present in both cancerous and noncancerous tissues of LCa patients and showed associations with smoking-related parameters.
Topical nitroglycerin for management of peripheral extravasation of vasopressors: a case report
Authors: Shrestha Ninadini , Acharya Utsav , Shrestha Pramesh Sunder , Acharya Subhash Prasad , Karki Bipin , Dhakal Subodh Sagar 
Published: August 2020

ABSTRACT
Peripheral route for administration of vasopressors is often opted due to resource limitations or as a rescue until central venous access is established. This, however, is not devoid of complications, the most common being extravasation and tissue injury. Phentolamine is the only drug approved for management of vasopressor extravasation; however, successful use of other agents has been reported. Here we report a case of peripheral extravasation of vasopressors, successfully managed with topical nitroglycerin in intensive care unit in Kathmandu. To our knowledge, this is the first report of such kind from Nepal.
Loneliness and COVID-19 preventive behaviours among Japanese adults
Authors: Stickley Andrew , Matsubayashi Tetsuya , Ueda Michiko 
Published: August 2020

Abstract

Background
There is some evidence that loneliness may be linked to poorer health behaviours. Despite this, there has been little research to date on the relationship between loneliness and COVID-19 preventive behaviours. We studied these associations in a sample of the Japanese population.

Methods
Data were analysed from an online survey of 2000 adults undertaken in April and May 2020. Loneliness was assessed with the Three-Item Loneliness Scale. Information was also collected on 13 COVID-19 preventive behaviours. Regression analyses were used to examine associations.

Results
In linear regression models adjusted for demographic and mental health variables, both dichotomous and continuous loneliness measures were negatively associated with engaging in COVID-19 preventive behaviours. Logistic regression analyses further showed that loneliness was also associated with reduced odds for a variety of individual preventive behaviours including wearing a mask (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.62–0.95), disinfecting hands (OR: 0.80, 95% CI: 0.67–0.94) and social distancing when outdoors (OR: 0.75, 95% CI: 0.61–0.92).

Conclusions
Loneliness is associated with lower engagement in COVID-19 preventive behaviours. Interventions to prevent or ameliorate loneliness during the ongoing pandemic may be important in combating the spread of the coronavirus.
Mortality over 14 years in MTX-refractory patients randomized to a strategy of addition of infliximab or sulfasalazine and hydroxychloroquine
Authors: Miller Heather , Wallman Johan K , Petersson Ingemar F , Saevarsdottir Saedis , Söderling Jonas , Ernestam Sofia , Askling Johan , van Vollenhoven Ronald , Neovius Martin 
Published: August 2020

Abstract

Objective
To compare mortality risk over up to 14 years of follow-up in methotrexate-refractory patients with early RA randomized to a strategy starting with addition of infliximab vs addition of SSZ and HCQ.

Methods
Data was from the two-arm, parallel, randomized, active-controlled, open-label Swefot trial in which patients with early RA (symptom duration &lt;1 y) were recruited from 15 rheumatology clinics in Sweden (2002–2005). Patients who did not achieve low disease activity after 3–4 months of MTX were randomized to addition of infliximab (n = 128) or SSZ and HCQ (n = 130). Participants were followed until death, emigration, or end of follow-up, whichever came first. Analyses were by intention-to-treat.

Results
Over an average follow-up of 13 years, there were 13 and 16 deaths, respectively [8.8 vs 10.6 deaths per 1000 person-years; mortality hazard ratio 1.2 (95% CI: 0.6, 2.5); P =0.62]. The 1-year mortality was 0.8% in both treatment arms, the 5-year mortality was 2.3% for the infliximab arm compared with 1.5% for the conventional combination treatment arm, while the 10-year mortality was 7.8% and 7.7%, respectively. After 5 years, ∼50% of patients in the conventional combination therapy arm had switched to biologic treatment, and 50% in the biologic arm had discontinued treatment with a biologic DMARD.

Conclusion
No difference in mortality risk could be observed over up to 14 years of follow-up between treatment strategy groups. At 5 years (3 years after trial cessation), 50% of patients remained on their assigned therapy, reflecting that DMARD combination is an adequate treatment strategy in 50% of patients.

Trial registration
clinicaltrials.gov, identifier: NCT00764725.
Successful management with Janus kinase inhibitor tofacitinib in refractory juvenile dermatomyositis: a pilot study and literature review
Authors: Yu Zhongxun , Wang Lin , Quan Meiying , Zhang Tiannan , Song Hongmei 
Published: August 2020

Abstract

Objectives
JDM is a rare autoimmune inflammatory muscle disease with a pronounced IFN signature. Treatment for children with JDM has improved over the years with the use of steroids and immunosuppressive agents. However, there remains a subset of children who have refractory disease. Janus kinase and type I IFN signalling production are suspected to contribute to the pathogenesis of JDM. Our pilot study investigated the use of tofacitinib, a Janus kinase inhibitor, in refractory JDM cases to provide new therapeutic options for better treatment.

