bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of pancreatic neoplasia in theKRAS/TP53Oncopig
Authors: Mondal Pinaki , Patel Neesha S. , Bailey Katie , Aravind Shruthishree , Hollingsworth Michael A. , Lazenby Audrey J. , Carlson Mark A.
Published: June 2020

Introduction

Five year survival of pancreatic cancer (PC) remains low. Current murine models may not adequately mimic human PC and can be too small for medical device development. A large animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine with a somatic floxed cassette containingKRASG12DandTP53R167H).

Methods

Oncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) +/– interleukin 8 (IL-8) into one of the main pancreatic ducts (induction procedure). Subjects were necropsied after ≤10 week, followed by histological analysis, cytokine expression analysis, exome sequencing and transcriptome analysis of resultant tumors.

Results

Fourteen Oncopigs underwent the induction procedure; ten (71%) had gross tumor within three weeks, one of these subjects expired suddenly and the other 9 required premature euthanasia secondary to lack of oral intake. At necropsy all of ten of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Two Oncopigs underwent a control injection (no AdCre) and four WT littermates of the Oncopigs underwent AdCre injection without notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity with the molecular signatures and pathways of human PC.

Conclusion

Oncopigs with ductal injection of AdCre developed pancreatic tumor in a short period of time with molecular characteristics similar to human PC. While further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC.
A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors
Authors: Crowley Laura , Cambuli Francesco , Aparicio Luis , Shibata Maho , Robinson Brian D. , Xuan Shouhong , Li Weiping , Hibshoosh Hanina , Loda Massimo , Rabadan Raul , Shen Michael M.
Published: June 2020

Understanding the cellular constituents of the prostate is essential for identifying the cell of origin for benign prostatic hyperplasia and prostate adenocarcinoma. Here we describe a comprehensive single-cell atlas of the adult mouse prostate epithelium, which demonstrates extensive heterogeneity. We observe distinct lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV) in the distal region of the four prostate lobes, a proximally-enriched luminal population (LumP) that is not lobe-specific, as well as a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about the anatomical relationships between the mouse and human prostate.
A Time-Dependent SEIRD Model for Forecasting the COVID-19 Transmission Dynamics
Authors: Rapolu Taarak , Nutakki Brahmani , Rani T. Sobha , Bhavani S. Durga
Published: June 2020

The spread of a disease caused by a virus can happen through human to human contact or could be from the environment. A mathematical model could be used to capture the dynamics of the disease spread to estimate the infections, recoveries, and fatalities that may result from the disease. An estimation is crucial to make policy decisions and for the alerts for the medical emergencies that may arise. Many epidemiological models are being used to make such an estimation. One major factor that is important in the forecasts using the models is the dynamic nature of the disease spread. Unless we can come up with a way of estimating the parameters that guide this dynamic spread, the models may not give accurate forecasts. The main principle is to keep the model generic while making minimal assumptions. In this work, we have derived a data-driven model from SEIRD, where we attempt to forecast Infected, Recovered and Deceased rates of COVID-19 up to a week. A method of estimating the parameters of the model is also discussed thoroughly in this work. The model is tested for India at a district level along with the most affected foreign cities like Lombardia from Italy and Moscow from Russia.

The forecasts can help the governments in planning for emergencies such as ICU requirements, PPEs, hospitalizations, and so on as the infection is going to be prevalent for some time until a vaccine or cure is invented.
Dose-response effect of dietary nitrate on muscle contractility and blood pressure in older subjects
Authors: Gallardo Edgar J. , Gray Derrick A. , Hoffman Richard L. , Yates Brandon A. , Moorthi Ranjani N. , Coggan Andrew R.
Published: June 2020

Purpose

We have recently demonstrated that dietary nitrate, a source of nitric oxide via the enterosalivary pathway, can improve muscle contractile function in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown.

Methods

A randomized, double-blind, placebo-controlled crossover study was performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice (BRJ) containing 0, 200, or 400 µmol/kg of nitrate in nine healthy older subjects (one man, eight women; mean age 70±1 y). Maximal knee extensor power (Pmax) and speed (Vmax) were measured 2 h after BRJ ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study.

Results

Pmax (in W/kg) was higher (P< 0.05) after the low dose (3.9±0.4) compared to the placebo (3.7±0.4) or high dose (3.7±0.4). Vmax (in rad/s) also tended higher (P = 0.08) in the low (11.9±0.7) compared to the placebo (10.8±0.8) or high dose (11.2±0.8) trials. Eight out of nine subjects achieved a higher Pmax and Vmax after the lower vs. the higher dose. These dose-related changes in muscle contractility paralleled changes in nitric oxide (NO) bioavailability, as reflected by changes in breath NO and plasma 3-nitrotyrosine levels. No significant changes were found in systolic, diastolic, or mean arterial pressure.

