bluuebunny/crossref_metadata_2025 huggingface dataset:
Telephone-based assessment of walking confidence in older people
Authors: Menezes Kênia K.P. , Avelino Patrick R. , Costa Gabriela Azevedo , Viana Jhonniter Bragança , Gomes Wanda Lucia , Nascimento Lucas R.
Published: May 2021

To validate the telephone-based application of the modified Gait Efficacy Scale (mGES) for the assessment of walking confidence in older people. Participants answered the mGES-Brazil on two randomized occasions, face-to-face and by telephone. The mean difference (MD) between the interviews was reported. Intraclass correlation coefficient (ICC3,1) was used to investigate the levels of agreement between the two occasions for total mGES-Brazil scores and for the individual items. A total of 78 individuals were included. There was no significant difference in the MD obtained between applications of the mGES (1 point, 95% confidence interval −6 to 7). A very high level of agreement was found between the mGES total scores during face-to-face and telephone applications (ICC = 0.98; 95% CI 0.97–0.99). All items, except one (item 3), had a very high agreement between the two applications. The mGES showed to be reliable to be applied for telephone assessments of walking confidence in older people.
Reliability and validity of the Korean version of the Caregiver Burden Inventory
Authors: Uhm Kyeong Eun , Jung Heeyoune , Oh-Park Mooyeon , Lee Bo Ram , Kim Eun Joo , Kim Jung Hwan , Lee Seung Ah , Shin Jinyoung , Kim Yoon-Sook , Hyun Cheolhwan , Ko Nayeon , Lee Jongmin
Published: May 2021

The purpose of this study was to demonstrate the reliability and validity of the Korean version of the Caregiver Burden Inventory (CBI). The study was conducted as a multicenter cross-sectional survey for caregivers caring for patients with disabilities in outpatient or inpatient rehabilitation clinics. Sociodemographic characteristics and health-related quality of life were collected via questionnaires. The CBI and Burden Interview (BI) were administered, after which internal consistency and factor analysis of the CBI and correlation between the CBI and BI were explored. A total of 151 caregivers participated. The mean age of caregivers was 53.7 ± 12.4 years, and 80.8 % were women. The majority of caregivers were the main caregivers of stroke, spinal cord injury or traumatic brain injury. The factor analysis confirmed its five factorial structure. The time-dependence and physical burden scores of CBI were higher than those of other factors. All five-dimensional and total scores of CBI showed high internal consistency and were well correlated with BI. In conclusion, the CBI has proven its reliability, construct validity and concurrent validity for caregivers of disabled people and has shown its advantage as a multidimensional measure.
Measurement properties of the L Test with fast walking speed in patients after lower limb amputation in initial prosthetic training phase
Authors: Podlogar Veronika , Burger Helena , Puh Urska
Published: May 2021

The L Test is a clinical mobility test used in patients after lower limb amputation. To assess dynamic balance, it should be performed with fast walking speed. Its measurement properties in the initial prosthetic training phase are not known yet. The objective of the study was to establish intra- and interrater reliability, concurrent and discriminant validity, minimal detectable change, effect size between the rehabilitation time points and ceiling effect of the L Test with fast walking speed in patients after lower limb amputation in initial prosthetic training phase. The study included 36 inpatients aged 19–86 years who were provided with a prosthesis for the first time. They were assessed repeatedly with the L Test, Ten-meter Walk Test and 6-min Walk Test. The intra- (ICC3, k = 0.94) and interrater reliability (ICC2, k = 0.96) of the L Test were excellent. Correlations with the walking tests were very good (r = 0.75–0.86). Regression analysis with respect to the level of lower limb amputation showed a linear relationship with other variables (R
2 = 0.55). Influences of age, cause of lower limb amputation and walking aid were statistically significant. The L Test was responsive to change after two weeks of prosthetic training (Cohen’s d = 1.21). No ceiling effect was identified. The L Test with fast walking speed is a feasible, reliable, valid, and responsive measure of basic mobility skills in patients after lower limb amputation in the initial prosthetic training phase.
Rasch validation and comparison of the German versions of the Locomotor Capabilities Index-5 and Prosthetic Mobility Questionnaire 2.0 in lower-limb prosthesis users
Authors: Ranker Alexander , Gutenbrunner Christoph , Eckhardt Isabelle , Giordano Andrea , Burger Helena , Franchignoni Franco
Published: May 2021