Methods
Refractory JDM was defined as patients who failed two or more steroid sparing agents or high-dose steroids. Tofacitinib was given to three refractory JDM patients with a dose of 5 mg twice per day for at least 6 months. Core set measures defined by Pediatric Rheumatology International Trials Organization were evaluated at month 0, 3 and 6 along with other systemic evaluations. A literature review was conducted to identify all the cases using Janus kinase inhibitors in JDM.

Results
All three subjects tolerated and responded well to tofacitinib with significant improvement in Child Myositis Assessment Scale, manual muscle testing-8, physician global disease activity and inflammatory indices without occurrence of severe adverse events.

Conclusion
This pilot study showed improvement of muscle strength, resolution of cutaneous lesions, increased daily quality of life and successful tapering of steroids when tofacitinib used in selected cases. Tofacitinib can be considered with caution when treating refractory JDM cases. Further randomized controlled trials are warranted to assess its efficacy in JDM.
An Innovative Approach to Advancing Academic Success for Underrepresented Nursing Students Using the Collective Impact Model
Authors: Ackerman-Barger Kupiri , DeWitty Vernell P. , Cooper Jazmine , Anderson Maija R. 
Published: August 2020

Abstract
This article describes the application of the Collective Impact Model as an innovative conceptual framework for developing a pedagogical process for advancing academic success and retention for underrepresented nursing students. A more diverse nursing workforce is critical to promoting health equity and supporting a culture of health by providing access to culturally and linguistically appropriate care. By strategically applying this framework to a complex issue in nursing education, we discuss a process that may lead to increased academic success and NCLEX®RN pass rates for underrepresented students.
The Effects of a Deliberate Practice Debriefing During a Response to Rescue Patient Simulation With Undergraduate Nursing Students
Authors: Aronson Barbara , Bell Arleigh , Andrighetti Tia , Meyer Mary , Shepherd Karen , Bambini Deborah 
Published: August 2020

Abstract
The purpose of this multisite, randomized, pretest/posttest quasi-experimental study was to compare student nurse competency, learning retention, and perceived student support after exposure to a deliberate practice debriefing versus standardized debriefing. Fifty undergraduate students participated in the complex response to rescue simulation. The intervention group had significantly higher total mean and three subscale scores on the competency tool than the comparison group, although differences in learning retention and student support were not significant. This study provides preliminary support for the effectiveness of deliberate practice debriefing to enhance students’ mastery of skills and behaviors in complex simulations.
Pregnancy and Hymenoptera venom allergy
Authors: Bonadonna Patrizia , Mauro Marina , Preziosi Donatella , Pravettoni Valerio 
Published: August 2020

Purpose of review
To evaluate the indication to perform venom immunotherapy (VIT) during pregnancy considering the risks of adverse events during the build-up phase or the maintenance phase and analyzing specific articles and guidelines on VIT.

Recent findings
Only few studies treat this argument and literature only counts one recent study on the topic, whereas recent guidelines state the behavior to keep in pregnancy.

Summary

Hymenoptera venom allergy (HVA) affects about 7.5% of the European population. VIT is the only effective disease-modifying treatment for patients presenting anaphylactic reactions. VIT counts several mechanisms of action, with the increase of IgG1 and IgG4 and a cytokine impairment inducing a Th2–Th1 shift. Pregnancy is a health condition where a Th2 profile is required to prevent fetal rejection, so VIT could be a problem for the fetus when started during pregnancy.
Volatile Anesthetics Activate a Leak Sodium Conductance in Retrotrapezoid Nucleus Neurons to Maintain Breathing during Anesthesia in Mice
Authors: Yang Yaoxin , Ou Mengchan , Liu Jin , Zhao Wenling , Zhuoma Lamu , Liang Yan , Zhu Tao , Mulkey Daniel K. , Zhou Cheng 
Published: August 2020

Background
Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output.

Methods
The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity.

Results
Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel–mediated holding currents and conductance from −75.0 ± 12.9 to −130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel–mediated holding conductance.

Conclusions
Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics.

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Machine Learning Predicts Prolonged Acute Hypoxemic Respiratory Failure in Pediatric Severe Influenza
Authors: Sauthier Michaël S. , Jouvet Philippe A. , Newhams, Margaret M. , Randolph Adrienne G. 
Published: August 2020

Background:
Influenza virus is a major cause of acute hypoxemic respiratory failure. Early identification of patients who will suffer severe complications can help stratify patients for clinical trials and plan for resource use in case of pandemic.

