bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Handheld Continuous Electroencephalogram (EEG) Has the Potential to Detect Delirium in Older Adults
Authors: Mulkey Malissa A. , Gantt Laura T. , Hardin Sonya R. , Munro Cindy L. , Everhart D. Erik , Kim Sunghan , Schoeman Alexander M. , Roberson Donna W. , McAuliffe Maura , Olson DaiWai M.
Published: November 2021

Background

Delirium-related biochemical derangements lead to electrical changes that can be detected in electroencephalographic (EEG) patterns followed by behavioral signs and symptoms. Studies using limited lead EEG show a large difference between patients with and without delirium while discriminating delirium from other causes. Handheld rapid EEG devices may be capable of detecting delirium before symptom onset, thus providing an objective physiological method to detect delirium when it is most amenable to interventions.

Objective

The aim of this study was to explore the potential for rapid EEG to detect waveform pattern changes consistent with delirium status.

Methods

This prospective exploratory pilot study used a correlational design and mixed models to explore the relationships between handheld portable EEG data and delirium status.

Results

While being under powered minimized opportunities to detect statistical differences in EEG-derived ratios using spectral density analysis, sleep-to-wake ratios tended to be higher in patients with delirium.

Conclusions

Limited lead EEG may be useful in predicting adverse outcomes and risk for delirium in older critically ill patients. Although this population is at the highest risk for mortality, delirium is not easily identified by current clinical assessments. Therefore, further investigation of limited lead EEG for delirium detection is warranted.
Parent Perception of Their Role in the Pediatric Cardiac Intensive Care Unit
Authors: Fisk Anna C. , Mott Sandra , Meyer Shannon , Connor Jean A.
Published: November 2021

Background/Introduction

One way the goal of establishing a partnership with families is accomplished, specific to the pediatric intensive care units, is 24-hour visitation and presence/participation during medical rounds and procedures. Despite the breadth of literature on the positive effect of parent presence, as well as the nearly nationwide adoption of 24-hour pediatric intensive care unit visitation, there is little to no research about how these changes have affected parents' perception of their role in the pediatric cardiac intensive care unit (PCICU).

Objectives/Aims

The purpose of this study was to explore and better understand the experience of parents in the PCICU within a patient/family-centered care model.

Methods

Using a qualitative descriptive approach, interviews were conducted with parents of children currently admitted as inpatients in the PCICU. Participants were asked broad, open-ended questions and probes to attain qualitative descriptions of their experiences and perceptions of their parental role in the PCICU. The research design for this study was based on naturalistic inquiry and was used to describe rather than interpret parental experiences in their own words.

Results

Eleven parents from 7 families were interviewed; parents described their role in terms of 2 main categories, as one who is an advocate and decision maker and one who provides emotional and physical support. Parents valued the expertise of the PCICU team but also shared the significance of the team recognizing their role as parents. Incorporating parents as an integral member of the health care team is a fundamental component to PCICU care.

Discussion/Conclusion

The role of parents is irreplaceable, particularly in the PCICU. The medical complexity of the intensive care can be a barrier to act as parents resulting in a disruption of family-centered care. Nursing staff avert this disruption through modeling parenting to their child's present circumstances and involvement in normal parenting tasks.
Risk of Malnutrition and Clinical Outcomes Among Mechanically Ventilated Patients in Intensive Care Units
Authors: Al Tamimi Dua'a , Ahmad Muayyad
Published: November 2021

Background

Critically ill patients who are mechanically ventilated are at a high risk for malnutrition, which is associated with poor clinical outcomes.

Aim

The aim of this study was to determine whether the modified version of Nutrition Risk in the Critically Ill (mNUTRIC) score predicts patients' clinical and functional outcomes in intensive care units (ICUs) in Jordan.

Methods

A prospective, observational, quantitative research design was used. A convenience sample of 129 mechanically ventilated patients was recruited from ICUs in 7 hospitals across the different Jordanian health care sectors. Each patient was assessed and scored by the mNUTRIC tool.

Results

Of the total 129 mechanically ventilated patients, the mean (SD) age of critically ill participants was 66.38 (17.46) years, 69.8% of the participants were male (n = 90), and 30.2% were female (n = 39). Approximately 88.4% of mechanical ventilator patients were at a high risk of malnutrition at the time of ICU admission. Overall, high mNUTRIC score (≥5) was significantly associated with MV duration (P = .004), ICU length of stay (P = .002), mortality (odds ratio, 5.43; P = .005), and functional outcomes (odds ratio, 0.184; P = .009).

Relevance to Clinical Practice

Using nutrition risk screening tools such as the mNUTRIC score will add great benefits to nursing practice through identifying patients who are at a high risk of malnutrition within the first 48 hours of their admission in the ICU.
Estimating Associations Between Annual Concentrations of Particulate Matter and Mortality in the United States, Using Data Linkage and Bayesian Maximum Entropy
Authors: Rudolph Jacqueline E. , Cole Stephen R. , Edwards Jessie K. , Whitsel Eric A. , Serre Marc L. , Richardson David B.
Published: November 2021

Background:

Exposure to fine particulate matter (PM2.5) is an established risk factor for human mortality. However, previous US studies have been limited to select cities or regions or to population subsets (e.g., older adults).

