bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontline healthcare workers’ mental health and wellbeing during the first year of the COVID-19 pandemic: Analysis of interviews and social media data
Authors: San Juan Norha Vera , Martin Sam , Badley Anna , Maio Laura , Gronholm Petra C. , Buck Caroline , Flores Elaine C. , Vanderslott Samantha , Syversen Aron , Symmons Sophie Mulcahy , Uddin Inayah , Karia Amelia , Iqbal Syka , Vindrola-Padros Cecilia 
Published: May 2022

ABSTRACTBackgroundThe COVID-19 pandemic has shed light on the fractures of healthcare systems around the world, particularly in relation to the healthcare workforce. Frontline staff have been exposed to unprecedented strain and delivering care during the pandemic has impacted their safety, mental health and wellbeing. Rapid Research methods and big qualitative data offered a unique opportunity to gain insight into perceptions and experiences during this time.ObjectiveThe aim of this paper was to explore the experiences of Health Care Workers (HCWs) delivering care in the UK during the COVID-19 pandemic to understand their wellbeing needs, experiences and strategies used to maintain wellbeing at individual and organizational levels.MethodsWe analysed 94 telephone interviews with HCWs and 2000 tweets about HCWs mental health during the first year of the COVID-19 pandemic applying Collaborative and Digital Analysis of Big Qualitative Data in Time Sensitive Contexts (LISTEN).ResultsResults fell under six themes: redeployment, clinical work, and sense of duty; wellbeing support and HCW’s coping strategies; negative mental health effects; organisational support; social network and support; and public and government support. Redeployment generated anxiety mainly due to limited prior training and risk assessments, and the barriers of adapting to a new working environment while wearing PPE. HCWs struggled to access wellbeing support due to time constraints. In terms of ill mental health, mentions of feelings of trauma, PTSD and anxiety were prominent. HCWs’ mental health was particularly affected by the copious amount of bad news on media and at home and the fear of infecting their loved ones.ConclusionsThese findings demonstrate a need for open conversations, where staff wellbeing needs and the strategies they adopted can be shared and encouraged, rather than implementing solely top-down psychological interventions. At the macro level, findings also highlighted the impact on HCW’s wellbeing of public and government support, as well as the need for ensuring protection through PPE, testing, and/or vaccines for frontline workers.
Boosting polygenic risk scores
Authors: Klinkhammer Hannah , Staerk Christian , Maj Carlo , Krawitz Peter M. , Mayr Andreas 
Published: May 2022

AbstractPolygenic risk scores (PRS) evaluate the individual genetic liability to a certain trait and are expected to play an increasingly important role in the field of clinical risk stratification. Most often, PRS are estimated based on summary statistics of univariate effects derived from genome-wide association studies. To improve the predictive performance of PRS, it is desirable to fit multivariable models directly on the genetic data. Due to the large and high-dimensional data, a direct application of existing methods is often not feasible and new efficient algorithms are required to overcome the computational burden regarding efficiency and memory demands.We develop an adapted component-wise L2-boosting algorithm to fit genotype data from large cohort studies to continuous outcomes using linear base-learners for the genetic variants. Similar to the snpnet approach implementing lasso regression, the proposed snpboost approach iteratively works on smaller batches of variants. By restricting the set of possible base-learners in each boosting step to variants most correlated with the residuals from previous iterations, the computational efficiency can be substantially increased without losing prediction accuracy. Furthermore, for large-scale data based on various traits from the UK Biobank we show that our method yields competitive prediction accuracy and computational efficiency compared to the snpnet approach. Due to the modular structure of boosting, our framework can be further extended to construct PRS for different outcome data and effect types.
Sexually dimorphic activation of innate antitumour immunity prevents adrenocortical carcinoma development
Authors: Wilmouth James J , Olabe Julie , Garcia-Garcia Diana , Lucas Cécily , Guiton Rachel , Roucher-Boulez Florence , Dufour Damien , Damon-Soubeyrand Christelle , Sahut-Barnola Isabelle , Pointud Jean-Christophe , Renaud Yoan , Levasseur Adrien , Tauveron Igor , Lefrançois-Martinez Anne-Marie , Martinez Antoine , Val Pierre 
Published: May 2022