Conclusions

Varying doses of dietary nitrate have differential effects on muscle function and blood pressure in older individuals. A moderate dose of nitrate increases muscle speed and power, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.
Antibody profiling of COVID-19 patients in an urban low-incidence region in Northern Germany
Authors: Solbach Werner , Schiffner Julia , Backhaus Insa , Burger David , Staiger Ralf , Tiemer Bettina , Bobrowski Andreas , Hutchings Timothy , Mischnik Alexander
Published: June 2020

This explorative monocentric study shows IgA and IgG antibody profiles from 110 patients with self-reported mild to moderate, or no COVID-19 related symptoms after laboratory-confirmed infection with SARS-CoV-2. The study region is in an urban and well-defined environment in a low-incidence region in Northern Germany. We found that approx. 70 % of the patients developed sustainable antibodies 3 weeks or later after the infection. In about 30 % of the patients with mild to moderate symptoms, no significant antibodies could be detected in two consecutive analyses. Conversely, out of ten patients without symptoms, four were repeatedly positive. Expectedly, six had no specific antibodies. The data indicate that antibody-positivity is a useful indicator of a previous SARS-CoV-2 infection. Negative antibodies do not rule out SARS-CoV-2 infection. Future studies need to determine the functionality of the antibodies in terms of personal protection and ability to transmit the virus.
A Scalable Topical Vectored Vaccine Candidate Against SARS-CoV-2
Authors: Rohaim Mohammed A , Munir Muhammad
Published: June 2020

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose ade novosynthesised avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of Newcastle disease virus, proto-type virus of AOaV-1, was engineered to express full length spike (S) glycoprotein which is highly neutralizing and major protective antigen of the SARS-CoV-2. Broad-scalein vitrocharacterization of recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagation in chicken embryonated eggs, and this expression did not significantly impact thein vitrogrowth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primatesper se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies.
Performance evaluation of Xpert HBV viral load (VL) assay: Point-of-care molecular test to strengthen and decentralize management of chronic hepatitis B (CHB) infection
Authors: Arvind Khodare , Ekta Gupta , Rani Nitiksha , Gaurav Singh , Kavita Aggarwal , Manoj Sharma , Sarin SK
Published: June 2020

Introduction

Estimation of hepatitis B (HBV) viral load (VL) is critical in hepatitis-B cascade-of-care and currently there is no point of care (POC) molecular assay available for that. This study evaluated the performance of a new near point of care molecular assay Xpert HBV-VL assay against FDA approved Real time PCR assays.

Materials & methods

In this retrospective study 119 archived plasma samples from HBV infected patients, and 53 hepatitis B surface antigen (HBsAg) patients were simultaneously tested for HBV DNA quantification on 2 real time PCR conventional assays and Xpert assay. The routine method for reporting to patient was Abbott Real Time PCR.

Results

The range of HBV DNA load in samples was 1 to 8.76 log10IU/ml with a median load of 4.46 (IQR: 1-8.76) log10IU/ml as detected by routine assay (Abbott Real-Time HBV VL assay). Genotyping could be done in 95 (79.8%) samples and genotype D (83; 87.37%) was found commonest. The Xpert assay demonstrated good correlation with Abbott (R2= 0.944) and Roche (R2= 0.963). On comparison the mean difference (95% Confidence Interval) in average viral load was −0.018 log10 IU/ml and −0.043 log10 IU/ml when Xpert was compared with the Abbott and Roche assay, respectively. The overall sensitivity, specificity, negative predictive value and positive predictive value of the Xpert assay was found 97.5%, 100%, 94.65 & 100% respectively.

Conclusion

Xpert HBV-VL assay which has a potential for near point of care molecular testing has shown excellent performance and found to be a reliable method for HBV DNA quantification.
An open resource for T cell phenotype changes in COVID-19 identifies IL-10-producing regulatory T cells as characteristic of severe cases
Authors: Neumann Julika , Prezzemolo Teresa , Vanderbeke Lore , Roca Carlos P. , Gerbaux Margaux , Janssens Silke , Willemsen Mathijs , Burton Oliver , Van Mol Pierre , Van Herck Yannick ,   CONTAGIOUS co-authors, Wauters Joost , Wauters Els , Liston Adrian , Humblet-Baron Stephanie
Published: June 2020