Methods:

Here, we demonstrate how to use the novel geostatistical method Bayesian maximum entropy to obtain estimates of PM2.5 concentrations in all contiguous US counties, 2000–2016. We then demonstrate how one could use these estimates in a traditional epidemiologic analysis examining the association between PM2.5 and rates of all-cause, cardiovascular, respiratory, and (as a negative control outcome) accidental mortality.

Results:

We estimated that, for a 1 log(μg/m3) increase in PM2.5 concentration, the conditional all-cause mortality incidence rate ratio (IRR) was 1.029 (95% confidence interval [CI]: 1.006, 1.053). This implies that the rate of all-cause mortality at 10 µg/m3 would be 1.020 times the rate at 5 µg/m3. IRRs were larger for cardiovascular mortality than for all-cause mortality in all gender and race–ethnicity groups. We observed larger IRRs for all-cause, nonaccidental, and respiratory mortality in Black non-Hispanic Americans than White non-Hispanic Americans. However, our negative control analysis indicated the possibility for unmeasured confounding.

Conclusion:

We used a novel method that allowed us to estimate PM2.5 concentrations in all contiguous US counties and obtained estimates of the association between PM2.5 and mortality comparable to previous studies. Our analysis provides one example of how Bayesian maximum entropy could be used in epidemiologic analyses; future work could explore other ways to use this approach to inform important public health questions.
Association between benzodiazepine premedication and 30-day mortality rate
Authors: Kowark Ana , Berger Moritz , Rossaint Rolf , Schmid Matthias , Coburn Mark
Published: November 2021

BACKGROUND

Recent guidelines suggest that benzodiazepine premedication should be avoided in elderly patients, though with limited supporting evidence.

OBJECTIVE

We conducted a secondary analysis of the POSE data to explore the association of premedication in patients aged 80 years or older with 30-day mortality.

DESIGN

We used propensity score methods to perform a confounder-adjusted time-to-event analysis of the association between benzodiazepine premedication and 30-day mortality of the POSE study.

SETTING

POSE was conducted as a European multicentre prospective cohort study.

PATIENTS

Adults aged 80 years or older scheduled for surgical or nonsurgical intervention under anaesthesia.

RESULTS

A total of 9497 patients were analysed. One thousand five hundred and twenty-one patients received benzodiazepine premedication, 7936 patients received no benzodiazepine premedication, 30 received clonidine and 10 had missing premedication data. Inverse propensity-score-weighted log-rank analysis did not provide unambiguous evidence for an association between benzodiazepine premedication and 30-day mortality; median [range] P = 0.048 [0.044 to 0.078], estimated 30-day mortality rates 3.21% and 4.45% in benzodiazepine-premedicated and nonbenzodiazepine-premedicated patients, respectively. Inverse propensity-score-weighted Cox regression resulted in a hazard ratio of 0.71 (95% CI 0.49 to 1.04), pointing at a possible reduction of 30-day mortality in the benzodiazepine premedication group. Sensitivity analyses, which constituted subgroup, matched-pairs, and subclassification analyses, resulted in similar findings.

CONCLUSION

This secondary analysis of the POSE data did not find evidence for an unambiguous association between benzodiazepine premedication and 30-day mortality. Point estimates indicated a reduction of 30-day mortality in benzodiazepine-premedicated patients. The results presented here might be affected by unmeasured confounding factors, which could be addressed in a randomised trial.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03152734.
Ciprofloxacin-associated Peripheral Neuropathy in a Child: A Case Report and Review of the Literature
Authors: Morley Carla , Carvalho de Almeida Carla , Moloney Susan , Grimwood Keith
Published: November 2021

Fluoroquinolones are reported to have peripheral nerve toxic effects that can be severe and permanent in adults. However, limited data exist for children. We describe a case of acute-onset peripheral neuropathy associated with ciprofloxacin in a 13-year-old boy who was characterized by severe dysesthesia and erythema of both hands and feet, but which resolved promptly after ceasing the antibiotic.
Disparities in Outcomes During Lower Respiratory Tract Infection in American Indian Children
Authors: Palmer Geralyn M. , Kooima Travis R. , Van Hove Christopher M. , Withrow Landon L. , Gurumoorthy Aarabhi , Lopez Santiago M.C.
Published: November 2021

Background:

American Indian (AI) children are at increased risk for severe disease during lower respiratory tract infection (LRTI). The reasons for this increased severity are poorly understood. The objective of this study was to define the clinical presentations of LRTI and highlight the differences between AI and non-AI previously healthy patients under the age of 24 months.

Methods:

We performed a retrospective chart review between October 2010 and December 2019. We reviewed 1245 patient charts and 691 children met inclusion criteria for this study. Data records included demographics, clinical, laboratory data, and illness outcomes.

Results:

Of 691 patients, 120 were AI and 571 were non-AI. There was a significant difference in breast-feeding history (10% of AI vs. 28% of non-AI, P < 0.0001) and in secondhand smoke exposure (37% of AI vs. 21% of non-AI, P < 0.0001). AI children had increased length of hospitalization compared with non-AI children (median of 3 vs. 2 days, P < 0.001). In addition, AI children had higher rates of pediatric intensive unit admission (30%, n = 37) compared with non-AI children (11%; n = 67, P < 0.01). AI children also had higher rates (62.5%, n = 75) and duration of oxygen supplementation (median 3 days) than non-AI children (48%, n = 274, P = 0.004; median 2 days, P = 0.0002). On a multivariate analysis, AI race was an independent predictor of severe disease during LRTI.

