bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tackling the first COVID-19 wave at the Cape Town Hospital of Hope: Why was it such a positive experience for staff?
Authors: Reid Steve , Nana Mitan , Abrahams Theo , Hussey Nadia , Okun-Netter Ronit , Ras Tasleem , von Pressentin Klaus 
Published: February 2022

ABSTRACTBackgroundIn contrast to alarming reports of exhaustion and burnout amongst healthcare workers in the first wave of the COVID-19 pandemic, we noticed surprisingly positive staff experiences of working in a COVID-19 field hospital in South Africa. The 862-bed ‘Hospital of Hope’ was established at the Cape Town International Convention Centre specifically to cope with the effects of the first wave of the COVID-19 pandemic in Cape Town.MethodsWe aimed to systematically describe and assess the effects on staff and the local health system. A cross-sectional descriptive study design was employed using mixed methods including record reviews and interviews with key informants.ResultsQuantitative results confirmed high job satisfaction and low staff infection rates. The emerging themes from the qualitative data are grouped around a “bull’s eye” of the common purpose of person-centredness, from both patient and staff perspectives, and include staff safety and support, rapid communication, continuous learning and adaptability, underpinned by excellent teamwork. The explanations for the positive feedback included good disaster planning, adequate resources, and an extraordinary responsiveness to the need.ConclusionsThe ‘Hospital of Hope’ staff experience produced significant learnings for the design and management of routine health services outside of a disaster situation. The adaptability and responsiveness of the facility and its staff was largely a product of the unprecedented nature of the pandemic, but such approaches could benefit routine health services enormously, as individual hospitals and health facilities realize their place in a system that is ‘more than the sum of its parts’.
Breast and colorectal cancer awareness in Malaysians and barriers towards screening: A systematic review
Authors: Paramasivam Darishiani , Schliemann Désirée , Dahlui Maznah , Donnelly Michael , Su Tin Tin 
Published: February 2022

AbstractBackgroundBreast cancer (BC) and colorectal cancer (CRC) are considered primary cancers that affect both male and females globally. In Malaysia, BC is the most commonly diagnosed cancer among women of all ethnic groups and CRC is the second most common cancer in males and the second most common cancer in females. This systematic review was carried out to assess cancer symptom awareness and barriers to undergoing cancer screening for BC and CRC.MethodsA pre-defined search was conducted between January 2008 and December 2018 using the following databases: MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus and Cochrane Library for relevant articles. The search was updated in June 2020. Reviewers independently performed the data extraction and quality assessment of the included study according to the Joanna Briggs Institute assessment tools.Result22 studies met the inclusion criteria (BC n=11; CRC n=11). Nine studies assessed symptom knowledge for BC and eight for CRC. Two studies described barriers towards cancer screening for BC and one for CRC. Four CRC studies assessed symptoms knowledge and cancer screening barriers. The most commonly reported BC symptoms were ‘painless breast lump’(27.6% - 90.8%), ‘nipple discharge’ (1.6% - 74.5%) and ‘pain in breast/ breast region’ (11.5% - 82.8%) meanwhile CRC symptoms were ‘change in bowel habits (new-onset diarrhoea or constipation)’ (28.4% - 86.6%), ‘bleeding and/or bleeding from the back passage’ (11.5% - 71.9%) and ‘weight loss’ (9.3% - 83.4%). ‘Financial issue’ (10% - 17.5%) was the most frequent blockade identified towards BC screening meanwhile ‘fear of result’ (27.6% - 32.1%) for CRC screening by Malaysians. Overall the studies carried out in Malaysia, six studies on BC symptom knowledge and one study on BC screening barrier were scored as medium study quality while four studies on CRC symptom knowledge and three studies on CRC screening barriers were scored as medium study quality.ConclusionStudies described varied and overall, limited, symptom awareness and barriers towards BC and CRC screening which likely contributes to the delayed presentation of cancers in Malaysia. There is a need for improving the awareness of BC and CRC symptoms as well as the importance of screening to encourage the early presentation of symptomatic cancer patients and down-staging of cancer.
piRNA-like small RNAs target transposable elements in a Clade IV parasitic nematode
Authors: Suleiman Mona , Kohnosu Asuka , Murcott Ben , Dayi Mehmet , Pawluk Rebecca , Yoshida Akemi , Viney Mark , Kikuchi Taisei , Hunt Vicky L. 
Published: February 2022

