bluuebunny/crossref_metadata_2025 huggingface dataset:
Spin evolution of neutron stars in wind-fed high-mass X-ray binaries
Authors: Karino Shigeyuki
Published: September 2020

The observed X-ray pulse period of OB-type high-mass X-ray binary (HMXB) pulsars is typically longer than 100 seconds. It is considered that the interaction between the strong magnetic field of a neutron star and the wind matter could cause such a long pulse period. In this study, we follow the spin evolution of neutron stars, taking into account the interaction between the magnetic field and wind matter. In this line, as new challenges, we solve the evolution of the magnetic field of the neutron star at the same time, and additionally we focus on the effects of the wind properties of the donor. As a result, evolutionary tracks were obtained in which the neutron star spends some duration in the ejector phase after birth, then rapidly spins down, becomes quasi-equilibrium, and gradually spins up. Such evolution is similar to previous studies, but we found that its dominant physics depends on the velocity of the donor wind. When the wind velocity is fast, the spin-down occurs due to magnetic inhibition, while the classical propeller effect and settling accretion shell causes rapid spin-down in the slow wind accretion. Since the wind velocity of the donor could depend on the irradiated X-ray luminosity, the spin evolution track of the neutron star in a wind-fed HMXB could be more complicated than considered.
Mothering Solidarity: Infant-Feeding, Vulnerability and Poverty in West Africa Since the Seventeenth Century*
Authors: Whyte Christine
Published: September 2020

Poor and marginalized people have always distributed the labour of mothering, among their extended kin networks, with friends and neighbours and within their communities. This essay argues that taking a long historical view on the distribution of infant-feeding as labour serves as a useful corrective to modern western or imperial models which reify exclusive breastfeeding in the mother–baby dyad, and opens up questions about how the work of feeding babies has played a role in generating and sustaining rigid gender binaries. The article excavates traces of information about the feeding practices of people in West Africa who are members of gender-segregated solidarity societies, from the eighteenth to the twenty-first century. These institutions regulate much of economic and social life in the region, which incorporates parts of Sierra Leone, Liberia and Guinea, reflecting the endurance of institutions of social reproduction through widespread political change. Practices of infant-feeding show similar endurance, shaped more by economic necessity than political pressure. The article focuses on the experiences of West African men and women, along with the babies they feed with milk of all kinds, rice, palm oil and water. This mothering labour is part of a wider knowledge of the body which has been passed down among Africans and the African diaspora, and with which historians of labour, the body and emotions could usefully engage.
Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy
Authors: Sopracordevole Francesco , Clemente Nicolò , Di Giuseppe Jacopo , Barbero Maggiorino , Fallani Maria Grazia , Cattani Paolo , Agarossi Alberto , Del Fabro Anna , De Piero Giovanni , Pieralli Annalisa , Giannella Luca , Morini Stefano , Parin Alberto , Boselli Fausto , Buttignol Monica , Nicodemo Martina , Delli Carpini Giovanni , Ciavattini Andrea
Published: September 2020

Objectives

The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed.

Materials and Methods

The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series.

Results

Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus–related disease, or VaIN 3 on colposcopic-guided biopsy.

Conclusions

The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus–related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.

In any case, long-term follow-up is advisable in women treated for HG-VaIN.
Independent risk factors evaluation for overall survival and cancer-specific survival in thyroid cancer patients with bone metastasis
Authors: Tong Yuexin , Huang Zhangheng , Hu Chuan , Chi Changxing , Lv Meng , Li Pengfei , Zhao Chengliang , Song Youxin
Published: September 2020