SummaryIn contrast with most cancers, adrenocortical carcinomas (ACC) are more frequent in women than men, but the underlying mechanisms of this sexual dimorphism remain elusive. Homozygous deletion of the negative WNT pathway regulator ZNRF3 is the most frequent alteration in ACC patients. Here, we show that Cre-mediated inactivation of Znrf3 in steroidogenic cells of the mouse adrenal cortex is associated with sexually dimorphic tumour progression. Indeed, although most knockout female mice develop metastatic carcinomas over an 18 month-time course, adrenal hyperplasia gradually regresses in male knockout mice. This male-specific regression is associated with induction of senescence and recruitment of macrophages, which differentiate as active phagocytes that clear-out senescent preneoplastic cells. Macrophage recruitment is also observed in female mice. However, it is delayed and dampened compared to males, which allows for tumour progression. Interestingly, testosterone treatment of female knockouts is sufficient to induce senescence, recruitment of phagocytic macrophages and regression of hyperplasia. We further show that although macrophages are present within adrenal tumours at 18 months, MERTKhigh active phagocytes are mostly found in indolent lesions in males but not in aggressive tumours in females. Consistent with our observations in mice, analysis of RNA sequencing data from the TCGA cohort of ACC shows that phagocytic macrophages are more prominent in men than women and associated with better prognosis. Altogether, these data establish that phagocytic macrophages prevent aggressive ACC development in male mice and suggest that they may play a key role in the unusual sexual dimorphism of ACC in patients.
Inter-organ Wingless/Ror/Akt signaling regulates nutrient-dependent hyperarborization of somatosensory neurons
Authors: Kanaoka Yasutetsu , Onodera Koun , Watanabe Kaori , Usui Tadao , Uemura Tadashi , Hattori Yukako 
Published: May 2022

ABSTRACTNutrition in early life has profound effects on an organism, altering processes such as organogenesis. However, little is known about how specific nutrients affect neuronal development. Dendrites of class IV neurons in Drosophila larvae become more complex when the larvae are reared on a low-yeast diet compared to a high-yeast diet. Our systematic search for key nutrients revealed that the neurons increase their dendrite densities in response to a combined deficiency in vitamins, metal ions, and cholesterol. These nutrients affect dendrite branching through the Wingless/Ror/Akt pathway between the neuron and closely located muscles, and this short range-pathway is regulated by a systemic Upd2-Stat92E pathway between the fat body and muscles. Additionally, the low-yeast diet blunts neuronal light responsiveness and light avoidance behavior, which may help larvae optimize their survival strategies under low-nutritional conditions. Together, our studies illustrate how the availability of specific nutrients affects neuronal development through inter-organ signaling.
A new species of deep-water Lethrinops (Cichlidae) from Lake Malawi
Authors: Turner George F. 
Published: May 2022

AbstractA new species of cichlid fish, Lethrinops atrilabris is described from specimens collected by trawling at a depth of around 90m off Monkey Bay, southern Lake Malawi. It is assigned to the genus Lethrinops on the basis of its vertical flank barring, lack of enlarged cephalic lateral line canal pores and the form of the lower jaw dental arcade. It can be distinguished from congeneric species by its male breeding dress of contrasting flank barring and dark ventral surface, most strikingly on the lips, throat and chest, its relatively small known maximum size (<75mm SL), large eyes (38-41% head length), laterally compressed body (depth 2.5-2.7 times max head width) and lower gillraker count (13-14).
Quantum pBac: An effective, high-capacitypiggyBac-based gene integration vector system for unlocking gene therapy potential
Authors: Hua Wei-Kai , Hsu Jeff C. , Chen Yi-Chun , Chang Peter S. , Wen Kuo-Lan Karen , Wang Po-Nan , Yu Yi-Shan , Chen Ying-Chun , Cheng I-Cheng , Wu Sareina Chiung-Yuan 
Published: May 2022