AbstractThe small RNA (sRNA) pathways identified in the model organism Caenorhabditis elegans are not widely conserved across nematodes. For example, the PIWI pathway and PIWI-interacting RNAs (piRNAs) are involved in regulating and silencing transposable elements (TE) in most animals but have been lost in nematodes outside of the Caenorhabditis elegans group (Clade V), and little is known about how nematodes regulate TEs in the absence of the PIWI pathway. Here, we investigated the role of sRNAs in the Clade IV parasitic nematode Strongyloides ratti by comparing two genetically identical adult stages (the parasitic female and free-living female). We identified putative small-interfering RNAs, microRNAs and tRNA-derived sRNA fragments that are differentially expressed between the two adult stages. Two classes of sRNAs were predicted to regulate TE activity including (i) a parasite-associated class of 21-22 nt long sRNAs with a 5’ uracil (21-22Us) and monophosphate modification, and (ii) 27 nt long sRNAs with a 5’ guanine/adenine (27GAs) and polyphosphate modification. The 21-22Us show striking resemblance to the 21U PIWI-interacting RNAs found in C. elegans, including an AT rich upstream sequence, overlapping loci and physical clustering in the genome.
A Novel Chronic in vivo Oral Cadmium Exposure-Washout Mouse Model for Studying Cadmium Toxicity and Complex Diabetogenic Effects
Authors: Wong Winifred P.S. , Wang Janice C. , Meyers Matthew S. , Wang Nathan J. , Sponenburg Rebecca A. , Allen Norrina B. , Edwards Joshua E. , El Muayed Malek 
Published: February 2022

AbstractType II diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction and hyperglycemia. In addition to well known risk factors such as lifestyle and genetic risk score, accumulation of environmental toxicants in organs relevant to glucose metabolism is increasingly recognized as additional risk factors for T2DM. Here, we describe the development of an in vivo oral cadmium (Cd) exposure model. It was shown that oral Cd exposure in drinking water followed by washout and high fat diet (HFD) in C57BL/6N mice results in islet Cd bioaccumulation comparable to that found in native human islets while mitigating the anorexic effects of Cd to achieve the same weight gain required to induce insulin resistance as in Cd naïve control mice. Inter individual variation in plasma glucose and insulin levels as well as islet Cd bioaccumulation was observed in both female and male mice. Regression analysis showed an inverse correlation between islet Cd level and plasma insulin following a glucose challenge in males but not in females. This finding highlights the need to account for inter individual target tissue Cd concentrations when interpreting results from in vivo Cd exposure models. No effect of Cd on insulin secretion was observed in islets ex vivo, highlighting differences between in vivo and ex vivo cadmium exposure models. In summary, our oral in vivo Cd exposure-washout with HFD model resulted in islet Cd bioaccumulation that is relevant in the context of environmental cadmium exposure in humans. Here, we showed that islet Cd bioaccumulation is associated with complex cadmium-mediated changes in glucose clearance and β-cell function. The model described here will serve as a useful tool to further examine the relationship between Cd exposure, islet Cd bioaccumulation, dysglycemia and their underlying mechanisms.
Truvari: Refined Structural Variant Comparison Preserves Allelic Diversity
Authors: English Adam C. , Menon Vipin K. , Gibbs Richard , Metcalf Ginger A. , Sedlazeck Fritz J. 
Published: February 2022

