bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of Online Doctor of Nursing Practice Students' Perceptions of Effective Teaching Methods Using the Critical Incident Technique
Authors: Robb Meigan , Spadaro Kathleen C.
Published: May 2022

Background:

The online learning environment presents unique challenges for engaging students in the learning process. Current research is limited regarding online doctor of nursing practice (DNP) students' perceptions of effective faculty involvement related to their engagement in learning.

Purpose:

This qualitative study explored DNP students' perceptions of effective methods used by faculty to help them learn and be engaged in the asynchronous online classroom.

Methods:

The Community of Inquiry (COI) framework provided the theoretical support for this study. The critical incident technique was used to explore DNP students' perceptions of effective methods used by faculty teaching in an asynchronous online program. Perceptions of effective methods were analyzed using the inductive approach of thematic analysis.

Results:

Three themes emerged from the data analysis: providing clarity, staying on track, and making it personalized.

Conclusions:

Findings suggest nurse educators should follow the COI framework to establish teacher presence and promote student engagement in online courses.
Impact of distress screening and referral on health care utilization and cost among breast cancer patients: a retrospective cohort study ∗
Authors: Miller Melissa F. , Zaleta Alexandra K. , Allen Melyssa L. , Nichols Helen M. , Robinson Diane C.
Published: May 2022

Background:

Addressing cancer patient distress and unmet needs may reduce health care costs and enhance care utilization. This study examined the impact of a distress screening program CancerSupportSource™ (CSS) on health care utilization and costs for breast cancer patients.

Methods:

In a retrospective cohort study with 2 years’ follow-up, breast cancer patients receiving care at a community cancer center in Orlando, FL, between 2016 and 2019 were categorized according to exposure status: screened using CSS and acted by using supportive care services (SA); screened only (SO); and not screened (NS). Patients were matched on breast tumor location and age; screened patients were additionally matched on referral need. Outcomes abstracted from medical records included utilization and cost of emergency department (ED) services, hospital inpatient admissions, and outpatient services; and utilization of integrative medicine department, patient/family counseling, and allied health services.

Results:

SA patients (n = 36), compared to NS (n = 37), had significantly lower rates of ED visits in negative binomial regression analysis (incidence rate ratio [IRR] 0.43; 95% confidence interval [CI] 0.20–0.93; P = .031). There were significantly higher rates of integrative medicine department visits in SA (IRR 4.20; 95% CI 1.63–10.9; P = .003) and SO (IRR 3.71; 95% CI 1.49–9.24; P = .005) groups compared to NS, and higher rates of patient/family counseling visits in SA (IRR 6.21; 95% CI 1.52–25.3; P = .011). There were no significant differences in 2-year health care costs between groups, controlling for age and race/ethnicity.

Conclusions:

These findings highlight the potential value of distress screening and referral for health care utilization, shifting use of higher cost services to lower cost nonemergent and preventive care in cancer, and can inform future prospective research on cost outcomes.
Versatility of Medial Sural Artery Islanded Pedicled Perforator Flap for Resurfacing Areas Around the Knee
Authors: Suba Santanu , Giri Sanjay Kumar , Pant Priyanka , Kanungo Aparna
Published: May 2022

Soft tissue defects with exposed tendon, bones, and joints around the knee are difficult and challenging to treat because of its location over a joint, requires a stable cover that is supple and stretchable. For any knee defects, the gastrocnemius muscle flap is the first choice for the reconstruction, although it causes less functional deficit; however, because of its less reach, it is difficult to cover the defect in the superolateral aspect of knee joint and anterior to the tibial tuberosity with the other disadvantage being the bulkiness. The medial sural artery perforator flap (MSAPF) provides thin fasciocutaneous tissue similar to the adjacent normal soft tissue in the knee and so, its use leads to an improved reconstruction of contour and eliminating the need of a skin graft over the primary defect. Here, we will be discussing a case series using MSAPF to cover the defects around the knee.
Cannabinoids and Pain for the Plastic Surgeon
Authors: Stephens Kristen L. , Heineman John T. , Forster Grace L. , Timko Michael P. , DeGeorge Brent R.
Published: May 2022

Background

Since the passage of the 2018 Farm Bill, practitioners have encountered more patients self-treating pain with over-the-counter topical cannabidiol (CBD) derived from hemp—Cannabis sativa with less than 0.3% delta-9-tetrahydrocannabinol—with reported improvements in pain control and activities of daily living. Cannabidiol has been touted for its capacity to improve inflammatory, arthritic, and neuropathic pain conditions, and increasing numbers of patients are exploring its use as potential replacement for opioids. However, limited rigorous clinical trials have been performed evaluating the safety and efficacy of cannabinoids for the treatment of pain.

Methods

A systematic search of PubMed was performed using the Medical Subject Headings (MeSH) terms “cannabinoid” or “CBD” or “cannabidiol” or “cannabis” or “medical marijuana” and “pain.” It yielded 340 article titles. Twelve full-text primary studies of oral or topical CBD for chronic pain were selected for review, including 6 animal (2 randomized clinical trial and 4 prospective trials) and 6 human (4 randomized clinical trial and 2 prospective trials) studies.

Results

With respect to the safety and efficacy of oral and topical CBD for treating pain, animal and human studies have shown early positive results with limited minor side effects. However, all human studies may be underpowered with small sample sizes.