This study aimed to compare, through Rasch analysis, the psychometric properties of the Locomotor Capabilities Index (LCI-5) and Prosthetic Mobility Questionnaire (PMQ 2.0) in German lower-limb prosthesis users. The questionnaires were concurrently administered to a convenience sample of 98 consecutively recruited individuals with lower limb amputation (LLA) (male/female = 61/37; mean age 57 ± 14 years). LCI-5 showed disordered rating scale thresholds (one response option in three items required collapsing); local dependence between two items (resolved by creating a testlet); underfit of one item (‘Get up from the floor’); and presence of a second weak dimension. PMQ 2.0 showed a correctly functioning rating scale; good fit of the data to the model (apart from some overfit); local dependence between two items (absorbed by creating a testlet); and essential unidimensionality. At scale co-calibration onto a common interval-scaled metric, PMQ 2.0 was better targeted than LCI-5 (i.e. the extent of item difficulty was more appropriate for the sample) and its operational range allowed a more precise measurement of higher locomotor abilities. The correlation between LCI-5 and PMQ 2.0 scores was rho =  0.78. In conclusion, LCI-5 revealed some drawbacks, confirming a previous Rasch study; refinement of its rating scale and item selection seems therefore warranted. The PMQ 2.0 demonstrated good overall measurement quality, in line with previous Italian and Slovene studies. The operational range of the PMQ 2.0 makes it more suitable than LCI-5 for assessing people with high locomotor abilities.
Relationship Distress at Home and Burnout Among 254 Pediatric Intensive Care Nurses*
Authors: Lawrence Jessica N. , Schadler Aric D. , Shenoi Asha N.
Published: May 2021

OBJECTIVES:

To assess the prevalence of relationship distress and burnout among PICU nurses.

DESIGN:

Cross-sectional, web-based survey.

SETTING:

Pediatric intensive care nursing practices in the United States.

Subjects:

Pediatric intensive care nurses.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 254 pediatric intensive care nurses in the United States completed the survey consisting of demographic data, practice, and personal characteristics, Revised Dyadic Adjustment Scale, and modified Maslach Burnout Inventory. Relationship distress in consensus was noted in 45.6% of participants, and 26.3% reported distress in relationship satisfaction. Moderate to high burnout was reported by 65% nurses in the emotional exhaustion domain, 43% in depersonalization, and 27% of nurses reported low personal accomplishment. A significant difference in relationship satisfaction was found among nurses identified in different domains of burnout, showing that nurses who scored higher in depersonalization also reported higher distress in relationship satisfaction (p = 0.045). Interestingly, nurses who reported high personal accomplishment (thereby less burnout) reported higher distress in relationship consensus (p = 0.015). The difference in the satisfaction subscale between different age groups was significant, suggesting distress in satisfaction among nurses over the age of 40 (p = 0.004). Comparison of nurses actively involved in marriage counseling with those not actively involved in marriage counseling demonstrated a significant difference in relationship consensus (p = 0.046; odds ratio = 2.46; 95% CI, 0.99–6.06) and satisfaction (p = 0.004; odds ratio = 3.26; 95% CI, 1.42–7.47), suggesting an association between higher relationship distress and counseling.

CONCLUSIONS:

This study reflects the prevalence of relationship distress and its association with burnout and other practice and personal factors among PICU nurses. Nurses with high depersonalization experienced significantly higher distress in relationship satisfaction, and nurses who reported high personal satisfaction had significantly higher distress in relationship consensus.
Reconstruction of a Large Traumatic Medial Cheek Defect Using an Anterior-Based Subcutaneous Cervicofacial Rotation Advancement Flap
Authors: Chakraborty Sourabh Shankar , Kotu Suresh , Sahu Ranjit Kumar , Nath Machhendra
Published: May 2021

In this article, we describe reconstruction of a large left-side medial cheek defect in a 78-year-old woman using a cervicofacial rotation advancement flap. To our knowledge, this is the second case of reconstruction of a large traumatic medial cheek defect using an anterior-based subcutaneous cervicofacial rotation advancement flap that has ever been reported. We applied retention sutures at the level of the jawline and zygomatic eminence using 3–0 nonabsorbable sutures between the subcutaneous tissue of the flap and the periosteum. Despite the limitation of having partially injured adjacent tissue available for reconstruction, meticulous dissection together with skilled postoperative nursing care yielded a good aesthetic outcome in this case.
Factors Involved in the Decision of Iranian Men to Undergo Rhinoplasty: A Grounded Theory Study
Authors: Jalali Amir , Abasi Parvin , Ghaffari Zeinab
Published: May 2021

Undergoing a rhinoplasty can affect an individual's mental health either positively or negatively, depending upon how he or she perceives the results. Because of the impact that rhinoplasty may have on an individual's mental health and the cost of this surgery, it is important to understand the reasons that men decide to undergo rhinoplasty and the challenges they face when making the decision to have a rhinoplasty. Using a grounded theory method, we collected data by conducting interviews with 20 participants. We analyzed the data and initially obtained 684 initial codes. After we removed duplicate codes and carefully analyzed participants' interviews, a total of 497 codes remained. We developed these codes into 10 main categories and 32 subcategories. We found that the causal factors affecting the decision of Iranian men to undergo rhinoplasty included the following 5 categories: a lack of confidence; a desire to improve their appearance; a desire for attention from others; a need to keep up with the Joneses (i.e., a desire to show that one is as good as other people by getting what others have and doing what others do); and persuasion by others. Intervening factors affecting the decision of Iranian men to undergo rhinoplasty included the following 4 categories: family challenge; social atmosphere; financial problems; and unwanted consequences. Iranian men make the decision to undergo rhinoplasty by overcoming and ignoring these intervening factors. The primary variable in participants' decision to undergo rhinoplasty was the desire to improve their appearance.
Longitudinal typing of molecular HIV clusters in a statewide epidemic
Authors: Novitsky Vlad , Steingrimsson Jon , Howison Mark , Dunn Casey , Gillani Fizza S. , Manne Akarsh , Li Yuanning , Spence Matthew , Parillo Zoanne , Fulton John , Marak Theodore , Chan Philip , Bertrand Thomas , Bandy Utpala , Alexander-Scott Nicole , Hogan Joseph , Kantor Rami
Published: May 2021

Background:

HIV molecular epidemiology is increasingly integrated into public health prevention. We conducted cluster typing to enhance characterization of a densely sampled statewide epidemic towards informing public health.

