bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synchronicity of P53 Mutation and Multiple High-Risk HPV Genotypes, and the Risk of Cervical Cancer among Women in Osogbo, Nigeria
Authors: Oyenike Musiliu A. , Akinbo Frederick O. , Adedokun Kamoru A. , Ojokuku Hammed O. , Imodoye Sikiru O. , Yunus Lukman A. , Lasisi Ismaila A. , Jimoh Abdulahi A. 
Published: June 2022

AbstractBackgroundIn low-and middle-income countries, high burden of cervical cancer is associated with human papillomavirus (HPV) due to poor screening and diagnostic methods at early stage. Reports showed that there are discrepancies in data correlating HPV-infection with development of cervical cancer while the functional roles of P53 oncogenic mutation are controversial. Furthermore, the molecular pathogenesis of multiple HPV-genotypes remains an open question. Thus, advancing investigations on HPV-associated cervical abnormalities would add to early diagnostic precision.MethodsTwo hundred (n=200) cervical samples were collected from apparently healthy, active adult women following an ethical approval. Laboratory analyses were conducted through cytological assessment and histochemistry screening using the Papanicolaou smear. PCR methods were used to characterize HPV-DNA genotypes and P53 gene mutations. Positive cervical dysplasia cases were matched with HPV-DNA, and the HPV-genotypes were used to evaluate the prevalence of various HPV-subtypes and the risk of cervical cancer.ResultsTwenty-six (n=26) cervical dysplasia and fifty-one (n=51) HPV+ were identified comprising single and multiple genotypes. While nine cases (n=9) showed p53 gene mutation with concurrent multiple high-risk HPV (hrHPV) genotypes, none of the single hrHPV genotypes had p53 mutation. More so, individuals with coexisting p53 mutation and multiple hrHPV-genotypes already manifesting cervical dysplasia were 22.2% of the group, while 77.8% had normal cervical architecture, the fate of whom was unknown during investigation. There was a higher cervical dysplasia among those with HPV oncogenes; there were connections between the HPV positivity with some genotypes (hrHPV16,18,31 and 33, respectively) and p53 mutation.ConclusionP53 gene mutation was independent of HPV-associated cervical abnormalities in single hrHPV-genotype, though other mechanistic drivers attributed to p53 dysfunction by E6 and E7 remain plausible. On the other hand, infection with multiple hrHPVs showed a concomitant predominance with the P53 mutation, implying a potential interplay and an increased risk of cervical cancer.
Differential COVID-19 infection rates in children, adults, and elderly: evidence from 38 pre-vaccination national seroprevalence studies
Authors: Axfors Cathrine , Pezzullo Angelo Maria , Contopoulos-Ioannidis Despina G. , Apostolatos Alexandre , Ioannidis John P.A. 
Published: June 2022

ABSTRACTBackgroundCOVID-19 exhibits a steep age gradient of infection fatality rate. There has been debate about whether extra protection of elderly and other vulnerable individuals (precision shielding) is feasible, and, if so, to what extent.MethodsWe used systematically retrieved data from national seroprevalence studies conducted in the pre-vaccination era. Studies were identified through SeroTracker and PubMed searches (last update May 17, 2022). Studies were eligible if they targeted representative general populations without high risk of bias. Seroprevalence estimates were noted for children, non-elderly adults, and elderly adults, using cut-offs of 20, and 60 years (or as close to these ages, if they were not available).ResultsThirty-eight national seroprevalence studies from 36 different countries were included in the analysis. 26/38 also included pediatric populations. 25/38 studies were from high-income countries. The median ratio of seroprevalence in the elderly versus non-elderly adults (or non-elderly in general, if pediatric and adult population data were not offered separately) was 0.90-0.95 in different analyses with large variability across studies. In 5 studies (all of them in high-income countries), there was significant protection of the elderly with ratio <0.40. The median was 0.83 in high-income countries and 1.02 in other countries. The median ratio of seroprevalence in children versus adults was 0.89 and only one study showed a significant ratio of <0.40.ConclusionPrecision shielding of elderly community-dwelling populations before the availability of vaccines was feasible in some high-income countries, but most countries failed to achieve any substantial focused protection of this age group.summary38 COVID-19 nationally representative seroprevalence studies conducted before vaccination campaigns were systematically identified. Median seroprevalence ratio in elderly versus non-elderly adults was 0.90-0.95, indicating no generally achieved precision shielding of elderly. In 5 studies, substantial protection (ratio <0.40) was observed.
Suppressor mutations that make the essential transcription factor Spn1/Iws1 dispensable in Saccharomyces cerevisiae
Authors: López-Rivera Francheska , Chuang James , Spatt Dan , Gopalakrishnan Rajaraman , Winston Fred 
Published: June 2022

