bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home working and its association with social and mental wellbeing at different stages of the COVID-19 pandemic: Evidence from seven UK longitudinal population surveys
Authors: Wels Jacques , Wielgoszewska Bożena , Moltrecht Bettina , Booth Charlotte , Green Michael J , Hamilton Olivia KL , Demou Evangelia , Gessa Giorgio Di , Huggins Charlotte , Zhu Jingmin , Santorelli Gillian , Silverwood Richard J. , Kopasker Daniel , Shaw Richard J. , Hughes Alun , Patalay Praveetha , Steves Claire , Chaturvedi Nish , Porteous David , Rhead Rebecca , Katikireddi Srinivasa Vittal , Ploubidis George B. 
Published: October 2022

AbstractBackgroundHome working rates have increased since the COVID-19 pandemic’s onset, but the health implications of this transformation are unclear. We assessed the association between home working and social and mental wellbeing through harmonised analyses of seven UK longitudinal studies.MethodsWe estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across three different stages of the COVID-19 pandemic (T1= Apr-Jun 2020 – first lockdown, T2=Jul-Oct 2020 – eased restrictions, T3=Nov 2020-Mar 2021 – second lockdown), in seven population-based cohort studies using modified Poisson regression and meta-analyses to pool results across studies.FindingsAmong 34,131 observations spread over three time points, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR=0.92, 95%CI=0.79-1.08) or T2 (RR=0.99, 95%CI=0.88-1.11), but a detrimental association was found with psychological distress at T3 (RR=1.17, 95%CI=1.05-1.30). Poorer psychological distress associated with home working was observed for those educated to below degree level at T2 and T3. Men working from home reported poorer self-reported health at T2.InterpretationNo clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress associated with home working during the second lockdown, but differences across sub-groups may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required.FundingNational Core Studies, funded by UKRI, NIHR and the Health and Safety Executive.
Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain
Authors: Demetriou Lysia , Krassowski Michal , Mendes Pedro Abreu , Garbutt Kurtis , Vitonis Allison F. , Wilkins Elizabeth , Coxon Lydia , Arendt-Nielsen Lars , Aziz Qasim , Birch Judy , Horne Andrew W , Hoffman Anja , Hummelshoj Lone , Lunde Claire E , Meijlink Jane , Perro Danielle , Rahmioglu Nilufer , Terry Kathryn L. , Pogatzki-Zahn Esther , Sieberg Christine B , Treede Rolf-Detlef , Becker Christian M , Cruz Francisco , Missmer Stacey A , Zondervan Krina T , Nagel Jens , Vincent Katy 
Published: October 2022

AbstractChronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP report different clinical symptoms and differing impact of pain on their quality of life (QoL).The study is part of the Translational Research in Pelvic Pain (TRiPP) project which is a cross-sectional observational cohort study. The study includes 769 female participants of reproductive age who completed an extensive set of questions derived from standardised WERF EPHect questionnaires. Within this population we defined a control group (reporting no pelvic pain, no bladder pain syndrome, and no endometriosis diagnosis, N=230) and four pain groups: endometriosis-associated pain (EAP, N=237), interstitial cystitis/bladder pain syndrome (BPS, N=72), comorbid endometriosis-associated pain and BPS (EABP, N=120), and pelvic pain only (PP, N=127).Clinical profiles of women with CPP (13-50 years old) show variability of clinical symptoms. The EAP and EABP groups scored higher than the PP group (p<0.001) on the pain intensity scales for non-cyclical pelvic pain and higher than both the BPS and PP groups (p<0.001) on the dysmenorrhoea scale. The EABP group also had significantly higher scores for dyspareunia (p<0.001), even though more than 50% of sexually active participants in each pain group reported interrupting and/or avoiding sexual intercourse due to pain in the last 12 months.Scores for the QoL questionnaire (SF-36) reveal that CPP patients had significantly lower QoL across all SF-36 subscales (p<0.001). Significant effects were also observed between the pain groups for pain interference with their work (p<0.001) and daily lives (p<0.001), with the EABP suffering more compared to the EAP and PP groups (p<0.001).Our results demonstrate the negative impact that chronic pain has on CPP patients’ QoL and reveal an increased negative impact of pain on the comorbid EABP group. Furthermore, it demonstrates the importance of dyspareunia in women with CPP. Overall, our results demonstrate the need for further exploration of interventions targeting QoL more broadly and suggest that novel approaches to classifying women with CPP are needed.
A Nursing Philosophy of Women Empowerment Based on Self Efficacy toward Sexual and Reproductive Health
Authors: Pradanie Retnayu , Pandin Moses Glorino Rumambo , Yunitasari Esti 
Published: October 2022