Methods:

We identified HIV clusters, categorized them into types, and evaluated their dynamics between 2004 and 2019 in Rhode Island. We grouped sequences by diagnosis year, assessed cluster changes between paired phylogenies, t
0 and t
1, representing adjacent years and categorized clusters as stable (cluster in t
0 phylogeny = cluster in t
1 phylogeny) or unstable (cluster in t
0 ≠ cluster in t
1). Unstable clusters were further categorized as emerging (t
1 phylogeny only) or growing (larger in t
1 phylogeny). We determined proportions of each cluster type, of individuals in each cluster type, and of newly diagnosed individuals in each cluster type, and assessed trends over time.

Results:

A total of 1727 individuals with available HIV-1 subtype B pol sequences were diagnosed in Rhode Island by 2019. Over time, stable clusters and individuals in them dominated the epidemic, increasing over time, with reciprocally decreasing unstable clusters and individuals in them. Conversely, proportions of newly diagnosed individuals in unstable clusters significantly increased. Within unstable clusters, proportions of emerging clusters and of individuals in them declined; whereas proportions of newly diagnosed individuals in growing clusters significantly increased over time.

Conclusion:

Distinct molecular cluster types were identified in the Rhode Island epidemic. Cluster dynamics demonstrated increasing stable and decreasing unstable clusters driven by growing, rather than emerging clusters, suggesting consistent in-state transmission networks. Cluster typing could inform public health beyond conventional approaches and direct interventions.
False-Positive Uptake in Splenic Hemangioma on 68Ga-PSMA PET/CT Scan for Late Biochemical Recurrence of Prostate Cancer
Authors: Brazão Éder Silveira , Ribeiro André Marcondes Braga , Lima Eduardo Nobrega Pereira , da Costa Walter Henriques , Zequi Stênio de Cássio
Published: May 2021

A 71-year-old man underwent 68Ga-PSMA PET/CT for evaluation of a late biochemical recurrence after radical prostatectomy. An intense PSMA uptake was identified in spleen. Additional evaluation with a contrast-enhanced MRI showed a splenic lesion consistent with splenic hemangioma.
Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Surgically Treated Stage I Lung Adenocarcinoma Patients
Authors: Tosi Davide , Pieropan Sara , Cattoni Maria , Bonitta Gianluca , Franzi Sara , Mendogni Paolo , Imperatori Andrea , Rotolo Nicola , Castellani Massimo , Cuzzocrea Marco , Schiorlin Ilaria , Casagrande Sabrina , De Palma Diego , Nosotti Mario , Dominioni Lorenzo
Published: May 2021

Purpose of the Report

This article aims to explore the prognostic role of 18F-FDG PET/CT metabolic parameters in stage I lung adenocarcinoma patients.

Patients and Methods

One hundred eighty pathological stage I lung adenocarcinoma patients were retrospectively reviewed. Semiquantitative analysis of FDG tumor uptake was performed with TrueD software on the Siemens Leonardo workstation. SUVmean and MTV were calculated using SUV threshold of 41% of SUVmax; the total lesion glycolysis (TLG) was calculated as the product of SUVmean and MTV. Correlation was evaluated using Spearman correlation coefficient. Maximally selected rank statistics was performed to detect the optimal cutoff used for dichotomizing each PET parameter (6.5 for SUVmean, 9.6 for SUVmax, and 19.1 for TLG).

Results

Our main finding was the significant correlation between 18F-FDG PET/CT parameters (SUVmean, SUVmax, and TLG) and disease-free survival in pathologic stage I non–small cell lung cancer. SUVmean has the greatest accuracy in recurrence prediction (integrated area under the curve, 0.803; 95% confidence interval, 0.689–0.918). We run the maximally selected rank statistics to provide the classification of observations in 2 groups by a continuous predictor parameter; the free from recurrence rate was significantly greater in patients with SUVmean ≤6.5, SUVmax ≤9.6, and TLG ≤19.1.