AbstractSpn1/Iws1 is an essential eukaryotic transcription elongation factor that is conserved from yeast to humans as an integral member of the RNA polymerase II elongation complex. Several studies have shown that Spn1 functions as a histone chaperone to control transcription, RNA splicing, genome stability, and histone modifications. However, the precise role of Spn1 is not understood, and there is little understanding of why it is essential for viability. To address these issues, we have isolated eight suppressor mutations that bypass the essential requirement for Spn1 in Saccharomyces cerevisiae. Unexpectedly, the suppressors identify several functionally distinct complexes and activities, including the histone chaperone FACT, the histone methyltransferase Set2, the Rpd3S histone deacetylase complex, the histone acetyltransferase Rtt109, the nucleosome remodeler Chd1, and a member of the SAGA co-activator complex, Sgf73. The identification of these distinct groups suggests that there are multiple ways in which Spn1 bypass can occur, including changes in histone acetylation and alterations of other histone chaperones. Thus, Spn1 may function to overcome repressive chromatin by multiple mechanisms during transcription. Our results suggest that bypassing a subset of these functions allows viability in the absence of Spn1.
The value of freedom: extending the evaluative space of capability
Authors: Ubels Jasper , Hernandez-Villafuerte Karla , Niebauer Erica , Schlander Michael 
Published: June 2022

AbstractIntroductionDeveloping an instrument with an ambiguous construct can be challenging. With the capability approach, this is argued to be case, since the concept of capability by Sen is ambiguous in respect to the burdens that people experience whilst achieving their capabilities. A potential solution is to develop instruments with a more comprehensive concept of capability, such as the concept ‘option-freedom’. The concept option-freedom stresses the importance of achieving capabilities without impediments. However, this concept has not been operationalized for wellbeing assessment. The aim of this study is to develop a theoretical framework of wellbeing with the concept option-freedom.MethodsA best-fit framework synthesis was conducted with seven papers that report qualitative findings which underpin capability instruments. First, the a-priori concept option-freedom was used to deductively code against. New codes, subthemes and themes were developed inductively when data did not match the a-priori concept.ResultsFour themes emerged from the synthesis. (1) Option Wellbeing represents a range of options that need to be satisfied in order for individuals to experience wellbeing. (2) Self-Realization represents that there are experiences in an individual’s live that have value beyond realizing options. (3) Perceived Access to Options represents the perceived ability of individuals to realize freedoms. (4) Perceived Control represents the experience of having control.ConclusionDeveloping an instrument with the proposed framework has two benefits. First, it acknowledges the importance of assessing impediments in realizing capabilities for the assessment of wellbeing. Second, the themes form a broad informational base by including themes related to subjective wellbeing. The framework could be used as a broad base on which to assess the value of health technologies. Future research should study the feasibility of implementing the framework for the assessment of wellbeing.
Long-term Neurocognitive Outcomes after Pediatric Intensive Care Unit Admission: Exploring the Role of Drug Exposure
Authors: de Sonnaville Eleonore S.V. , Oosterlaan Jaap , Ghiassi Sima A. , van Leijden Ouke , van Ewijk Hanneke , Knoester Hennie , van Woensel Job B.M. , Königs Marsh 
Published: June 2022