AbstractFor multi-sample structural variant analyses like merging, benchmarking, and annotation, the fundamental operation is to identify when two SVs are the same. Commonly applied approaches for comparing SVs were developed alongside technologies which produce ill-defined boundaries. As SV detection becomes more exact, algorithms to preserve this refined signal are needed. Here we present Truvari - a SV comparison, annotation and analysis toolkit - and demonstrate the effect of SV comparison choices by building population-level VCFs from 36 haplotype-resolved long-read assemblies. We observe over-merging from other SV merging approaches which causes up to a 2.2x inflation of allele frequency relative to Truvari.
Functional networks of the human bromodomain-containing proteins
Authors: Gao Cong , Glass Karen C. , Frietze Seth 
Published: February 2022

AbstractBackgroundBromodomains are a structurally conserved epigenetic reader domain that bind to acetylated lysine residues in both histone and non-histone proteins. Bromodomain-containing proteins (BRD proteins) function are established scaffolds in the assembly of multi-protein complexes to regulate diverse biological processes. BRD proteins have been classified based on biological and functional similarity, however the functions of many BRD proteins remains unknown. PPI network analysis is useful for revealing organizational roles, identifying functional clusters, and predicting function for BRD proteins.ResultsWe used available data to construct protein-protein interaction networks (PPINs) to study the properties of the human bromodomain protein family. The network properties of the BRD PPIN establishes that the BRD proteins serve as hub proteins that are enriched near the global center to form an inter-connected PPIN. We identified dense subgraphs formed by BRD proteins and find that different BRD proteins share topological similarity and functional associations. We explored the functional relationships through clustering and Hallmark pathway gene set enrichment analysis and identify potential biological roles for different BRD proteins.ConclusionsIn our network analysis we confirmed that BRD proteins are conserved central nodes in the human PPI network and function as scaffolds to form distinctive functional clusters. Overall, this study provides detailed insight into the predictive functions of BRD proteins in the context of functional complexes and biological pathways.
Nucleosome conformation dictates the histone code
Authors: Marunde Matthew R. , Fuchs Harrison A. , Burg Jonathan M. , Popova Irina K. , Vaidya Anup , Hall Nathan W. , Meiners Matthew J. , Watson Rachel , Howard Sarah A. , Novitzky Katherine , McAnarney Eileen , Cheek Marcus A. , Sun Zu-Wen , Venters Bryan J. , Keogh Michael-C. , Musselman Catherine A. 
Published: February 2022

ABSTRACTHistone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized ‘codes’ that are read by specialized regions (reader domains) in chromatin associated proteins (CAPs) to regulate downstream function. Substantial effort has been made to define [CAP-histone PTM] specificity, and thus decipher the histone code / guide epigenetic therapies. However, this has largely been done using a reductive approach of isolated reader domains and histone peptides, with the assumption that PTM readout is unaffected by any higher order factors. Here we show that CAP-histone PTM interaction is in fact dependent on nucleosome context. Our results indicate this is due to histone tail accessibility and the associated impact on binding potential of reader domains. We further demonstrate that the in vitro specificity of a tandem reader for PTM-defined nucleosomes is recapitulated in a cellular context. This necessitates we refine the ‘histone code’ concept and interrogate it at the nucleosome level.
A highly sensitive LC-MS/MS method for quantitative determination of 7 vitamin D metabolites in mouse brain tissue
Authors: Stephenson Andrea , Hunter Ben , Shaw Paul Nicholas , Abu Kassim Nur Sofiah , Trengrove Rob , Takechi Ryu , Lam Virginie , Mamo John 
Published: February 2022