Conclusions

With respect to the safety and efficacy of oral and topical CBD for treating pain, the evidence remains inconclusive in that we have a paucity of data to share with our patients who are considering the use of these products, which may be associated with significant costs.
Trapezius Perforator Flaps Based on Superficial Cervical Artery and Dorsal Scapular Artery
Authors: Wang Qianwen , Li Zhiqiang , Xu Xiaohuan , Zhou Xu , Wang Tailing
Published: May 2022

Background

The flaps in the trapezius region are routinely elevated as musculocutaneous flaps. The anatomy of trapezius perforators and their clinical application are unclear.

Methods

The number and distribution of superficial cervical artery perforators (SCAPs) and dorsal scapular artery perforators (DSAPs) were studied on 8 cadavers. The clinical usage of SCAP and DSAP flaps was investigated through a systematic literature review.

Results

A total of 27 SCAPs and 28 DSAPs were found in the 16 hemibacks. The mean calibers of SCAP and DSAP were 0.9 ± 0.2 and 0.8 ± 0.2 mm, respectively. The vascular length to the takeoff of the source artery was 7.3 ± 2.0 cm (range, 4.7–9.7 cm) for SCAPs and was 8.1 ± 2.8 cm (range, 3.2–13.6 cm) for DSAPs. Contour and density heat maps showed that the SCAPs were clustered within approximately 3 to 5 cm above the horizontal line through the medial point of the scapular spine (x-axis) and 5 to 8 cm from the midline (y-axis, P = 0.001) and clustered DSAPs located in approximately 4 to 9 cm below the x-axis and 4 to 10 cm from the y-axis (P = 0.002). Four SCAP and 19 DSAP flaps were found in literature. The mean sizes of SCAP flaps and DSAP flaps were 18.5 × 7.8 and 16.5 × 8.7 cm, respectively.

Conclusions

Both SCAP and DSAP flaps can be elevated with a relatively long pedicle. The anatomical knowledge of the location of major clusters of perforators contributes to the application of these flaps.
One-Stage Reconstruction of Large Upper Vermillion Defects Using a Lower to Upper Bipedicle Axial Cross-Lip Vermillion Flap
Authors: Qiu Yajing , Gao Bowen , Chen Hui , Lin Xiaoxi
Published: May 2022

Background

Vermilion deformities after intralesional bleomycin A5 injections for hemangiomas of the upper lip have not been rare during the past 2 decades in China. In this article, we summarized our 10 years of experience using a lower to upper axial cross-lip musculomucosal flap with bipedicle lower labial coronary arteries for 1-stage reconstruction of large upper vermillion defects. Based on several years of experience, we also created some modified approaches to achieve satisfactory cosmetic outcomes.

Patients and Methods

From July 2006 to July 2016, a total of 25 patients with moderate and severe vermilion defects of the upper lip were treated with this method at the Department of Plastic and Reconstructive Surgery in Shanghai Ninth People’s Hospital. The cosmetic outcomes and complications were reviewed.

Results

The overall mean follow-up time was 14.9 months. No patients had infection or hematoma. All the flaps survived, and all the patients were satisfied with the postoperative appearance.

Conclusions

Our experience has proven that a lower to upper axial cross-lip musculomucosal flap with bipedicle lower labial coronary arteries is a safe and effective approach for correcting large upper vermillion defects. It is a 1-stage operation for the overall length of upper vermillion reconstruction. This method could improve upper-lip aesthetics and achieve reconstructive goals while avoiding lower-lip deformities.
Bilateral Transverse Upper Gracilis Flaps for Unilateral Breast Reconstruction
Authors: Christopoulos Georgios , Khoury Alexandra , Sergentanis Theodoros N. , Mackey Simon P. , Jones Martin E.
Published: May 2022

Introduction

The transverse upper gracilis (TUG) flap is a reliable alternative to abdominally based breast reconstruction because of its advantageous anatomy. However, the limited tissue volume prevents reconstruction of large breasts. The bilateral TUG flaps for unilateral breast reconstruction can overcome this problem.

Methods

A retrospective analysis was performed regarding unilateral breast reconstruction with bilateral TUGs at the Queen Victoria Hospital from 2015 to 2019. Associations between categorical variables were examined with Fisher exact test, and any differences in continuous variables by complication status were evaluated with Mann-Whitney-Wilcoxon test for independent samples. A relevant systematic review was conducted with a meta-analysis of proportions using the Freeman-Tukey arcsine transformation for the estimation of the overall survival rates.

Results

Ten cases were identified with 6 having a delayed reconstruction. Median age and body mass index were 50.8 years and 23.9 kg/m2, respectively, and average flap weight was 268.3 g. One flap was placed superiorly with its pedicle anastomosed to the retrograde internal mammary vessels, except of half of the cases where a second anterograde vein was used. The mean follow-up was 21.4 months, and all flaps survived. Two patients returned to theater, and 4 experienced donor-site problems. The presence of complications was not associated with age, ever smoking, body mass index, TUG weight, or anastomosis to retrograde internal mammary vein. The systematic review resulted in 8 eligible articles with a total sample of 156 flaps. The overall survival rate was 96.8%. In 6 cases, the indication was Poland syndrome (7.7%), and in 48.7%, axillary vessels were also used as recipient vessels. The estimated overall flap survival rate was 100% (95% confidence interval, 99%–100%), and no significant heterogeneity was noted (I
2 = 0%, P = 0.71).