Conclusions

Our research supports the hypothesis that SUVmean, SUVmax, and TLG are well correlated with free from recurrence rate in stage I adenocarcinoma patients, subjected to pulmonary lobectomy. Our findings also indicate these markers as promising prognostic indicators.
68Ga-FAPI PET/CT Versus 18F-FDG PET/CT for Detecting Metastatic Lesions in a Case of Radioiodine-Refractory Differentiated Thyroid Cancer
Authors: Fu Hao , Fu Jie , Huang Jingxiong , Pang Yizhen , Chen Haojun
Published: May 2021

18F-FDG PET/CT is a useful imaging modality for detecting disease recurrence and metastases in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). However, the sensitivity of 18F-FDG PET/CT in RAIR-DTC is not very satisfactory. 68Ga-FAPI is a promising PET tracer that allowed imaging of various types of cancer. In this case, 68Ga-FAPI showed a far better signal-to-background ratio than 18F-FDG for detecting the RAIR-DTC metastatic lesions, especially for detecting the small pulmonary metastases. Therefore, 68Ga-FAPI may be a promising alternative to 18F-FDG for detecting tumor recurrence and metastases in RAIR-DTC. It could also be used for guiding FAP-targeted radionuclide therapy.
Geographic Distribution of Cytomegalovirus Serology in Kidney and Pancreas Transplant Recipients in the United States
Authors: Jorgenson Margaret R. , Parajuli Sandesh , Marka Nicholas , Leverson Glen E. , Smith Jeannina A. , Mandelbrot Didier A. , Odorico Jon S.
Published: May 2021

Backgrounds.

Cytomegalovirus (CMV) negatively affects transplant outcomes. The current geographic distribution of CMV risk within the US has not been described.

Methods.

CMV serostatus of donors and recipients in each US state were collected from the Scientific Registry of Transplant Recipients between April 1, 2015, and March 31, 2019. The objective was to describe rates of CMV recipient seropositivity (R+) and high-risk serostatus (D+/R−) across the US in kidney transplant recipient (KTR) and pancreas transplant recipient (PTR) and explore geographic disparities.

Results.

A total of 79 276 KTRs and 4023 PTRs were included. The average KTR R+ rate across states was 59.5% (range 39%–76%); PTR R+ rate was 49.5% but with a broader range (0%–100%). The average KTR D+/R− rate across the US was 19% (range 8.7%–25%); PTR D+/R− rate was notably higher (26.9%, range 0%–50%). KTR seropositivity varied geographically with more R+ recipients in the southern states, Alaska, and Hawaii. D+/R− KTRs also varied by region, with higher rates in the Rocky Mountain Region as well as the Midwest and the northern-most states of the Northeast. Trends found in KTR persisted in PTR.

Conclusions.

The distribution of CMV serostatus in the US varies by state and allograft type. These data may be useful in further discussion of national CMV donor-matching strategies.
Donor-derived Cell-free DNA Kinetics Post-kidney Transplant Biopsy
Authors: Kyeso Yousuf , Bhalla Anshul , Smith Alyssa P. , Jia Yaqi , Alakhdhair Safa , Ogir Stephanie C. , Abuzeineh Mohammad , Brennan Daniel C. , Alasfar Sami
Published: May 2021

Background.

Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney injury including transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the postbiopsy period. We evaluated the effect of KT biopsy on the kinetics of dd-cfDNA.

Methods.

We conducted a single-arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within 8 h before the biopsy (prebiopsy), within 20 min (hour 0), 2 h (hour 2), and 24–48 h (hours 24–48) after the biopsy. We evaluated the change in dd-cfDNA from the prebiopsy time point to the following 3 time points after the biopsy.

Results.

At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate 0.4 [0.17-0.63] and 0.39 [0.09-0.68], respectively). By 24–28 h postbiopsy, there was no significant difference in log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate −0.21 [−0.6 to 0.19]).

Conclusions.

Mechanical injury from a KT biopsy can transiently increase circulating dd-cfDNA. The increase resolves by 24–48 h after the biopsy. Providers should wait 48 h postbiopsy to obtain dd-cfDNA levels to establish the correct baseline to be used for monitoring.
Clinical Care and Unmet Needs of Individuals With Dementia With Lewy Bodies and Caregivers
Authors: Armstrong Melissa J. , Gamez Noheli , Alliance Slande , Majid Tabassum , Taylor Angela S. , Kurasz Andrea M. , Patel Bhavana , Smith Glenn E.
Published: May 2021

Background:

Patient-centered care requires understanding patient preferences and needs, but research on the clinical care preferences of individuals living with dementia and caregivers is sparse, particularly in dementia with Lewy bodies (DLB).

Methods:

Investigators conducted telephone interviews with individuals living with DLB and caregivers from a Lewy body dementia specialty center. Interviews employed a semistructured questionnaire querying helpful aspects of care and unmet needs. Investigators used a qualitative descriptive approach to analyze transcripts and identify themes.

Results:

Twenty individuals with DLB and 25 caregivers participated. Twenty-three of the caregivers were spouses, 2 were daughters. Aspects of clinical care valued by individuals with DLB and caregivers included clinician time, diagnosis, education, symptom management, communication, and caring staff. Unmet needs or challenges included patient/caregiver education, education of nonspecialist clinicians and community care providers, scheduling difficulties, caregiver support, financial concerns, assistance with advance care planning and finding local resources, and effective treatments for DLB symptoms.