ABSTRACTIntroductionConcerns exist regarding the impact of widely-used clinical drugs on brain development. This study investigates long-term neurocognitive functioning in relation to frequently used drug exposure at the Pediatric Intensive Care Unit (PICU).MethodsThis study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation (patient group, n=65) to a demographically comparable control group (n=76) on a broad range of neurocognitive outcomes. The patient group was selected because bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. The relation between exposure to sedatives, analgesics and anesthetics and neurocognitive outcomes was assessed by regression analyses.ResultsThe patient group had lower intelligence than the control group (p<.001, d=-0.59) and poorer performance in neurocognitive functions; i.e. speed and attention (p=.009, d=-0.41) and verbal memory (p<.001, d=-0.60). Exposure to sedatives, analgesics and anesthetics was not related to neurocognitive outcomes.ConclusionChildren with PICU admission for bronchiolitis requiring mechanical ventilation are at risk of long-term neurocognitive impairment. This study found no evidence for a role of exposure to sedatives, analgesics or anesthetics. Findings underline the importance of long-term follow-up after PICU admission, even in absence of disease with neurological manifestation.Category of studyClinical population studyImpactAnimal studies have indicated that exposure of the maturing brain to clinical drugs may cause neurodegeneration. Clinical studies show mixed evidence for an association between clinical drugs and neurocognitive outcomes.This study provides evidence for long-term neurocognitive impairment among children with a history of PICU admission for bronchiolitis, a condition that seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself.We found no evidence for a relation between drug exposure (i.e. sedatives, analgesics and anesthetics) and long-term neurocognitive outcomes, suggesting that the observed neurocognitive impairments are not accounted for by drug exposure.Findings underline the importance of structured follow-up after PICU admission, even in absence of disease with neurological manifestation.
Sonographic Diaphragm Abnormalities are an Unexpectedly Frequent Feature of Long COVID Outpatients with Unexplained Dyspnea and Fatigue
Authors: Deo Prabhav P. , Bailey Joseph I. , Jensen Alexandra S. , Farr Ellen , Fahey Meghan , Isherwood Matthew , Chakka Keerthana , Wolfe Lisa F. , Roy Ishan , Sala Marc A. , Franz Colin K. 
Published: June 2022

AbstractIntroduction/AimsThe primary aim of this study is to define the sonographic diaphragm phenotype of Long COVID rehabilitation outpatients with non-specific dyspnea and fatigue. We analyzed patients referred from a pulmonary post-COVID clinic that were lacking a specific cardiopulmonary diagnosis for their symptoms. Additionally, we report the functional outcomes of subset of patients who completed an outpatient cardiopulmonary physical therapy program.MethodsThis was a retrospective cohort study (n = 58) of consecutive patients referred for neuromuscular ultrasound assessment of diaphragm muscle using B-mode technique. Patients were recruited from a single academic hospital between February 25, 2021 and November 22, 2022.ResultsSonographic abnormalities were identified in 57% (33/58) of patients, and in the vast majority of cases (33/33) was defined by a low diaphragm muscle thickness. Thinner diaphragm muscles are correlated with lower serum creatinine and creatine kinase values, but there was no association with markers of systemic inflammation. Thirty three patients participated in outpatient cardiopulmonary physical therapy that included respiratory muscle training, and 75.8% (25/33) had documented improvement.DiscussionIn the outpatient rehabilitation setting, patients with Long COVID display low diaphragm muscle thickness, but intact muscle contractility, with surprising frequency on neuromuscular ultrasound. We speculate this represents a form of disuse atrophy. Also, these patients appear to have a favorable response to cardiopulmonary physical therapy that includes respiratory muscle training.
Single-nuclei Transcriptome of Human AT Reveals Metabolically Distinct Depot-Specific Adipose Progenitor Subpopulations
Authors: Strieder-Barboza Clarissa , Flesher Carmen G. , Geletka Lynn M. , Delproposto Jennifer B. , Eichler Tad , Akinleye Olukemi , Ky Alexander , Ehlers Anne P. , O’Rourke Robert W. , Lumeng Carey N. 
Published: June 2022

