bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal Priming between Receptor Tyrosine Kinases at Recycling Endosomes Orchestrates Cellular Signalling Outputs
Authors: Smith Michael P. , Ferguson Harriet R. , Ferguson Jennifer , Zindy Egor , Kowalczyk Katarzyna M. , Kedward Thomas , Bates Christian , Parsons Joseph , Watson Joanne , Chandler Sarah , Fullwood Paul , Warwood Stacey , Knight David , Clarke Robert B. , Francavilla Chiara 
Published: January 2021

SUMMARYIntegration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains poorly elucidated. Combining quantitative phosphoproteomics and targeted assays, we generated a detailed picture of recycling-dependent fibroblast growth factor (FGF) signalling in breast cancer cells, with a focus on distinct FGF receptors (FGFRs). We discovered reciprocal priming between FGFRs and epidermal growth factor (EGF) receptor (EGFR) that is coordinated at recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR-mediated proliferation but not cell invasion. In turn, FGFR signalling primes EGF-mediated outputs via EGFR threonine 693 phosphorylation. This reciprocal priming between distinct families of RTKs from recycling endosomes exemplifies a novel signalling integration hub where recycling endosomes orchestrate cellular behaviour. Therefore, targeting reciprocal priming over individual receptors may improve personalized therapies in breast and other cancers.
A read count-based method to detect multiplets and their cellular origins from snATAC-seq data
Authors: Thibodeau Asa , Eroglu Alper , Lawlor Nathan , Nehar-Belaid Djamel , Kursawe Romy , Marches Radu , Kuchel George A. , Banchereau Jacques , Stitzel Michael L. , Cicek A. Ercument , Ucar Duygu 
Published: January 2021

ABSTRACTSimilar to other droplet-based single cell assays, single nucleus ATAC-seq (snATAC-seq) data harbor multiplets that confound downstream analyses. Detecting multiplets in snATAC-seq data is particularly challenging due to its sparsity and trinary nature (0 reads: closed chromatin, 1: open in one allele, 2: open in both alleles), yet offers a unique opportunity to infer multiplets when >2 uniquely aligned reads are observed at multiple loci. Here, we implemented the first read count-based multiplet detection method, ATAC-DoubletDetector, that detects multiplets independently of cell-type. Using PBMC and pancreatic islet datasets, ATAC-DoubletDetector captured simulated heterotypic multiplets (different cell-types) with ∼0.60 recall, showing ∼24% improvement over state of the art. ATAC-DoubletDetector detected homotypic multiplets with ∼0.61 recall, representing the first method to detect multiplets originating from the same cell type. Using our novel clustering-based algorithm, multiplets were annotated to their cellular origins with ∼85% accuracy. Application of ATAC-DoubletDetector will improve downstream analysis of snATAC-seq.
Why extinction estimates from extant phylogenies are so often zero
Authors: Louca Stilianos , Pennell Matthew W. 
Published: January 2021

AbstractTime-calibrated phylogenies comprising only extant lineages are widely used to estimate historical speciation and extinction rates. Such extinction rate estimates have long been controversial as many phylogenetic studies report zero extinction in many taxa, a finding in conflict with the fossil record. To date, the causes of this widely observed discrepancy remain unresolved. Here we provide a novel and simple explanation for these “zero-inflated” extinction rate estimates, based on the recent discovery that there exist many alternative “congruent” diversification scenarios that cannot possibly be distinguished on the sole basis of extant timetrees. Consequently, estimation methods tend to converge to some scenario congruent to (i.e., statistically indistinguishable from) the true diversification scenario, but not necessarily to the true diversification scenario itself. This congruent scenario may in principle exhibit negative extinction rates, a biologically meaningless but mathematically feasible situation, in which case estimators will tend to hit and stick to the boundary estimate of zero extinction. To test this explanation, we estimated extinction rates using maximum likelihood for a set of simulated trees and for 121 empirical trees, while either allowing or preventing negative extinction rates. We find that the existence of congruence classes and imposed bounds on extinction rates can explain the zero-inflation of previous extinction rate estimates, even for large trees (1000 tips) and in the absence of any detectable model violations. Not only do our results likely resolve a long-standing mystery in phylogenetics, they demonstrate that model congruencies can have severe consequences in practice.
Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2
Authors: Amjadi Maya F. , O’Connell Sarah E. , Armbrust Tammy , Mergaert Aisha M. , Narpala Sandeep R. , Halfmann Peter J. , Bashar S. Janna , Glover Christopher R. , Heffron Anna S. , Taylor Alison , Flach Britta , O’Connor David H. , Kawaoka Yoshihiro , McDermott Adrian B. , Sethi Ajay K. , Shelef Miriam A. 
Published: January 2021

ABSTRACTLasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain unclear. Our objective was to comprehensively evaluate anti-SARS-CoV-2 antibodies in a clinically diverse COVID-19 convalescent cohort at defined time points to determine if anti-SARS-CoV-2 antibodies persist and to identify clinical and demographic factors that correlate with high titers. Using a novel multiplex assay to quantify IgG against four SARS-CoV-2 antigens, a receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralization assay, we found that 98% of COVID-19 convalescent subjects had anti-SARS-CoV-2 antibodies five weeks after symptom resolution (n=113). Further, antibody levels did not decline three months after symptom resolution (n=79). As expected, greater disease severity, older age, male sex, obesity, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 antibody levels. We demonstrated for the first time that COVID-19 symptoms, namely fever, abdominal pain, diarrhea and low appetite, correlated consistently with higher anti-SARS-CoV-2 antibody levels. Our results provide new insights into the development and persistence of anti-SARS-CoV-2 antibodies.
Post operative acute kidney injury in abdominal Surgeries – A retrospective analysis of single center in western India
Authors: Vasavada Bhavin , Patel Hardik 
Published: January 2021

ABSTRACTAIMThe aim of our study was to evaluate the incidence and causative factors for acute kidney injury in abdominal surgeries.Material and MethodsAll the abdominal surgeries performed between April 2018 to December 2020, in our institution have been analyzed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi-square t-test or fisher’s t-test wherever appropriate and continuous variables by Mann Whitney U test for nonparametric data and student t-test for parametric test after skewness and kurtosis analysis. Statistical analysis was done using SPSS version 23. P< 0.05 was considered statistically significant.ResultsWe performed 402 gastrointestinal and hepatobiliary surgery from April 2018 to December 2020. After exclusion 372 patients were included in the study population. 20 patients (5.37%) were defined as having acute kidney injury according to acute kidney injury network classifications. On univariate analysis acute kidney injury was associated with open surgery (p= 0.003), Intraoperative hypotension (p<0.001), Colorectal surgeries (p<0.0001), Emergency surgery (p=0.028), CDC grade of surgery (p<0.001), increased used to blood products (p=0.001), higher ASA grade (p<0.0001), increased operative time(p<0.0001). On multivariate logistic regression analysis higher ASA grade (p<0.0001) and increased operative time (0.049) independently predicted acute kidney injury. Acute kidney injury was also significantly associated with 90 days mortality. (p= <0.0001).ConclusionPost-operative acute kidney injury was associated with significant mortality in abdominal surgery. Higher ASA grades and increased operative time predicted acute kidney injury.
Modelling Decay of Population Immunity With Proposed Second Dose Deferral Strategy
Authors: Graham Jurgens 
Published: January 2021

AbstractA second dose deferred strategy has been proposed to increase initial population immunity as an alternative to the default two dose vaccine regimen with spacing of 21 or 28 days between vaccine doses for the mRNA vaccines from Pfizer and Moderna. This increased initial population immunity is only of value if one dose immunity does not decay so fast as to nullify the benefit. Because decay rates of one dose and two dose efficacy are currently unknown, a model to project population immunity between the two strategies was created. By evaluating the decay rate of one dose efficacy, two dose efficacy, and time until the second dose is given, the model shows that if there is an increased decay rate of one dose efficacy relative to the two dose decay rate, it is highly unlikely to nullify the benefit of increased population immunity seen in a second dose deferral strategy. Rather, all reasonable scenarios strongly favour a second dose deferral strategy with much higher projected population immunity in comparison to the default regimen.
Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats
Authors: Da Silva Joyce T. , Tricou Christina , Zhang Youping , Tofighbakhsh Amir , Seminowicz David A. , Ro Jin Y. 
Published: January 2021