Conclusion and Relevance:

Improving care for individuals with DLB and their families will require a multipronged strategy including education for nonspecialist care providers, increasing specialty care access, improved clinical care services, research to support disease prognosis and treatment decisions, and local and national strategies for enhanced caregiver support.
Antibiotic resistance profiles and population structure of disease-associated Staphylococcus aureus infecting patients in Fort Portal Regional Referral Hospital, Western Uganda
Authors: Ackers-Johnson Gavin , Kibombo Daniel , Kusiima Brenda , Nsubuga Moses L. , Kigozi Edgar , Kajumbula Henry M. , Kateete David Patrick , Walwema Richard , Ackers Helen Louise , Goodhead Ian B. , Birtles Richard J. , James Chloë E.
Published: May 2021

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41

Staphylococcus aureus

isolates (2017–2019). AST revealed 73 % (30 of 41) of isolates were resistant to one or more antibiotics and 29 % (12 of 41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant

S. aureus

(MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24 % carriage of erm genes suggests potential for rapid development of resistance. We inferred a population structure for the

S. aureus

isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive

S. aureus

(MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton–Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating

S. aureus

and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.
COVID-19 County Level Severity Classification with Imbalanced Dataset: A NearMiss Under-sampling Approach
Authors: Oladunni Timothy , Tossou Sourou , Haile Yayehyrad , Kidane Adonias
Published: May 2021

COVID-19 pandemic that broke out in the late 2019 has spread across the globe. The disease has infected millions of people. Thousands of lives have been lost. The momentum of the disease has been slowed by the introduction of vaccine; however, some countries are still recording high number of casualties. The focus of this work is to design, develop and evaluate a machine learning county level COVID-19 severity classifier. The proposed model will predict severity of the pandemic in a county into low, moderate, or high. Policy makers will find the work useful in the distribution of vaccines. Four learning algorithms (two ensembles and two non-ensembles) were trained and evaluated. Class imbalance was addressed using NearMiss under-sampling of the majority classes. The result of our experiment shows that the ensemble models outperformed the non-ensemble models by a considerable margin.
Transcriptional overlap links DNA hypomethylation with DNA hypermethylation at adjacent promoters in cancer
Authors: Fain Jean , Loriot Axelle , Diacofotaki Anna , Van Tongelen Aurélie , De Smet Charles
Published: May 2021

DNA methylation is an epigenetic mark associated with gene repression. It is now well established that tumor development involves alterations in DNA methylation patterns, which include both gains (hypermethylation) and losses (hypomethylation) of methylation marks in different genomic regions. The mechanisms underlying these two opposite, yet co-existing, alterations in tumors remain unclear. While studying the human MAGEA6/GABRA3 gene locus, we observed that DNA hypomethylation in tumor cells can lead to the activation of a long transcript (CT-GABRA3) that overlaps downstream promoters (GABRQ and GABRA3) and triggers their hypermethylation. Overlapped promoters displayed increases in H3K36me3, a histone mark known to be deposited during progression of the transcription machinery and to stimulate de novo DNA methylation. Consistent with such a processive mechanism, increases in H3K36me3 and DNA methylation were observed over the entire region covered by the CT-GABRA3 overlapping transcript. Importantly, experimental induction of CT-GABRA3 by depletion of DNMT1 DNA methyltransferase, resulted in a similar pattern of increased DNA methylation in the MAGEA6/GABRA3 locus. Bioinformatics analyses in lung cancer datasets identified other genomic loci displaying this process of coupled DNA hypo- and hypermethylation. In several of these loci, DNA hypermethylation affected tumor suppressor genes, e.g. RERG and PTPRO. Together, our work reveals that focal DNA hypomethylation in tumors can indirectly contribute to hypermethylation of nearby promoters through activation of overlapping transcription, and establishes therefore an unsuspected connection between these two opposite epigenetic alterations.
Age- and airway disease related gene expression patterns of key SARS-CoV-2 entry factors in human nasal epithelia
Authors: Plaas Mihkel , Seppa Kadri , Gaur Nayana , Kasenõmm Priit , Plaas Mario
Published: May 2021

The global COVID-19 pandemic caused by SARS-CoV-2 predominantly affects the elderly. Differential expression of SARS-CoV-2 entry genes may underlie the variable susceptibility in different patient groups. Here, we examined the gene expression of key SARS-CoV-2 entry factors in mucosal biopsies to delineate the roles of age and existing chronic airway disease. A significant inverse correlation between ACE2 and age and a downregulation of NRP1 in patients with airway disease were noted. These results indicate that the interplay between various factors may influence susceptibility and the disease course.
A comparative study of SIR Model, Linear Regression, Logistic Function and ARIMA Model for forecasting COVID-19 cases
Authors: Abolmaali Saina
Published: May 2021