Conclusions:

AI children have increased disease severity during LRTI with longer duration of hospitalization and oxygen supplementation, a higher rate of oxygen requirement and Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation pediatric intensive care unit admissions, and a greater need for mechanical ventilation. These results emphasize the need for improvement in health policies and access to health care in this vulnerable population.
Common bacterial metabolite indole directly activates nociceptive neuron through transient receptor potential ankyrin 1 channel
Authors: Chung Sena , Kim Hayun , Kim Doyun , Lee Jung Moo , Lee C. Justin , Oh Seog Bae
Published: November 2021

Nociceptors are known to directly recognize bacterial cell wall components or secreted toxins, thereby leading to pain induced by bacterial infection. However, direct activation of nociceptors by bacterial metabolites remains unclear although bacteria produce numerous metabolites related to health and disease. In this study, we investigated whether and how a common bacterial metabolite, indole, which is produced by normal microflora of the gastrointestinal tract and oral cavity, can directly activate nociceptive sensory neurons. We found that indole elicits calcium response and evokes inward currents in subsets of dorsal root ganglia (DRG) neurons. Intraplantar (i.pl.) injection of indole produced nocifensive behaviors in adult mice, which were enhanced in complete Freund’s adjuvant–induced chronic inflammatory condition. Indole increased calcitonin gene-related peptide release in DRG neurons, and i.pl. injection of indole increased hind paw thickness, suggesting its role in generation of neurogenic inflammation. These in vitro and in vivo indole-induced responses were pharmacologically blocked by transient receptor potential ankyrin 1 (TRPA1) antagonist, HC-030031, and significantly abolished in TRPA1 knockout (KO) mice, indicating that indole targets TRPA1 for its action in DRG neurons. Nocifensive licking behavior induced by the injection of live Escherichia coli was significantly decreased in tryptophanase mutant (TnaA KO) E. coli-injected mice that lack indole production, further supporting the idea that bacteria-derived indole can induce pain during infection. Identifying the mechanism of action of indole through TRPA1 provides insights into bacteria–neuron interactions and the role of bacterial metabolites in pain signaling, especially in inflammation-accompanied bacterial infection.
The Prospective Association Between Physical Activity, Insomnia Symptoms, and Productivity in an Australian Population-Based Cohort
Authors: Oftedal Stina , Fenwick Matthew J. , Duncan Mitch J.
Published: November 2021

Objectives:

To investigate the joint, prospective associations of physical inactivity and insomnia symptoms and productivity using the 2013 and 2014 household income and labor dynamics in Australia Survey panel data.

Methods:

The association between (i) presenteeism (yes/no, n = 5864) and (ii) absenteeism (sick leave days, n = 4324) and the mutually exclusive groups “active without insomnia,” “active with insomnia,” “inactive without insomnia,” and “inactive with insomnia” was assessed.

Results:

Participants “active with insomnia” or “inactive with insomnia” had greater odds of presenteeism than those “active without insomnia” (odds ratio [OR] = 1.41, 95% confidence interval [CI]: 1.07 to 1.85 and OR = 1.44, 95% CI: 1.14 to 1.83, respectively). Participants “inactive with insomnia” had a greater incidence of absenteeism than participants “active without insomnia” (incidence rate ratio [IRR] = 1.28, 95% CI: 1.07 to 1.54).

Conclusions:

Findings suggest improving physical activity levels and insomnia symptoms concurrently may improve productivity by reducing presenteeism and sick leave.
Finding Success in Scholarship: How Physician Assistant Educators Can Overcome Barriers to Publication
Authors: Reed Harrison , Artino Anthony R.
Published: November 2021

Publishing scholarly work offers several benefits for physician assistants (PAs) in faculty roles. It allows them to establish expertise, disseminate knowledge, and advance their careers. However, due to a variety of barriers, PAs are often unable to build a portfolio of scholarly articles. They frequently lack the time, training, experience, and resources to complete large academic projects and navigate the complex publication process. This article offers 6 key strategies to help PAs in academic settings pursue scholarly work and achieve publication.
The Utility of the Modified Dionne's Egress Test as a Predictor of Falls in Adult Medical and Surgical Patients
Authors: Barbay Kathryn , Williams Karen B. , Berning Paul
Published: November 2021

OBJECTIVE

The aim of this study was to compare the efficacy of a modified Dionne's Egress Test (Egress) as a predictor of falls with the Morse Fall Scale (MFS) in adult medical and surgical patients in an acute care setting.

BACKGROUND

Nurses must identify fall risk while balancing fall prevention and early mobility in their care delivery. Fall risk screening tools alone are not enough to assist nurses in predicting patients at risk of falling.

METHODS

A retrospective observational study design was used to compare the Egress as a predictor of falls to the MFS. The sample included data abstracted from 197 electronic health records and internal falls data.