Conclusions

The “2-in-1” technique can lead to symmetrical aesthetically pleasant results for both recipient and donor sites. Our case series and the conducted systematic review reiterate the reliability of this approach.
Alteribacter keqinensis sp. nov., a moderately halophilic bacterium isolated from a soda lake
Authors: Liu Jiading , Zhang Xinyu , Cao Hao , Guo Liwei , Zhao Baisuo , Zhang Xiaoxia , Wang Yanan , Wang Haisheng
Published: May 2022

A Gram-stain-positive, aerobic, endospore-forming and rod-shaped bacterium (KQ-3T), which grew at 10–45 °C (optimum 35 °C), pH 8.0–10.5 (optimum pH 9.0) and in the presence of 0–16 % (w/v) NaCl (optimum 3.0 %), was isolated from a soda lake and identified as representing a novel species using a polyphasic taxonomic approach. Strain KQ-3T was catalase-positive, oxidase-negative and non-motile. Phylogenetic analysis based on 16S rRNA gene sequence affiliated KQ-3T to the genus

Alteribacter

and showed the highest similarities to

Alteribacter natronophilus

M30T (97.90 %),

Alteribacter aurantiacus

K1-5T (97.84 %) and

Alteribacter populi

FJAT-45347T (97.22 %). Digital DNA–DNA hybridization and average nucleotide identity analyses revealed that KQ-3T displayed 21.4 and 72.81% genomic DNA relatedness with the most closely related strain,

A. natronophilus

M30T, respectively. KQ-3T contained all of the conserved signature indels that are specific for members of the genus

Alteribacter

. The DNA G+C content was 45.03 mol%. The cell-wall peptidoglycan contained meso-diaminopimelic acid and the polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and one unidentified phospholipid. The predominant menaquinone was MK-7 (100%) and the major fatty acids (>10 %) comprised anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0. Based on the data from the current polyphasic studies, KQ-3T represents a novel species of the genus

Alteribacter

, for which the name Alteribacter keqinensis sp. nov. is proposed. The type strain is KQ-3T (=ACCC 61799T=KCTC 33933T).
Vaccine Stockpile Sharing For Selfish Objectives
Authors: Shivam Shashwat , Weitz Joshua S. , Wardi Yorai
Published: May 2022

The COVAX program aims to provide global equitable access to life-saving vaccines. However, vaccine protectionism by wealthy nations has limited progress towards vaccine sharing goals. For example, as of April 2022 only ∼20% of the population in Africa has received at least one COVID-19 vaccine dose. Here we use a two-nation coupled epidemic model to evaluate optimal vaccine-sharing policies given a selfish objective: in which countries with vaccine stockpiles aim to minimize fatalities in their own populations. Despite the selfish objective, we find it is often optimal for a donor nation to share a significant fraction of its vaccine stockpile. Mechanistically, sharing a vaccine stockpile reduces the intensity of outbreaks in the recipient nation, in turn reducing travel-associated incidence in the donor nation. This effect is intensified as vaccination rates decrease and epidemic coupling increases. Despite acting selfishly, vaccine sharing by a donor nation significantly reduces transmission and fatalities in the recipient nation. Moreover, we find that there are hybrid sharing policies that have a negligible effect on fatalities in the donor nation compared to the optimal policy while significantly reducing fatalities in the recipient nation. Altogether, these findings provide a rationale for nations with extensive vaccine stockpiles to share with other nations.
Data-driven Identification of Total RNA Expression Genes (TREGs) for Estimation of RNA Abundance in Heterogeneous Cell Types
Authors: Huuki-Myers Louise A. , Montgomery Kelsey D. , Kwon Sang Ho , Page Stephanie C. , Hicks Stephanie C. , Maynard Kristen R. , Collado-Torres Leonardo
Published: May 2022

Next-generation sequencing technologies have facilitated data-driven identification of gene sets with different features including genes with stable expression, cell-type specific expression, or spatially variable expression. Here, we aimed to define and identify a new class of “control” genes called Total RNA Expression Genes (TREGs), which correlate with total RNA abundance in heterogeneous cell types of different sizes and transcriptional activity. We provide a data-driven method to identify TREGs from single cell RNA-sequencing (RNA-seq) data, available as an R/Bioconductor package at https://bioconductor.org/packages/TREG. We demonstrated the utility of our method in the postmortem human brain using multiplex single molecule fluorescent in situ hybridization (smFISH) and compared candidate TREGs against classic housekeeping genes. We identified AKT3 as a top TREG across five brain regions, especially in the dorsolateral prefrontal cortex.
Prevalence and Genotypic Characterization of Extended Spectrum Beta-Lactamase Uropathogens Isolated from Refugees with Urinary Tract Infections in Nakivale Refugee Settlement camp, Southwestern Uganda
Authors: Hussein Ayan Ahmed , Kassaza Kennedy , Mwesigye James , Mwamibi Bashir , Kabanda Taseera , Bazira Joel
Published: May 2022

Background

World Health Organization approximates that one in four individuals have had at least one UTI episode requiring treatment with an antimicrobial agent by the teen age. At Nakivale refugee camp, the overwhelming number of refugees often associated with poor living conditions such as communal bathrooms and toilets and multiple sex partners do predispose the refuges to urinary tract infections.

