bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotional Intelligence: Changes Over the First Year of Physician Assistant Education
Authors: Cleveland Tracy , Canales Roberto , Carr W. David
Published: November 2021

Purpose

To investigate emotional intelligence (EI) development in physician assistant (PA) students as they progress through their didactic education.

Methods

Data were gathered through an online survey of EI distributed to a purposeful sample of 5 institutions with similar curriculum length and start dates. Program directors forwarded the survey to students at the start of their didactic education (pretest). Follow-up surveys were distributed via email to the students at the end of their didactic education (posttest). The survey consisted of 33 items related to 4 subscales of EI. Participants' age, gender, and previous healthcare experience were gathered. Five repeated measures ANOVAs were calculated for each EI summary score. Independent sample t-tests were conducted between pretest scores and a previously established EI mean.

Results

A total of 192 first-year students were solicited. A sample of 68 (16 males; 52 females) served as participants. No results were attained for gender or age due to unbalanced sample sizes. Significant results were realized for total EI and the Managing Others' Emotions subscale.

Conclusion

Participants with more than one healthcare experience demonstrated significantly high emotional intelligence on the pretest. Participants with one healthcare experience demonstrated a significant increase in total EI and the Managing Others' Emotions subscale. The main limitation of the study was the attrition of participants between measures. Future research is needed to assess EI at the end of the clinical year, after a period of clinical experience, and to determine which educational activities are most likely to enhance EI.
Responsiveness of 2 Different Ability Outcome Measures in Guillain-Barré Syndrome
Authors: Stojanov Aleksandar , Basta Ivana , Berisavac Ivana , Stojiljkovic-Tamas Olivera , Bozovic Ivo , Arsenijevic Mirjana , Palibrk Aleksa , Peric Stojan
Published: November 2021

Background:

The most frequently used ability outcome measure in Guillain-Barré syndrome (GBS) is the GBS disability scale (GDS). Recently developed inflammatory Rasch-built overall disability (I-RODS) scale has been suggested to be used in inflammatory polyneuropathies. In the present study, we wanted to assess the comparative responsiveness of I-RODS and GDS in subjects who were diagnosed with GBS during a follow-up period of 6 months.

Methods:

Our prospective, multicentric study included 72 subjects. Patients were tested, using GDS and I-RODS, on day 14, day 28, month 3, and month 6 from the start of the symptoms. We defined improvement as a reduction for 1 or more points on GDS or improvement on I-RODS as defined by Draak (2014).

Results:

Between days 14 and 28 there was an improvement in 28% of patients as measured with GDS and only in 10% patients as measured with I-RODS. At month 3 compared with day 14, we noticed an improvement in GDS score in 90% of GBS patients and I-RODS score in 65%. At month 6 improvements were noticed in 94% of patients measured by GDS and 78% according to I-RODS.

Conclusion:

Our findings support the use of GDS in an acute phase of GBS. I-RODS have their role mostly during a longer follow-up period when the majority of patients are ambulant and their other abilities besides walking are also of great importance.
COVID-19 Exposure During Neurology Practice
Authors: Qureshi Adnan I. , Rheaume Carol , Huang Wei , Lobanova Iryna , Govindarajan Raghav , French Brandi R. , Siddiq Farhan , Gomez Camilo R. , Sahota Pradeep K.
Published: November 2021

Background:

To determine the exposure risk for coronavirus 2019 (COVID-19) during neurology practice. Neurological manifestations of COVID-19 are increasingly being recognized mandating high level of participation by neurologists.

Methods:

An American Academy of Neurology survey inquiring about various aspects of COVID-19 exposure was sent to a random sample of 800 active American Academy of Neurology members who work in the United States. Use of second tier protection (1 or more including sterile gloves, surgical gown, protective goggles/face shield but not N95 mask) or maximum protection (N95 mask in addition to second tier protection) during clinical encounter with suspected/confirmed COVID-19 patients was inquired.

Results:

Of the 81 respondents, 38% indicated exposure to COVID-19 at work, 1% at home, and none outside of work/home. Of the 28 respondents who did experience at least 1 symptom of COVID-19, tiredness (32%) or diarrhea (8%) were reported. One respondent tested positive out of 12 (17%) of respondents who were tested for COVID-19 within the last 2 weeks. One respondent received health care at an emergency department/urgent care or was hospitalized related to COVID-19. When seeing patients, maximum protection personal protective equipment was used either always or most of the times by 16% of respondents in outpatient setting and 56% of respondents in inpatient settings, respectively.

Conclusions:

The data could enhance our knowledge of the factors that contribute to COVID-19 exposure during neurology practice in United States, and inform education and advocacy efforts to neurology providers, trainees, and patients in this unprecedented pandemic.
A Call for a Stroke Referral Network Between Primary Care and Stroke-Ready Hospitals in the Philippines
Authors: Espiritu Adrian I. , San Jose Maria Cristina Z.
Published: November 2021

Background:

The increasing stroke burden, inequity in the distribution of local neurologists, and the recent signing of the Universal Health Care Law in the Philippines provide compelling reasons for policy-makers to devise strategies to establish networks between primary care and stroke-ready hospitals. In this review, we explored the current literature and evidence that emphasized the roles of primary care providers (PCPs) and specialists, care transition, and telemedicine/teleneurology in various stages of stroke management.