RESULTS

The Egress and the MFS are moderately and negatively correlated; however, only Egress was a significant predictor of falls. Passing the Egress, not being on benzodiazepines, and having a longer length of stay (LOS) results were associated with being less likely to fall.

CONCLUSION

Egress is a better predictor of falls than MFS when benzodiazepines and LOS are controlled in the model.
Controversies in Systemic Lupus Erythematosus
Authors: Porta Sabrina Valeria , Ugarte-Gil Manuel F. , García-de la Torre Ignacio , Bonfá Eloísa , Gómez-Puerta José A. , Arnaud Laurent , Cardiel Mario H. , Alarcón Graciela S. , Pons-Estel Bernardo A. , Pons-Estel Guillermo
Published: November 2021

Systemic lupus erythematosus (SLE) is characterized by great clinical heterogeneity. The objectives of its management are to make a timely diagnosis and to initiate treatment as promptly as possible so organ damage can be avoided while at the same time exposure to potentially toxic drugs is minimized so that its overall course and outcome improve. In reviewing the current literature, it became quite clear that there are specific topics in which controversies do exist. These include how to treat patients with incomplete lupus erythematosus, the real possibility of abandoning altogether the use of oral glucocorticoids, and the pros and cons of the use of cyclophosphamide and mycophenolate mofetil for the induction treatment of lupus nephritis. Herein we discuss different points of view regarding these still unresolved issues; these comments represent a debate that took place during the PANLAR Virtual Congress (Pan American League of Associations for Rheumatology) and that was organized by the PANLAR Lupus study group, GLADEL (Grupo Latino Americano De Estudio del Lupus) on September 19, 2020.
Transabdominal Ultrasound Evaluation of Pancreaticobiliary Maljunction in Children
Authors: Ma Ya , Wang Zhengrong , Ye Mao , Yang Yang , Liu Luyu
Published: November 2021

The development of high-frequency ultrasound made the diagnosis of pancreaticobiliary maljunction (PBM) possible. However, no study has been performed to clarify the sensitivity and specificity of transabdominal ultrasound (TAUS) in the diagnosis of PBM. The purpose of this study was to evaluate the accuracy of TAUS in the diagnosis of pediatric PBM and to assess factors that may influence the accuracy of ultrasound. This was a prospective study and 43 patients with suspected PBM were enrolled. All of these patients underwent TAUS examination to detect the pancreaticobiliary ductal union. Final diagnoses were determined by endoscopic retrograde cholangiopancreatography or intraoperative cholangiography. Sensitivity and specificity were calculated. Fisher exact test was used to analyze the difference of sonographic features between false-negative group and true-positive group. Transabdominal ultrasound demonstrated 77.4% (95% confidence interval, 58.5%–89.7%) sensitivity and 100% (95% confidence interval, 69.9%–100%) specificity for PMB diagnosis. In the false-negative group, infant patients (71.4% vs 16.7%, P = 0.012), cystic dilatation of the common bile duct (CBD) (71.4% vs 16.7%, P = 0.012), and stenosis of the distal CBD (71.4% vs 16.7%, P = 0.012) were more frequently observed than in the true-positive group. On the other hand, the true-positive group showed a higher incidence of protein plugs than the false-negative group (62.5% vs 0%, P = 0.007). Transabdominal ultrasound may serve as a potential alternative detection modality for pediatric patients with suspected PBM. Nondetection of the anomaly may be attributed to factors, such as younger age, cystic dilatation of the CBD, and stenosis of the distal CBD.
Proboscis Lateralis: A Novel Surgical Technique Using Tape Elongation and One-Stage Tunneling
Authors: Engström Olof , Svee Andreas , Hakelius Malin
Published: November 2021

Proboscis lateralis is a rare craniofacial anomaly characterized by a tubular, trunk-like appendage, often arising from the medial canthal region. It can occur in isolation or in association with a variety of other anomalies. Several treatment options have been described depending on the characteristics of the defect, but due to its infrequency, the body of knowledge is limited. Here, the authors present a case of proboscis lateralis in an 18-month-old girl, being successfully treated with a novel technique including tape elongation and a 1 stage tunneling procedure.
Linking cognition to ecology in wild sympatric mouse lemur species
Authors: Henke-von der Malsburg Johanna , Kappeler Peter M. , Fichtel Claudia
Published: November 2021

Cognitive abilities covary with both social and ecological factors across animal taxa. Ecological generalists have been attributed with enhanced cognitive abilities, but which specific ecological factors may have shaped the evolution of which specific cognitive abilities remains poorly known. To explore these links, we applied a cognitive test battery (two personality, ten cognitive tests;
n
= 1104 tests) to wild individuals of two sympatric mouse lemur species (
n
= 120
Microcebus murinus, n
= 34
M. berthae
) varying in ecological adaptations but sharing key features of their social systems. The habitat and dietary generalist grey mouse lemurs were more innovative and exhibited better spatial learning abilities; a cognitive advantage in responding adaptively to dynamic environmental conditions. The more specialized Madame Berthe's mouse lemurs were faster in learning associative reward contingencies, providing relative advantages in stable environmental conditions. Hence, our study revealed key cognitive correlates of ecological adaptations and indicates potential cognitive constraints of specialists that may help explain why they face a greater extinction risk in the context of current environmental changes.
Simulated vector transmission differentially influences dynamics of two viral variants of deformed wing virus in honey bees (Apis mellifera)
Authors: Ray Allyson M. , Davis Sheldon L. , Rasgon Jason L. , Grozinger Christina M.
Published: November 2021