Bone is a frequent site for the occurrence of metastasis of thyroid cancer (TC). TC with bone metastasis (TCBM) is associated with skeletal-related events (SREs), with poor prognosis and low overall survival (OS). Therefore, it is necessary to develop a predictive nomogram for prognostic evaluation. This study aimed to construct an effective nomogram for predicting the OS and cancer-specific survival (CSS) of TC patients with BM. Those TC patients with newly diagnosed BM were retrospectively examined over a period of 6 years from 2010 to 2016 using data from the Surveillance, Epidemiology and End Results (SEER) database. Demographics and clinicopathological data were collected for further analysis. Patients were randomly allocated into training and validation cohorts with a ratio of ∼7:3. OS and CSS were retrieved as research endpoints. Univariate and multivariate Cox regression analyses were performed for identifying independent predictors. Overall, 242 patients were enrolled in this study. Age, histologic grade, histological subtype, tumor size, radiotherapy, liver metastatic status, and lung metastatic status were determined as the independent prognostic factors for predicting the OS and CSS in TCBM patients. Based on the results, visual nomograms were separately developed and validated for predicting 1-, 2-, and 3-year OS and CSS in TCBM patients on the ground of above results. The calibration, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) also demonstrated the reliability and accuracy of the clinical prediction model. Our predictive model is expected to be a personalized and easily applicable tool for evaluating the prognosis of TCBM patients, and may contribute toward making an accurate judgment in clinical practice.
Diagnostic accuracy of ultrasound superb microvascular imaging for lymph nodes
Authors: Li Xuejiao , Wang Cong , Hou Xiukun , Tao Ye
Published: September 2020

Background:

As a novel ultrasound technique, superb microvascular imaging can quickly, simply and noninvasively study the microvascular distribution in the tumor and evaluate the microvascular perfusion. Studies suggested that superb microvascular imaging is helpful for the differentiation between benign and malignant lymph nodes. However, the results of these studies have been contradictory. Therefore, the present meta-analysis aimed at determining the accuracy of superb microvascular imaging in the differential diagnosis between benign and malignant lymph nodes.

Methods:

We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the July 30, 2020, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis.

Results:

This systematic review will determine the accuracy of superb microvascular imaging in the differential diagnosis between benign and malignant lymph nodes.

Conclusion:

Its findings will provide helpful evidence for the accuracy of superb microvascular imaging in the differential diagnosis between benign and malignant lymph nodes.

Systematic review registration:

INPLASY202070133.
Significance of nuclear medicine scan in comparison with diethylenetriamine pentaacetic acid and ultrasound imaging in diagnosing renal disorders
Authors: Bafaraj Saeed M.
Published: September 2020

The effectiveness of diethylenetriamine pentaacetic acid scan is regularly monitored for the assessment of any potential modifications in treatment responses or kidney functions in the pediatric population.

This study attempts to compare the usefulness of diethylenetriamine pentaacetic acid and ultrasound imaging of renal disorders among paediatric patients.

A retrospective observational study was conducted by enrolling 106 children. The demographic details such as: participant's age, gender, and the history of renal disease of each patient were recorded. Patients were administered radiopharmaceuticals in a fixed dose and were later subjected to computed tomography (CT) scan. The obtained data was analysed using descriptive statistics.

Findings indicated increased sensitivity for CT (61.20%); whereas, a major decrease in specificity (23.68%) was observed. Comparison of Single-photon emission CT (SPECT) and CT findings revealed the increased sensitivity (90.90%) for ultrasound; whereas, there was a slight decrease in the specificity (40%) for SPECT. However, SPECT findings show 91% sensitivity among patients with 71.42% positive predictive value. Moreover, an increase in sensitivity for CT (61.20%), followed by a major decrease in specificity (23.68%) was observed.

Ultrasonography has been proved to be the safest and the most effective method for the diagnosis and the treatment of most renal disorders, due to the higher predictive value of SPECT scans. It is thus suggested that patients with ureteral calculi should be diagnosed with renal scintigraphy and unenhanced helical computerized tomography.
Evaluation of the usefulness of red blood cell distribution width in critically ill pediatric patients
Authors: Kim Da Hyun , Ha Eun Ju , Park Seong Jong , Jhang Won Kyoung
Published: September 2020