AbstractDespite its critical role in neurodevelopment and brain function, vitamin-D (vit-D) homeostasis, metabolism and kinetics within the central nervous system remain largely undetermined. Thus, it is of critical importance to establish an accurate, highly sensitive and reproducible method to quantitate vit-D in brain tissue. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method and for the first time, demonstrate detection of seven major vit-D metabolites in brain tissues of C57BL/6J wild-type mice, namely: 1,25(OH)2D3, 3-epi-1,25(OH)2D3, 1,25(OH)2D2, 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 24,25(OH)2D2. Chromatographic separation was achieved on a pentaflurophenyol column 3 mM ammonium formate with water/methanol [A] and methanol/isopropanol [B] phases. Detection was by positive-ion electrospray tandem mass spectrometry. We used calibration standards of each metabolite prepared in brain matrices to validate the detection range, precision, accuracy and recovery. Isotopically labelled analogues, 1,25(OH)2D3-d3, 25(OH)D3-C5 and 24,25(OH)2D3-d6, served as the internal standards for the closest molecular related metabolite in all measurements. The calibration range was between 1 fg/mL to 10 ng/mL with an LLOD and LLOQ of 10 fg/mL and 3 fg/mL, respectively. The intra-/inter-day precision and accuracy for measuring brain vit-D metabolites ranged between 0.12-11.53% and 0.28-9.11%, respectively. Recovery ranged between 99.06% and 106.9% for all metabolites. Collectively, the sensitivity and efficiency of our method supersedes previously reported protocols used to measure vit-D and to our knowledge, the first protocol to reveal the abundance of 25(OH)D2, 1,25(OH)D2 and 24,25(OH)2D2, in brain tissue of any species. This technique may be important in supporting the future advancement of pre-clinical research into the function of vit-D in neurophysiological, neuropsychiatric, and neurodegeneration.
Association Between Cannabis Smoking and Academic Achievement in Colombian High-School Students
Authors: Pérez-Martínez Yegson , Ceballos-Ospino Guillermo Augusto , Campo-Arias Adalberto 
Published: February 2022

ABSTRACTBackgroundCannabis smoking can affect academic achievement, and depressive symptoms and family dysfunction are also associated it. The study’s objective was to establish the relationship between cannabis smoking and academic achievement, controlling clinically important depressive symptoms and family dysfunction.MethodsA cross-sectional study was designed. The authors quantified lifetime cannabis smoking, perception of academic achievement, clinically important depressive symptoms, and family dysfunction. The crude association between cannabis smoking and academic achievement was computed; after it was adjusted by clinically important depressive symptoms and family dysfunction.Results1,462 students between 13 and 17 participated in the research; 11.6% reported lifetime cannabis smoking, 30.8% poor-fair academic achievement; 7.1% clinically important depressive symptoms; and 76.1% family dysfunction. Lifetime cannabis smoking was significantly associated with poor-fair academic achievement after adjusting for clinically important depressive symptoms and family dysfunction (OR = 1.61, 95%CI 1.16 - 2.24).ConclusionsLifetime cannabis smoking is related to poor-fair academic achievement among high-school students in Santa Marta, Colombia.Data availability statementThe data supporting this study’s findings are available from the corresponding author upon reasonable request.Authors biographyYegson Pérez-MartínezHe is a young psychologist interested in researching school psychology, academic achievement, and health-compromising behaviours.Guillermo Augusto Ceballos-Ospino, psychologist He is a psychologist and occasional professor at the Program of Psychology, University of Magdalena, Santa Marta, Colombia. His action areas are mental health, especially suicide prevention, and psychometrics. He is interested in studies with populations of university students.Adalberto Campo-Arias, MD, MSc He is a psychiatrist, magister in sexual and reproductive health and professor at the School of Medicine, Faculty of Health Science, University of Magdalena, Santa Marta, Colombia. His research interests include sexual and reproductive health, human rights, prejudice and discrimination, and health-compromising behaviours.
The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α
Authors: Chandra Vikash , Ibrahim Hazem , Halliez Clémentine , Prasad Rashmi , Vecchio Federica , Dwivedi Om Prakash , Kvist Jouni , Balboa Diego , Saarimäki-Vire Jonna , Montaser Hossam , Barsby Tom , Lithovius Väinö , Artner Isabella , Gopalakrishnan Swetha , Groop Leif , Mallone Roberto , Eizirik Decio L. , Otonkoski Timo 
Published: February 2022