Understanding how vectors alter the interactions between viruses and their hosts is a fundamental question in virology and disease ecology. In honey bees, transmission of deformed wing virus (DWV) by parasitic Varroa mites has been associated with elevated disease and host mortality, and Varroa transmission has been hypothesized to lead to increased viral titres or select for more virulent variants. Here, we mimicked Varroa transmission by serially passaging a mixed population of two DWV variants, A and B, by injection through in vitro reared honey bee pupae and tracking these viral populations through five passages. The DWV-A and DWV-B variant proportions shifted dynamically through passaging, with DWV-B outcompeting DWV-A after one passage, but levels of both variants becoming equivalent by Passage 5. Sequencing analysis revealed a dominant, recombinant DWV-B strain (DWV-A derived 5′ IRES region with the rest of the genome DWV-B), with low nucleotide diversity that decreased through passaging. DWV-A populations had higher nucleotide diversity compared to DWV-B, but this also decreased through passaging. Selection signatures were found across functional regions of the DWV-A and DWV-B genomes, including amino acid mutations in the putative capsid protein region. Simulated vector transmission differentially impacted two closely related viral variants which could influence viral interactions with the host, demonstrating surprising plasticity in vector-host-viral dynamics.
Probing Gut-Brain Links in Alzheimer’s Disease with Rifaximin
Authors: Suhocki Paul V. , Ronald James S. , Diehl Anna Mae E. , Murdoch David M. , Doraiswamy P. Murali
Published: November 2021

Gut-microbiome-inflammation interactions have been linked to neurodegeneration in Alzheimer’s disease (AD) and other disorders. We hypothesized that treatment with rifaximin, a minimally absorbed gut-specific antibiotic, may modify the neurodegenerative process by changing gut flora and reducing neurotoxic microbial drivers of inflammation. In a pilot, open-label trial, we treated 10 subjects with mild to moderate probable AD dementia (MMSE = 17 ± 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (p <0.004) and a significant increase in fecal phylum Firmicutes microbiota. Serum pTau181 and GFAP levels were reduced (effect sizes of -0.41 and -0.48 respectively) but did not reach significance. There was also a non-significant downward trend in serum cytokine IL-6 and IL-13 levels. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau 181 and serum GFAP. Insights from this pilot trial are being used to design a larger placebo-controlled clinical trial to determine if specific microbial flora/products underlie neurodegeneration, and whether rifaximin is clinically efficacious as a therapeutic.

Research in Context

Systematic Review

PubMed reviews showed emerging evidence for gut-microbiome-inflammation links in Alzheimer’s disease (AD).

Interpretation

Our pilot study revealed that rifaximin, a minimally absorbed, gut-specific antibiotic, reduced surrogate markers of neurodegeneration while increasing, potentially beneficial, microbiota in phylum Firmicutes. These data provide initial support to the hypothesis that microbiome related products may play a role in neurodegenerative disorders.

Future Directions

We plan to conduct additional human and pre-clinical studies to confirm these findings and determine the potential of rifaximin as a therapeutic for AD.
Hospital admissions for respiratory tract infections in children aged 0-5 years for 2017/2023
Authors: Methi Fredrik , Størdal Ketil , Telle Kjetil , Larsen Vilde Bergstad , Magnusson Karin
Published: November 2021

Aim

To compare hospital admissions across common respiratory tract infections (RTI) in 2017-21, and project possible hospital admissions for the RTIs among children aged 0-12 months and 1-5 years in 2022 and 2023.

Methods

In 644 885 children aged 0-12 months and 1-5 years, we plotted the observed monthly number of RTI admissions (upper- and lower RTI, influenza, respiratory syncytial virus (RSV), and COVID-19) from January 1st, 2017 until October 31st, 2021. We also plotted the number of RTI admissions with a need for respiratory support. We used the observed data to project four different scenarios of RTI admissions for the rest of 2021 until 2023, with different impacts on hospital wards: 1) “Business as usual”, 2) “Continuous lockdown”, 3) “Children’s immunity debt”, and 4) “Maternal and child immunity debt”.

Results

By October 31st, 2021, the number of simultaneous RTI admissions had exceeded the numbers usually observed at the typical season peak in January, i.e. ∼900. Based on our observed data and assuming that children and their mothers (who transfer antibodies to the very youngest) have not been exposed to RTI over the last one and a half years, our scenarios suggest that hospitals should be prepared to handle two to three times as many RTI admissions, and two to three times as many RTI admissions requiring respiratory support among 0-5-year-olds as normal, from November 2021 to April 2022.

