bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized logical models to investigate cancer response to BRAF treatments in melanomas and colorectal cancers
Authors: Béal Jonas , Pantolini Lorenzo , Noël Vincent , Barillot Emmanuel , Calzone Laurence
Published: January 2021

The study of response to cancer treatments has benefited greatly from the contribution of different omics data but their interpretation is sometimes difficult. Some mathematical models based on prior biological knowledge of signaling pathways facilitate this interpretation but often require fitting of their parameters using perturbation data. We propose a more qualitative mechanistic approach, based on logical formalism and on the sole mapping and interpretation of omics data, and able to recover differences in sensitivity to gene inhibition without model training. This approach is showcased by the study of BRAF inhibition in patients with melanomas and colorectal cancers who experience significant differences in sensitivity despite similar omics profiles.

We first gather information from literature and build a logical model summarizing the regulatory network of the mitogen-activated protein kinase (MAPK) pathway surrounding BRAF, with factors involved in the BRAF inhibition resistance mechanisms. The relevance of this model is verified by automatically assessing that it qualitatively reproduces response or resistance behaviors identified in the literature. Data from over 100 melanoma and colorectal cancer cell lines are then used to validate the model’s ability to explain differences in sensitivity. This generic model is transformed into personalized cell line-specific logical models by integrating the omics information of the cell lines as constraints of the model. The use of mutations alone allows personalized models to correlate significantly with experimental sensitivities to BRAF inhibition, both from drug and CRISPR targeting, and even better with the joint use of mutations and RNA, supporting multi-omics mechanistic models. A comparison of these untrained models with learning approaches highlights similarities in interpretation and complementarity depending on the size of the datasets.

This parsimonious pipeline, which can easily be extended to other biological questions, makes it possible to explore the mechanistic causes of the response to treatment, on an individualized basis.
Graph neural fields: A framework for spatiotemporal dynamical models on the human connectome
Authors: Aqil Marco , Atasoy Selen , Kringelbach Morten L. , Hindriks Rikkert
Published: January 2021

Tools from the field of graph signal processing, in particular the graph Laplacian operator, have recently been successfully applied to the investigation of structure-function relationships in the human brain. The eigenvectors of the human connectome graph Laplacian, dubbed “connectome harmonics”, have been shown to relate to the functionally relevant resting-state networks. Whole-brain modelling of brain activity combines structural connectivity with local dynamical models to provide insight into the large-scale functional organization of the human brain. In this study, we employ the graph Laplacian and its properties to define and implement a large class of neural activity models directly on the human connectome. These models, consisting of systems of stochastic integrodifferential equations on graphs, are dubbed graph neural fields, in analogy with the well-established continuous neural fields. We obtain analytic predictions for harmonic and temporal power spectra, as well as functional connectivity and coherence matrices, of graph neural fields, with a technique dubbed CHAOSS (shorthand for Connectome-Harmonic Analysis Of Spatiotemporal Spectra). Combining graph neural fields with appropriate observation models allows for estimating model parameters from experimental data as obtained from electroencephalography (EEG), magnetoencephalography (MEG), or functional magnetic resonance imaging (fMRI). As an example application, we study a stochastic Wilson-Cowan graph neural field model on a high-resolution connectome graph constructed from diffusion tensor imaging (DTI) and structural MRI data. We show that the model equilibrium fluctuations can reproduce the empirically observed harmonic power spectrum of resting-state fMRI data, and predict its functional connectivity, with a high level of detail. Graph neural fields natively allow the inclusion of important features of cortical anatomy and fast computations of observable quantities for comparison with multimodal empirical data. They thus appear particularly suitable for modelling whole-brain activity at mesoscopic scales, and opening new potential avenues for connectome-graph-based investigations of structure-function relationships.
Evaluation of oral dextrose gel for prevention of neonatal hypoglycemia (hPOD): A multicenter, double-blind randomized controlled trial
Authors: Harding Jane E. , Hegarty Joanne E. , Crowther Caroline A. , Edlin Richard P. , Gamble Gregory D. , Alsweiler Jane M. ,   for the hPOD Study Group
Published: January 2021

Background

Neonatal hypoglycemia is common and can cause brain injury. Buccal dextrose gel is effective for treatment of neonatal hypoglycemia, and when used for prevention may reduce the incidence of hypoglycemia in babies at risk, but its clinical utility remains uncertain.