Review Summary:

Clear delegation of stroke care responsibilities among PCPs and specialists is needed. Due to the limited number of specialists/neurologists, PCPs may contribute to addressing the insufficiency of community knowledge of acute stroke symptoms/risk factors, coordination with specialists and stroke-ready hospitals during acute stroke, and continuity of care during the poststroke stage. At present, the Philippines has only 49 stroke-ready hospitals; thus, an efficient and functional referral system for the care transition between the PCPs and specialists must be organized in our country. To provide remote access to expert stroke care for underserved areas and to increase thrombolysis utilization, the establishment of an effective telestroke system is indispensable. The empowerment of PCPs in teleneurology may assist in strengthening communication and networking with specialists with the ultimate goal of improving patient outcomes.

Conclusions:

In the era of Universal Health Care in the Philippines, the roles of PCP and specialists must be delineated. Increased access to stroke care through the establishment of networks among PCPs and stroke-ready hospitals (ie, via effective transition of care/teleneurology) must be prioritized especially in resource-constrained settings.
Recurrence of COVID-19 in a Patient With NMO Spectrum Disorder While Treating With Rituximab
Authors: Paybast Sepideh , Shahrab Fereshteh , Hejazi Seyed A.
Published: November 2021

Introduction:

In the context of coronavirus disease 2019 (COVID-19) pandemic, patients with neuromyelitis optica spectrum disorder (NMOSD) are vulnerable to develop COVID-19 due to the immunosuppressive therapy. The objective of this study is to describe a known case of NMOSD on rituximab who experienced 2 episodes of COVID-19.

Case Report:

A 25-year-old woman, a known case of NMOSD on rituximab was diagnosed with asymptomatic COVID-19. Eight months later, following her last infusion of rituximab, she developed moderate COVID-19. After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and the decision was made to start rituximab again.

Conclusions:

Our case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus-2 in a patient with NMOSD and rituximab therapy. We aimed to emphasize a precise consideration of management of patients with NMOSD during the COVID-19 pandemic.
Sex significantly impacts the function of major depression-linked variantsin vivo
Authors: Mulvey Bernard , Selmanovic Din , Dougherty Joseph D.
Published: November 2021

Genome-wide association studies have discovered blocks of common variants—likely transcriptional-regulatory—associated with major depressive disorder (MDD), though the functional subset and their biological impacts remain unknown. Likewise, why depression occurs in females more frequently than males is unclear. We therefore tested the hypothesis that risk-associated functional variants interact with sex and produce greater impact in female brains. We developed methods to directly measure regulatory variant activity and sex interactions using massively parallel reporter assays (MPRAs) in the mouse brainin vivo, in a cell type-specific manner. We measured activity of >1,000 variants from >30 MDD loci, identifying extensive sex-by-allele effects in mature hippocampal neurons and suggesting sex-differentiated impacts of genetic risk may underlie sex bias in disease. Unbiased informatics approaches indicated that functional MDD variants recurrently disrupt sex hormone receptor binding sequences. We confirmed this with MPRAs in neonatal brains, comparing brains undergoing the masculinizing hormone surge to hormonally-quiescent juveniles. Our study provides novel insights into the influence of age, biological sex, and cell type on regulatory-variant function, and provides a framework forin vivoparallel assays to functionally define interactions between organismal variables like sex and regulatory variation.

One-Sentence Summary

Massively parallel assaysin vivoidentified extensive functional and sex-interacting common variants in depression risk loci.
Black and Native Overdose Mortality Overtook that of White Individuals During the COVID-19 Pandemic
Authors: Friedman Joseph , Hansen Helena
Published: November 2021

Drug overdose mortality rates have increased sharply during the COVID-19 pandemic. In recent years, overdose death rates were rising most rapidly among racial/ethnic minority communities. The pandemic has disproportionately affected communities of color in a wide swath of health, social, and economic outcomes. Careful attention is therefore warranted to trends in overdose mortality by race/ethnicity during COVID-19. We calculated total drug overdose death rates per 100,000 population by race/ethnicity for the 1999-2020 time period. We find that Black overdose mortality overtook that of White individuals in 2020 for the first time since 1999. Between 2019 and 2020 Black individuals had the largest percent increase in overdose mortality, of 48.8%, compared to 26.3% among White individuals. In 2020, Black overdose death rates rose to 36.8 per 100,000, representing 16.3% higher than the rate for White individuals for the same period. American Indian and Alaska Native (AI/AN) individuals experienced the highest rate of overdose mortality in 2020, of 41.4 per 100,000, representing 30.8% higher than the rate among White individuals. Our findings suggest that drug overdose mortality is increasingly becoming a racial justice issue in the United States and appears to have been exacerbated by the COVID-19 pandemic. Providing individuals with a safer supply of drugs, closing gaps in access to MOUD and harm reductions services, and ending routine incarceration of individuals with substance use disorders represent urgently needed, evidence-based strategies that can be employed to reduce rising inequalities in overdose.
Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)
Authors: Talaei Mohammad , Faustini Sian , Holt Hayley , Jolliffe David A. , Vivaldi Giulia , Greenig Matthew , Perdek Natalia , Maltby Sheena , Bigogno Carola M , Symons Jane , Davies Gwyneth A , Lyons Ronan A , Griffiths Christopher J , Kee Frank , Sheikh Aziz , Richter Alex G , Shaheen Seif O , Martineau Adrian R
Published: November 2021