The pandemic spread of the novel coronavirus SARS-CoV-2 is due, in part, to the immunological properties of the host-viral interaction. The clinical presentation varies greatly from individual to individual, with asymptomatic carriers, mild to moderate-presenting patients and severely affected patients. Variation in immune response to SARS-CoV-2 may underlie this clinical variation. Using a high dimensional systems immunology platform, we have analyzed the peripheral blood compartment of 6 healthy individuals, 23 mild-to-moderate COVID-19 patients and 20 severe COVID-19 patients. We identify distinct immunological signatures in the peripheral blood of the mild-to-moderate and severe COVID-19 patients, including T cell lymphopenia, more consistent with peripheral hypo-than hyper-immune activation. Unique to the severe COVID-19 cases was a large increase in the proportion of IL-10-secreting regulatory T cells, a lineage known to possess anti-inflammatory properties in the lung. Annotated data is openly available (https://flowrepository.ors/experiments/2713) with clinical correlates, as a systems immunology resource for the COVID-19 research community.
Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large metropolitan region
Authors: Emmenegger Marc , Cecco Elena De , Lamparter David , Jacquat Raphaël P. B. , Riou Julien , Menges Dominik , Ballouz Tala , Ebner Daniel , Schneider Mathias M. , Morales Itzel Condado , Doğançay Berre , Guo Jingjing , Wiedmer Anne , Domange Julie , Imeri Marigona , Moos Rita , Zografou Chryssa , Batkitar Leyla , Madrigal Lidia , Schneider Dezirae , Trevisan Chiara , Gonzalez-Guerra Andres , Carrella Alessandra , Dubach Irina L. , Xu Catherine K. , Meisl Georg , Kosmoliaptsis Vasilis , Malinauskas Tomas , Burgess-Brown Nicola , Owens Ray , Hatch Stephanie , Mongkolsapaya Juthathip , Screaton Gavin R. , Schubert Katharina , Huck John D. , Liu Feimei , Pojer Florence , Lau Kelvin , Hacker David , Probst-Müller Elsbeth , Cervia Carlo , Nilsson Jakob , Boyman Onur , Saleh Lanja , Spanaus Katharina , von Eckardstein Arnold , Schaer Dominik J. , Ban Nenad , Tsai Ching-Ju , Marino Jacopo , Schertler Gebhard F. X. , Ebert Nadine , Thiel Volker , Gottschalk Jochen , Frey Beat M. , Reimann Regina , Hornemann Simone , Ring Aaron M. , Knowles Tuomas P. J. , Puhan Milo A. , Althaus Christian L. , Xenarios Ioannis , Stuart David I. , Aguzzi Adriano
Published: June 2020

Effective public-health measures and vaccination campaigns against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against the ectodomain and the receptor-binding domain of the spike protein as well as the nucleocapsid protein of SARS-CoV-2. We used TRABI for continuous seromonitoring of hospital patients and healthy blood donors (n=72’222) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). Seroprevalence peaked in May 2020 and rose again in November 2020 in both cohorts. Validations of results included antibody diffusional sizing and Western Blotting. Using an extended Susceptible-Exposed-Infectious-Removed model, we found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020 in the population of the canton of Zurich. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19 and up to the timepoint of survey participation. Crucially, we found no evidence for a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2- infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.
Machine Learning Models for Diagnosis of Cushing’s Syndrome Using Retrospective Data
Authors: Isci Senol , Kalender Derya Sema Yaman , Bayraktar Firat , Yaman Alper
Published: June 2020

Accurate classification of Cushing’s Syndrome (CS) plays a critical role in providing early and correct diagnosis of CS that may facilitate treatment and improve patient outcomes. Diagnosis of CS is a complex process, which requires careful and concurrent interpretation of signs and symptoms, multiple biochemical test results, and findings of medical imaging by physicians with a high degree of specialty and knowledge to make correct judgments. In this article, we explore the state of the art machine learning algorithms to demonstrate their potential as a clinical decision support system to analyze and classify CS in order to facilitate the diagnosis, prognosis, and treatment of CS. Prominent algorithms are compared using nested cross-validation and various class comparison strategies including multiclass, one vs. all, and one vs. one binary classification. Our findings show that Random Forest (RF) algorithm is most suitable for the classification of CS. We demonstrate that the proposed approach can classify CS subjects with an average accuracy of 92% and an average F1 score of 91.5%, depending on the class comparison strategy and selected features. RF-based one vs. all binary classification model achieves sensitivity of 97.6%, precision of 91.1%, and specificity of 87.1% to discriminate CS from non-CS on the test dataset. RF-based multiclass classification model achieves average per class sensitivity of 91.8%, average per class specificity of 97.1%, and average per class precision of 92.1% to classify different subtypes of CS on the test dataset. Clinical performance evaluation suggests that the developed models can help improve physician’s judgment in diagnosing CS.
Peripersonal and reaching space differ: evidence from their spatial extent and multisensory facilitation pattern
Authors: Zanini A. , Patané I. , Blini E. , Salemme R. , Koun E. , Farnè A. , Brozzoli C.
Published: June 2020