Methods and findings

We conducted a multicenter, double-blinded, placebo-controlled randomized trial in 18 New Zealand and Australian maternity hospitals from January 2015 to May 2019. Babies at risk of neonatal hypoglycemia (maternal diabetes, late preterm, or high or low birthweight) without indications for neonatal intensive care unit (NICU) admission were randomized to 0.5 ml/kg buccal 40% dextrose or placebo gel at 1 hour of age. Primary outcome was NICU admission, with power to detect a 4% absolute reduction. Secondary outcomes included hypoglycemia, NICU admission for hypoglycemia, hyperglycemia, breastfeeding at discharge, formula feeding at 6 weeks, and maternal satisfaction. Families and clinical and study staff were unaware of treatment allocation. A total of 2,149 babies were randomized (48.7% girls). NICU admission occurred for 111/1,070 (10.4%) randomized to dextrose gel and 100/1,063 (9.4%) randomized to placebo (adjusted relative risk [aRR] 1.10; 95% CI 0.86, 1.42; p = 0.44). Babies randomized to dextrose gel were less likely to become hypoglycemic (blood glucose < 2.6 mmol/l) (399/1,070, 37%, versus 448/1,063, 42%; aRR 0.88; 95% CI 0.80, 0.98; p = 0.02) although NICU admission for hypoglycemia was similar between groups (65/1,070, 6.1%, versus 48/1,063, 4.5%; aRR 1.35; 95% CI 0.94, 1.94; p = 0.10). There were no differences between groups in breastfeeding at discharge from hospital (aRR 1.00; 95% CI 0.99, 1.02; p = 0.67), receipt of formula before discharge (aRR 0.99; 95% CI 0.92, 1.08; p = 0.90), and formula feeding at 6 weeks (aRR 1.01; 95% CI 0.93, 1.10; p = 0.81), and there was no hyperglycemia. Most mothers (95%) would recommend the study to friends. No adverse effects, including 2 deaths in each group, were attributable to dextrose gel. Limitations of this study included that most participants (81%) were infants of mothers with diabetes, which may limit generalizability, and a less reliable analyzer was used in 16.5% of glucose measurements.

Conclusions

In this placebo-controlled randomized trial, prophylactic dextrose gel 200 mg/kg did not reduce NICU admission in babies at risk of hypoglycemia but did reduce hypoglycemia. Long-term follow-up is needed to determine the clinical utility of this strategy.

Trial registration

ACTRN 12614001263684.
Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy—A retrospective analysis
Authors: Kämink Suzette , Masih Boota , Ali Noor , Ullah Aman , Khan Syed Juma , Ashraf Shakil , Pylypenko Tetyana , Grobusch Martin P. , Fernhout Jena , den Boer Margriet , Ritmeijer Koert
Published: January 2021

Background

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by Leishmania protozoa. In Pakistan, where CL caused by L. tropica is highly endemic, therapy with pentavalent antimonials is the standard of care, but has significant toxicity when used in systemic therapy, while are no evidence-based safer alternative treatment options for L. tropica. The efficacy of oral miltefosine has not been studied in CL caused by L. tropica. We evaluated effectiveness and tolerability of miltefosine in patients with previous treatment failure or with contraindications to systemic antimonial treatment.

Methods

A retrospective review was conducted of a cohort of CL patients who were treated with a 28-day course of miltefosine between December 2017 and August 2019, in urban Quetta, Pakistan, an area endemic for L. tropica. Descriptive analyses were performed, and effectiveness was assessed by initial response after treatment, and final cure at routine follow up visits, six weeks to three months post-treatment. Tolerability was assessed by routinely reported adverse events.

Results

Of the 76 CL patients in the cohort, 42 (55%) had contraindications to systemic antimonial treatment, and 34 (45%) had failure or relapse after antimonial treatment. Twelve patients defaulted during treatment and 12 patients were lost to follow up. In the remaining 52 patients, final cure rate was 77% (40/52). In those with contraindications to systemic antimonial treatment the final cure rate was 83% (24/29) and in the failure and relapse group 70% (16/23). Twenty-eight patients (40.0%) reported 39 mild to moderate adverse events with the main complaints being nausea (41.0%), general malaise (25.6%), and stomach pain (12.8%).

Conclusion

Results indicate that miltefosine is an effective second line treatment in CL in areas endemic for L. tropica. Prospective studies with systematic follow up are needed to obtain definitive evidence of effectiveness and tolerability, including identification of risk factors for miltefosine treatment failure.
Severe hepatobiliary morbidity is associated with Clonorchis sinensis infection: The evidence from a cross-sectional community study
Authors: Qian Men-Bao , Li Hong-Mei , Jiang Zhi-Hua , Yang Yi-Chao , Lu Ming-Fei , Wei Kang , Wei Si-Liang , Chen Yu , Zhou Chang-Hai , Chen Ying-Dan , Zhou Xiao-Nong
Published: January 2021