AbstractSingle-cell and single-nuclei RNA sequencing data (scRNAseq and snRNAseq, respectively) have revealed substantial heterogeneity in the AT (AT) cellular landscape in rodents and humans depending on depot and disease status. We used snRNAseq to characterize the cellular landscape of human visceral (VAT) and subcutaneous AT (SAT) samples from lean subjects and subjects with obesity. We identified multiple cell types in the AT cellular repertoire, including three major AT stromal cell (ASC) subpopulations, multiple types of adipocyte (ADIPO) populations that retain properties similar to ASC, endothelial cell (EC), T-cell, and macrophage (MAC) populations that are in concordance and expand upon other published datasets. ADIP and EC are more prominent in SAT compared to VAT which has a higher proportion of ASC. Of two dominant ASC subpopulations, one (inflammatory-mesothelial, IM- ASC) is present in VAT, but absent in SAT, while the other (fibroadipogenic, FA-ASC) is present in both VAT and SAT. Both populations retain their properties in in vitro culture and have adipogenic capacity with different metabolic features. Informatic and in situ studies support ADIP derived from IM- and FA- ASC are found in human VAT. We also identified a wide range of EC subtypes in human AT with features of lymphatic, venous, and arterial EC, with identification of a PRDM16 expression EC population with features of an EC progenitor. Immune cell populations match recent experimental validation of lipid activated macrophage (LAM) phenotypes, TIM4 macrophages, and a prominent population of MRC1/CD206+ resident AT macrophages with gene expression signatures related to glucocorticoid activation. Overall, our study demonstrates depot-specific cellular diversity in human VAT and SAT in which distinct ASC subpopulations may differently contribute to AT dysfunction in obesity. Also, our results highlight an unprecedented EC heterogeneity suggesting AT EC as highly specialized cells and potentially important regulators of depot-specific functions.METHODS STATEMENTHuman subjects provided informed consent and were enrolled with approval from Institutional Review Boards at the University of Michigan and Veterans Affairs Ann Arbor Healthcare System. Enrollment, consent, and all aspects of human subject research were carried out in accordance with the Belmont Report from the National Research Act of 1974, and the Declaration of Helsinki set forth by the World Medical Association. This manuscript contains no human participants’ names or other HIPAA identifiers.
Identifying novel interactions of the colon-cancer related APC protein with Wnt-pathway nuclear transcription factors
Authors: Al-Thani Nayra M. , Schaefer-Ramadan Stephanie , Aleksic Jovana , Mohamoud Yasmin A. , Malek Joel A. 
Published: June 2022