Starting February 2020, COVID-19 was confirmed in 11,946 people worldwide, with a mortality rate of almost 2%. A significant number of epidemic diseases including human Coronavirus display patterns. In this study with the benefit of data analytic, we develop regression models and a Susceptible-Infected-Recovered (SIR) model for the contagion to compare the performance of models to predict number of cases. first, we implement a good understanding of data and perform Exploratory Data Analysis (EDA). Then, we derive the parameters of the model from the available data corresponding to the top 4 regions based on the history of infections and the most infected people as of the end of August 2020. Then models are compared and further research are introduced.
Adaptation to chronic ER stress enforces pancreatic β-cell plasticity
Authors: Chen Chien-Wen , Guan Bo-Jhih , Alzahrani Mohammed R. , Gao Zhaofeng , Gao Long , Bracey Syrena , Haataja Leena , Schaffer Ashleigh E. , Lee Hugo , Laframboise Thomas , Bederman Ilya , Arvan Peter , Mathews Clayton E. , Gerling Ivan C. , Kaestner Klaus H. , Tirosh Boaz , Engin Feyza , Hatzoglou Maria
Published: May 2021

Pancreatic β-cells undergo high levels of endoplasmic reticulum (ER) stress due to their role in insulin secretion. Hence, they require sustainable and efficient adaptive stress responses to cope with the stress. Whether duration and episodes of chronic ER stress directly compromises β-cell identity is largely unknown. We show that under reversible, chronic ER stress, β-cells undergo a distinct transcriptional and translational reprogramming. During reprogramming, expression of master regulators of β-cell function and identity and proinsulin processing is impaired. Upon recovery from stress, β-cells regain their identity, highlighting a high-degree of adaptive β-cell plasticity. Remarkably, when stress episodes exceed a certain threshold, β-cell identity is gradually lost. Single cell RNA-seq analysis of islets from type 1 diabetes (T1D) patients, identifies the severe deregulation of the chronic stress-adaptation program, and reveals novel biomarkers for progression of T1D. Our results suggest β-cell adaptive exhaustion (βEAR) is a significant component of the pathogenesis of T1D.
Severe Acute Respiratory Syndrome Coronavirus-2 genome sequence variations relate to morbidity and mortality in Coronavirus Disease-19
Authors: Mehta Poonam , Sarkar Saumya , Ghoshal Ujjala , Pandey Ankita , Singh Ratender , Singh Dharamveer , Vishvkarma Rahul , Ghoshal Uday Chand , Maurya Ranjeet , Pandey Rajesh , Ramachandran Ravishankar , Bhadury Punyasloke , Kundu Tapas K , Singh Rajender
Published: May 2021

Outcome of infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may depend on the host, virus or the host-virus interaction related factors. Complete SARS-CoV-2 genome was sequenced using Illumina and Nanopore platforms from naso-/oro-pharyngeal ri-bonucleic acid (RNA) specimens from COVID-19 patients of varying severity and outcomes, including patients with mild upper respiratory symptoms (n=35), severe disease admitted to intensive care with respiratory and gastrointestinal symptoms (n=21), fatal COVID-19 outcome (n=17) and asymptomatic (n=42). Of a number of genome variants observed, p.16L>L (Nsp1), p.39C>C (Nsp3), p.57Q>H (ORF3a), p.71Y>Y (Membrane glycoprotein), p.194S>L (Nucleocapsid protein) were observed in similar frequencies in different patient subgroups. However, seventeen other variants were observed only in symptomatic patients with severe and fatal COVID-19. Out of the latter, one was in the 5UTR (g.241C>T), eight were synonymous (p.14V>V and p.92L>L in Nsp1 protein, p.226D>D, p.253V>V, and p.305N>N in Nsp3, p.34G>G and p.79C>C in Nsp10 protein, p.789Y>Y in Spike protein), and eight were non-synonymous (p.106P>S, p.157V>F and p.159A>V in Nsp2, p.1197S>R and p.1198T>K in Nsp3, p.97A>V in RdRp, p.614D>G in Spike protein, p.13P>L in nucleocapsid). These were completely absent in the asymptomatic group. SARS-CoV-2 genome variations have a significant impact on COVID-19 presentation, severity and outcome.
Old data and friends improve with age: Advancements with the updated tools of GeneNetwork
Authors: Chunduri Alisha , Ashbrook David G.
Published: May 2021

Understanding gene-by-environment interactions is important across biology, particularly behaviour. Families of isogenic strains are excellently placed, as the same genome can be tested in multiple environments. The BXD’s recent expansion to 140 strains makes them the largest family of murine isogenic genomes, and therefore give great power to detect QTL. Indefinite reproducible genometypes can be leveraged; old data can be reanalysed with emerging tools to produce novel biological insights.

To highlight the importance of reanalyses, we obtained drug- and behavioural-phenotypes from Philipet al.2010, and reanalysed their data with new genotypes from sequencing, and new models (GEMMA and R/qtl2). We discover QTL on chromosomes 3, 5, 9, 11, and 14, not found in the original study.

We narrowed down the candidate genes based on their ability to alter gene expression and/or protein function, usingcis-eQTL analysis, and variants predicted to be deleterious. Co-expression analysis (‘gene friends’) and human PheWAS were used to further narrow candidates.

Prominent candidate genes include:Slitrk6in a Chr 14 QTL for locomotion in the center of an open field, we show to be part of a coexpression network involved in voluntary movement, and association with neuropsychiatric phenotypes in PheWAS; andCdk14, one of only 3 genes in a Chr 5 QTL for handling induced convulsions after ethanol treatment, that is regulated by the anticonvulsant drug valproic acid.