Background

Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.

Methods

We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020 and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.

Results

1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.29, 1.06-1.57, P-trend=0.01), body mass index (BMI) ≥25 vs <25 kg/m2 (1.24, 1.11–1.39), Asian/Asian British vs White ethnicity (1.65, 1.10–2.49), and alcohol consumption ≥15 vs 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with decreased risk (0.80, 0.70–0.93, for ≥10 vs 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥30 vs <25 kg/m2 (aGMR 1.10, 1.02–1.19), Asian/Asian British vs White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16), and number of visits to shops and other indoor public places (≥5 vs. 0/week: 1.12, 1.02-1.23, P-trend=0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.

Conclusions

Higher alcohol consumption and reduced light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.

Funding

Barts Charity, Health Data Research UK.
Autism in gifted youth is associated with low processing speed and high verbal ability
Authors: Michaelson Jacob J. , Doobay Alissa , Casten Lucas , Schabilion Katherine , Foley-Nicpon Megan , Nickl-Jockschat Thomas , Abel Ted , Assouline Susan
Published: November 2021

Background

High cognitive ability is an almost universally positive prognostic indicator in the context of neurodevelopmental, neuropsychiatric, and neurodegenerative conditions. However, “twice-exceptional” individuals, those who demonstrate exceptionally high cognitive ability (gifted) and exhibit profound behavioral and mental health challenges, are a striking exception to this rule.

Methods

We digitized the clinical records of N=1,074 clients from a US-based specialty clinic serving gifted students. This included a broad array of diagnostic, cognitive, achievement, and behavioral data, including self, teacher, and parent reported items. We conducted both hypothesis-driven and unsupervised learning analyses to 1) identify characteristics whose association with full-scale IQ (FSIQ) was dependent on autism diagnosis and 2) identify cognitive archetypes associated with autism diagnosis and related behaviors. We tested the generalization of our findings using data from the SPARK (N=17,634) and ABCD studies (N=10,602).

Results

Autistic individuals with IQ >= 120 were nearly 15 times more likely to enter adulthood undiagnosed compared to lower-IQ (IQ < 70) counterparts. Self-reported sense of inadequacy was most strongly associated with increasing FSIQ specifically among autistic clients (beta=0.3, 95% CI:[0.15,0.45], p=7.1×10−5). Similarly, self, parent, and teacher reports of anxiety increased with FSIQ (all p<0.05) in autistic individuals, in striking opposition to the ameliorating effect of FSIQ seen in non-autistic individuals. We uncovered a pattern of decreased processing speed (PS) coupled with very high verbal comprehension (VC), a PS/VC discrepancy, that was associated with autism, inattention, and internalizing problems. Similar cognitive-behavioral links were also observed in the ABCD study. Finally, we found a significant association between the PS/VC discrepancy and polygenic risk for autism in the ABCD sample (t=2.9, p=0.004).

Conclusions

Our results suggest that autistic individuals with exceptional ability are underserved and suffer disproportionately from high anxiety and low self-worth. In addition, elevated IQ with a significant PS/VC discrepancy appears to be a clinically and genetically meaningful biotype linked to autism.
Locus Coeruleus Integrity in Older Adults with and without Chronic Pain
Authors: Bell Tyler R. , Franz Carol E. , Eyler Lisa T. , Fennema-Notestine Christine , Puckett Olivia K. , Dorros Stephen M. , Panizzon Matthew S. , Pearce Rahul C. , Hagler Donald J. , Lyons Michael J. , Beck Asad , Elman Jeremy A. , Kremen William S.
Published: November 2021