Peripersonal space (PPS) is a multisensory representation of the space near body parts facilitating interactions with the close environment. Studies on non-human and human primates converge in showing that PPS is a body-part-centred representation that guides actions. Because of these characteristics, growing confusion conflates peripersonal and arm-reaching space (ARS), that is the space one’s arm can reach. Despite neuroanatomical evidence favors their distinction, no study has contrasted directly their respective extent and behavioral features. Here, in five experiments (N=140) we found that PPS differs from ARS, as evidenced both by participants’ spatial and temporal performance and its modeling. We mapped PPS and ARS using both their respective gold standard tasks and a novel multisensory facilitation paradigm. Results show that 1) PPS is smaller than ARS; 2) multivariate analyses of spatial patterns of multisensory facilitation predict participants’ hand locations within ARS; 3) the multisensory facilitation map shifts isomorphically following hand positions, revealing hand-centred coding of PPS, therefore pointing to a functional similarity to the receptive fields of monkeys’ multisensory neurons. A control experiment further corroborated these results and additionally ruled out the orienting of attention as driving mechanism for the increased multisensory facilitation near the hand. In sharp contrast, ARS mapping results in a larger spatial extent, with undistinguishable patterns across hand positions, cross-validating the conclusion that PPS and ARS are distinct spatial representations. These findings urge for a refinement of theoretical models of PPS, which is relevant to constructs as diverse as self-representation, social interpersonal distance, and motor control.
Recording site placement on planar silicon-based probes affects neural signal quality: edge sites enhance acute recording performance
Authors: Fiáth Richárd , Meszéna Domokos , Boda Mihály , Barthó Péter , Ruther Patrick , Ulbert István
Published: June 2020

Objective

Multisite, silicon-based probes are widely used tools to record the electrical activity of neuronal populations. Several physical features of these devices (e.g. shank thickness, tip geometry) are designed to improve their recording performance. Here, our goal was to investigate whether the position of recording sites on the silicon shank might affect the quality of the recorded neural signal in acute experiments.

Approach

Neural recordings obtained with five different types of high-density, single-shank, planar silicon probes from anesthetized rats were analyzed. Wideband data were filtered (500 - 5000 Hz) to extract spiking activity, then various quantitative properties (e.g. amplitude distribution of the filtered potential, single unit yield) of the recorded cortical and thalamic activity were compared between sites located at different positions of the silicon shank, focusing particularly on edge and center sites.

Main results

Edge sites outperformed center sites: mean values of the examined properties of the spiking activity were in most cases higher for edge sites (~94%, 33/35) and a large fraction of these differences were also statistically significant (~45%, 15/33) with effect sizes ranging from small to large. Although the single unit yield was similar between site positions, the difference in signal quality was remarkable in the range corresponding to high-amplitude spikes. Furthermore, the advantage of edge sites slightly decreased for probes having a narrower shank.

Significance

The better signal quality on edge sites might be the result of the reduced shielding effect of the silicon shank providing a larger field of view for edge sites to detect spikes, or the less tissue damage caused near the edges of the shank. Our results might aid the design of novel neural implants in enhancing their recording performance by identifying more efficient recording site placements.
Extensive genetic diversity inPlasmodium vivaxfrom Sudan and its genetic relationships with other geographical isolates
Authors: Albsheer Musab M Ali. , Gebremeskel Eyoab Iyasu , Kepple Daniel , Lo Eugenia , Rougeron Virginie , Ibrahim Muntaser E. , Abdel Hamid Muzamil M.
Published: June 2020

Plasmodium vivaxmalaria is a neglected tropical disease in Africa due to low occurrence rates and lack of accurate diagnosis. Recently, there has been a dramatic increase inP. vivaxcases in East Africa and reportedly spreading to western countries. This study investigated the geographical origin and genetic diversity ofP. vivaxin Sudan by 14 microsatellite markers. A total of 113 clinicalP. vivaxsamples were collected from two districts, New Halfa and Khartoum in Sudan. In addition, data from 841 geographical samples retrieved from the database for global genetic analysis were included in the analysis to further the genetic relationships among theP. vivaxisolates at regional and worldwide scales. On a regional scale, we observed 91 unique and 8 shared haplotypes amongst the Sudan samples. Such a high genetic diversity compared to other geographical isolates lends support to hypothesis thatP. vivaxwas originated from Africa. On a global scale, as already demonstrated, we observed distinct genetic clustering ofP. vivaxisolates from Africa, South America, and Asia (including Papua New Guinea and Solomon Island) with limited admixture in all three clusters. The principal component analysis and phylogenetic tree showed similar clustering patterns and highlighted the contribution of the African isolates to the genetic variation observed globally. The East AfricanP. vivaxshowed similarity with some of the Asian isolates suggesting potential recent introductions. Our results show extensive genetic diversity co-occurring with significant multi-locus linkage disequilibrium, demonstrating the effectiveness of using microsatellite markers to implement effective control measures.
Outcomes of Isoniazid Preventive Therapy among people living with HIV in Kenya: A retrospective study of routine health care data
Authors: Karanja Muthoni , Kingwara Leonard , Kiende Polly , Owiti Philip , Kirui Elvis , Ngari Faith , Onyango Elizabeth , Ngugi Catherine , Maina Maurice , Masini Enos
Published: June 2020

Introduction

Isoniazid preventive therapy (IPT) taken by People Living with HIV (PLHIV) protects against tuberculosis (TB). Despite its recommendation, there is scarcity of data on the uptake of IPT among PLHIV and factors associated with treatment outcomes. We aimed to determine the proportion of PLHIV initiated on IPT, IPT treatment outcomes and screening for TB during and after IPT.