AbstractIntroductionSexual and reproductive health of women will affect their health in general at every stage of their lives. Empowerment of women is a strategic step to improving health status. Nurses have an essential role to empower women to improve their health. Women empowerment can be built by improving their self-efficacy. This paper aimed to provide a review of articles about the role of nurses and strategies to empower women in sexual and reproductive health based on self-efficacy.MethodThis paper is the result of a literature review. Data were accessed from the database of Scopus, Pubmed, and Ebscohost limited on publication in 2017-2022. Twelve journal articles were selected using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).ResultsThe results of the article review obtained information about the important role of women in the health sector, factors associated with sexual and reproductive health, nursing philosophy women health, women empowerment models for sexual and reproductive health, and strategies to increase women empowerment through self-efficacy enhancement.ConclusionAn evidence-based practice approach found that women empowerment is a strategic step for health development. The women empowerment program still needs to be developed because it can increase their capacity in maintaining health.
Using deep convolutional neural networks to predict patients age based on ECGs from an independent test cohort
Authors: Singstad Bjørn-Jostein , Tavashi Belal 
Published: October 2022

AbstractElectrocardiography is one of the most frequently used methods to evaluate cardiovascular diseases. However, the last decade has shown that deep convolutional neural networks (CNN) can extract information from the electrocardiogram (ECG) that goes beyond traditional diagnostics, such as predicting a persons age. In this study, we trained two different 1-dimensional CNNs on open datasets to predict age from a persons ECG.The models were trained and validated using 10 seconds long 12-lead ECG records, resampled to 100Hz. 59355 ECGs were used for training and cross-validation, while 21748 ECGs from a separate cohort were used as the test set. We compared the performance achieved on the cross-validation with the performance on the test set. Furthermore, we used cardiologist annotated cardiovascular conditions to categorize the patients in the test set in order to assess whether some cardiac condition leads to greater discrepancies between CNN-predicted age and chronological age.The best CNN model, using an Inception Time architecture, showed a significant drop in performance, in terms of mean absolute error (MAE), from cross-validation on the training set (7.90 ± 0.04 years) to the performance on the test set (8.3 years). On the other hand, the mean squared error (MSE) improved from the training set (117.5 ± 2.7 years2) to the test set (111 years2). We also observed that the cardiovascular condition that showed the highest deviation between predicted and biological age, in terms of MAE, was the patients with pacing rhythm (10.5 years), while the patients with prolonged QT-interval had the smallest deviation (7.4 years) in terms of MAE.This work contributes to existing knowledge of age prediction using deep CNNs on ECGs by showing how a trained model performs on a test set from a separate cohort to that used in the training set.
Impact of vaccination on COVID-19-associated admissions to critical care in England: a population cohort study of linked data
Authors: Harrison David A , Watkinson Peter J , Doidge James C , Shankar-Hari Manu , Mouncey Paul R , Patone Martina , Coupland Carol A C , Hippisley-Cox Julia , Rowan Kathryn M 
Published: October 2022

AbstractIntroductionThis study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England’s Delta wave, by age group, dose, and over time.MethodsWe used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine.ResultsCompared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18–29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60–69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose.ConclusionImportant demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during England’s Delta wave, with evidence of waning predominantly restricted to those aged 70+.
Site-Specific Knockdown of Microglia in the Locus Coeruleus Regulates Hypervigilant Responses to Social Stress in Female Rats
Authors: Pate Brittany S. , Bouknight Samantha J. , Harrington Evelynn N. , Mott Sarah E. , Augenblick Lee M. , Smiley Cora E. , Morgan Christopher G. , Calatayud Brittney M. , Martinez-Muniz Gustavo A. , Thayer Julian F. , Wood Susan K. 
Published: October 2022

AbstractBackgroundWomen are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking.MethodsMicroglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3μg/side, n=5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25μg/side, n=13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance.ResultsIntra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1β (IL-1β). Further, the efficacy and selectivity of microinjected m-CLD was determined. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1β. Intra-central amygdala m-CLD had no effect on witness stress-evoked behavior.ConclusionsThese studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.HIGHLIGHTSIntra-LC LPS augments behavioral and physiological responses to social stressMannosylated liposomal clodronate site-specifically reduces microglial expressionMicroglia within the locus coeruleus regulate stress-evoked behavior in female rats
Leaf hydraulic maze; Differential effect of ABA on bundle-sheath, palisade, and spongy mesophyll hydraulic conductance
Authors: Yaaran Adi , Erez Eyal , Procko Carl , Moshelion Menachem 
Published: October 2022