The locus coeruleus (LC) is a brainstem region involved in regulating pain. Chronic pain is common in older adulthood, but no studies have examined its association with the LC in humans. We used neuromelanin-sensitive imaging to study differences in LC integrity in older adults with and without chronic pain. Chronic pain was assessed in community-dwelling men from the Vietnam Era Twin Study of Aging (VETSA) in 3 study waves covering an average of 12 years. Pain was self-reported on the SF-36 Bodily Pain Scale. Chronic pain was defined as moderate to severe pain severity at the current and at least one prior wave; 17% had chronic pain (n=80). At the third wave, 481 participants (mean age=67.57) underwent neuromelanin-sensitive MRI scans from which we calculated an LC contrast-to-noise ratio (LCCNR) – an index of LC integrity. We examined associations between chronic pain and LCCNR (in the rostral LC and caudal regions) with generalized estimating equations after adjusting for age, race, education, depressive symptoms, medical comorbidities, and opioid medication use. Individuals with chronic pain had .35 standard deviation lower rostral LCCNR (95% CI: -.62 to -.05) compared to those without chronic pain. No differences in the caudal LCCNR were detected. Chronic pain was associated with decreased rostral LC integrity in older adults. Differences in the rostral LC, rather than caudal LC, suggest the association between lower LC integrity and chronic pain may be related to pain processing in cortical regions where rostral LC projections typically connect.
Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis
Authors: Morrison-Ham Jordan , Clark Gillian M. , Ellis Elizabeth G. , Cerins Andris , Joutsa Juho , Enticott Peter G. , Corp Daniel T.
Published: November 2021

Background

Deep brain stimulation is a highly effective treatment of dystonia, but is invasive and associated with risks, such as intraoperative bleeding and infections. Previous research has used non-invasive brain stimulation (NIBS) in an attempt to alleviate symptoms of dystonia. The results of these studies, however, have been variable, leaving efficacy unclear. This study aimed to evaluate the effects of NIBS on symptoms of dystonia and determine whether methodological characteristics are associated with variability in effect size.

Methods

Embase and MEDLINE Complete databases were searched for articles using any type of NIBS as an intervention in dystonia patients, with changes in dystonia symptoms the primary outcome of interest.

Results

Meta-analysis of 26 studies demonstrated a small effect size for NIBS in reducing symptoms of dystonia (random-effects Hedges’ g = 0.21, p = .002). Differences in the type of NIBS, type of dystonia, and brain region stimulated had a significant effect on dystonia symptoms. Meta-regression revealed that 10 sessions of active stimulation, and the application of concurrent motor training programs resulted in significantly larger mean effect sizes.

Conclusion

NIBS has yielded small improvements to dystonic symptoms, but effect sizes depended on methodological characteristics, with more sessions of stimulation producing a larger response. Future research should further investigate the application of NIBS parallel to motor training, in addition to providing a greater quantity of sessions, to help define optimal parameters for NIBS protocols in dystonia.

Registration

PROSPERO 2020, CRD42020175944.
A RCT of a third dose CoronaVac or BNT162b2 vaccine in adults with two doses of CoronaVac
Authors: Pun Mok Chris Ka , Cheng Samuel M.S. , Chen Chunke , Yiu Karen , Chan Tat-On , Lai Kiu Cheung , Ling Kwun Cheung , Sun Yuanxin , Ho Lun Lai , Peiris Malik , Hui David S
Published: November 2021

Background

Poor immunogenicity and antibody waning were found in vaccinees of CoronaVac. There is lack of randomized controlled trial (RCT) data to compare the immunogenicity and safety of schedules using homologous and heterologous vaccine as a booster dose.

Methods

We randomly assigned adults who had received 2 doses of CoronaVac with low antibody response to receive an additional booster dose of either BNT162b2 or CoronaVac. The local and systemic adverse reactions were recorded. Levels of SARS-CoV-2 neutralizing and spike binding antibody in plasma were measured.

Findings

At one month after the third dose of vaccine, BNT162b2 vaccines elicited significantly higher surrogate virus neutralizing test (sVNT), spike receptor binding, spike N terminal domain binding, spike S2 domain binding levels than CoronaVac. More participants from the BNT162b2 group reported injection site pain and swelling as well as fatigue and muscle pain than those who received CoronaVac as the third dose. The mean results of the sVNT against the wild type, beta, gamma and delta variants in the BNT162b2 boosted group was 96.83%, 92.29%, 92.51% and 95.33% respectively which were significantly higher than the CoronaVac boosted group (Wild type: 57.75%; Beta: 38.79 %; Gamma: 32.22%; Delta: 48.87%)

Conclusion

Our RCT study shows that BNT162b2 booster dose for those people who poorly responded to the previous vaccination of CoronaVac is significantly more immunogenic than a CoronaVac booster. BNT162b2 also elicits higher levels of SARS-CoV-2 specific neutralizing antibodies to different variants of concern. The adverse reactions were only mild and short-lived.

At a Glance Commentary

Scientific Knowledge on the Subject

Poor immunogenicity and antibody waning were found in vaccinees of CoronaVac. There is lack of randomized controlled trial (RCT) data to compare the immunogenicity and safety of schedules using homologous and heterologous vaccine as a booster dose.