AbstractRecent advances in gene therapy have brought novel treatment options for cancer. However, the full potential of this approach has yet to be unlocked due to the safety concerns and limited payload capacity of commonly utilized viral vectors. Virus-free DNA transposons, includingpiggyBac, have potential to obviate these shortcomings. In this study, we improved a previously developed modifiedpiggyBacsystem with superior transposition efficiency. We demonstrated that the internal domain sequences (IDS) within the 3’ terminal repeat domain of hyperactivepiggyBac(hyPB) donor vector contain dominant enhancer elements. Plasmid-free donor vector devoid of IDS was used in conjunction with a helper plasmid expressingQuantum PBase™ v2 to generate an optimalpiggyBacsystem,Quantum pBac™ (qPB), for use in T cells. Cells transfected withqPBexpressing CD20/CD19 CAR outperformed those transfected with the same donor vector and plasmid expressinghyPBtransposase in terms of CAR-T cell production. Importantly,qPByielded mainly CD8+CAR-TSCMcells, and theqPB-induced CAR-T cells effectively eliminated CD20/CD19-expressing tumor cells bothin vitroandin vivo. Our findings confirmqPBas a promising virus-free vector system with a payload capacity to incorporate multiple genes. This system is highly efficient and potentially safe for mediating transgene integration.
The dual character of the inhibitory functions of CD6
Authors: Santos Rita F. , De Sousa Linhares Annika , Cardoso Marcos S. , Nóvoa Ana , Luche Hervé , Gärtner Fátima , Malissen Bernard , Steinberger Peter , Davis Simon. J. , Mallo Moisés , Oliveira Liliana , Carmo Alexandre M. 
Published: May 2022

AbstractT-cell membrane scaffold proteins play important roles in T cell biology, functioning as multi-functional signaling hubs. CD6 assembles a large intracellular signalosome but, unlike typical membrane-attached scaffolds like LAT or PAG, it has a sizeable ectodomain that binds a well-characterized ligand, CD166. It is unclear whether CD6 has net inhibitory or costimulatory functions or how its ectodomain influences these activities. To explore these questions, we dissected the signaling functions of the extracellular and cytoplasmic regions of CD6. We found that CD6 was delivered to the immunological synapse and suppressed T cell responsivenessin vitrowholly dependently of its cytoplasmic domain, indicating that CD6 very potently imposes tonic inhibition, acting as a structural and signaling inhibitory hub. However, the cell-intrinsic suppression of autoimmunity by CD6in vivowas also impacted by extracellular interactions, demonstrated by the increased susceptibility of mice to experimental autoimmune encephalomyelitis after removal of the ligand binding region of the ectodomain of CD6. Our work identifies CD6 as a new class of ‘on/off switching’ scaffold-receptor that constrains immune responsiveness at two speeds. First, it sets signaling thresholds via tonic inhibition, functioning as a cytoplasmic membrane-bound scaffold and, second, by cycling between signaling-enabling and signalinginhibiting ectodomain isoforms it functions as an immune checkpoint.
Non-Invasive Cancer Detection in Canine Urine through C. elegans Chemotaxis
Authors: Namgong Chan , Kim Jong Hyuk , Lee Myon-Hee , Midkiff Daniel 
Published: May 2022

AbstractCancer is the leading cause of death of companion animals, and successful early treatment has been a challenge in the veterinary field. We have developed the Non-Invasive Cancer Screening (N.C.S.) Study to perform cancer detection through the analysis of canine urine samples. The test makes use of the strong olfactory system of the nematode C. elegans, which was previously shown to positively respond to urine samples from human cancer patients. We performed a proof-of-concept study to optimize the detection capability in urine samples obtained from dogs with naturally occurring cancers. In this study, we established a scale for identifying the cancer risk based on the magnitude of the chemotaxis index of C. elegans towards a canine urine sample. Through validation, the N.C.S. Study achieved a sensitivity of 85%, showing that it is highly sensitive to indicating the presence of cancer across multiple types of common canine cancers. The test also showed a 93% specificity to cancer samples, indicating a low rate of over-identifying cancer risk. From these results, we have demonstrated the ability to perform low-cost, non-invasive cancer detection in companion animals, a method which can increase the ability to perform cancer diagnosis and treatment.
Heterogeneity of Interaction Strengths and Its Consequences on Ecological Systems
Authors: Jackson Zachary , Xue BingKan 
Published: May 2022