AbstractBackgroundColon cancer is often driven by mutations of the adenomatous polyposis coli (APC) gene, an essential tumor suppressor gene of the Wnt β-catenin signaling pathway. APC and its interactions in the cytoplasm have been well studied, however various groups have also observed its presence in the nucleus. Identifying novel interactions of APC in the Wnt pathway will provide an opportunity to better understand the nuclear role of APC and ultimately identify potential cancer treatment targets.MethodsWe used the all-vs-all sequencing (AVA-Seq) method to interrogate the interactome of protein fragments spanning most of the 60 Wnt β-catenin pathway proteins. Using protein fragments identified the interacting regions between the proteins with more resolution than a full-length protein approach. Pull-down assays were used to validate a subset of these interactions.Results74 known and 703 novel Wnt β-catenin pathway protein-protein interactions were recovered in this study. There were 8 known and 31 novel APC protein-protein interactions. Novel interactions of APC and nuclear transcription factors TCF7, JUN, FOSL1, and SOX17 were particularly interesting and confirmed in validation assays.ConclusionBased on our findings of novel interactions between APC and transcription factors and previous evidence of APC localizing to the nucleus, we suggest APC may compete and repress CTNNB1. This would occur through the binding of the transcription factors (JUN, FOSL1, TCF7) to regulate the Wnt signaling pathway including through enhanced marking of CTNNB1 for degradation in the nucleus by APC binding with SOX17. Additional novel Wnt β-catenin pathway protein-protein interactions from this study could lead researchers to novel drug designs for cancer.
Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease
Authors: Ameen Mohamed , Sundaram Laksshman , Banerjee Abhimanyu , Shen Mengcheng , Kundu Soumya , Nair Surag , Shcherbina Anna , Gu Mingxia , Wilson Kitchener D. , Varadarajan Avyay , Vadgama Nirmal , Balsubramani Akshay , Wu Joseph C. , Engreitz Jesse , Farh Kyle , Karakikes Ioannis , Wang Kevin C , Quertermous Thomas , Greenleaf William , Kundaje Anshul 
Published: June 2022

SummaryCongenital heart defects, the most common birth disorders, are the clinical manifestation of anomalies in fetal heart development - a complex process involving dynamic spatiotemporal coordination among various precursor cell lineages. This complexity underlies the incomplete understanding of the genetic architecture of congenital heart diseases (CHDs). To define the multi-cellular epigenomic and transcriptional landscape of cardiac cellular development, we generated single-cell chromatin accessibility maps of human fetal heart tissues. We identified eight major differentiation trajectories involving primary cardiac cell types, each associated with dynamic transcription factor (TF) activity signatures. We identified similarities and differences of regulatory landscapes of iPSC-derived cardiac cell types and their in vivo counterparts. We interpreted deep learning models that predict cell-type resolved, base-resolution chromatin accessibility profiles from DNA sequence to decipher underlying TF motif lexicons and infer the regulatory impact of non-coding variants. De novo mutations predicted to affect chromatin accessibility in arterial endothelium were enriched in CHD cases versus controls. We used CRISPR-based perturbations to validate an enhancer harboring a nominated regulatory CHD mutation, linking it to effects on the expression of a known CHD gene JARID2. Together, this work defines the cell-type resolved cis-regulatory sequence determinants of heart development and identifies disruption of cell type-specific regulatory elements as a component of the genetic etiology of CHD.
A value adoption approach to sustainable consumption in retail stores
Authors: Lin Ying-Tzu , Tseng Timmy H. , Chang Ariana , Yang Chun-Chi 
Published: June 2022

PurposeThe United Nations Sustainable Development Goals (SDGs) have urged retail companies to transform by adopting more sustainable practices. One of the key goals is to motivate responsible consumption and production. How to facilitate sustainable consumption of retail consumers is a research question of high theoretical and practical relevance. This research investigates the drivers of less examined sustainable consumer behaviour (reuse) from the perspective of consumers by integrating a value-based adoption model and the theory of planned behaviour (TPB).Design/methodology/approachTwo samples of data were collected by using offline and online surveys. The offline survey was conducted at a university in northern Taiwan emphasizing sustainability practices. The online survey was implemented by a market research firm. A total of 518 useable questionnaires were obtained for data analysis by using the structural equation modelling.FindingsConsistent with TPB, perceived behavioural control, subjective norms, and attitude, generate reuse intention in retail stores. Furthermore, the results also show the validity of the value adoption approach in predicting reuse intention in retail stores. Economic benefits and identity expressiveness are key facilitators and perceived inconvenience is a key barrier to perceived value and perceived value influences reuse intention in retail stores.Originality/valueThis research contributes by moving beyond TPB and proposing a value-based adoption approach to explain sustainable consumer behaviour in retail stores from the consumer perspectives. Based on the findings, value adoption strategies for retailers to facilitate sustainable consumer behaviour are proposed.