Red blood cell distribution width (RDW) is a component of routine complete blood count, which reflects variability in the size of circulating erythrocytes. Recently, there have been many reports about RDW as a strong prognostic marker in various disease conditions in the adult population. However, only a few studies have been performed in children. This study aimed to investigate the association between RDW and pediatric intensive care unit (PICU) mortality in critically ill children. This study includes 960 patients admitted to the PICU from November 2012 to May 2018. We evaluated the associations between RDW and clinical parameters including PICU mortality outcomes. The median age of the study population was 15.5 (interquartile range, 4.8–54.5) months. The mean RDW was 15.6% ± 3.3%. The overall PICU mortality was 8.8%. As we categorized patients into 3 groups with respect to RDW values (Group 1: ≤14.5%; Group 2: 14.5%–16.5%; and Group 3: >16.5%) and compared clinical parameters, the higher RDW groups (Groups 2 and 3) showed more use of vasoactive-inotropic drugs, mechanical ventilator support, higher severity scores, including pediatric risk of mortality III, pediatric sequential organ failure assessment, pediatric logistic organ dysfunction-2 (PELOD-2), and pediatric multiple organ dysfunction syndrome scores, and higher PICU mortality than the lower RDW group (Group 1) (P < .05). Based on multivariate logistic regression analysis adjusted for age and sex, higher RDW value (≥14.5%) was an independent risk factor of PICU mortality. Moreover, adding RDW improved the performance of the PELOD-2 score in predicting PICU mortality (category-free net reclassification index 0.357, 95% confidence interval 0.153–0.562, P = .001). In conclusion, higher RDW value was significantly associated with worse clinical parameters including PICU mortality. RDW was an independent risk factor of PICU mortality and the addition of RDW significantly improved the performance of PELOD-2 score in predicting PICU mortality. Thus, RDW could be a promising prognostic factor with advantages of simple and easy measurement in critically ill pediatric patients.
Operative Trauma and Blood Loss — Impact on Tumor Growth and Recurrence
Authors: Pretzsch Elise , Bösch Florian , Renz Bernhard , Werner Jens , Angele Martin , Chaudry Irshad H.
Published: September 2020

In cancer patients, surgical removal of the primary tumor is one of the major steps within a multimodal therapy concept toward eliminating the disease and limiting further progression. In this respect, surgical trauma can have potent effects on the patient's immune system. Intraoperative blood loss associated with major surgical trauma leads to reduced blood flow, regional hypoxia, metabolic, and microenvironmental alterations stimulating an inflammatory response characterized by the release of pro-inflammatory cytokines (i.e., TNF-α, IL-6) and acute-phase proteins. The inflammatory state is accompanied by and intertwined with a counter-regulatory anti-inflammatory response reflected in the rise of anti-inflammatory cytokines (i.e., transforming growth factor-β) and prostaglandins (i.e., prostaglandin E2) which can lead to a depression of cell-mediated immunity and systemic immunosuppression. This results in a highly vulnerable state with concurrent expression of pro- and anti-inflammatory cytokines alternately predominating. The immunosuppressive state is characterized by a reduced antigen-presentation capacity of macrophages, alterations in lymphocyte proliferation, and activation as well as a shift of the Th1/Th2 (T helper cells 1 and 2) balance toward Th2 and a decrease in natural killer cell activity. The severity of the immunosuppression thereby correlates with the extent and the duration of the surgical procedure. Growing evidence suggests that the immunosuppressive state following hemorrhage and surgical trauma might not only be a risk factor for postoperative complications but also facilitate tumor proliferation, metastatic growth, and recurrence. This article provides an overview of the cascade of events and underlying mechanisms resulting in immunosuppression and describes the impact of hemorrhage and major surgical trauma on tumor growth and recurrence. Attempts to control for perioperative inflammation thereby reducing the adverse effects of postoperative immunosuppression could have positive effects on tumor growth, metastasis formation, and recurrence.
Childhood Mortality After Fluid Bolus With Septic or Severe Infection Shock: A Systematic Review and Meta-Analysis
Authors: Yue Jing , Zheng Ronghao , Wei Huiping , Li Jie , Wu Jiannan , Wang Ping , Zhao Hui
Published: September 2020

Background:

A considerable debate on whether fluid bolus could decrease childhood mortality in pediatric patients with septic or severe infection shock is still unresolved. A systematic review and meta-analysis was conducted to investigate the mortality rates after fluid bolus among children with septic or severe infection shock.

Methods:

A systematic electronic search of PubMed, MEDLINE, Cochrane Library, and EMBASE databases was conducted to identify relevant published studies till March 30, 2020.