AbstractEcosystems are formed by networks of species and their interactions. Traditional models of such interactions assume a constant interaction strength between a given pair of species. However, there is often significant trait variation among individual organisms even within the same species, causing heterogeneity in their interaction strengths with other species. The consequences of such heterogeneous interactions for the ecosystem have not been studied systematically. As a theoretical exploration, we analyze a simple ecosystem with trophic interactions between two predators and a shared prey, which would exhibit competitive exclusion in models with homogeneous interactions. We consider several scenarios where individuals of the prey species differentiate into subpopulations with different interaction strengths. We show that in all these cases, whether the heterogeneity is inherent, reversible, or adaptive, the ecosystem can stabilize at a new equilibrium where all three species coexist. Moreover, the prey population that has heterogeneous interactions with its predators reaches a higher density than it would without heterogeneity, and can even reach a higher density in the presence of two predators than with just one. Our results suggest that heterogeneity may be a naturally selected feature of ecological interactions that have important consequences for the stability and diversity of ecosystems.
Variant Polycomb complexes in Drosophila consistent with ancient functional diversity
Authors: Kang Hyuckjoon , Cabrera Janel R. , Zee Barry M. , Kang Heather A. , Jobe Jenny Marie , Hegarty Maeve B. , Barry Aurelie E. , Glotov Alexander , Schwartz Yuri B. , Kuroda Mitzi I. 
Published: May 2022

AbstractPolycomb group (PcG) mutants were first identified in Drosophila based on their failure to maintain proper Hox gene repression during development. The proteins encoded by the corresponding fly genes mainly assemble into one of two discrete Polycomb Repressive Complexes: PRC1 or PRC2. However, biochemical analyses in mammals have revealed alternative forms of PRC2, and multiple distinct types of non-canonical or variant PRC1. Through a series of proteomic analyses, we identify analogous PRC2 and variant PRC1 complexes in Drosophila, as well as a broader repertoire of interactions implicated in early development. Our data provide strong support for the ancient diversity of PcG complexes, and a framework for future analysis in a longstanding and versatile genetic system.
People exposed to proton pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: a nation-wide matched cohort study
Authors: Kodvanj Ivan , Homolak Jan , Trkulja Vladimir 
Published: May 2022

AbstractAimTo assess whether exposure to proton pump inhibitors (PPIs) shortly preceding COVID-19 diagnosis affected the risk of subsequent hospitalizations and mortality.MethodsThis population-based study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Patients were classified based on exposure to PPIs and burden of PPI-requiring morbidities as “non-users” (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), “possible users” (no issued prescriptions, but morbidities present; self-medication possible) and “users” (at least one prescription within 3 months prior to the COVID-19 diagnosis; morbidities present). Subsets were mutually exactly matched for pre-COVID-19 characteristics. The contrast between “users” and “possible users” informed about the effect of PPIs that is separate of the effect of PPI-requiring conditions.ResultsAmong 433609 patients, “users” and “possible users” were matched 41195 (of 55098) to 17334 (of 18170) in the primary and 33272 to 16434 in the sensitivity analysis. There was no relevant difference between them regarding mortality [primary: RR=0.93 (95%CI 0.85-1.02; RD= - 0.34% (−0.73, 0.03); sensitivity: RR=0.88 (0.78-0.98); RD=-0.45% (−0.80, -0.11)] or hospitalizations [primary: RR=1.04 (0.97-1.13); RD=0.29% (−0.16, 0.73); sensitivity: RR=1.05 (0.97-1.15); RD=0.32% (−0.12, 0.75)]. The risks of both were slightly higher in “possible users” or “users” than in “non-users” (absolutely by ∼0.4%-1.6%) indicating the effect of PPI-requiring morbidities.ConclusionPre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients, but PPI-requiring morbidities seemingly slightly increase the risk of both.What is already known about this subject?It appears biologically plausible that pre-morbid exposure to proton pump inhibitors (PPIs) might contribute to unfavorable course of COVID-19 diseaseTwo population-based studies in the early pandemics stage indicated no effect of PPIs, while one suggested a higher risk of death/severe COVID-19 disease in PPI pre-exposed subjectsWhat this study adds?Exposure to PPIs directly preceding SarsCov-2 infection has no effect on the risk of subsequent hospitalizations and mortalityConditions requiring PPI treatment seem to mildly increase the risk of both
The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2
Authors: Janowski Andrew B , Jiang Hongbing , Fujii Chika , Owen Macee C , Bricker Traci L , Darling Tamarand L , Harastani Houda H. , Seehra Kuljeet , Tahan Stephen , Jung Ana , Febles Binita , Blatter Joshua A , Handley Scott A , Parikh Bijal A , Lulla Valeria , Boon Adrianus CM , Wang David 
Published: May 2022