Clonorchis sinensis infection is highly prevalent in Asia. Diverse hepatobiliary morbidity has been documented for C. sinensis infection. This study aimed to assess the association between C. sinensis infection and hepatobiliary morbidity, taking into consideration of the control, confounders and infection intensity. A cross-sectional community survey was implemented in Hengxian county, southeastern China. Helminth infections were detected by fecal examination. Physical examination and abdominal ultrasonography were then conducted. After excluding confounding effects from gender, age and alcohol drinking, quantitative association between C. sinensis infection and hepatobiliary morbidity was assessed, and the effect from infection intensity was also evaluated, through adjusted odds ratio (aOR) and 95% confidence intervals (95% CI). 696 villagers older than 10 years were enrolled. The prevalence and infection intensity of C. sinensis were higher in male, elder people and the individuals consuming alcohol. Light C. sinensis infection was associated with the increase of diarrhoea (aOR: 2.2, 95% CI: 1.1–4.5). C. sinensis infection was associated with the increase of fatty liver (aOR: 2.7, 95% CI: 1.4–5.2), and the effect was similar in different infection intensities. Moderate C. sinensis infection was associated with the increase of gallbladder stone (aOR: 3.0, 95% CI: 1.1–8.6), while moderate and heavy infections with the increase of intrahepatic bile duct dilatation (aOR: 2.2, 95% CI: 1.0–4.9 and aOR: 4.3, 95% CI: 1.9–9.9, respectively). C. sinensis infection had an effect on the development of periductal fibrosis (aOR: 3.2, 95% CI: 2.1–4.9), which showed increasing trend by infection intensity. The length and width of gallbladder in those with C. sinensis infection were enlarged, especially in those over 30 years old. C. sinensis infection is significantly associated with hepatobiliary morbidity. The occurrence of some morbidity was strongly related to the infection intensity. Awareness on harm of clonorchiasis should be raised both for policy-makers and villagers to adopt effective interventions.
An integrated model for evaluation of maternal health care in China
Authors: Zhao Qianlong , Chen Junyi , Li Fulun , Li Aishu , Li Qian
Published: January 2021

In recent years, in the context of China’s continuous medical and health reforms, the health status of Chinese women and children has been significantly improved through the continuous efforts of staff at all levels of maternal and child health care institutions. Many indicators in maternal health care have improved significantly, but the speed and magnitude of changes have varied. The purpose of this study is to evaluate the dynamic changes in China’s maternal health status from 2004 to 2018, in order to determine whether China’s medical and health reform measures in recent years have improved maternal health. A total of 6 evaluation indicators from the data of China Health Statistics Yearbook 2019 were selected. Then, based on the multi-criteria decision-making (MCDA) methodology, the entropy weighted technique for order preference by similarity to an ideal solution (TOPSIS), entropy weighted rank-sum ratio (RSR) method and the fuzzy comprehensive evaluation were employed in this study. In addition, sensitivity analysis was engaged to validate the stability and accuracy of the achieved results. The study results shows the ranking values of various methods were not exactly the same, but the overall trend was consistent. Overall, the maternal health care in China improved from 2004 to 2018 year by year, of which the top four were ranked from 2015 to 2018, and relatively poor from 2004 to 2006. This means that the policies and measures implemented in China’s medical and health reform in the past few decades have effectively promoted China’s maternal health care, and this will also provide a theoretical basis for future decisions to promote maternal health care.
Perinatal determinants of growth trajectories in children born preterm
Authors: Jasper Elizabeth A. , Cho Hyunkeun , Breheny Patrick J. , Bao Wei , Dagle John M. , Ryckman Kelli K.
Published: January 2021

Background

A growing amount of evidence indicates in utero and early life growth has profound, long-term consequences for an individual’s health throughout the life course; however, there is limited data in preterm infants, a vulnerable population at risk for growth abnormalities.

Objective

To address the gap in knowledge concerning early growth and its determinants in preterm infants.

Methods

A retrospective cohort study was performed using a population of preterm (< 37 weeks gestation) infants obtained from an electronic medical record database. Weight z-scores were acquired from discharge until roughly two years corrected age. Linear mixed effects modeling, with random slopes and intercepts, was employed to estimate growth trajectories.

Results

Thirteen variables, including maternal race, hypertension during pregnancy, preeclampsia, first trimester body mass index, multiple status, gestational age, birth weight, birth length, head circumference, year of birth, length of birth hospitalization stay, total parenteral nutrition, and dextrose treatment, were significantly associated with growth rates of preterm infants in univariate analyses. A small percentage (1.32% - 2.07%) of the variation in the growth of preterm infants can be explained in a joint model of these perinatal factors. In extremely preterm infants, additional variation in growth trajectories can be explained by conditions whose risk differs by degree of prematurity. Specifically, infants with periventricular leukomalacia or retinopathy of prematurity experienced decelerated rates of growth compared to infants without such conditions.