AbstractOld age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre‐OA) and during the early and late phases of monosodium iodoacetate‐induced OA in rats. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients.
Variability in agricultural productivity and rural household consumption inequality: Evidence from Nigeria and Uganda
Authors: Amare Mulubrhan , Shiferaw Bekele , Takeshima Hiroyuki , Mavrotas George 
Published: January 2021

AbstractThis paper uses multiple rounds of panel data to assess the distributional implications of the variability in agricultural productivity in Nigeria and Uganda. It uses both a conventional decomposition and a regression‐based inequality decomposition approach to estimate the impact of climate‐induced variability in agricultural productivity. To mitigate the endogeneity associated with unobserved time‐invariant and time‐variant household fixed effects, we use rainfall shocks as a proxy for estimating the exogenous variability in agricultural productivity that affects consumption. Results suggest that a 10% increase in the variability of agricultural productivity tends to decrease household consumption by 3.7 and 5.2% on average for Nigeria and Uganda, respectively. Controlling for other factors, variability in agricultural productivity contributed to between 25% and 43% of consumption inequality between 2010 and 2015 for Nigeria; and 16% and 31% of consumption inequality between 2009 and 2011 for Uganda. We also show that variability in agricultural productivity increases changes in consumption inequality over time.
Productivity impact of drought tolerant maize varieties under rainfall stress in Malawi: A continuous treatment approach
Authors: Katengeza Samson P. , Holden Stein T. 
Published: January 2021

AbstractDrought tolerant (DT) maize varieties have received massive support in sub‐Saharan Africa because of their potential to protect smallholder farmers against drought‐related maize yield losses. Using four waves of household farm panel data from six districts in Malawi, we examine the impact heterogeneity of this technology on maize productivity using a continuous treatment approach. We find strong evidence of positive correlation between maize yield and adoption of DT maize varieties. On average, an increase by one hectare in the area allocated to DT varieties increases maize yield by 547 Kg/ha representing a 44% increase from the average maize yield of 1,254 Kg/ha for our sample. Our findings give evidence that DT maize technology has potential to protect smallholder farmers against drought‐related production losses. Policies that promote increased allocation of maize area to DT maize hold potential to enhance food security. Smallholder farmers especially in drought‐prone areas should be encouraged to allocate at least one‐third of the maize plot to DT varieties while breeders continue with the efforts of breeding a DT variety that is not only drought tolerant but also adapted to all weather conditions. More importantly, the government should ensure provision of timely ex ante weather information to guide farmers on decision‐making with respect to maize varietal choices.
Malignant hyperthermia 2020
Authors: Hopkins P. M. , Girard T. , Dalay S. , Jenkins B. , Thacker A. , Patteril M. , McGrady E. 
Published: January 2021

SummaryMalignant hyperthermia is defined in the International Classification of Diseases as a progressive life‐threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri‐operative management of the patients.
Effectiveness of acceptance and commitment therapy for mental illness in cancer patients: A systematic review and meta‐analysis of randomised controlled trials
Authors: Li Zhihong , Li Yanfei , Guo Liping , Li Meixuan , Yang Kehu 
Published: January 2021

AbstractBackgroundDisease awareness is an important aspect of psychological adjustment in cancer patients; however, there is limited evidence that acceptance and commitment therapy (ACT) is recommended for the treatment of mental illness in cancer patients.PurposeTo assess the effectiveness of ACT for cancer patients with mental illness.MethodsTen databases were searched for publications up to July 25, 2020, using combinations of search terms related to mental health, cancer, and randomised controlled trials (RCTs). Two researchers independently screened the literature, extracted data, and assessed the quality of the study.ResultsSeventeen RCTs (877 cancer patients) were mainly of low quality, compared with control group, ACT was associated with improved outcomes after treatment completion and at 1‐3 months and at 3‐6 months of follow‐up for depression (Standardised mean difference [SMD] = −0.93, 95% CI, −1.36 to −0.51, P < .001), anxiety (SMD = −1.22, 95% CI, −2.16 to −0.29, P = .01), quality of life (SMD = 0.85, 95% CI, 0.17 to 1.11, P = .01), psychological distress (SMD = −0.80, 95% CI, −1.24 to 0.35, P < .001), and stress (SMD = −0.54, 95% CI, −1.02 to −0.07, P = .03). After 6 months of follow‐up, depression, anxiety, quality of life, and stress were still significant. ACT was associated with psychological flexibility and was not associated with a reduction in fear at treatment completion. However, psychological flexibility (1‐3 months) decreased and fear (1‐6 months) decreased, and the longer‐term effect was still significant.ConclusionACT can be an important component of future cancer care, as it may alleviate depression, anxiety, stress, and fear, and improve quality of life. However, further research is required to determine long‐term treatment effects. High‐quality RCTs are needed to more reliably estimate treatment effects.
Coffee and type 2 diabetes risk: Is the association mediated by adiponectin, leptin, c‐reactive protein or Interleukin‐6? A systematic review and meta‐analysis
Authors: Osama Hasnaa , Abdelrahman Mona A. , Madney Yasmin M. , Harb Hadeer S. , Saeed Haitham , Abdelrahim Mohamed E. A. 
Published: January 2021