Aim

To determine the prevalence of bacterial community-onset urinary tract infections among refugees in Nakivale refugee settlement and determine the antimicrobial susceptibility patterns of the isolated pathogens.

Methods

This study was a cross-sectional study, that included 216 outpatients attending Nakivale Health Centre III between July and September 2020.

Results

Prevalence of UTI was 24.1% (52/216). The majority 86(39.81%) of the refugees were from DR Congo, followed by those from Somalia 58(26.85%). The commonest causative agent was Staphylococcus aureus 22/52 (42.31%) of total isolates, followed by Escherichia coli 21/52(40.38%). Multidrug resistant isolates accounted for 71.15% (37/52) and mono resistance was 26.92% (14/52). Out of the 52 bacterial isolates, 30 (58%) were Extended-Spectrum Beta-Lactamase organisms (ESBLs). Twenty-one (70.0%) isolates were ESBL producers while 9(30%) were non-ESBL producers. Both blaTEM and blaCTX-M were 62.5% each while blaSHV detected was 37.5%.

Conclusions

The prevalence of UTI among refugees in Nakivale settlement is high with Staphylococcus aureus and Escherichia coli as the commonest causes of UTI. There is a high rate of multidrug resistance to common drugs used to treat UTI. The prevalence of ESBL-producing Enterobacteriaceae is high and the common ESBL genes are blaTEM and blaCTX-
Effectiveness of ChAdOx1-S COVID-19 Booster Vaccination against the Omicron and Delta variants in England
Authors: Kirsebom Freja , Andrews Nick , Sachdeva Ruchira , Stowe Julia , Ramsay Mary , Bernal Jamie Lopez
Published: May 2022

Background

Despite the potential widespread global use of the ChAdOx1-S booster, to date there are no published data on the real-world effectiveness. VE studies have found one and two doses of the ChAdOx1-S vaccine to be highly effective, and clinical trial data have demonstrated enhanced immunity following a ChAdOx1-S booster. In England, some individuals received a ChAdOx1-S booster where vaccination with mRNA vaccines was clinically contraindicated.

Methods

The demographic characteristics of those who received a ChAdOx1-S booster were compared to those who received a BNT162b2 booster. A test-negative case control design was used to estimate vaccine effectiveness of the ChAdOx1-S booster against symptomatic disease and hospitalisation in England.

Findings

Those who received a ChAdOx1-S booster were more likely to be female (adjusted odds ratio (OR) 1.67 (1.64-1.71)), in a clinical risk group (adjusted OR 1.58 (1.54-1.63)), in the CEV group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)).

Protection against symptomatic disease in those aged 65 years and older peaked at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) amongst those who received the ChAdOx1-S and BNT162b2 booster vaccines, respectively. Protection waned to 44.5% (22.4 to 60.2%) and 54.1% (50.5 to 57.5%) after 5-9 weeks. Protection against hospitalisation following Omicron infection peaked at 82.3% (64.2 to 91.3%) after receiving a ChAdOx1-S booster, as compared to 90.9% (88.7 to 92.7%) for those who received a BNT162b2 booster.

Interpretation

Differences in the population boosted with ChAdOx1-S in England renders direct comparison of vaccine effectiveness by manufacturer challenging. Nonetheless, this study supports the use of the ChAdOx1-S booster for protection against severe disease with COVID-19 in settings that have not yet offered booster doses and suggests that those who received ChAdOx1-S as a booster in England do not require re-vaccination ahead of others.

Funding

UKHSA
Human behaviour, NPI and mobility reduction effects on COVID-19 transmission in different countries of the world
Authors: Mohammadi Zahra , Cojocaru Monica Gabriela , Thommes Edward Wolfgang
Published: May 2022

Background

The outbreak of Coronavirus disease, which originated in Wuhan, China in 2019, has affected the lives of billions of people globally. Throughout 2020, the reproduction number of COVID-19 was widely used by decision-makers to explain their strategies to control the pandemic.

Methods

In this work, we deduce and analyze both initial and effective reproduction numbers for 12 diverse world regions between February and December of 2020. We consider mobility reductions, mask wearing and compliance with masks, mask efficacy values alongside other non-pharmaceutical interventions (NPIs) in each region to get further insights in how each of the above factored into each region’s SARS-COV-2 transmission dynamic.

Results

We quantify in each region the following reductions in the observed effective reproduction numbers of the pandemic: i) reduction due to decrease in mobility (as captured in Google mobility reports); ii) reduction due to mask wearing and mask compliance; iii) reduction due to other NPI’s, over and above the ones identified in i) and ii).

Conclusion

In most cases mobility reduction coming from nationwide lockdown measures has helped stave off the initial wave in countries who took these types of measures. Beyond the first waves, mask mandates and compliance, together with social-distancing measures (which we refer to as other NPI’s) have allowed some control of subsequent disease spread. The methodology we propose here is novel and can be applied to other respiratory diseases such as influenza or RSV.
Clinicopathological and Imaging Features of Primary Biliary Cholangitis
Authors: Xie Mengdan , Nyabanga Custon Tafadzwa , Sehmbhi Mantej , Khalili Nour Al , Chon Christy , Kamath Amita , Dinani Amreen M. , Weisberg Ilan S.
Published: May 2022

Abstract/Keywords

Background and Aims

Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune disease of the biliary epithelial cells, causing slow progression of cholestasis and fibrosis. The aim of the study is to summarize the imaging features of PBC and examine the correlation between its clinicopathological and radiologic features, elucidating the specific clinicopathological and radiologic differences between male and female PBC patients, as well as between AMA-positive and AMA-negative PBC patients.