Conclusions

Factors found to influence growth over time in children born at term also affect growth of preterm infants. The strength of association and the magnitude of the effect varied by gestational age, revealing that significant heterogeneity in growth and its determinants exists within the preterm population.
Clarification of electrical current importance in plasma gene transfection by equivalent circuit analysis
Authors: Kido Yugo , Motomura Hideki , Ikeda Yoshihisa , Satoh Susumu , Jinno Masafumi
Published: January 2021

We have been developing a method of plasma gene transfection that uses microdischarge plasma (MDP) and is highly efficient, minimally invasive, and safe. Using this technique, electrical factors (such as the electrical current and electric field created through processing discharge plasma) and the chemical factors of active species and other substances focusing on radicals are supplied to the cells and then collectively work to introduce nucleic acids in the cell. In this paper, we focus on the electrical factors to identify whether the electric field or electrical current is the major factor acting on the cells. More specifically, we built a spatial distribution model that uses an electrical network to represent the buffer solution and cells separately, as a substitute for the previously reported uniform medium model (based on the finite element method), calculated the voltage and electrical current acting on cells, and examined their intensity. Although equivalent circuit models of single cells are widely used, this study was a novel attempt to build a model wherein adherent cells distributed in two dimensions were represented as a group of equivalent cell circuits and analyzed as an electrical network that included a buffer solution and a 96-well plate. Using this model, we could demonstrate the feasibility of applying equivalent circuit network analysis to calculate electrical factors using fewer components than those required for the finite element method, with regard to electrical processing systems targeting organisms. The results obtained through this equivalent circuit network analysis revealed for the first time that the distribution of voltage and current applied to a cellular membrane matched the spatial distribution of experimentally determined gene transfection efficiency and that the electrical current is the major factor contributing to introduction.
The Epidemiology of first and second-line drug-resistance Mycobacterium tuberculosis complex common species: Evidence from selected TB treatment initiating centers in Ethiopia
Authors: Dagne Biniyam , Desta Kassu , Fekade Rahel , Amare Misikir , Tadesse Mengistu , Diriba Getu , Zerihun Betselot , Getu Melak , Sinshaw Waganeh , Seid Getachew , Gamtesa Dinka Fekadu , Assefa Gebeyehu , Alemu Ayinalem
Published: January 2021

Background

Drug-resistance in Mycobacterium tuberculosis complex remains a major health burden in human history and still is a major leading cause of death in developing countries including Ethiopia. Early detection of all forms of drug-resistant Tuberculosis(TB) is a key factor to reduce and contain the spread of these resistant strains.

Methods

A health facility-based cross-sectional study was employed, based on demographic, clinical, and laboratory data collected from 204 patients with bacteriological confirmed TB. Sputum samples were analyzed using conventional TB culture and identification test followed by molecular species identification, and then phenotypic drug susceptibility tests. Data were entered using an excel spreadsheet and exported to SPSS version 20 for analysis. Descriptive analysis; frequencies, and proportions were computed.

Results

Among the 204 sputum samples inoculated in culture media, Mycobacterium species were recovered from 165 specimens, with 160 Mycobacterium tuberculosis complex and five Non- Tuberculosis Mycobacterium(NTM) species. All Mycobacterium tuberculosis complex was found to be M. tuberculosis. Of the five NTM species, 2 M.fortuitum, 2 M.intracellulare, and 1 M.gordonae were identified. Among 160 species of M. tuberculosis isolates, 110(68.8%) were resistant to any of the anti-TB drugs. The resistance pattern was; INH (109, 68.1%), RIF (99, 61.9%), STM (73,45.6%), and EMB (32,20.0%). Mono-resistance was found for INH (7,4.3%) and STM (1,0.6%). Ninety-nine (61.9%) isolates become MDR, while resistance to any of the second-line anti-TB drugs was detected in 9 (5.6%) strains, with 8(5%) Pre-XDR and one (0.6%) XDR cases.

Conclusion

Our findings highlight high frequencies of drug resistance to first and second-line anti-TB drugs.Determining the drug-resistance pattern of MTB is important for programmatic management of drug-resistant TB in Ethiopia. The circulating Pre-XDR and XDR case identified in the current study is alarming to the tuberculosis control program in the country.
Evaluation of a multiplex PCR method for the detection of porcine parvovirus types 1 through 7 using various field samples
Authors: Kim Seung-Chai , Jeong Chang-Gi , Nazki Salik , Lee Sim-In , Baek Ye-Chan , Jung Yong-Jin , Kim Won-Il
Published: January 2021

Porcine parvoviruses (PPVs) are small, nonenveloped DNA viruses that are widespread in the global pig population. PPV type 1 (PPV1) is a major causative agent of reproductive failure and has been recognized since the 1960s. In recent decades, novel PPVs have been identified and designated as PPVs 2 through 7 (PPV2~PPV7). Although the epidemiological impacts of these newly recognized parvoviruses on pigs are largely unknown, continuous surveillance of these PPVs is needed. The aim of this study was to develop an improved and efficient detection tool for these PPVs and to assess the developed method with field samples. Using 7 sets of newly designed primers, a multiplex polymerase chain reaction (mPCR) protocol was developed for the simultaneous detection of the seven genotypes of PPV (PPV1~PPV7). The sensitivity of the mPCR assay was analyzed, and the detection limit was determined to be 3×103 viral copies. The assay was highly specific in detecting one or more of the viruses in various combinations in specimens. The mPCR method was evaluated with 80 serum samples, 40 lung or lymph node samples and 40 intestine or fecal samples. When applied to these samples, the mPCR method could detect the 7 viruses simultaneously, providing rapid results regarding infection and coinfection status. In conclusion, the developed mPCR assay can be utilized as an effective and accurate diagnostic tool for rapid differential detection and epidemiological surveillance of various PPVs in numerous types of field samples.
Association between maternal vegetable intake during pregnancy and allergy in offspring: Japan Environment and Children’s Study
Authors: Ogawa Kohei , Pak Kyongsun , Yamamoto-Hanada Kiwako , Ishitsuka Kazue , Sasaki Hatoko , Mezawa Hidetoshi , Saito-Abe Mayako , Sato Miori , Yang Limin , Nishizato Minaho , Konishi Mizuho , Sago Haruhiko , Ohya Yukihiro ,   on behalf of Japan Environment and Children’s Study (JECS) Group
Published: January 2021