Methods

A retrospective cohort study of a representative sample of PLHIV initiated on IPT between July 2015 and June 2018 in Kenya. We abstracted information on socio-demographic, TB screening practices, IPT initiation, follow up, and outcomes from health facilities’ patient record cards, IPT cards and IPT registers. Further, we assessed baseline characteristics as potential correlates of developing TB during and after treatment and IPT completion using multivariable logistic regression.

Results

We enrolled 138,442 PLHIV into ART during the study period and initiated 95,431 (68.9%) into IPT. Abstracted files for 4708 patients initiated on IPT, out of which 3891(82.6%) had IPT treatment outcomes documented, 4356(92.5%) had ever been screened for TB at every clinic visit and 4,243(90.1%) had documentation of TB screening on the IPT tool before IPT initiation. 3712(95.4%) of patients with documented IPT treatment outcomes completed their treatment. 42(0.89%) of the abstracted patients developed active TB, 16(38.1%) during and 26(61.9%) after completing IPT. Follow up for TB at 6-month post-IPT completion was done for 2729(73.5%) of patients with IPT treatment outcomes. Sex, Viral load suppression and clinic type were associated with TB development (p<0.05). Levels 4, 5, FBO, and private facilities and IPT prescription practices were associated with IPT completion (p<0.05).

Conclusion

Two-thirds of PLHIV were initiated on IPT, with a high completion rate. TB screening practices were better during IPT than after completion. Development of TB during and after IPT emphasises need for keen follow up.
Predicting Collaborative Learning Quality through Physiological Synchrony Recorded by Wearable Biosensors
Authors: Liu Yang , Wang Tingting , Wang Kun , Zhang Yu
Published: June 2020

Interpersonal physiological synchrony has been consistently found during collaborative tasks. However, few studies have applied synchrony to predict collaborative learning quality in real classroom. This study collected electrodermal activity (EDA) and heart rate (HR) in naturalistic class sessions, and compared the physiological synchrony between independent task and group discussion task. Since each student learn differently and not everyone prefers collaborative learning, participants were sorted into collaboration and independent dyads based on collaborative behaviors before data analysis. The result showed that during groups discussions, high collaboration pairs produced significantly higher synchrony than low collaboration dyads (p= 0.010). Given the equivalent engagement level during independent and collaborative tasks, the difference of physiological synchrony between high and low collaboration dyads was triggered by collaboration quality. Building upon this result, the classification analysis was conducted, indicating that EDA synchrony can predict collaboration quality (AUC = 0.767,p= 0.015).
Bacterial isolates from CSF sample and their antimicrobial resistance patters in among under-five children suspected for meningitis in Dilla University Referral Hospital
Authors: Awulachew Ephrem , Diriba Kuma , Awoke Netsanet
Published: June 2020

Introduction

Bacterial meningitis is medical emergency that requires immediate medical attention. It is a cause of an estimated 288, 649 deaths worldwide per year, of which 94 883 death occur among Under-five children. Up to 24% of the survivors suffer from long-term sequelae such as epilepsy, mental retardation, or sensorineural deafness especially when the disease is contracted during early childhood.

Objective

the aim of this study was to assess bacterial isolates of CSF sample and their antimicrobial resistance patterns among under-five children in Dilla University Referral Hospital.

Material and Methods

Hospital based cross-sectional study design was used to collect clinical data and CSF sample from under-five children who was suspected for meningitis. Sediment of CSF sample was inoculated to Blood Agar plate, Chocolate Agar plate and Mackonkey Agar for bacterial isolation and identification. Chemical analysis and cytological analysis was also conducted based on standard operating procedures.

Results

From a total of 287 CSF sample cultured, causative bacteria were detected in 38 (13.2%). From culture positive cases the most frequent isolate wasStreptococcus pneumoniae13 (34.2%) followed byStaphylococcus aureas7 (18.4%),Neisseria meningitidis6 (16%) andEscherichia coli6 (16%).Haemophilus influenzaeb was isolated in 4 (10.5%) of children with meningitis. The other cause of meningitis wasStreptococcus agalactiaewhich accounted (10.5%). Cryptococcus neoformans have been detected in 4 (1.9%) cases of meningitis. Of all bacterial isolates about 42.1% (16/38) bacterial isolates were multidrug resistant. About 38.5% ofS. pneumoniaewas multidrug resistance while about 33.3%N. meningitis, 50% of H. influenzae, 57.1% of S. aureasand 40% ofE. colishowed multidrug resistance

Conclusions

High prevalence of bacterial meningitis and high rate of drug resistance were observed.S. pneumoniaewas the leading cause of bacterial meningitis among under-five children.
Detection of Envelope Glycoprotein Assembly from Old-World Hantaviruses in the Golgi Apparatus of Living Cells
Authors: Petazzi R. A. , Koikkarah A. A. , Tischler N.D. , Chiantia S.
Published: June 2020