What This Study Adds to the Field

Our RCT study shows that BNT162b2 booster dose for those people who poorly responded to the previous vaccination of CoronaVac is significantly more immunogenic than a CoronaVac booster. The adverse reactions were only mild and short-lived.
Comprehensive RNA-Seq Reveals Molecular Changes in Kidney Malignancy Among People Living with HIV
Authors: Bao Juan , Ye Jianqing , Xu Jingjing , Liu Shanshan , Wang Lin , Li Zehuan , Li Qiuyue , Liu Feng , He Xiaomeng , Zou Heng , Feng Yanling , Corpe Christopher , Zhang Xiaoyan , Xu Jianqing , Zhu Tongyu , Wang Jin
Published: November 2021

Background

Malignancy of the kidney is a rapidly progressive kidney disease and a major source of morbidity and mortality among people living with HIV (PLWH). Patients with HIV-associated kidey cancer experience higher cancer-specific mortality than the general population, and its mechanism remains poorly understood.

Methods

To heighten the awareness of kidney malignancy in patients with HIV infection to facilitate the early diagnosis of kidney cancer, we identified 2460 protein-coding transcripts in HIV-associated kidney cancer using comprehensive RNA sequencing (RNA-seq).

Results

KISS1R, CAIX, and NPTX2 mRNA expression levels were specifically increased in HIV-associated kidney cancer, and UMOD and TMEM213 mRNA were decreased in most cases based on real-time PCR analyses. These findings were similar to those noted for the general population with renal cell carcinoma. Immunohistochemical staining analysis also showed that a total of 16 of 18 kidney malignant cases among PLWH exhibited positive staining for KISS1R and CAIX.

Conclusion

Pathway analysis of the differentially expressed mRNAs in HIV-associated kidney cancer revealed that several key pathways were involved, including voltage-gated chloride channel activity, distal tubule development, collecting duct development, fructose metabolic processes, and negative regulation of lipase activity. The identified molecular changes in kidney malignancy may offer a helpful explanation for cancer progression and open up new therapeutic avenues that may decrease mortality after a cancer diagnosis among PLWH.
Single-cell epigenetic analysis reveals principles of chromatin states in H3.3-K27M gliomas
Authors: Harpaz Nofar , Mittelman Tamir , Beresh Olga , Griess Ofir , Furth Noa , Salame Tomer-Meir , Oren Roni , Fellus-Alyagor Liat , Harmelin Alon , Alexandrescu Sanda , Marques Joana Graca , Filbin Mariella G. , Ron Guy , Shema Efrat
Published: November 2021

Cancer cells are highly heterogeneous at the transcriptional level and in their epigenetic state. Methods to study epigenetic heterogeneity are limited in throughput and information obtained per cell. Here, we adapted Cytometry by Time of Flight (CyTOF) to analyze a wide panel of histone modifications in primary tumor-derived lines of Diffused Intrinsic Pontine Glioma (DIPG). DIPG is a lethal glioma, driven by histone H3 lysine 27 mutation (H3-K27M). We identified two epigenetically distinct subpopulations in DIGP, reflecting inherent heterogeneity in expression of the mutant histone. These two subpopulations are robust across tumor lines derived from different patients and show differential proliferation capacity and expression of stem-cell and differentiation markers. Moreover, we demonstrate the use of this high-dimensional data to elucidate potential interactions between histone modifications and epigenetic alterations during the cell-cycle. Our work establishes new concepts for the analysis of epigenetic heterogeneity in cancer that could be applied to diverse biological systems.
Pseudomonas zeiradicisfrom corn andPseudomonas soyaefrom soybean, two newPseudomonasspecies and endophytes from agricultural crops
Authors: Lemaire Jacqueline , Seaton Sarah , Inderbitzin Patrik , Trujillo Martha E.
Published: November 2021

Two novelPseudomonasspecies associated with healthy plants and other habitats are described from the United States. They arePseudomonas zeiradicisstrain PI116 from corn in Missouri, compost from Massachusetts, urban soil from Iowa and water of Lake Erie; andPseudomonas soyaestrain JL117 from soybean in Indiana and Wisconsin, and soil in Wyoming. No plant pathogenic strains are known for any of the novel species based on genome comparisons to assemblies in GenBank.
The role of the gut microbiota in the effects of early-life stress and dietary fatty acids on later-life central and metabolic outcomes in mice
Authors: Reemst Kitty , Tims Sebastian , Yam Kit-Yi , Mischke Mona , Knol Jan , Brul Stanley , Schipper Lidewij , Korosi Aniko
Published: November 2021

Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that dietary low ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio is able to protect against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as determinants of long-term health, we here study the impact of ELS and dietary PUFA’s on the gut microbiota, and how this relates to the previously described cognitive, metabolic and fatty acid profiles.

Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 – P9) and to an early diet (P2 – P42) with either high (15) or low (1) ω-6 linoleic acid to ω-3 alpha-linolenic acid ratio. 16S ribosomal RNA was sequenced and analyzed from fecal samples at P21, P42 and P180.