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children’s Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year.
LACTB mRNA expression is increased in pancreatic adenocarcinoma and high expression indicates a poor prognosis
Authors: Xie Jian , Peng Yang , Chen Xiaoyu , Li Qigang , Jian Bin , Wen Zelin , Liu Shengchun
Published: January 2021

This study aimed to find the prognostic value of Beta-lactamase-like (LACTB) in pancreatic adenocarcinoma (PAAD) patients. The mRNA expression of LACTB was upregulated in PAAD and was correlated with vital status (P = 0.0199). The immunoreactive scores of LACTB protein in human PAAD tissues were significantly higher than those in adjacent noncancerous pancreatic tissues. Receiver operating characteristic (ROC) curve assessment showed that LACTB mRNA expression has high diagnostic value in PAAD. Kaplan-Meier curve and Cox analyses suggested that patients with high LACTB mRNA expression have a poor prognosis, indicating that LACTB mRNA is an independent prognostic factor for overall survival [hazard ratio (HR) = 1.72, P = 0.015, 95% confidence interval (CI) = 1.106–2.253] and disease-specific survival (HR = 1.97, P = 0.004, 95% CI = 1.238–3.152) of PAAD patients. Gene set enrichment analysis (GSEA) revealed that hallmark_g2m_checkpoint, hallmark_myc_targets_v1, hallmark_e2f_targets, and kegg_cell_cycle were differentially enriched in phenotypes with high LACTB expression. In addition, CDC20, CDK4, MCM6, MAD2L1, MCM2 and MCM5 were leading genes intersecting in these four pathways, and a positive correlation between mRNA expression and LACTB was observed in most normal and cancer tissues. Finally, elevated LACTB mRNA expression was significantly related to multiple immune marker sets. Our results elucidate that LACTB is involved in the development of cancer, and that high LACTB expression in patients with PAAD can predict a poor prognosis. High LACTB expression was significantly correlated with cell cycle-related genes and multiple immune marker sets.
Joint species distribution models of Everglades wading birds to inform restoration planning
Authors: D’Acunto Laura E. , Pearlstine Leonard , Romañach Stephanie S.
Published: January 2021

Restoration of the Florida Everglades, a substantial wetland ecosystem within the United States, is one of the largest ongoing restoration projects in the world. Decision-makers and managers within the Everglades ecosystem rely on ecological models forecasting indicator wildlife response to changes in the management of water flows within the system. One such indicator of ecosystem health, the presence of wading bird communities on the landscape, is currently assessed using three species distribution models that assume perfect detection and report output on different scales that are challenging to compare against one another. We sought to use current advancements in species distribution modeling to improve models of Everglades wading bird distribution. Using a joint species distribution model that accounted for imperfect detection, we modeled the presence of nine species of wading bird simultaneously in response to annual hydrologic conditions and landscape characteristics within the Everglades system. Our resulting model improved upon the previous model in three key ways: 1) the model predicts probability of occupancy for the nine species on a scale of 0–1, making the output more intuitive and easily comparable for managers and decision-makers that must consider the responses of several species simultaneously; 2) through joint species modeling, we were able to consider rarer species within the modeling that otherwise are detected in too few numbers to fit as individual models; and 3) the model explicitly allows detection probability of species to be less than 1 which can reduce bias in the site occupancy estimates. These improvements are essential as Everglades restoration continues and managers require models that consider the impacts of water management on key indicator wildlife such as the wading bird community.
Variational-LSTM autoencoder to forecast the spread of coronavirus across the globe
Authors: Ibrahim Mohamed R. , Haworth James , Lipani Aldo , Aslam Nilufer , Cheng Tao , Christie Nicola
Published: January 2021