ABSTRACTLeaf hydraulic conductance (Kleaf) facilitates the movement of water for transpiration, enabling continual CO2uptake while the plant maintains its water status. We hypothesized that bundle-sheath and mesophyll cells play key roles in regulating the radial flow of water out of the xylem under optimal and stress conditions. To examine that hypothesis, we generated transgenicArabidopsisplants that were insensitive to abscisic acid (ABA) in their bundle sheath (BSabi) or mesophyll (MCabi) cells. Both BSabi and MCabi plants showed greater Kleafand transpiration under optimal conditions. Yet, the stomatal apertures, stomatal indices and vein densities of the BSabi plants were similar to those of WT plants. MCabi plants had larger stomatal apertures, a higher stomatal index and greater vascular diameter and biomass, relative to the WT and BSabi. In response to xylem-fed ABA, both transgenic and WT plants reduced their Kleafand transpiration. However, leaf water potential was reduced only in the WT. The membrane osmotic water permeability (Pf) of the WTs’ spongy mesophyll was higher than that of its palisade mesophyll. Moreover, only the spongy cells reduced theirPfin response to ABA. ABA-insensitive spongy mesophyll cells had a lowPf; whereas ABA-insensitive bundle-sheath cells had a higherPf.Palisade cells maintained a lowPfat all ABA levels. ABA increased the symplastic water pathway, but its contribution to Kleafwas negligible. We suggest that the bundle sheath–spongy mesophyll pathway may control Kleafto maintain steady-state conditions in the palisade cells and optimal whole-leaf water-use efficiency.
Tregcells drive MYCN-mediated immunosuppression and tumor aggressiveness in high-risk neuroblastoma
Authors: Qin Xiaodan , Lam Andrew , Zhang Xu , Sengupta Satyaki , Iorgulescu J. Bryan , Zuo Tao , Floru Alexander E. , Meara Grace , Lin Liang , Lloyd Kenneth , Kwok Lauren , Smith Kaylee , Nagaraju Raghavendar T. , Meijers Rob , Ceol Craig , Liu Ching-Ti , Alexandrescu Sanda , Wu Catherine J. , Keskin Derin B. , George Rani E. , Feng Hui 
Published: October 2022

AbstractSolid tumors, especially those with aberrant MYCN activation, harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance1,2, yet the underlying mechanisms are elusive and effective strategies to tackle this challenge are lacking. Here we demonstrated the crucial role of T regulatory (Treg) cells in MYCN-mediated immune repression and tumor aggression using high-risk neuroblastoma (NB) as a model system. Human MYCN-activated NB attracts CD4+Tregcells, which are also found enriched in MYCN-high primary patient samples. ZebrafishMYCN-overexpressing neural crests recruit Cd4+cells before tumor formation and induce an immunosuppressive microenvironment, thereby promoting tumor onset and progression. Strikingly, disruption of Tregcells through depletion of forkhead box protein 3a restores anti-tumor immunity and impairs NB development. Together, our studies establish Tregcells as the key driver of MYCN-mediated immunosuppression and tumor aggressiveness, providing mechanistic insights and therapeutic implications.
Landscape of semi-extractable RNAs across five human cell lines
Authors: Zeng Chao , Chujo Takeshi , Hirose Tetsuro , Hamada Michiaki 
Published: October 2022

ABSTRACTPhase-separated membraneless organelles often contain RNAs that exhibit unusual semi-extractability upon the conventional RNA extraction method, and can be efficiently retrieved by needle shearing or heating during RNA extraction. Semi-extractable RNAs are promising resources for understanding RNA-centric phase separation. However, limited assessments have been performed to systematically identify and characterize semi-extractable RNAs. In this study, 1,074 semi-extractable RNAs were identified across five human cell lines, including ASAP1, DANT2, EXT1, FTX, IGF1R, LIMS1, NEAT1, PHF21A, PVT1, SCMH1, STRG.3024.1, TBL1X, TCF7L2, TVP23C-CDRT4, UBE2E2, ZCCHC7, ZFAND3, and ZSWIM6, which exhibited consistent semi-extractability. By integrating publicly available datasets, we found that semi-extractable RNAs tend to be distributed in the nuclear compartments but are dissociated from the chromatin. Long and repeat-containing semi-extractable RNAs act as hubs to provide global RNA-RNA interactions. Semi-extractable RNAs were divided into four groups based on their k-mer content. The NEAT1 group preferred to interact with paraspeckle proteins, such as FUS and NONO, implying that RNAs in this group are potential candidates of architectural RNAs that constitute nuclear bodies.
Mining novel cis-regulatory elements from the emergent host Rhodosporidium toruloides using transcriptomic data
Authors: Nora Luísa Czamanski , Anzolini Cassiano Murilo Henrique , Santana Ítalo Paulino , Guazzaroni María-Eugenia , Silva-Rocha Rafael , da Silva Ricardo Roberto 
Published: October 2022