Hantaviruses are emerging pathogens that occasionally cause deadly outbreaks in the human population. While the structure of the viral envelope has been characterized with high precision, the protein-protein interactions leading to the formation of new virions in infected cells are not fully understood yet. In this work, we use quantitative fluorescence microscopy (i.e. Number&Brightness analysis and fluorescence fluctuation spectroscopy) to quantify the interactions that lead to oligomeric spike complex formation in the physiological context of living cells. To this aim, we have analyzed proteins from Puumala and Hantaan orthohantaviruses in several cellular models. For the first time, we quantified the oligomerization state of each protein in relation to its subcellular localization, concentration and the concentration of its interaction partner. Our results indicate that when expressed separately, both glycoproteins can form homo-multimers in a concentration-dependent manner. Fluorescence fluctuation analysis was applied to prove that Gc:Gc contacts observed on virions are also relevant for Gc-Gc interactions in living cells, in the absence of Gn. Furthermore, we proved that the membrane-distal lobes of Gn are not necessary for Gn homo-multimerization. In cells co-expressing both glycoproteins, we observe clear indication of Gn-Gc interactions and the formation of protein complexes with different sizes, while using various labelling schemes to minimize the influence of the fluorescent tags. Our data are compatible with an assembly model according to which hantavirus spikes are formed via the assembly of Gn-Gc hetero-dimers. Furthermore, our results indicate the interconnection of large Gn-Gc hetero-multimers in the Golgi apparatus. Such large glycoprotein multimers may be identified as multiple interacting viral spikes and provide a possible first evidence for the initial assembly steps of the viral envelope, within this organelle, directly in living cells.
De novo enteric neurogenesis in post-embryonic zebrafish from Schwann cell precursors rather than resident cell types
Authors: El-Nachef Wael Noor , Bronner Marianne E.
Published: June 2020

The enteric nervous system is essential for normal gastrointestinal function, but evidence regarding postnatal enteric neurogenesis is conflicting. Using zebrafish as a model, we explored the origin of enteric neurons that arise in post-embryonic life in normal development and injury, and tested effects of the 5-HT4receptor agonist, prucalopride.

To assess enteric neurogenesis, all enteric neurons were photoconverted prior to time-lapse imaging to detect emergence of new neurons. Injury was modeled by two-photon laser ablation of enteric neurons. Lineage tracing was performed with neural tube injections of lipophilic dye and with an inducible Sox10-Cre line. Lastly, we tested prucalopride’s effect on post-embryonic enteric neurogenesis.

The post-embryonic zebrafish intestine appears to lack resident neurogenic precursors and enteric glia. However, enteric neurogenesis persists post-embryonically during development and after injury. New enteric neurons arise from trunk neural crest-derived Schwann cell precursors. Prucalopride increases enteric neurogenesis in normal development and after injury if exposure occurs prior to injury.

Enteric neurogenesis persists in the post-embryonic period in both normal development and injury, appears to arise from gut-extrinsic Schwann cell precursors, and is promoted by prucalopride.

SUMMARY STATEMENT

Trunk crest-derived enteric neurogenesis is poorly understood. We find post-embryonic zebrafish lack resident neuronal precursors yet enteric neurogenesis from trunk crest-derived precursors occurs in development, injury, and is promoted by prucalopride.
R7 photoreceptor axon targeting depends on the relative levels oflost and foundexpression in R7 and its synaptic partners
Authors: Douthit Jessica , Hairston Ariel , Lee Gina , Morrison Carolyn A. , Holguera Isabel , Treisman Jessica E.
Published: June 2020

As neural circuits form, growing processes select the correct synaptic partners through interactions between cell surface proteins. The presence of such proteins on two neuronal processes may lead to either adhesion or repulsion; however, the consequences of mismatched expression have rarely been explored. Here we show that theDrosophilaCUB-LDL protein Lost and found (Loaf) is required in the UV-sensitive R7 photoreceptor for normal axon targeting only when Loaf is also present in its synaptic partners. Although targeting occurs normally inloafmutant animals, removingloaffrom photoreceptors or expressing it in their postsynaptic neurons Tm5a/b or Dm9 in aloafmutant causes mistargeting of R7 axons. Loaf localizes primarily to intracellular vesicles including endosomes. We propose that Loaf regulates the trafficking or function of one or more cell surface proteins, and an excess of these proteins on the synaptic partners of R7 prevents the formation of stable connections.
Novel ionic liquids-based extraction method that preserves molecular structure from cutin
Authors: Moreira Carlos J.S. , Bento Artur , Pais Joana , Petit Johann , Escórcio Rita , Correia Vanessa G. , Pinheiro Ângela , Haliński Łukasz P. , Mykhaylyk Oleksandr O. , Rothan Christophe , Pereira Cristina Silva
Published: June 2020