Objective:
We aimed to identify which clinical variables best predict prolonged acute hypoxemic respiratory failure in influenza-infected critically ill children. Acute hypoxemic respiratory failure was defined using hypoxemia cutoffs from international consensus definitions of acute respiratory distress syndrome in patients with ventilatory support. Prolonged acute hypoxemic respiratory failure was defined by acute hypoxemic respiratory failure criteria still present at PICU day 7.

Derivation Cohort:
In this prospective multicenter study across 34 PICUs from November 2009 to April 2018, we included children (< 18 yr) without comorbid risk factors for severe disease.

Validation Cohort:
We used a Monte Carlo cross validation method with N
2 random train-test splits at a 70–30% proportion per model.

Prediction Model:
Using clinical data at admission (day 1) and closest to 8 am on PICU day 2, we calculated the area under the receiver operating characteristic curve using random forests machine learning algorithms and logistic regression.

Results:
We included 258 children (median age = 6.5 yr) and 11 (4.2%) died. By day 2, 65% (n = 165) had acute hypoxemic respiratory failure dropping to 26% (n = 67) with prolonged acute hypoxemic respiratory failure by day 7. Those with prolonged acute hypoxemic respiratory failure had a longer ICU stay (16.5 vs 4.0 d; p < 0.001) and higher mortality (13.4% vs 1.0%). A multivariable model using random forests with 10 admission and eight day 2 variables performed best (0.93 area under the receiver operating characteristic curve; 95 CI%: 0.90–0.95) where respiratory rate, Fio
2, and pH on day 2 were the most important factors.

Conclusions:
In this prospective multicentric study, most children with influenza virus–related respiratory failure with prolonged acute hypoxemic respiratory failure can be identified early in their hospital course applying machine learning onto routine clinical data. Further validation is needed prior to bedside implementation.
Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients
Authors: Taccone Fabio Silvio , Gevenois Pierre Alain , Peluso Lorenzo , Pletchette Zoe , Lheureux Olivier , Brasseur Alexandre , Garufi Alessandra , Talamonti Marta , Motte Serge , Nobile Leda , Grimaldi David , Creteur Jacques , Vincent Jean-Louis 
Published: August 2020

Objectives:
To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients.

Design:
Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020.

Setting:
ICU of an University Hospital in Belgium.

Patients and Interventions:
Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin).

Measurements and Main Results:
Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4–8 d) since ICU admission and 12 days (9–16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78–1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%—odds ratio 0.13 [0.02–0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24–3.26]; p = 0.99).

Conclusions:
In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.
Traffic-related Noise Exposure and Late-life Dementia and Cognitive Impairment in Mexican–Americans
Authors: Yu Yu , Mayeda Elizabeth Rose , Paul Kimberly C. , Lee Eunice , Jerrett Michael , Su Jason , Wu Jun , Shih I-Fan , Haan Mary , Ritz Beate 
Published: August 2020

Background:
Recently, it has been suggested that environmental exposures from traffic sources including noise may play a role in cognitive impairment in the elderly. The objective of the study was to investigate the association between local traffic-related noise pollution and incident dementia or cognitive impairment without dementia (CIND) during a 10-year follow-up period.

Methods:
1612 Mexican–American participants from the Sacramento Area Latino Study on Aging (SALSA) were followed every 12–15 months via home visits from 1998 to 2007. We used the SoundPLAN software package to estimate noise originating from local traffic with the input of Annual Average Daily Traffic (AADT) data from Metropolitan Planning Organizations (MPO) based on geocoded residential addresses at baseline (1998–1999). We estimated the risks of incident dementia or CIND from 24-hour and nighttime noise exposure using Cox proportional hazard models.

Results:
During the follow-up, we identified 159 incident dementia or CIND cases in total. Per 11.6 dB (interquartile range width) increase in 24-hour noise, the hazard of developing dementia or CIND increased (hazard ratio = 1.3 [1.0, 1.6]) during follow-up; estimates were slightly lower (hazard ratio = 1.2 [0.97, 1.6]) when adjusting for modeled local air pollution exposure from traffic sources. Overall, the risk of dementia/CIND was elevated when 24-hour and nighttime noise were higher than 75 and 65 dB respectively. See video Abstract: http://links.lww.com/EDE/B728.

Conclusions:
In our study, traffic-related noise exposure was associated with increased risk of dementia or CIND in elderly Mexican–Americans. Future studies taking into account other noise sources and occupational noise exposure before retirement are needed.