Methods

Demographic, laboratory, radiologic and survival data were collected retrospectively for patients diagnosed and treated for PBC at the Mount Sinai Health System between 2016 and 2020 with at least one ultrasound, CT, or MRI of abdomen available for assessment. Biochemical and radiologic data were compared between male v.s. female groups, and AMA-positive v.s. AMA-negative group.

Results

A total of 273 patients diagnosed with PBC were included. Non-specific hepatic parenchymal disease, cirrhosis, cholelithiasis, splenomegaly, lymphadenopathy, benign liver masses/cysts were the most common features on abdominal images. 24% of PBC patients had biliary tree abnormalities on MRI. LAD was reported in 38-47% of PBC patients. There was no significant difference in age, race, or ethnicity between the sexes of patients with PBC, however imaging characteristics of portal hypertension were more frequently seen in men. AMA-negative PBC patients had similar distributions of age, race/ethnicity and survival to AMA-positive PBC patients.

Conclusion

Our study summarized the clinicopathological and imaging features of PBC and distinct subgroups. This would assist in the diagnosis of PBC and avoid over-testing in real-world practice.
Comparison of selective genotyping strategies in genomic selection programs for broilers using stochastic simulation
Authors: Alemu Setegn. W. , Sørensen Anders C. , Wang Lei , Henshall John , Hawken Rachel , Madsen Per , Jensen Just
Published: May 2022

Breeding programs using genomic information have become common in broilers. In broilers, the main traits for selection are body weight and feed efficiency. These traits are measured in both sexes and before sexual maturity. Thus, increases in genetic gain in broiler breeding programs due to the use of genomic information are attributable primarily to the increased accuracy of predicted breeding values of potential parents. As not all birds can be genotyped due to economic constraints, an optimal genotyping strategy needs to be chosen. The objective of this study was to investigate the rates of genetic gain and inbreeding obtained by varying three factors: the percentage of birds genotyped (PG), the percentage of birds genotyped randomly (PRG) or selectively, and the percentage of males among genotyped birds (PMG). Stochastic computer simulation with a full factorial experimental design was used. Significant interaction among the factors (PG, PRG, and PMG) was observed for the rate of genetic gain in body weight and aggregate breeding value, but not for the gain in residual feed intake or the rate of inbreeding per generation. Our findings indicate that the PG, PRG, and PMG need to be considered when selecting a genotyping strategy for a broiler breeding program. If available resources allow only to genotype a small percentage (e.g., 2.5% or 5%) of all birds, the genotyping of 50–100% of male birds and selection of birds to be genotyped using phenotypic information is best. If resources allow to genotype more (e.g., ≥20%) candidates, genotyping of equal numbers of each sex, and low PRG level (i.e., preselection of the majority of candidate based on performance) is best. Provided that a proper genotyping strategy is chosen, we conclude that the incorporation of genomic information in broiler breeding programs can substantially increase the rate of genetic gain.
Reprogramming of cardiac phosphoproteome, proteome and transcriptome confers resilience to chronic adenylyl cyclase-driven stress
Authors: Qu Jia-Hua , Chakir Khalid , Tarasov Kirill V. , Riordon Daniel R. , Perino Maria Grazia , Silvester Allwin Jennifa , Lakatta Edward G.
Published: May 2022

Our prior study (Tarasov, K. V. et al., 2022) discovered that numerous adaptive mechanisms emerge in response to cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8) which included overexpression of a large number of proteins. Here we conducted an unbiased phosphoproteomics analysis in order to determine the role of altered protein phosphorylation in the adaptive heart performance and protection profile of adult TGAC8 left ventricle (LV) at 3-4 months of age, and integrated the phosphoproteome with transcriptome and proteome. Based on differentially regulated phosphoproteins by genotype, numerous stress-response pathways within reprogrammed TGAC8 LV, including PKA, PI3K and AMPK signaling pathways, predicted upstream regulators (e.g., PDPK1, PAK1 and PTK2B), and downstream functions (e.g., cell viability, protein quality control), and metabolism were enriched. In addition to PKA, numerous other kinases and phosphatases were hyper-phosphorylated in TGAC8 vs. WT. Hyper-phosphorylated transcriptional factors in TGAC8 were associated with increased mRNA transcription, immune responses and metabolic pathways. Combination of the phosphoproteome with its proteome and with the previously published TGAC8 transcriptome enabled the elucidation of cardiac performance and adaptive protection profiles coordinately regulated at post-translational modification (PTM) (phosphorylation), translational and transcriptional levels. Many stress-response signaling pathways, i.e., PI3K/AKT, ERK/MAPK and ubiquitin labeling, were consistently enriched and activated in the TGAC8 LV at transcriptional, translational and PTM levels. Thus, reprogramming of the cardiac phosphoproteome, proteome and transcriptome confers resilience to chronic adenylyl cyclase-driven stress. We identified numerous pathways/function predictions via gene sets, phosphopeptides, and phosphoproteins, which may point to potential novel therapeutic targets to enhance heart adaptivity, maintaining heart performance while avoiding cardiac dysfunction.
Taxonomically Restricted Genes are Associated with Responses to Biotic and Abiotic Stresses in Sugarcane (Saccharum spp.)
Authors: Cardoso-Silva Claudio Benicio , Aono Alexandre Hild , Mancini Melina Cristina , Sforca Danilo Augusto , da Silva Carla Cristina , Pinto Luciana Rossini , Adams Keith L. , de Souza Anete Pereira
Published: May 2022