By using families of isogenic strains, we can reuse and reanalyse data to discover novel and highly plausible candidate genes involved in response to the environment.
miRNA-34c suppresses osteosarcoma progression in vivo by targeting Notch and E2F
Authors: Bae Yangjin , Zeng Huan-Chang , Chen Yi-Ting , Ketkar Shamika , Munivez Elda , Yu Zhiyin , Gannon Francis H. , Lee Brendan H.
Published: May 2021

The expression of microRNAs (miRNAs) is dysregulated in many types of cancers including osteosarcoma (OS) due to genetic and epigenetic alterations. Among these, miR-34c, an effector of tumor suppressor P53 and an upstream negative regulator of Notch signaling in osteoblast differentiation, is dysregulated in OS. Here, we demonstrated a tumor suppressive role of miR-34c in OS progression using in vitro assays and in vivo genetic mouse models. We found that miR-34c inhibits the proliferation and the invasion of metastatic OS cells, which resulted in reduction of the tumor burden and increased overall survival in an orthotopic xenograft model. Moreover, the osteoblast specific over expression of miR-34c increased survival in the osteoblast specific p53 mutant OS mouse model. We found that miR-34c regulates the transcription of several genes in Notch signaling (NOTCH1, JAG1 and HEY2) and in p53 mediated cell cycle and apoptosis (CCNE2, E2F5, E2F2 and HDAC1). More interestingly, we found that the metastatic free survival probability was increased among a patient cohort from TARGET OS which has lower expression of direct targets of miR-34c that was identified in our transcriptome analysis such as E2F5 and NOTCH1. In conclusion, we demonstrate that miR-34c is a tumor suppressive miRNA in OS progression in vivo. In addition, we highlight the therapeutic potential of targeting miR-34c in OS.
Multiple Causal Variants Underlie Genetic Associations in Humans
Authors: Abell Nathan S. , DeGorter Marianne K. , Gloudemans Michael , Greenwald Emily , Smith Kevin S. , He Zihuai , Montgomery Stephen B.
Published: May 2021

The majority of associations between genetic variation and human traits and diseases are non-coding and in strong linkage disequilibrium (LD) with surrounding genetic variation. In these cases, a single causal variant is often assumed to underlie the association, however no systematic assessment of the number of causal variants has been performed. In this study, we applied a massively parallel reporter assay (MPRA) in lymphoblastoid cells to functionally evaluate 49,256 allelic pairs, representing 30,893 genetic variants in high, local linkage disequilibrium for 744 independent cis-expression quantitative trait loci (eQTL) and assessed each for colocalization across 114 traits. We identified 8,502 allele-independent regulatory regions containing 1,264 allele-specific regulatory variants, and found that 17.7% of eQTL contained more than one significant allelic effect. We show that detected regulatory variants are highly and specifically enriched for activating chromatin structures and allelic transcription factor binding, for which ETS-domain family members are a large driver. Integration of MPRA profiles with eQTL/complex trait colocalizations identified causal variant sets for associations with blood cell measurements, Asthma, Multiple Sclerosis, Inflammatory Bowel Disease, and Crohn’s Disease. These results demonstrate that a sizable number of association signals are manifest through multiple, tightly-linked causal variants requiring high-throughput functional assays for fine-mapping.
On the sparsity of fitness functions and implications for learning
Authors: Brookes David H. , Aghazadeh Amirali , Listgarten Jennifer
Published: May 2021

Fitness functions map biological sequences to a scalar property of interest. Accurate estimation of these functions yields biological insight and sets the foundation for model-based sequence design. However, the amount of fitness data available to learn these functions is typically small relative to the large combinatorial space of sequences; characterizing how much data is needed for accurate estimation remains an open problem. There is a growing body of evidence demonstrating that empirical fitness functions display substantial sparsity when represented in terms of epistatic interactions. Moreover, the theory of Compressed Sensing provides scaling laws for the number of samples required to exactly recover a sparse function. Motivated by these results, we develop a framework to study the sparsity of fitness functions sampled from a generalization of the NK model, a widely-used random field model of fitness functions. In particular, we present results that allow us to test the effect of the Generalized NK (GNK) model’s interpretable parameters—sequence length, alphabet size, and assumed interactions between sequence positions—on the sparsity of fitness functions sampled from the model and, consequently, the number of measurements required to exactly recover these functions. We validate our framework by demonstrating that GNK models with parameters set according to structural considerations can be used to accurately approximate the number of samples required to recover two empirical protein fitness functions and an RNA fitness function. In addition, we show that these GNK models identify important higher-order epistatic interactions in the empirical fitness functions using only structural information.
Vapor exposure to Δ9-tetrahydrocannabinol (THC) slows locomotion of the Maine Lobster (Homarus americanus)
Authors: Gutierrez Arnold , Creehan Kevin M. , Turner Mitchell L. , Tran Rachelle N , Kerr Tony M. , Nguyen Jacques D. , Taffe Michael A.
Published: May 2021

Rationale

Despite a long history of use in synaptic physiology, the lobster has been a neglected model for behavioral pharmacology. A restaurateur proposed that exposing lobster to cannabis smoke reduces anxiety and pain during the cooking process. It is unknown if lobster gill respiration in air would result in significant Δ9-tetrahydrocannabinol (THC) uptake and whether this would have any detectable behavioral effects.