Modelling the spread of coronavirus globally while learning trends at global and country levels remains crucial for tackling the pandemic. We introduce a novel variational-LSTM Autoencoder model to predict the spread of coronavirus for each country across the globe. This deep Spatio-temporal model does not only rely on historical data of the virus spread but also includes factors related to urban characteristics represented in locational and demographic data (such as population density, urban population, and fertility rate), an index that represents the governmental measures and response amid toward mitigating the outbreak (includes 13 measures such as: 1) school closing, 2) workplace closing, 3) cancelling public events, 4) close public transport, 5) public information campaigns, 6) restrictions on internal movements, 7) international travel controls, 8) fiscal measures, 9) monetary measures, 10) emergency investment in health care, 11) investment in vaccines, 12) virus testing framework, and 13) contact tracing). In addition, the introduced method learns to generate a graph to adjust the spatial dependences among different countries while forecasting the spread. We trained two models for short and long-term forecasts. The first one is trained to output one step in future with three previous timestamps of all features across the globe, whereas the second model is trained to output 10 steps in future. Overall, the trained models show high validation for forecasting the spread for each country for short and long-term forecasts, which makes the introduce method a useful tool to assist decision and policymaking for the different corners of the globe.
Comparing lifeact and phalloidin for super-resolution imaging of actin in fixed cells
Authors: Mazloom-Farsibaf Hanieh , Farzam Farzin , Fazel Mohamadreza , Wester Michael J. , Meddens Marjolein B. M. , Lidke Keith A.
Published: January 2021

Visualizing actin filaments in fixed cells is of great interest for a variety of topics in cell biology such as cell division, cell movement, and cell signaling. We investigated the possibility of replacing phalloidin, the standard reagent for super-resolution imaging of F-actin in fixed cells, with the actin binding peptide ‘lifeact’. We compared the labels for use in single molecule based super-resolution microscopy, where AlexaFluor 647 labeled phalloidin was used in a dSTORM modality and Atto 655 labeled lifeact was used in a single molecule imaging, reversible binding modality. We found that imaging with lifeact had a comparable resolution in reconstructed images and provided several advantages over phalloidin including lower costs, the ability to image multiple regions of interest on a coverslip without degradation, simplified sequential super-resolution imaging, and more continuous labeling of thin filaments.
Time restricted eating as a weight loss intervention in adults with obesity
Authors: Przulj Dunja , Ladmore Daniella , Smith Katie Myers , Phillips-Waller Anna , Hajek Peter
Published: January 2021

Objectives

Time-restricted eating (TRE) is a weight management approach in which food is consumed only within a specific period each day. The simplicity of this approach is appealing, but its efficacy is not known. The aim of this pilot cohort study was to assess adherence to TRE and its effects on weight and lipid profile.

Methods

Fifty participants with obesity attempted to follow TRE for 12 weeks. Surveys were conducted weekly over the phone to assess treatment adherence and ratings; and at 6 and 12 weeks, participants attended the clinic to be weighed, have their blood pressure taken and provide a blood sample for lipid profile. Treatment results were compared with data from previous comparable cohorts using other weight management methods.

Results

Mean age of the participants was 50 (SD = 12.0), mean weight 97kg (SD = 17.1), mean BMI = 35 (SD = 4.0) and most were female (74%). At weeks 6 and 12, 64% and 58% of participants continued to practice TRE on at least five days/week. Using the ‘last observation carried forward’ imputation, mean (SD) weight loss was 2.0 (1.7) kg and 2.6 (2.6) kg at 6 and 12 weeks. Among participants who provided follow-up data, those who adhered to the intervention for at least five days/week recorded greater weight loss than those with lower adherence (week 6: 2.5 (1.7) vs 1.0 (1.3), p = 0.003; week 12: 3.5 (2.7) vs 1.3 (2.0), p = 0.001). A total of 26% of the sample lost at least 5% of their body weight at 12 weeks. The intervention had no effect on blood pressure or lipid profile.

Conclusions

TRE results were modest, but at least on par with those achieved with more complex interventions, and weight loss did not decline at 12 weeks. A formal trial of the intervention is warranted.
Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane
Authors: Marlaire Simon , Dehio Christoph
Published: January 2021