AbstractThe demand for robust microbial cell factories that can produce valuable biomaterials while being resistant to stresses imposed by current bioprocesses is rapidly growing. R. toruloides is an emerging host that presents desirable features for bioproduction, since it can grow in a wide range of substrates and tolerate a variety of toxic compounds. In order to explore R. toruloides suitability for application as a cell factory in biorefineries, we sought to understand the transcriptional responses of this yeast when growing under experimental settings that simulated those used in biofuels-related industries. Thus, we performed RNA sequencing of the oleaginous, carotenogenic yeast in different contexts. The first ones were stress-related: two conditions of high temperature (37 °C and 42 °C) and two ethanol concentrations (2% and 4%), while the other was using the inexpensive and abundant sugarcane juice as substrate. Using transcriptomic data, differential expression and functional analysis were implemented to select differentially expressed genes and enriched pathways from each set-up. A reproducible bioinformatics workflow was developed for mining new regulatory elements. We then predicted, for the first time in this yeast, binding motifs for several transcription factors, including HAC1, ARG80, RPN4, ADR1, and DAL81. Most of the putative transcription factors uncovered here were involved in stress responses and found in the yeast genome. Our method for motif discovery provides a new realm of possibilities in the study of gene regulatory networks, not only for the emerging host R. toruloides, but for other organisms of biotechnological importance.
Differential expression of RSK4 transcript isoforms in cancer and its clinical relevance
Authors: Chen Sisi , Seckl Michael J , Lorentzen Marc PG , Pardo Olivier E. 
Published: October 2022

AbstractRSK4 belongs to the p90 Ribosomal S6 Kinase family which lies downstream of the MAPK pathway. While we previously revealed this kinase to be a therapeutic target in lung and bladder cancers, there is conflicting evidence for its wider role in other cancer types. Indeed, RSK4 was instead suggested to be a tumour suppressor in colorectal and gastric cancers, and reports of its role in breast malignancies are contradictory. One possible explanation for these discrepancies may be the expression of different RSK4 isoforms across cancers. Four RNAs are produced from the RSK4 gene with two being protein-coding. Here, we analysed the expression of the two RSK4 protein-coding mRNAs across 30 normal and 33 cancer tissue types from the combined GTEx/TCGA dataset and correlated it with associated clinical features. This analysis revealed the mRNA expression of RSK4 isoform 1 and 2 to be independent prognostic factors for patient survival, pathological stage, cancer metastasis, recurrence, and immune infiltration in brain, stomach, cervical, and kidney cancers. However, we found that the upregulation of either RSK4 isoform can equally be associated with good or bad prognosis depending on the cancer type considered, and changes in the expression ratio of isoforms fail to predict clinical outcome. Taken together, we show that differential isoform expression alone cannot explain the contradictory roles of RSK4 in cancers and that further research is needed to highlight the underlying mechanisms for the context-dependent function of this kinase.
Phosphoproteomic analysis of the AKT signalling axis in cutaneous squamous carcinoma progression reveals novel therapeutic targets
Authors: Button R , Harwood C , O’Shaughnessy RFL 
Published: October 2022

AbstractCutaneous Squamous Cell Carcinoma (cSCC) represents about 20% of all non-melanoma skin cancers. Whilst generally low risk to patients, metastases are associated with a poor prognosis. cSCC incidence is increasing, owing to an ageing population, greater exposure to UV radiation, and more patients receiving immunosuppressive treatments associated with organ transplants. Therefore, there is interest in identifying new biomarkers that may be to track progression of the disease and to exploit as therapeutic vulnerabilities. We show dynamic changes in AKT expression in precursor lesions and in SCC tumour tissue, with initial loss of AKT activity followed by progressive and widespread increase in AKT activity in SCC.Phosphoproteomic analysis and kinase substrate enrichment analysis on a panel of isogenic cSCC cell lines representing different stages of the disease from premalignancy to metastasis revealed several up-regulated kinases and AKT-targets. From this analysis we chose DNA dependent protein kinase (DNA-PK), a key kinase upstream of AKT phoshorlyation, and N-Myc downstream-regulated gene 2 (NDRG2) a downstream AKT phosphorylation target, to investigate in further detail. Both proteins were up-regulated and mis-expressed in a panel of SCC tissue from different patients. We therefore explored the potential of inhibiting DNA-PK and NDRG2 as cSCC treatments. Treatment with the iron chelator Dp44mT decreased levels of phosphorylated NDRG2 and led to significant losses to viability and reduced migration in our cSCC cell lines, while DNA-PK inhibition promoted the differentiation of premalignant and early-stage SCC cell lines. Our results suggest that NDRG2 and DNA-PK may be viable targets in cSCC treatment, with effectiveness at different stages of SCC progression.