Conclusion

Scenarios with immunity debt suggest that pediatric hospital wards and policy makers should plan for extended capacity.
The Failures of an Ideal COVID-19 Vaccine: A Simulation Study
Authors: Kosinski Robert J.
Published: November 2021

This paper simulates an ideal COVID-19 vaccine that confers immediate sterilizing immunity against all SARS-CoV-2 variants. The purpose was to explore how well this ideal vaccine could protect a population against common conditions (such as vaccine hesitancy) that might impair vaccine effectiveness. Simulations were done with an SEIRS spreadsheet model that ran two parallel subpopulations: one that accepted vaccination, and another that refused it. The two subpopulations could transmit infections to one another. Success was judged by the rate of new cases in the period from 1-5 years after the introduction of the vaccine.

Under good conditions, including a small subpopulation that refused vaccination, rapid distribution of the vaccine, duration of vaccinal immunity longer than 12 months, good retention of interest in getting vaccinated after the first year, strict maintenance of nonpharmaceutical interventions (NPIs) such as masking, and new variants with R0s less than 4.0, the vaccine was able to end the epidemic. With violation of these conditions, the post-vaccine era futures ranged from endemic COVID at a low or medium level to rates of COVID cases worse than anything seen in the US up to late 2021. The most important conditions for keeping case rates low were a fast speed of vaccine distribution, a low percentage of the population that refuses vaccination, a long duration of vaccinal immunity, and continuing maintenance of NPIs after vaccination began. On the other hand, a short duration of vaccinal immunity, abandonment of NPIs, and new variants with a high R0 were powerful barriers to disease control. New variants with high R0s were particularly damaging, producing high case rates except when vaccination speed was unrealistically rapid. A recurring finding was that most disease afflicting the vaccinated population in these simulations originated in the unvaccinated population, and cutting off interaction with the unvaccinated population caused a sharp drop in the case rate of the vaccinated population.

In conclusion, multiple common conditions can compromise the effectiveness of even an “ideal” vaccine.
Polygenic scores clarify the relationship between mental health and gender diversity
Authors: Thomas Taylor R. , Tener Ashton J. , Pearlman Amy M. , Imborek Katherine L. , Yang Ji Seung , Strang John F. , Michaelson Jacob J.
Published: November 2021

BACKGROUND

Gender diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors.

METHODS

In two SPARK samples, we tested for 16 polygenic scores (PGS) effects on quantitative measures of gender diversity and mental health. In Study 1,N= 639 independent adults (59% autistic) reported their mental health with the Adult Self Report and their gender diversity with the Gender Self Report (GSR). The GSR has two dimensions: Binary (degree of identification with the gender opposite that implied by sex designated at birth) and Nonbinary (degree of identification with a gender that is neither male nor female). In Study 2 (N= 5, 165), we used categorical gender identity.

RESULTS

In Study 1, neuropsychiatric PGS were positively associated with mental health problems. Externalizing was positively associated with ADHD PGS (ρ= 0.12,p <0.001, FDR = 0.10), and Internalizing was positively associated with PGS for depression (ρ= 0.08,p= 0.04, FDR = 1) and neuroticism (ρ= 0.11,p= 0.01, FDR = 0.41). Interestingly, we found no associations between gender diversity and neuropsychiatric PGS (80% powered to detectρ > ±0.11). However, the GSR was positively associated with cognitive performance PGS (Binaryρ= 0.11,p <0.001, FDR = 0.23 and Nonbinaryρ= 0.12,p <0.001, FDR = 0.13). Binary was also positively associated with PGS for non-heterosexual sexual behavior (ρ= 0.09,p= 0.03, FDR = 0.69). In Study 2, the cognitive performance PGS effect replicated; transgender and non-binary individuals had higher PGS:t= 4.16,p <0.001, FDR<0.001. They also had higher risky behavior and anorexia PGS.

CONCLUSIONS

We show that while gender diversity as a trait is positively associated with mental health problems, the strongest PGS associations with gender diversity were with cognitive performance, not neuropsychiatric conditions.
In VitroNasal Tissue Model for the Validation of Nasopharyngeal and Mid-turbinate Swabs for SARS-CoV-2 Testing
Authors: Hartigan Devon R. , Adelfio Miryam , Shutt Molly E. , Jones Stephanie M. , Patel Shreya , Marchand Joshua T. , McGuinness Pamela D. , Buchholz Bryan O. , Ghezzi Chiara E.
Published: November 2021

Large-scale population testing is a key tool to mitigate the spread of respiratory pathogens, as in the current COVID-19 pandemic, where swabs are used to collect samples in the upper airways (e.g. nasopharyngeal and mid-turbinate nasal cavities) for diagnostics. However, the high volume of supplies required to achieve large-scale population testing has posed unprecedented challenges for swab manufacturing and distribution, resulting in a global shortage that has heavily impacted testing capacity world-wide and prompted the development of new swabs suitable for large-scale production. Newly designed swabs require rigorous pre-clinical and clinical validation studies that are costly and time consuming (i.e. months to years long); reducing the risks associated with swab validation is therefore paramount for their rapid deployment. To address these shortages, we developed a 3D-printed tissue model that mimics the nasopharyngeal and mid-turbinate nasal cavities, and we validated its use as a new tool to rapidly test swab performance. In addition to the nasal architecture, the tissue model mimics the soft nasal tissue with a silk-based sponge lining, and the physiological nasal fluid with asymptomatic and symptomatic viscosities of synthetic mucus. We performed several assays comparing standard flocked and injection-molded swabs. We quantified the swab pick-up and release, and determined the effect of viral load and mucus viscosity on swab efficacy by spiking the synthetic mucus with heat-inactivated SARS-CoV-2 virus. By molecular assays, we found that injected molded swabs performed similarly or superiorly in comparison to standard flocked swabs and we underscored a viscosity-dependent difference in cycle threshold values between the asymptomatic and symptomatic mucus for both swabs. To conclude, we developed anin vitronasal tissue model, that corroborated previous swab performance data from clinical studies, with the potential of providing researchers with a clinically relevant, reproducible, safe, and cost-effective validation tool for the rapid development of newly designed swabs.
A multi-class gene classifier for SARS-CoV-2 variants based on convolutional neural network
Authors: Fan Junyu , Chen Chutao , Song Chen , Pan Jiajie , Wu Guifu
Published: November 2021