Bartonellaeare Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail ofBartonellaeffector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially reported to act in concert with BepF in triggering major actin cytoskeletal rearrangements that result in the internalization of a large bacterial aggregate by the so-called ‘invasome’. Later, infection studies withbepCdeletion mutants and ectopic expression of BepC have implicated this effector in triggering an actin-dependent cell contractility phenotype characterized by fragmentation of migrating cells due to deficient rear detachment at the trailing edge, and BepE was shown to counterbalance this remarkable phenotype. However, the molecular mechanism of how BepC triggers cytoskeletal changes and the host factors involved remained elusive. Using infection assays, we show here that T4SS-mediated transfer of BepC is sufficient to trigger stress fiber formation in non-migrating epithelial cells and additionally cell fragmentation in migrating endothelial cells. Interactomic analysis revealed binding of BepC to a complex of the Rho guanine nucleotide exchange factor GEF-H1 and the serine/threonine-protein kinase MRCKα. Knock-out cell lines revealed that only GEF-H1 is required for mediating BepC-triggered stress fiber formation and inhibitor studies implicated activation of the RhoA/ROCK pathway downstream of GEF-H1. Ectopic co-expression of tagged versions of GEF-H1 and BepC truncations revealed that the C-terminal ‘Bepintracellulardelivery’ (BID) domain facilitated anchorage of BepC to the plasma membrane, whereas the N-terminal ‘filamentationinduced bycAMP’ (FIC) domain facilitated binding of GEF-H1. While FIC domains typically mediate post-translational modifications, most prominently AMPylation, a mutant with quadruple amino acid exchanges in the putative active site indicated that the BepC FIC domain acts in a non-catalytic manner to activate GEF-H1. Our data support a model in which BepC activates the RhoA/ROCK pathway by re-localization of GEF-H1 from microtubules to the plasma membrane.
The NF-κB regulator Bcl-3 restricts terminal differentiation and promotes memory cell formation of CD8+ T cells during viral infection
Authors: Jaiswal Hemant , Ciucci Thomas , Wang Hongshan , Tang Wanhu , Claudio Estefania , Murphy Philip M. , Bosselut Rémy , Siebenlist Ulrich
Published: January 2021

Bcl-3 is an atypical member of the IκB family that acts in the nucleus to modulate transcription of many NF-κB targets in a highly context-dependent manner. Accordingly, complete Bcl-3-/- mice have diverse defects in both innate and adaptive immune responses; however, direct effects of Bcl-3 action in individual immune cell types have not been clearly defined. Here, we document a cell-autonomous role for Bcl-3 in CD8+ T cell differentiation during the response to lymphocytic choriomeningitis virus infection. Single-cell RNA-seq and flow cytometric analysis of virus-specific Bcl3-/- CD8+ T cells revealed that differentiation was skewed towards terminal effector cells at the expense of memory precursor effector cells (MPECs). Accordingly, Bcl3-/- CD8+ T cells exhibited reduced memory cell formation and a defective recall response. Conversely, Bcl-3-overexpression in transgenic CD8+ T cells enhanced MPEC formation but reduced effector cell differentiation. Together, our results establish Bcl-3 as an autonomous determinant of memory/terminal effector cell balance during CD8+ T cell differentiation in response to acute viral infection. Our results provide proof-of-principle for targeting Bcl-3 pharmacologically to optimize adaptive immune responses to infectious agents, cancer cells, vaccines and other stimuli that induce CD8+ T cell differentiation.
Kaposi’s sarcoma-associated herpesvirus processivity factor (PF-8) recruits cellular E3 ubiquitin ligase CHFR to promote PARP1 degradation and lytic replication
Authors: Chung Woo-Chang , Lee Seungrae , Kim Yejin , Seo Jong Bok , Song Moon Jung
Published: January 2021

Kaposi’s sarcoma–associated herpesvirus (KSHV), which belongs to the gammaherpesvirus subfamily, is associated with the pathogenesis of various tumors. Nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the polymerization of ADP-ribose units on target proteins. In KSHV-infected cells, PARP1 inhibits replication and transcription activator (RTA), a molecular switch that initiates lytic replication, through direct interaction. Thus, for efficient replication, KSHV has to overcome the molecular barrier in the form of PARP1. Previously, we have demonstrated that KSHV downregulates the expression of PARP1 through PF-8, a viral processivity factor. PF-8 induces ubiquitin–proteasome system–mediated degradation of PARP1 via direct physical association and enhances RTA transactivation activity. Here, we showed that dimerization domains of PF-8 are crucial not only for PARP1 interaction and degradation but also for enhancement of the RTA transactivation activity. PF-8 recruited CHFR for the PARP1 degradation. A knockdown of CHFR attenuated the PF-8–induced PARP1 degradation and enhancement of the RTA transactivation activity, leading to reduced KSHV lytic replication. These findings reveal a mechanism by which KSHV PF-8 recruits a cellular E3 ligase to curtail the inhibitory effect of PARP1 on KSHV lytic replication.
Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
Authors: Fiege Jessica K. , Thiede Joshua M. , Nanda Hezkiel Arya , Matchett William E. , Moore Patrick J. , Montanari Noe Rico , Thielen Beth K. , Daniel Jerry , Stanley Emma , Hunter Ryan C. , Menachery Vineet D. , Shen Steven S. , Bold Tyler D. , Langlois Ryan A.
Published: January 2021

The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.
Re-Making fashion experience: A model for ‘participatory research through clothing design’
Authors: Townsend Katherine , Sadkowska Ania
Published: January 2021

The article presents a participatory research model based on two case studies, involving the making of the research and the making of the clothing. In recent years, there has been growing interest in participatory design research, especially in relation to textiles and clothing. Various practice-based initiatives focused around the role, value and use of clothing have demonstrated success in developing and applying research methodologies aimed at activating or recording creative outcomes while staying attuned to participants’ experiential knowledge and feedback. Researchers working across social and design innovation contexts point to the urgent need for new cultures of sustainable practice that challenge the growth model through the sharing of expert and amateur knowledge and skills. Consequently, an important opportunity now exists to more formally explicate a transferable model of principles for participatory engagement through making together.