ELS increased β-diversity at P42, which persisted into adulthood. The low ω-6/ω-3 diet prevented the ELS-induced increase in β-diversity, at P42. At the level of taxa abundance, for example, the abundance of the phyla Bacteroidetes increased while Actinobacteria and Verrucomicrobia decreased with age; ELS reduced the relative abundance of the genera RC9 gut group and Rikenella into adulthood and the low ω-6/ω-3 diet reduced the abundance of the Firmicutes Erysipelotrichia. At P42, species abundance correlated with body fat mass and circulating leptin (e.g. Bacteroidetes and Proteobacteria taxa) and fatty acid profiles (e.g. Firmicutes taxa).

This study gives novel insights into the impact of age, ELS and dietary PUFAs on microbiota composition, providing potential targets for non-invasive (nutritional) modulation of the ELS-induced deficits.

Importance

Early-life stress (ELS) leads to increased vulnerability to develop mental and metabolic disorders, however the biological mechanisms leading to such programming are not fully clear. Increased attention has been given to the importance of the gut microbiota as determinant of long term health and as potential target for non-invasive nutritional strategies to protect against the negative impact of ELS. Here we give novel insights in the complex interaction between ELS, early dietary ω-3 availability and the gut microbiota across ages and provides new potential targets for (nutritional) modulation of the long-term effects of the early-life environment via the microbiota.
Intra-tumor heterogeneity, turnover rate and karyotype space shape susceptibility to missegregation-induced extinction
Authors: Kimmel Gregory J. , Beck Richard J. , Yu Xiaoqing , Veith Thomas , Bakhoum Samuel , Altrock Philipp M. , Andor Noemi
Published: November 2021

The phenotypic efficacy of somatic copy number alterations (SCNAs) stems from their incidence per base pair of the genome, which is orders of magnitudes greater than that of point mutations. One mitotic event stands out in its potential to significantly change a cell’s SCNA burden–a chromosome missegregation. We present a general deterministic framework for modeling chromosome missegregations and use it to evaluate the possibility of missegregation-induced population extinction (MIE). The model predicts critical curves that separate viable from non-viable populations as a function of their turnover- and missegregation rates. Missegregation- and turnover rates estimated from a PAN-cancer scRNA-seq dataset of 15,464 cells are then compared to predictions. The majority of tumors across all cancer types had missegregation- and turnover rates that were within viable regions of the parameter space. When a dependency of missegregation rate on karyotype was introduced, karyotypes associated with low missegregation rates acted as a stabilizing refuge, rendering MIE impossible unless turnover rates are exceedingly high. Intra-tumor heterogeneity, including heterogeneity in missegregation rates, increases as tumors progress, rendering MIE unlikely.

Author Summary

When a cell missegregates a chromosome while dividing, the chance is high that its two daughter cells will behave drastically different from each other and from their parental cell. Chromosome missegregations are therefore one of the most powerful forces of phenotypic diversity. We developed a mathematical model of chromosome missegregations that allows for this cell-to-cell diversity to be accounted for. The model serves to help understand how selection acts upon cells with versatile chromosome contents, as a tool for genotype-to-phenotype mapping in various microenvironments. As a first application example we used the model to address whether there exists an upper limit on missegregation rate, beyond which cancer populations collapse. Chromosome missegregations are common. They occur in 1.2-2.3% per mitosis in normal cells [1] and in cancer cells their rate is between one and two orders of magnitudes higher [2]. The model revealed that the upper limit of missegregation rate is a function of the tumor’s turnover rate (i.e. how fast the tumor renews itself). In heterogenous populations however, cells with low missegregation rates protect the population from collapse. Intra-tumor heterogeneity, including heterogeneity in missegregation rates, increases as tumors progress, rendering missegregation-induced extinction unlikely.
Synthesis and antimicrobial evaluation of new cephalosporin derivatives containing cyclic disulfide moieties
Authors: Shchelik Inga S. , Gademann Karl
Published: November 2021

Due to a steady increase of microbial resistance, there is a need to increase the effectiveness of antibiotic performance by involving additional mechanisms of their penetration or retention for their better action. Cephalosporins are a successful group of antibiotics to combat pathogenic microorganisms, including drug-resistant strains. In this study, we investigated the effect of newly synthesized cephalosporin derivatives with cyclic disulfide modifications against several Gram-positive and Gram-negative strains as well as against biofilm formation. The incorporation of asparagusic acid was found to be effective in improving the activity of the drug against Gram-negative strains compared to the all carbon control compounds. Furthermore, we could demonstrate the successful reduction of biofilm formation forStaphylococcus aureusandPseudomonas aeruginosaat similar concentrations as obtained against planktonic cells. We propose that the incorporation of cyclic disulfides is one additional strategy to improve antibiotic activity and to combat bacterial infections.
QT-GILD: Quartet based gene tree imputation using deep learning improves phylogenomic analyses despite missing data
Authors: Mahbub Sazan , Sawmya Shashata , Saha Arpita , Reaz Rezwana , Rahman M. Sohel , Bayzid Md. Shamsuzzoha
Published: November 2021