Objective

The primary goal was to determine tissue THC levels in the lobster after exposure to THC vapor. Secondary goals were to determine if THC vapor altered locomotor behavior or nociception.

Methods

Tissue samples were collected (including muscle, brain and hemolymph) from Homarus americanus (N=3 per group) following 30 or 60 minutes of exposure to vapor generated by an e-cigarette device using THC (100 mg/mL in a propylene glycol vehicle). Separate experiments assessed locomotor behavior and hot water nociceptive responses following THC vapor exposure.

Results

THC vapor produced duration-related THC levels in all tissues examined. Locomotor activity was decreased (distance, speed, time-mobile) by 30 min inhalation of THC. Lobsters exhibit a temperature-dependent withdrawal response to immersion of tail, antennae or claws in warm water; this is novel evidence of thermal nociception for this species. THC exposure for 60 minutes had only marginal effect on nociception under the conditions assessed.

Conclusions

Vapor exposure of lobsters, using an e-cigarette based model, produces dose-dependent THC levels in all tissues and reduces locomotor activity. Hot water nociception was temperature dependent, but only minimal anti-nociceptive effect of THC exposure was confirmed.
Cellular calcium levels influenced by NCA-2 impact circadian period determination in Neurospora
Authors: Wang Bin , Zhou Xiaoying , Gerber Scott A. , Loros Jennifer J. , Dunlap Jay C.
Published: May 2021

Intracellular calcium signaling has been implicated in control of a variety of circadian processes in animals and plants but its role in microbial clocks has remained largely cryptic. To examine the role of intracellular Ca2+ in the Neurospora clock we screened knockouts of calcium transporter genes and identified a gene encoding a calcium exporter, nca-2, uniquely as having significant period effects. Loss of NCA-2 results in an increase in cytosolic calcium level, and this leads to hyper-phosphorylation of core clock components, FRQ and WC-1, and a short period as measured by both the core oscillator and overt clock. Genetic analyses showed that mutations in certain frq phospho-sites, and in Ca2+-calmodulin-dependent kinase (camk-2), are epistatic to nca-2 in controlling the pace of the oscillator. These data are consistent with a model in which elevated intracellular Ca+2 leads to increased activity of CAMK-2 leading to enhanced FRQ phosphorylation, accelerated closure of the circadian feedback loop, and a shortened circadian period length. At a mechanistic level some CAMKs undergo more auto-phosphorylations in Δnca-2, consistent with high calcium in the Δnca-2 mutant influencing the enzymatic activity of CAMKs. NCA-2 interacts with multiple proteins including CSP-6, a protein known to be required for circadian output. Most importantly, expression of nca-2 is circadian clock-controlled at both the transcriptional and translational levels, and this in combination with the period effects seen in strains lacking NCA-2, firmly places calcium signaling within the larger circadian system where it acts as both an input to and output from the core clock.

Importance

Circadian rhythms are based on cell-autonomous, auto-regulatory, feedback loops formed by interlocked positive and negative arms, and they regulate myriad molecular and cellular processes in most eukaryotes including fungi. Intracellular calcium signaling is also a process that impacts a broad range of biological events in most eukaryotes. Clues have suggested that calcium signaling can influence circadian oscillators through multiple pathways; however, mechanistic details have been lacking in microorganisms. Building on prior work describing calcium transporters in the fungus Neurospora, one such transporter, NCA-2, was identified as a regulator of circadian period length. Increased intracellular calcium levels caused by loss of NCA-2 results in over-activation of calcium-responsive protein kinases, in turn leading to a shortened circadian period length. Importantly, expression of NCA-2 is itself controlled by the molecular clock. In this way calcium signaling can be seen as providing both input to and output from the circadian system.
Single-dose SARS-CoV-2 vaccine in a prospective cohort of COVID-19 patients
Authors: van Gils Marit J. , van Willigen Hugo D. , Wynberg Elke , Han Alvin X. , van der Straten Karlijn , Verveen Anouk , Lebbink Romy , Dijkstra Maartje , Burger Judith A. , Oomen Melissa , Tejjani Khadija , Bouhuijs Joey H. , Appelman Brent , Lavell Ayesha H.A. , Poniman Meliawati , Caniels Tom G. , Bontjer Ilja , van Vught Lonneke A. , Vlaar Alexander P.J. , Sikkens Jonne J. , Bomers Marije K. , Sanders Rogier W. , Kootstra Neeltje A. , Russell Colin , Prins Maria , de Bree Godelieve J. , de Jong Menno D. ,   RECoVERED Study Group
Published: May 2021

Background

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection.

Methods

We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients.

Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses.

Results

Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: −0.16 to −0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response.

Conclusion

A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.