Orphan genes (OGs) are protein-coding genes that are restricted to particular clades or species and lack homology with genes from other organisms, making their biological function difficult to predict. OGs can rapidly originate and become functional; consequently, they may support rapid adaptation to environmental changes. Extensive spread of mobile elements, and whole genome duplication, occurred in the Saccharum group, which may have contributed to the origin and diversification of OGs in the sugarcane genome. Here, we identified and characterized OGs in sugarcane, examined their expression profiles across tissues and genotypes, and investigated their regulation under varying conditions. We identified 319 OGs in the Saccharum spontaneum genome without detected homology to protein-coding genes in green plants, except those belonging to Saccharinae. Transcriptomic analysis showed 288 sugarcane OGs with detectable expression levels in at least one tissue or genotype. We observed similar expression patterns of OGs in sugarcane genotypes originating from the closest geographical locations. We also observed tissue-specific expression of some OGs, possibly indicating a complex regulatory process for maintaining diverse functional activity of these genes across sugarcane tissues and genotypes. Sixty-six OGs were differentially expressed under stress conditions, especially cold and osmotic stresses. Gene co-expression network and functional enrichment analyses suggested that sugarcane OGs may be involved in several biological mechanisms, including stimulus response and defence mechanisms. These findings provide a valuable genomic resource for sugarcane researchers, especially those interested in selecting stress-responsive genes.
Human Neuronal Excitation/Inhibition Balance Explains and Predicts Neurostimulation Induced Learning Benefits
Authors: van Bueren Nienke E. R. , van der Ven Sanne H. G. , Hochman Shachar , Sella Francesco , Kadosh Roi Cohen
Published: May 2022

Previous research has highlighted the role of the excitation/inhibition ratio (E/I) for typical and atypical development, mental health, cognition, and learning. Other research has highlighted the benefits of high-frequency random noise stimulation (tRNS)—an excitatory form of neurostimulation—on learning. We examined the E/I as a potential mechanism and studied whether tRNS effect on learning depends on E/I as measured by the aperiodic exponent as its putative marker. In addition to manipulating E/I using tRNS, we also manipulated the level of learning (learning/overlearning) that has been shown to influence E/I. Participants (n=102) received either sham stimulation or 20 min tRNS over the dorsolateral prefrontal cortex (DLPFC) during a mathematical learning task. We showed that tRNS increased E/I, as reflected by the aperiodic exponent, and that lower E/I predicted greater benefit from tRNS specifically for the learning task. In contrast to previous Magnetic Resonance Spectroscopy-based E/I studies, we found no effect of the level of learning on E/I. A further analysis using a different data set suggest that both measures of E/I (EEG vs MRS) may reflect, at least partly, different biological mechanisms. Our results highlight the role of E/I as a marker for neurostimulation efficacy and learning. This mechanistic understanding provides better opportunities for augmented learning and personalized interventions.
Modelling mouse auditory response dynamics along a continuum of consciousness using a deep recurrent neural network
Authors: O’Reilly Jamie A.
Published: May 2022

Objective

Understanding neurophysiological changes that accompany transitions between anaesthetized and conscious states is a key objective of anesthesiology and consciousness science. This study aimed to characterize the dynamics of auditory-evoked potential morphology in mice along a continuum of consciousness.

Approach

Epidural field potentials were recorded from above the primary auditory cortices of two groups of laboratory mice: urethane-anaesthetized (A, n = 14) and conscious (C, n = 17). Both groups received auditory stimulation in the form of a repeated pure-tone stimulus, before and after receiving 10 mg/kg i.p. ketamine (AK and CK). Evoked responses were then ordered by ascending sample entropy into AK, A, CK, and C, considered to reflect physiological correlates of awareness. These data were used to train a recurrent neural network (RNN) with an input parameter encoding state. Model outputs were compared with grand-average event-related potential (ERP) waveforms. Subsequently, the state parameter was varied to simulate changes in the ERP that occur during transitions between states, and relationships with dominant peak amplitudes were quantified.

Main results

The RNN synthesized output waveforms that were in close agreement with grand-average ERPs for each group (r2 > 0.9, p < 0.0001). Varying the input state parameter generated model outputs reflecting changes in ERP morphology predicted to occur between states. Positive peak amplitudes within 25 to 50 ms, and negative peak amplitudes within 50 to 75 ms post-stimulus-onset, were found to display a sigmoidal characteristic during the transition from anaesthetized to conscious states. In contrast, negative peak amplitudes within 0 to 25 ms displayed greater linearity.