The biopolyester cutin is ubiquitous in land plants, building the polymeric matrix of the plant’s outermost defensive barrier - the cuticle. Cutin influences many biological processesin plantahowever due to its complexity and highly branched nature, the native structure remains partially unresolved. Our aim was to define an original workflow for the purification and systematic characterisation of the molecular structure of cutin. To purify cutin we tested the ionic liquids cholinium hexanoate and 1-butyl-3-methyl-imidazolium acetate. The ensuing polymers are highly esterified, amorphous and have the typical monomeric composition as demonstrated by solid state NMR, complemented by spectroscopic (GC-MS), thermal (DSC) and x-ray scattering (WAXS) analyses. A systematic study by solution-state NMR of cryogenically milled cutins extracted from Micro-Tom tomatoes (the wild type and thegpat6andcus1mutants) was undertaken. Their molecular structures, relative distribution of ester aliphatics, free acid end-groups and free hydroxyl groups, differentiating between those derived from primary and secondary esters, were solved. The acquired data demonstrate the existence of free hydroxyl groups in cutin and reveal novel insights on how the mutations impact the esterification arrangement of cutin. Compared to conventional approaches, the usage of ionic liquids for the study of plant polyesters opens new avenues since simple modifications can be applied to recover a biopolymer carrying distinct types/degrees of modifications (e.g. preservation of esters or cuticular polysaccharides), which in combination with the solution NMR methodologies developed here, constitutes now essential tools to fingerprint the multi-functionality and the structure of cutinin planta.
Cyanobacterial growth and morphology are influenced by carboxysome positioning and temperature
Authors: Rillema Rees , MacCready Joshua S. , Vecchiarelli Anthony G.
Published: June 2020

Cyanobacteria are the prokaryotic group of phytoplankton responsible for a significant fraction of global CO2fixation. Like plants, cyanobacteria use the enzyme Ribulose 1,5-bisphosphate Carboxylase/Oxidase (RuBisCO) to fix CO2into organic carbon molecules via the Calvin-Benson-Bassham cycle. Unlike plants, cyanobacteria evolved a carbon concentrating organelle called the carboxysome - a proteinaceous compartment that encapsulates and concentrates RuBisCO along with its CO2substrate. In the rod-shaped cyanobacteriumSynechococcus elongatusPCC7942, we recently identified the McdAB system responsible for uniformly distributing carboxysomes along the cell length. It remains unknown what role carboxysome positioning plays with respect to cellular physiology. Here, we show for the first time that a failure to distribute carboxysomes leads to a temperature-dependent decrease in cell growth rate, cell division arrest, cell elongation, asymmetric cell division, and a significant reduction in cellular levels of RuBisCO. Unexpectedly, we also report that even wild-typeS. elongatusundergoes filamentous growth at the cool, but environmentally-relevant, growth temperature of 20°C. The findings suggest that carboxysome positioning by the McdAB system functions to maintain the carbon-fixation efficiency of RuBisCO by preventing carboxysome aggregation, which is particularly important at temperatures where rod-shaped cyanobacteria adopt a filamentous morphology.

IMPORTANCE

Photosynthetic cyanobacteria are responsible for almost half of global CO2fixation. Due to eutrophication, rising temperatures, and increasing atmospheric CO2concentrations, cyanobacteria have recently gained notoriety for their ability to form massive blooms in both freshwater and marine ecosystems across the globe. Like plants, cyanobacteria use the most abundant enzyme on Earth, RuBisCO, to provide the sole source of organic carbon required for its photosynthetic growth. Unlike plants, cyanobacteria have evolved a carbon-concentrating organelle called the carboxysome that encapsulates and concentrates RuBisCO with its CO2substrate to significantly increase carbon-fixation efficiency and cell growth. We recently identified the positioning system that distributes carboxysomes in cyanobacteria. However, the physiological consequence of carboxysome mispositioning in the absence of this distribution system remains unknown. Here we find that carboxysome mispositioning triggers temperature-dependent changes in cell growth and morphology as well as a significant reduction in cellular levels of RuBisCO.
The use of negative control outcomes in Mendelian Randomisation to detect potential population stratification or selection bias
Authors: Sanderson Eleanor , Richardson Tom G , Hemani Gibran , Davey Smith George
Published: June 2020