Species tree estimation is frequently based on phylogenomic approaches that use multiple genes from throughout the genome. However, for a combination of reasons (ranging from sampling biases to more biological causes, as in gene birth and loss), gene trees are often incomplete, meaning that not all species of interest have a common set of genes. Incomplete gene trees can potentially impact the accuracy of phylogenomic inference. We, for the first time, introduce the problem of imputing the quartet distribution induced by a set of incomplete gene trees, which involves adding the missing quartets back to the quartet distribution. We present QT-GILD, an automated and specially tailored unsupervised deep learning technique, accompanied by cues from natural language processing (NLP), which learns the quartet distribution in a given set of incomplete gene trees and generates a complete set of quartets accordingly. QT-GILD is a general-purpose technique needing no explicit modeling of the subject system or reasons for missing data or gene tree heterogeneity. Experimental studies on a collection of simulated and empirical data sets suggest that QT-GILD can effectively impute the quartet distribution, which results in a dramatic improvement in the species tree accuracy. Remarkably, QT-GILD not only imputes the missing quartets but it can also account for gene tree estimation error. Therefore, QT-GILD advances the state-of-the-art in species tree estimation from gene trees in the face of missing data. QT-GILD is freely available in open source form at https://github.com/pythonLoader/QT-GILD.
Sleep and Alcohol Use Patterns During Federal Holidays in the United States
Authors: Heacock Rachel M , Capodilupo Emily R , Czeisler Mark É , Weaver Matthew D , Czeisler Charles A , Howard Mark E , Rajaratnam Shantha MW
Published: November 2021

We conducted a retrospective observational study using remote wearable and mobile application data to identify US public holidays associated with significant changes in sleep behaviors, including sleep duration, bedtime and waketime, and the consistency of sleep timing, as well as changes in the point prevalence of alcohol use. These metrics were collected and analyzed from objective, high resolution sleep-wake data and survey responses of 24,250 US subscribers to the wrist-worn biometric device platform, WHOOP (Boston, Massachusetts, USA), who were active users during May 1, 2020 through May 1, 2021. Compared to baseline, statistically significant differences in sleep and alcohol measures were found on the US public holidays and their eves. For example, New Year’s Eve corresponded with a sleep consistency decrease of 13.8% (± 0.3), a sleep onset of 88.9 minutes (± 3.2) later, a sleep offset of 78.1 minutes (± 3.1), and more than twice as many participants reported alcohol consumption (138.0% ± 6.7) compared to baseline. The majority of US public holidays and holiday eves were associated with sample-level increases in sleep duration, decreases in sleep consistency, later sleep onset and offset, and increases in the prevalence of alcohol consumption.

Significance Statement

US public holidays were associated with increased sleep duration, decreased sleep consistency, and later sleep timing among US adult users of an objective, validated commercial fitness tracker. Holidays were also associated with an increased prevalence of participants having reported alcohol use. Given the adverse health impacts of sleep timing variability on both weekends and during the transition to daylight savings time, and of increased alcohol use on weekends and public holidays, further investigation of the health impacts of these behavioral changes is warranted.
Prevalence of Antibodies to SARS-CoV-2 following natural infection and vaccination in Irish Hospital Healthcare Workers; changing epidemiology as the pandemic progresses
Authors: Allen Niamh , Brady Melissa , Riain Una Ni , Conlon Niall , Domegan Lisa , Carrion Martin Antonio Isidro , Walsh Cathal , Doherty Lorraine , Higgins Eibhlin , Kerr Colm ,   PRECISE Study Steering Group, Bergin Colm , Fleming Catherine
Published: November 2021

Background

In October 2020 SARS-CoV-2 seroprevalence among hospital healthcare workers (HCW) of two Irish hospitals was 15% and 4.1% respectively. We compare seroprevalence in the same HCW population six months later, assess changes in risk factors for seropositivity with progression of the pandemic and serological response to vaccination.

Methods

All staff of both hospitals (N=9038) were invited to participate in an online questionnaire and SARS-CoV-2 antibody testing in April 2021. We measured anti-nucleocapsid and anti-spike antibodies. Frequencies and percentages for positive SARS-CoV-2 antibodies were calculated and adjusted relative risks for participant characteristics were calculated using multivariable regression analysis.

Results

5085 HCW participated. Seroprevalence increased to 21% and 13% respectively; 26% of infections were previously undiagnosed. Black ethnicity (aRR 1.7, 95% CI 1.3-2.2, p<.001), lower level of education (aRR 1.4 for secondary level education, 95% CI 1.1-1.8, p=0.002), living with other HCW (aRR 1.2, 95% CI 1.0-1.4, p=0.007) were significantly associated with seropositivity. Having direct patient contact also carried a significant risk (being a healthcare assistant (aRR 1.8, 95% CI 1.3-2.3, p<.001), being a nurse (aRR 1.4, 95% CI 1.1-1.5, p=0.022), daily contact with COVID-19 patients (aRR 1.4, 95% CI 1.1-1.7, p=0.002), daily contact with patients without suspected or confirmed COVID-19 (aRR 1.3, 95% CI 1.1- 1.5, p=0.013) Breakthrough infection occurred in 23/4111(0.6%) of fully vaccinated participants; all had anti-S antibodies.