Significance

This study demonstrates a method for modelling changes in ERP morphology that accompany transitions between states of consciousness using a RNN. In future studies, this approach may be applied to human data to support the clinical use of ERPs to predict transition to consciousness.
PanCircBase: An online resource for the exploration of circular RNAs in pancreatic islets
Authors: Sinha Tanvi , Mishra Smruti Sambhav , Singh Suman , Panda Amaresh Chandra
Published: May 2022

Circular RNAs (circRNAs) are a novel class of covalently closed RNA molecules that recently emerged as a critical regulator of gene expression in development and diseases. Recent research has highlighted the importance of novel circRNAs in the biosynthesis and secretion of insulin from β-cells of pancreatic islets. However, all circRNAs expressed in pancreatic islets or β-cells are not readily available in the database. In this study, we analyzed publicly available RNA-sequencing datasets of the pancreatic islets to catalog all circRNAs expressed in pancreatic islets to construct the PanCircBase (www.pancircbase.net/) database that provides the following resources: (i) pancreatic islet circRNA annotation details (genomic position, host gene, exon information, splice length, sequence, other database IDs, cross-species conservation), (ii) divergent primers for PCR analysis of circRNAs, (iii) siRNAs for silencing of target circRNAs, (iv) miRNAs associated with circRNAs, (v) possible protein-coding circRNAs and their polypeptides. In summary, this is a comprehensive online resource for exploring circRNA expression and its possible function in pancreatic β-cells.
Concussive head trauma perturbs axon initial segment function in axotomized and intact layer 5 pyramidal neurons
Authors: Harris Alan C. , Sun Jianli , Jacobs Kimberle
Published: May 2022

The axon initial segment (AIS) is a critical locus of control of action potential (AP) generation and neuronal information synthesis. Concussive traumatic brain injury gives rise to diffuse axotomy, and the majority of neocortical axonal injury arises at the AIS. Consequently, concussive traumatic brain injury might profoundly disrupt the functional specialization of this region. To investigate this hypothesis, one and two days after mild central fluid percussion injury in Thy1-YFP-H mice, we recorded high-resolution APs from axotomized and adjacent intact layer 5 pyramidal neurons and applied a second derivative (2°) analysis to measure the AIS- and soma-regional contributions to the AP upstroke. All layer 5 pyramidal neurons recorded from sham animals manifested two stark 2° peaks separated by a negative intervening slope. In contrast, within injured mice, we discovered a subset of axotomized layer 5 pyramidal neurons in which the AIS-regional 2° peak was abolished, a functional perturbation associated with diminished excitability, axonal sprouting and distention of the AIS as assessed by staining for ankyrin-G. Our analysis revealed an additional subpopulation of both axotomized and intact layer 5 pyramidal neurons that manifested a melding together of the AIS- and soma-regional 2° peaks, suggesting a more subtle aberration of sodium channel function and/or translocation of the AIS initiation zone closer to the soma. When these experiments were repeated in animals in which cyclophilin-D was knocked out, these effects were ameliorated, suggesting that trauma-induced AIS functional perturbation is associated with mitochondrial calcium dysregulation.
Hybridization drives mitochondrial DNA degeneration and metabolic shift in a species with biparental mitochondrial inheritance
Authors: Hénault Mathieu , Marsit Souhir , Charron Guillaume , Landry Christian R.
Published: May 2022

Mitochondrial DNA (mtDNA) is a cytoplasmic genome that is essential for respiratory metabolism. While uniparental mtDNA inheritance is most common in animals and plants, distinct mtDNA haplotypes can coexist in a state of heteroplasmy, either because of paternal leakage or de novo mutations. MtDNA integrity and the resolution of heteroplasmy have important implications, notably for mitochondrial genetic disorders, speciation and genome evolution in hybrids. However, the impact of genetic variation on the transition to homoplasmy from initially heteroplasmic backgrounds remains largely unknown. Here, we useSaccharomycesyeasts, fungi with constitutive biparental mtDNA inheritance, to investigate the resolution of mtDNA heteroplasmy in a variety of hybrid genotypes. We previously designed 11 crosses along a gradient of parental evolutionary divergence using undomesticated isolates ofSaccharomyces paradoxusandSaccharomyces cerevisiae. Each cross was independently replicated 48 to 96 times, and the resulting 864 hybrids were evolved under relaxed selection for mitochondrial function. Genome sequencing of 446 MA lines revealed extensive mtDNA recombination, but recombination rate was not predicted by parental divergence level. We found a strong positive relationship between parental divergence and the rate of large-scale mtDNA deletions, which lead to the loss of respiratory metabolism. We also uncovered associations between mtDNA recombination, mtDNA deletion, and genome instability that were genotype-specific. Our results show that hybridization in yeast induces mtDNA degeneration through large-scale deletion and loss of function, with deep consequences for mtDNA evolution, metabolism and the emergence of reproductive isolation.
Health-Related Quality of Life and Coping Strategies adopted by COVID-19 survivors: A nationwide cross-sectional study in Bangladesh
Authors: Hossain Mohammad Anwar , Shafin Rubayet , Ahmed Md. Shahoriar , Rana Md. Shohag , Walton Lori Maria , Raigangar Veena , Ara Tasnim , Rasel Md. Aminul Haque , Hossain Mohammad Sohrab , Kabir Md. Feroz , Islam Mir Raihanul , Hasan Md. Nazmul , Hossain Delowar , Rumana Farjana Sharmin , Jahid Iqbal Kabir
Published: May 2022

This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh.