AbstractThe stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs. Compensatory substitutions that restored the G-C base-pair enabled recovery of VA1. For HAstV1, a partial deletion of the s2m resulted in decreased viral titers compared to wild-type virus, and reduced activity in a replicon system. In contrast, deletion or mutation of the SARS-CoV-2 s2m had no effect on the ability to rescue the virus, growth in vitro, or growth in Syrian hamsters. Our study demonstrates the importance of the s2m is virus-dependent.
A DNA segregation module for synthetic cells
Authors: Tran Mai P. , Chatterjee Rakesh , Dreher Yannik , Fichtler Julius , Jahnke Kevin , Hilbert Lennart , Zaburdaev Vasily , Göpfrich Kerstin 
Published: May 2022

AbstractThe bottom-up construction of an artificial cell requires the realization of synthetic cell division. Significant progress has been made towards reliable compartment division, yet mechanisms to segregate the DNA-encoded informational content are still in their infancy. Herein, droplets of DNA Y-motifs are formed by liquid-liquid phase separation (LLPS). Entropy-driven DNA droplet segregation is obtained by cleaving the linking component between two populations of DNA Y-motifs. In addition to enzymatic cleavage, photolabile sites are introduced for spatio-temporally controlled DNA segregation in bulk as well as in cell-sized water-in-oil droplets and giant unilamellar lipid vesicles (GUVs). Notably, the segregation process is slower in confinement than in bulk. The ionic strength of the solution and the nucleobase sequences are employed to regulate the segregation dynamics. The experimental results are corroborated in a lattice-based theoretical model which mimics the interactions between the DNA Y-motif populations. Altogether, engineered DNA droplets, reconstituted in GUVs, could represent a strategy towards an entropy-driven DNA segregation module within bottom-up assembled synthetic cells.Table of ContentsAn entropy-driven DNA segregation module for bottom-up assembled synthetic cells is realized. It is based on DNA droplets that are engineered to segregate upon enzymatic or photocleavage inside giant unilamellar lipid vesicles (GUVs). The segregation kinetics is altered by the confinement, as confirmed by lattice-based numerical simulations. DNA segregation is further controlled by temperature, ionic strengths and nucleobase sequence.
TME induced TRAIL secretion from engineered macrophages for anti-tumor therapy
Authors: Huang Xin , Deng Botian , Zhou Hui , Shi Binhe , Liu Junhua , Shan Xiaojiao , Fang Xiaobin , Yin Xiushan , Zhang Luo 
Published: May 2022

AbstractCapacity of tumor niche chemotaxis and long-term persistency making macrophage as great vehicles for anti-tumor factor delivery. Macrophages-based delivery of chemokines or cytokines have been tested for tissue homeostasis and cancer repression. TRAIL as a promising anti-tumor cytokine, made little clinical progress due to limited stability and off-target toxicity. Here we engineered macrophages with tumor micro-environment (TME)-induced trimerized CP1-TRAIL secretion under the TME specific promoter Arg1 (Tri-TRAIL-iM). The Tri-TRAIL-iM cells displayed high specific inducible activity in both cell-based co-culture assay and in tumor baring mice models. Compared to normal TRAIL over-expressed macrophages under none-inducible promoter, Tri-TRAIL-iM infiltrated to tumor sites and showed superior apoptosis induction of cancer cells and tumor growth repression as well as less systemic side effect. This inducible delivery TRAIL strategy can be effectively further applied in clinical studies and can be coupled with other engineered methods to maximize the therapeutic outcomes for solid tumors.