Surveillance of circulating variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance in controlling the coronavirus disease 2019 (COVID-19) pandemic. We propose an alignment-free in silico approach for classifying SARS-CoV-2 variants based on their genomic sequences. A deep learning model was constructed utilizing a stacked 1-D convolutional neural network and multilayer perceptron (MLP). The pre-processed genomic sequencing data of the four SARS-CoV-2 variants were first fed to three stacked convolution-pooling nets to extract local linkage patterns in the sequences. Then a 2-layer MLP was used to compute the correlations between the input and output. Finally, a logistic regression model transformed the output and returned the probability values. Learning curves and stratified 10-fold cross-validation showed that the proposed classifier enables robust variant classification. External validation of the classifier showed an accuracy of 0.9962, precision of 0.9963, recall of 0.9963 and F1 score of 0.9962, outperforming other machine learning methods, including logistic regression, K-nearest neighbor, support vector machine, and random forest. By comparing our model with an MLP model without the convolution-pooling network, we demonstrate the essential role of convolution in extracting viral variant features. Thus, our results indicate that the proposed convolution-based multi-class gene classifier is efficient for the variant classification of SARS-CoV-2.
Identification of occupations susceptible to high exposure and risk associated with multiple toxicants in an observational study: National Health and Nutrition Examination Survey 1999-2014
Authors: Nguyen Vy Kim , Colacino Justin , Patel Chirag J , Sartor Maureen , Jolliet Olivier
Published: November 2021

Background

According to the World Health Organization, occupational exposures to hazardous chemicals are estimated to cause over 370,000 premature annual deaths. The risks due to multiple workplace chemical exposures, and those occupations most susceptible to the resulting health effects, remain poorly characterized.

Objectives

The aim of this study is to identify occupations with elevated toxicant biomarker concentrations and increased health risk associated with toxicant exposures in a working US population from diverse categories of occupation. More specifically, we aim to 1) define differences in chemical exposures based on occupation description, 2) identify occupational groups with similar chemical exposure profiles, and 3) identify occupational groups with chemical biomarker levels exceeding acceptable health-based biomarker levels.

Methods

For this observational study of 51,008 participants, we used data from the 1999-2014 National Health and Nutrition Examination Survey. We characterized differences in chemical exposures by occupational group for 129 chemicals by applying a series of generalized linear models with the outcome as biomarker concentrations and the main predictor as the occupational groups, adjusting for age, sex, race/ethnicity, poverty income ratio, study period, and biomarker of tobacco use. We identified groups of occupations with similar chemical exposure profiles via hierarchical clustering. For each occupational group, we calculated percentages of participants with chemical biomarker levels exceeding acceptable health-based guidelines.

Results

Blue collar workers from “Construction”, “Professional, Scientific, Technical Services”, “Real Estate, Rental, Leasing”, “Manufacturing”, and “Wholesale Trade” have higher biomarker levels of toxic chemicals such as several heavy metals, acrylamide, glycideamide, and several volatile organic compounds compared to their white-collar counterparts. For these toxicants, 1-58% of blue-collar workers from these industries have toxicant concentrations exceeding acceptable levels.

Discussion

Blue collar workers have toxicant levels higher relative to their white-collar counterparts, often exceeding acceptable levels associated with noncancer effects. Our findings identify multiple occupations to prioritize for targeted interventions and health policies to monitor and reduce high toxicant exposures.
Plasticity of extrachromosomal and intrachromosomal BRAF amplifications in mediating targeted therapy dosage challenges
Authors: Song Kai , Minami Jenna K. , Crosson William P. , Salazar Jesus , Pazol Eli , Senaratne Niroshi T. , Rao Nagesh , Paraiso Kim , Graeber Thomas G.
Published: November 2021

Cancer cells display two modes of focal amplifications (FAs), extrachromosomal DNA/double-minutes (ecDNA/DMs) and intrachromosomal homogenously staining regions (HSRs). Understanding the plasticity of these two modes is critical for preventing targeted therapy resistance. We developed a combined BRAF plus MEK inhibitor resistance melanoma model that bears high BRAF amplifications through both DM and HSR modes, and investigated FA dynamics in the context of drug resistance plasticity. Cells harboring FAs displayed mode switching between DMs and HSRs, from both de novo genetic changes and selection of preexisting subpopulations. We found that copy number plasticity is not exclusive to DMs. Single cell-derived clones with HSRs also exhibit BRAF copy number and corresponding HSR length plasticity that allows them to respond to dose reduction and recover from drug addiction. Upon kinase inhibitor escalation, we observed reproducible selection for cells with BRAF kinase domain duplications residing on DMs. In sum, the plasticity of FAs allows cancer cells to respond to drug dose changes through a myriad of mechanisms. These mechanisms include increases or decreases in DMs, shortening of HSRs, acquisition of secondary resistance mechanisms, and expression of alternative slicing oncogene variants. These results highlight the challenges in targeting the cellular vulnerabilities tied to focal amplifications.