Methods

This is a cross-sectional study of 2198 adult, COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QOLBREF) questionnaires were used. The data collection period was from June 2020 to March 2021.

Results

Males 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations (p<0.005) with physical, psychological and social relationships; whereas, gender showed only significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed significant correlations with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategy (p<0.001); whereas gender and co-morbidities showed significant correlation with problem focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies (p<0.001).

Conclusion

Survivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem focused coping, with emotion focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants. This study represents the real scenario of nationwide health associated quality of life and coping strategy during and beyond the Delta pandemic.
Death by Round Numbers: Glass-Box Machine Learning Uncovers Biases in Medical Practice
Authors: Lengerich Benjamin J. , Caruana Rich , Nunnally Mark E. , Kellis Manolis
Published: May 2022

Real-world evidence is confounded by treatments, so data-driven systems can learn to recapitulate biases that influenced treatment decisions. This confounding presents a challenge: uninterpretable black-box systems can put patients at risk by confusing treatment benefits with intrinsic risk, but also an opportunity: interpretable “glass-box” models can improve medical practice by highlighting unexpected patterns which suggest biases in medical practice. We propose a glass-box model that enables clinical experts to find unexpected changes in patient mortality risk. By applying this model to four datasets, we identify two characteristic types of biases: (1) discontinuities where sharp treatment thresholds produce step-function changes in risk near clinically-important round-number cutoffs, and (2) counter-causal paradoxes where aggressive treatment produces non-monotone risk curves that contradict underlying causal risk by lowering the risk of treated patients below that of healthier, but untreated, patients. While these effects are learned by all accurate models, they are only revealed by interpretable models. We show that because these effects are the result of clinical practice rather than statistical aberration, they are pervasive even in large, canonical datasets. Finally, we apply this method to uncover opportunities for improvements in clinical practice, including 8000 excess deaths per year in the US, where paradoxically, patients with moderately-elevated serum creatinine have higher mortality risk than patients with severely-elevated serum creatinine.
A ratchet-like apical constriction drives cell ingression during the mouse gastrulation EMT
Authors: Francou Alexandre , Anderson Kathryn V. , Hadjantonakis Anna-Katerina
Published: May 2022

Epithelial-to-Mesenchymal Transition (EMT) is a fundamental process in which epithelial cells acquire mesenchymal phenotypes and the ability to migrate. EMT is the hallmark of gastrulation, an evolutionarily conserved developmental process. In mammals, epiblast cells lose pluripotency and ingress at the primitive streak to form mesoderm. Cell exit from the epiblast epithelial layer and the associated EMT are dynamically regulated processes involving a stereotypical sequence of cell behaviors. 3D time-lapse imaging of gastrulating mouse embryos combined with cell and tissue scale data analyses revealed the stochastic-like ingression of epiblast cells at the primitive streak. Ingressing cells constrict their apical surfaces in a pulsed ratchet-like fashion through asynchronous shrinkage of apical junctions. A quantitative analyses of the distribution of apical proteins, revealed the anisotropic and complementary distribution of members of the actomyosin network and Crumbs2 complexes, potential regulators of asynchronous shrinkage of cell junctions. The analysis of mutants demonstrated a requirement for Crumbs2 in Myosin2 localization and activity at apical junctions, and as a candidate for regulating actomyosin anisotropy.
Rebound Excitation of Epileptiform Activities by Transcranial Focused Ultrasound Stimulation
Authors: Choi Taewon , Koo Minseok , Joo Jaesoon , Kim Taekyung , Shon Young-Min , Park Jinhyoung
Published: May 2022

Background

Conventional neurostimulations to treat epilepsy have adverse effects caused by post-inhibitory rebound excitations. Although ultrasound brain stimulation is feasible in inducing anticonvulsant effects, its association with paradoxical rebound excitations is unknown.

Objective

This study aimed at demonstrating rebound excitations with transcranial focused ultrasound. The modulations of epileptiform activities toward both suppressive and excitatory responses were investigated by changing ultrasonic transmit sequences.

Methods

In a pentylenetetrazol-injected acute epilepsy rat model, transcranial focused ultrasound stimulation was applied on the thalamus to modulate epileptiform activities. The parameters differentiated for pulse sequences were the pulse length, pulse pressure, and interval between the pulses. Sonication effects were assessed by electroencephalography (n=38), immuno-histochemical analysis (n=24), and optical measurement of cerebral blood volume changes (n=18).

Results

While ultrasonic patterns of stimuli at long intervals showed antiepileptic effects on electroencephalography, those at short intervals showed rebound excitatory responses followed by inhibitory activities. Further, suppressive states induced by inhibitory stimulations were transformed into excitatory states by applying a consecutive series of short bursts at higher acoustic pressure. Cerebral blood volume changes demonstrated consistent results with electroencephalography. Immunohistochemistry revealed that both inhibitory and excitatory neuronal cells were activated to generate rebound excitatory conditions, while inhibitory cells were activated for suppressive conditions.

Conclusions

In our study, variations in ultrasound stimulation patterns could modulate epileptiform activities in both upregulated and downregulated directions.