Based on a critical analysis of two consecutive collaborative research inquiries, this article posits a working model of ‘participatory research through clothing design’. The authors suggest that the model, consisting of five stages of participation: (1) communicating and listening, (2) involving, (3) activating and responding, (4) consulting and (5) sharing, offers a useful pathway when considering craft-based research aspirations and goals. The authors seek to highlight some of the practical opportunities and ethical responsibilities faced by researchers when making with others, while delineating some of the challenges and potential pitfalls raised by both case studies.
Stitching story and life together: Participatory textile making practices at a Harlem gallery
Authors: van den Berg Sarah Gerth , Wong Maria Liu
Published: January 2021

What brings a tourist from Italy, a lifelong resident of Harlem and a graduate student from a local university together? Crochet hooks, knitting needles, an assortment of green acrylic yarn and time and space for community craftivism. This case study focuses on crossing boundaries through participatory textile making, making time and space for relationship building in the changing neighbourhood of Harlem and practicing institutional stewardship as a ‘good neighbour’. The Walls-Ortiz Gallery and Center – the arts and research space of City Seminary of New York, an intercultural urban theological learning community – affords an opportunity to explore what happens when lives and stories are stitched together through participatory textile practices. Through the lenses of the EcCoWell learning neighbourhood approach and craftivism, this documentation and reflection of data from collaborative yarn bombing and community quilt-making projects over the past two years provide insights on lessons, challenges and opportunities of these community-oriented practices.
‘Threads of Identity’: Uncovering the benefits and tensions found in the hand-sewn signature as a method of engagement to challenge stereotypes about embroidering with boys
Authors: Setterington Lynn
Published: January 2021

This article describes a stitch-based research project that took place in 2016 in Manchester. It involved the Ahmed Iqbal Ullah Race Relations Archive, Burnage Academy for Boys and a professional embroiderer. Central to the enquiry is a signature cloth – a textile made up of hand-sewn autographs – used as a vehicle to explore young male identity and stereotypes about embroidery. The investigation signposts the flexibility of the signature that is utilized in the research to locate accessible activities and processes. In so doing, it formulates new avenues to access historical textile artefacts and illuminates their significance and contemporary relevance. The enquiry also outlines some of the tensions and dilemmas that permeate socially engaged practice(s) and offers new insights into the stitch-based collaborative/participatory process, in which the production of the tactile artefact is but one element; for alongside the stitch workshops a commemorative banner was a second outcome, made to memorialize a pupil killed in the school in a racially motivated crime in 1986. Shedding light on embroidery as a form of social engagement, the investigation also provides evidence of its applicability as an alternative, tactile means of communication. It similarly reveals and elucidates the dynamics inherent in this stitch-based community collaboration and draws attention to some of the planned and unexpected outcomes that emerge. The methodology offers a transparent model for those who may engage in similar practices and highlights its applicability to different audiences.
El intraemprendimiento desde una perspectiva de género. Una revisión sistemática de la literatura y una agenda de investigación
Authors: Baena-Luna Pedro , García-Río Esther
Published: January 2021

En los últimos años se ha experimentado un importante auge en el número de trabajos de investigación en el ámbito del intraemprendimiento. Este interés creciente ha estado vinculado con distintas áreas de estudio y conocimiento. A tenor de los resultados de este trabajo se constata que no ha ocurrido lo mismo en relación con la producción científica que estudia los comportamientos intraemprendedores desde una perspectiva de género. El número de trabajos es aún bajo y no permite obtener resultados concluyentes y generalizables. La metodología seguida en este trabajo ha sido la de la revisión sistemática de la literatura relacionada.
De la exaltación virtuosa y los verdaderos liberales: Riego ante la fractura del liberalismo exaltado durante el Trienio Constitucional (1822-1823)
Authors: Sánchez Martín Víctor
Published: January 2021

A lo largo de 1820 y 1821 Rafael del Riego se había convertido en un referente indiscutible para el liberalismo exaltado, que no dudó en utilizar su imagen pública en el debate político contra el liberalismo moderado. ¿Por qué a partir de 1822 la actuación personal y política de Riego dejó de contentar a ciertos sectores exaltados? El fallido golpe de estado del 7 de julio de 1822 llevó al poder al liberalismo exaltado con el ministro San Miguel y evidenció aún más la fractura existente entre los exaltados pertenecientes a la masonería y los vinculados a la comunería. Riego, por su actuación y por su condición de símbolo del régimen constitucional, quedó envuelto en el debate político entre ambos grupos del liberalismo exaltado. Estos compitieron por su figura y su ascendencia, a través de la prensa y de los debates públicos en las sociedades patrióticas, hasta que se produjo la invasión francesa de 1823.