AbstractAimCoffee and diabetes risk association has been demonstrated in numerous studies; however, the exact mechanism has not been clarified yet. The present meta‐analysis was conducted to cover the current knowledge regarding the effect of coffee on Type 2 Diabetes (T2D), in addition to the evaluation of adiponectin, leptin, C‐reactive protein (CRP) and Interleukin‐6 (IL‐6) levels among coffee consumers as relatively possible mediators of this effect.MethodA comprehensive search of the literature was carried out using search engines up to March 2020. The effect sizes were investigated using the standardised mean difference (SMD) and odds ratios (OR) or relative risk (RR) with its 95% confidence interval (CI). A total of 69 cross‐sectional and cohort studies were included and divided as follows: 31 articles for T2D risk, 15 studies for adiponectin, 6 studies for leptin, 12 studies for CRP and 5 studies for IL‐6.ResultsOverall, coffee consumption was inversely associated with T2D risk with an estimated pooled RR of 0.73 (95% confidence interval [0.68, 0.80] for the highest vs lowest coffee consumption categories. The combined SMD between the different coffee intake categories, showed that coffee consumption was associated with higher adiponectin levels (P = .002), and lower level of leptin (P = .04) and CRP (P = .2), with apparently no change in IL‐6 levels (P = .91).ConclusionThe present meta‐analysis showed strong epidemiological evidence that coffee consumption is inversely associated with the risk of T2D. Also, adiponectin, leptin concentrations appeared to be potential mediators of the coffee effect on diabetes, while IL‐6 levels did not.
Central nervous system inflammatory demyelinating diseases and neuroimmunology in Singapore—Epidemiology and evolution of an emerging subspecialty
Authors: Tan Kevin , Yeo Tianrong , Yong Kok Pin , Thomas Terrence , Wang Furene , Tye Janis , Quek Amy May Lin 
Published: January 2021

AbstractThe clinico‐pathologic entity of central nervous system inflammatory demyelinating diseases (CNS IDD) such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) was recognized in Singapore as early as the 1960s but were previously under‐diagnosed and under‐researched. Access to neuroimmunology expertise, advanced neuroimaging and novel neural antibody biomarkers that distinguish aquaporin‐4 antibody‐positive NMOSD (AQP4 NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) from MS have revolutionized the clinical management of patients with CNS IDD in Singapore. Based on pooled cross‐sectional data from government‐funded hospitals in 2020, we identified 468 CNS IDD patients (265 MS, 152 AQP4 NMOSD, and 51 MOGAD) in Singapore. Based on a population size of approximately 4 million, the crude prevalence estimates of MS are 6.6 per 100 000, AQP4 NMOSD 3.8 per 100 000, and MOGAD 1.3 per 100 000. There are marked differences in MS and AQP4 NMOSD prevalence between ethnic groups; MS prevalence is highest in Eurasian (mixed Caucasian‐Asian ancestry) (23.9 per 100 000), followed by Indian (17.5 per 100 000), Malay (9.2 per 100 000), and Chinese (4 per 100 000); AQP4 NMOSD prevalence is highest in Chinese (4.5 per 100 000), followed by Eurasian (3.9 per 100 000), Malay (1.5 per 100 000), and Indian (1.1 per 100 000). The past decade has seen remarkable growth in neuroimmunology in Singapore. We aim to foster the development of interdisciplinary care, clinical, translational, and health services research that impact local healthcare policies and research priorities, and patient support groups to better navigate through this rapidly evolving landscape.