A key assumption of Mendelian randomisation (MR) analysis is that there is no association between the genetic variants used as instruments and the outcome other than through the exposure of interest. Two ways in which this assumption can be violated are through population stratification and selection bias which can introduce confounding of the relationship between the genetic variants and the outcome and so induce an association between them. Negative control outcomes are increasingly used to detect unobserved confounding in observational epidemiological studies. Here we consider the use of negative control outcomes in MR studies. As a negative control outcome in an MR study we propose the use of phenotypes which are determined before the exposure and outcome but which are likely to be subject to the same confounding as the exposure or outcome of interest. We illustrate our method with a two-sample MR analysis of a preselected set of exposures on self-reported tanning ability and hair colour. Our results show that, of the 33 exposures considered, GWAS studies of adiposity and education related traits are likely to be subject to population stratification and/or selection bias that is not controlled for through adjustment and so any MR study including these traits may be subject to bias that cannot be identified through standard pleiotropy robust methods.
Age differences in clinical features and outcomes in patients with COVID-19, Jiangsu, China: a retrospective, multi-center cohort study
Authors: Luo Huanyuan , Liu Songqiao , Wang Yuancheng , Phillips-Howard Penelope A. , Yang Yi , Ju Shenghong , Wang Duolao
Published: June 2020

Objectives To determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China.
Design and setting This is a retrospective, multi-center cohort study performed at twenty-four hospitals in Jiangsu, China.
Participants From January 10 to March 15, 2020, 625 patients with COVID-19 were involved.
Results Of the 625 patients (median age, 46 years; 329 [52.6%] males), 37 (5.9%) were children (18 years or less), 261 (40%) young adults (19-44 years), 248 (39.7%) middle-aged adults (45-64 years), and 79 (12.6%) elderly (65 years or more). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease, and diabetes comorbidities increased with age (trend test, P < .0001, P = 0.0003, P < .0001, and P < .0001 respectively). Fever, cough, and shortness of breath occurred more commonly among older patients, especially the elderly, compared to children (Chi-square test, P = 0.0008, 0.0146, and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both P < .0001). Older patients had significantly more abnormal values in many laboratory parameters than younger patients. Elderly patients contributed the highest proportion of severe or critically-ill cases (33.0%, Chi-square test P < 0.001), intensive care unit (ICU) (35.4%, Chi-square test P < 0.001), and respiratory failure (31.6%, Chi-square test P = 0.0266), and longest hospital stay (21 days, ANOVA-test P < 0.001).
Conclusions Elderly (≥65) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure, and the longest hospital stay, which may be due partly to that they had higher incidence of comorbidities and poor immune responses to COVID-19.
Use of amplicon-based sequencing for testing fetal identity and monogenic traits with single circulating trophoblast (SCT) prenatal diagnosis
Authors: Zhuo Xinming , Wang Qun , Liesbeth Vossaert , Salman Roseen , Kim Adriel , Van den Veyver Ignatia , Breman Amy , Beaudet Arthur
Published: June 2020

A major challenge for cell-based non-invasive prenatal testing (NIPT) is to distinguish individual presumptive fetal cells from maternal cells in female pregnancies. We have sought a rapid, robust, versatile, and low-cost next-generation sequencing method to facilitate this process. Toward this goal, single isolated cells underwent whole genome amplification prior to genotyping. Multiple highly polymorphic genomic regions (including HLA-A and HLA-B) with 10-20 very informative single nucleotide polymorphisms (SNPs) within a 200 bp interval were amplified with a modified method based on other publications. To enhance the power of cell identification, approximately 40 Human Identification SNP (Applied Biosystems) test amplicons were also utilized. This method allowed reliable differentiation of fetal and maternal cells. In fully informative cases, two haplotypes were found within the maternal reads, and fetal cells showed reads with one but not the second maternal haplotype while also showing a novel paternal haplotype absent in the mother. For SNP typing, at least 2 SNPs and 10% of informative SNPs were required to differentiate a fetal cell from a maternal cell. A paternal DNA sample is not required using this method. The assay also successfully detected point mutations causing Tay Sachs disease, cystic fibrosis, and hemoglobinopathies in single lymphoblastoid cells, and monogenic disease-causing mutations in three cell-based NIPT cases. This method could be applicable for any monogenic diagnosis.
Plasma ceramides as a sexually dimorphic biomarker of pancreatic cancer-induced cachexia
Authors: Chakedis Jeffery M. , Dillhoff Mary E. , Schmidt Carl R. , Rajasekera Priyani V. , Evans David C. , Williams Terence M. , Guttridge Denis C. , Talbert Erin E.
Published: June 2020

Background

Cancer patients who lose weight have low treatment tolerance and poor outcomes compared to cancer patients without weight loss, termed cachexia. Despite the clear increased risk for patients, diagnosing cachexia still primarily relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.

Methods

Targeted metabolomics, including panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer. Receiver Operating Characteristic (ROC) analysis was undertaken to establish if any metabolite could effectively serve as a biomarker of cachexia.

Results

Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only elevated in cachectic males.

Conclusion

Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.

Trial registration

None.

Funding

Support was provided through a pilot grant from U24DK100469 from the National Institute of Diabetes and Digestive and Kidney Diseases (The Mayo Clinic), National Cancer Institute P30CA016058 (The Ohio State University), National Cancer Institute R01CA180057 (DCG), American Cancer Society PF-15-156-01-CSM (EET), and a Weiss Postdoctoral Fellowship (EET).