Statement of Significance

Understanding the dynamics of oncogene amplifications is critical for appreciating tumorigenesis and preventing anticancer drug resistance. We found melanoma cells harboring BRAF amplifications in either DM or HSR formats to have high plasticity under different kinase inhibitor dosage challenges with evidence supporting de novo alterations, clonal selection, and coupling to additional resistance mechanisms. In in the absence of DMs, HSRs can offer comparable levels of plasticity as DMs.
Lymphatic Thrombosis and Impaired Lymph Drainage in Cigarette Smoke-Associated Emphysema
Authors: Summers Barbara D. , Kim Kihwan , Khan Zohaib , Thangaswamy Sangeetha , Clement Cristina C. , McCright Jacob , Maisel Katharina , Zamora Sofia , Quintero Stephanie , Racanelli Alexandra C. , Yang Jisheng , D’Armiento Jeanine , Monticelli Laurel , Kahn Mark L. , Choi Augustine M. K. , Santambrogio Laura , Reed Hasina Outtz
Published: November 2021

The lymphatic vasculature is critical for lung function, but defects in lymphatic function in the pathogenesis of lung disease is understudied. In mice, lymphatic dysfunction alone is sufficient to cause lung injury that resembles human emphysema. Whether lymphatic function is disrupted in cigarette smoke (CS)-induced emphysema is unknown. In this study, we investigated lung lymphatic function in the pathogenesis of CS-induced emphysema. Analysis of human lung tissue revealed significant lung lymphatic thrombosis in patients with emphysema compared to control smokers that increased with disease severity. In vitro assays demonstrated a direct effect of CS on lymphatic endothelial cell integrity. In a mouse model, CS exposure led to lung lymphatic thrombosis, decreased lymphatic drainage, and impaired leukocyte trafficking that preceded emphysema. Proteomic analysis of lymph confirmed upregulation of coagulation and inflammatory pathways in the lymphatics of CS-exposed mice compared to control mice. These data suggest that CS exposure results in lung lymphatic dysfunction with thrombosis, impaired leukocyte trafficking, and changes in the composition of lymph. In patients with emphysema, lung lymphatic thrombosis is seen with increasing disease severity. These studies for the first time demonstrate lung lymphatic dysfunction after cigarette smoke exposure and suggest a novel component in the pathogenesis of emphysema.
Activation of neuronal FLT3 promotes exaggerated sensorial and emotional pain-related behaviors facilitating the transition from acute to chronic pain
Authors: Tassou Adrien , Thouaye Maxime , Gilabert Damien , Jouvenel Antoine , Leyris Jean-Philippe , Sonrier Corinne , Diouloufet Lucie , Mechaly Ilana , Mallié Sylvie , Chentouf Myriam , Neiveyans Madeline , Pugnière Martine , Martineau Pierre , Robert Bruno , Capdevila Xavier , Valmier Jean , Rivat Cyril
Published: November 2021

Acute pain events have been associated with persistent pain sensitization of nociceptive pathways increasing the risk of transition from acute to chronic pain. However, it is unclear whether injuryinduced persistent pain sensitization can promote long-term mood disorders. The receptor tyrosine kinase FLT3 is causally required for pain chronification after peripheral nerve injury, questioning its role in the development of pain-induced mood alterations. Here, we evaluated the emotional and sensorial components of pain after a single (SI) or double paw incision (DI). We then investigated the role of FLT3 either by inhibition using transgenic knock-out mice and functional antibodies or by activation with FLT3 ligand (FL) administrations.

DI mice showed significant anxiodepressive-like and spontaneous pain behaviors as opposed to SI mice. DI also promoted and extended mechanical pain hypersensitivity compared to SI. This emotional and sensorial pain exaggeration correlated with spinal changes especially by increased microglia activation after DI versus SI. Intrathecal minocycline, a microglial inhibitor, specifically reversed DI inducedmechanical hypersensitivity in males. Repeated treatment with the microglia proliferation inhibitor GW2580 not only eliminated the exaggerated pain hypersensitivity produced by DI but also prevented anxiodepressive-related behaviors in DI animals. Finally, FL injections in naive animals provoked mechanical allodynia and anxiodepressive-like disorders concomitant with a strong microglial activation while Flt3 silencing in a genetic mouse line or FLT3 blocking via functional antibodies, blunted the development of persistent pain and depression after DI. Altogether our results show that the repetition of peripheral lesions facilitate not only exaggerated nociceptive behaviors but also induced anxiodepressive disorders supported by spinal central changes. The inhibition of FLT3 could thus become a promising therapy in the management of pain sensitization and related mood alterations.