Conclusion

The increase in seroprevalence reflects the magnitude of the third wave of the pandemic in Ireland. Genomic sequencing is needed to apportion risk to the workplace versus the household/community. Concerted efforts are needed to mitigate risk factors due to ethnicity and lower level of education, even at this stage of the pandemic. The undiagnosed and breakthrough infections call for ongoing infection prevention and control measures and testing of HCW in the setting of close contact. Vaccinated HCW with confirmed infection should be actively assessed, including SARS-CoV-2 whole genome sequencing (WGS), serology testing and assessment of host determinants, to advance understanding of the reasons for breakthrough infection.
Impaired ability in visual-spatial attention in Chinese children with developmental dyslexia
Authors: Tian Mengyu , Wang Runzhou , Bi Hong-Yan
Published: November 2021

Many studies demonstrated that alphabetic language speaking children with developmental dyslexia had a deficit in visual-spatial attention, especially in rapid orienting of the attentional spotlight. Chinese, as a logographic language, is characterized as highly visual-spatial complexity. To date, few studies explored the visual-spatial attention of Chinese children with developmental dyslexia. The present study examined the visual-spatial attention of Chinese children with developmental dyslexia using the visual search task. The results showed that Chinese children with developmental dyslexia had poor performances in conjunction search, indicating that they had a deficit in the rapid orienting of visual-spatial attention. Meanwhile, only the conjunction search was a significant predictor of Chinese characters reading when other variables were controlled. These results indicated that Chinese dyslexic children had a deficit in visual-spatial attention, and visual-spatial attention played a special role in Chinese reading development.
Extracting multi-way chromatin contacts from Hi-C data
Authors: Liu Lei , Zhang Bokai , Hyeon Changbong
Published: November 2021

There is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromosome structures can be mapped onto a network of Gaussian polymer, here we derive analytic expressions forn-body contact probabilities (n> 2) among chromatin loci based on pairwise genomic contact frequencies available in Hi-C, and show that multi-way contact probability maps can in principle be extracted from Hi-C. The three-body (triplet) contact probabilities, calculated from our theory, are in good correlation with those from measurements including Tri-C, MC-4C and SPRITE. Maps of multi-way chromatin contacts calculated from our analytic expressions can not only complement experimental measurements, but also can offer better understanding of the related issues, such as cell-line dependent assemblies of multiple genes and enhancers to chromatin hubs, competition between long-range and short-range multi-way contacts, and condensates of multiple CTCF anchors.

Author summary

The importance of DNA looping is often mentioned as the initiation step of gene expression. However, there are growing evidences that ‘chromatin hubs’ comprised of multiple genes and enhancers play vital roles in gene expressions and regulations. Currently a number of experimental techniques to detect and identify multi-way chromosome interactions are available; yet detection of such multi-body interactions is statistically challenging. This study proposes a method to predict multi-way chromatin contacts from pair-wise contact frequencies available in Hi-C dataset. Since chromosomes are made of polymer chains, the pairwise contact probabilities are not entirely independent from each other, but certain types of correlations are present reflecting the underlying chromosome structure. We extract these correlations hidden in Hi-C dataset by leveraging theoretical argument based on polymer physics.
Modelling liver cancer microenvironment: novel 3D culture system as a potential anti-cancer drug screening tool
Authors: Hrout Ala’a Al , Cervantes-Gracia Karla , Chahwan Richard , Amin Amr
Published: November 2021

The tumor microenvironment and its contribution to tumorigenesis has been a focal highlight in recent years. A two-way communication between the tumor and the surrounding microenvironment sustains and contributes to the growth and metastasis of tumors. Progression and metastasis of hepatocellular carcinoma have been reported to be exceedingly influenced by diverse microenvironmental cues. In this study, we present a 3D-culture model of liver cancer to better mimic in vivo tumor settings. By creating novel 3D co-culture model that combines free-floating and scaffold based 3D-culture techniques of liver cancer cells and fibroblasts, we aimed to establish a simple albeit reproducible ex vivo cancer microenvironment model that captures tumor-stroma interactions. The model presented herein exhibited unique gene expression and protein expression profiles when compared to 2D and 3D mono-cultures of liver cancer cells. Our results showed that in vivo like conditions cannot be mimicked by simply growing cancer cells as spheroids, but by co-culturing them with 3D fibroblast with which they were able to cross-talk. This was evident by the upregulation of several pathways involved in HCC, and the increase in secreted factors by co-cultured cancer cells, many of which are also involved in tumor-stroma interactions. Compared to the conventional 2D culture, the proposed model exhibits an increase in the expression of genes associated with development, progression, and poor prognosis of HCC. Our results correlated with an aggressive outcome that better mirrors in vivo HCC, and therefore, a more reliable platform for molecular understanding of HCC and possibly better anti-cancer drug screening.