AbstractType 1 diabetes (T1D) is an autoimmune disease that results in the destruction of insulin producing pancreatic β-cells. One of the genes associated with T1D is TYK2, which encodes a Janus kinase with critical roles in type-Ι interferon (IFN) mediated intracellular signaling. To study the role of TYK2 in human pancreatic β-cell development and response to IFNα, we generated TYK2 knockout human iPSCs and directed them into the pancreatic endocrine lineage. Here we show that loss of TYK2 compromised the emergence of endocrine precursors by regulating KRAS expression while mature stem cell-islets (SC-islets) function was not affected. In the maturing SC-islets, the loss or inhibition of TYK2 prevented IFNα-induced antigen processing and presentation, including MHC Class Ι expression in pancreatic endocrine and progenitor cells. Furthermore, in a CD8+ cytotoxic T-cell co-culture model, the survival of β-cells was enhanced by a selective TYK2 inhibitor. These results identify an unsuspected role for TYK2 on β-cell development and support TYK2 inhibition in adult β-cells as a potent therapeutic target to halt T1D progression.
Redifferentiated cardiomyocytes retain residual dedifferentiation signatures and are protected against ischaemic injury
Authors: Shakked Avraham , Petrover Zachary , Aharonov Alla , Ghiringhelli Matteo , Umansky Kfir-Baruch , Nguyen Phong Dang , Kain David , Elkahal Jacob , Divinsky Yalin , Miyara Shoval , Friedlander Gilgi , Savidor Alon , Zhang Lingling , Perez Dahlia , Kastan Nathaniel , Lendengolts Daria , Levin Yishai , Bakkers Jeroen , Gepstein Lior , Tzahor Eldad 
Published: February 2022

AbstractCardiomyocyte renewal by dedifferentiation and proliferation has fueled the field of regenerative cardiology in recent years, while the reverse process of redifferentiation remains largely unexplored. Redifferentiation is characterised by the restoration of function that is lost during dedifferentiation and is key to the healing process following injury. Previously, we showed that ERBB2-mediated heart regeneration has these two distinct phases: dedifferentiation, followed by redifferentiation. Here, using temporal RNAseq and proteomics, we survey the landscape of the dedifferentiation-redifferentiation process in the adult mouse heart. We find well characterised dedifferentiation pathways, such as reduced oxphos, increased proliferation and increased EMT-like features, largely return to normal, though elements of residual dedifferentiation remain, even after contractile function is restored. These hearts appeared rejuvenated and showed robust resistance to ischaemic injury. We find that redifferentiation is driven by negative feedback signalling, notably through LATS1/2 Hippo pathway activity. Disabling LATS1/2 in dedifferentiated cardiomyocytes augments dedifferentiation in vitro and prevents redifferentiation in vivo. Taken together, our data reveal the non-trivial nature of redifferentiation, whereby elements of dedifferentiation linger in a surprisingly beneficial manner. This cycle of dedifferentiation-redifferentiation protects against future insult, in what could become a novel prophylactic treatment against ischemic heart disease for at-risk patients.
Cell cycle-dependent binding between Cyclin B1 and Cdk1 revealed by time-resolved Fluorescence Correlation Spectroscopy
Authors: Barbiero Martina , Cirillo Luca , Veerapathiran Sapthaswaran , Coates Catherine , Ruffilli Camilla , Pines Jonathon 
Published: February 2022

AbstractMeasuring the dynamics with which the regulatory complexes of the cell cycle machinery assemble and disassemble is a crucial barrier to our understanding that until now has been difficult to address. This considerable gap in our understanding is due to the difficulty of reconciling biochemical assays with single cell-based techniques, but recent advances in microscopy and gene editing techniques now enable the measurement of protein-protein interaction kinetics in living cells.Here, we apply Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Cross-Correlation Spectroscopy (FCCS) to study the dynamics of the cell cycle machinery, beginning with Cyclin B1 and its binding to its partner kinase Cdk1 that together form the major mitotic kinase. Although Cyclin B1 and Cdk1 are known to bind with high affinity, our results reveal that in living cells there is a pool of Cyclin B1 that is not bound to Cdk1. Furthermore, we provide evidence that the affinity of Cyclin B1 for Cdk1 increases during the cell cycle, indicating that the assembly of the complex is a regulated step. Our work lays the groundwork for studying the kinetics of protein complex assembly and disassembly during the cell cycle in living cells.