Results:

A total of 19 studies with 9,321 severe sepsis or septic shock pediatric patients were included and exhibited an acceptable quality. Of the 17 studies that reported mortality at 48 h, no bolus group decreased the mortality rate when compared with bolus group with a risk ratio (RR) of 0.74 [95% confidence interval (CI) = 0.62–0.88, P < 0.01], and showed no heterogeneity (I
2 = 0%). Similar results were observed on colloids and crystalloids solution in malaria shock cases with a RR of 0.79 (95% CI = 0.62–1.02). For the subgroup of general shock patients, no significant difference was shown with an RR of 0.79 (95% CI = 0.62–1.02, P = 0.07) and no significant heterogeneity (I
2 = 0%). Two studies reported mortality at week 4 and pooled results indicated that no bolus group was protective against mortality when compared with bolus group with RR of 0.71 (95% CI = 0.57–0.88, I
2 = 0%).

Conclusion:

For the mortality at 48 h, the no bolus group showed decreased mortality when compared with the bolus group, especially in the malaria group. Similar results were found in the colloids and crystalloids solution in patients with malaria shock. Meta-analysis studies with long-term follow-up period and larger sample size are warranted to address the conclusion in the future.
High Versus Low Volume Fluid Resuscitation Strategies in a Porcine Model (Sus scrofa) of Combined Thermal and Traumatic Brain Injury
Authors: Guenther Timothy M. , Spruce Marguerite W. , Bach Lindsey M. , Caples Connor M. , Beyer Carl A. , Grayson John K. , Meyers Frederick J. , Palmieri Tina L. , Brown Ian E.
Published: September 2020

Background:

Combined burn and traumatic brain injury (TBI) treatment priorities may not align due to opposing fluid resuscitation paradigms used in treating burns and TBI. We developed a porcine model of combined thermal injury/TBI and compared an “aggressive” fluid resuscitation strategy using the Parkland formula and a “restrictive” resuscitation strategy using the modified Brooke formula.

Methods:

Twenty-eight swine were deeply anesthetized and received a 40% total body surface area full-thickness burn injury and TBI. Swine were then randomized to receive restrictive or aggressive resuscitation for 8 h after which time animals were euthanized and necropsy was performed. Volume of brain injury was assessed after analyzing segmental slices of brain tissue.

Results:

There were no differences between the restrictive and aggressive resuscitation groups in blood pressure, heart rate, central venous pressure, intra-cranial pressure (ICP), or serum lactate levels after 8 h of resuscitation. Urine output was higher in the aggressive resuscitation group. The restrictive group had a significantly higher serum blood urea nitrogen (BUN) compared with baseline and compared with the aggressive group. There was no significant difference in size of brain injury between groups.

Conclusions:

Both restrictive and aggressive resuscitation demonstrated adequate resuscitation at 8 h postinjury. Increased serum BUN in the restrictive group may be an indicator of early acute kidney injury, despite adequate urine output. Resuscitation strategy did not appear to affect ICP or the size of brain injury.
Transfer Language Space with Similar Domain Adaptation: A Case Study with Hepatocellular Carcinoma
Authors: Balthazar Patricia , Lee Scott Jeffery , Desser Terry , Rubin Daniel L. , Gichoya Judy Wawira , Banerjee Imon
Published: September 2020

Transfer learning is a common practice in image classification with deep learning where the available data is often limited for training a complex model with millions of parameters. However, transferring language models requires special attention since cross-domain vocabularies (e.g. between news articles and radiology reports) do not always overlap as the pixel intensity range overlaps mostly for images. We present a concept of similar domain adaptation where we transfer an inter-institutional language model between two different modalities (ultrasound to MRI) to capture liver abnormalities. Our experiments show that such transfer is more effective for performing shared targeted task than generic language space transfer. We use MRI screening exam reports for hepatocellular carcinoma as the use-case and apply the transfer language space strategy to automatically label thousands of imaging exams.
Potential reduction in transmission of COVID-19 by digital contact tracing systems: a modelling study
Authors: Plank Michael J. , James Alex , Lustig Audrey , Steyn Nicholas , Binny Rachelle N , Hendy Shaun C.
Published: September 2020

Background

Digital tools are being developed to support contact tracing as part of the global effort to control the spread of COVID-19. These include smartphone apps, Bluetooth-based proximity detection, location tracking, and automatic exposure notification features. Evidence on the effectiveness of alternative approaches to digital contact tracing is so far limited.

Methods

We use an age-structured branching process model of the transmission of COVID-19 in different settings to estimate the potential of manual contact tracing and digital tracing systems to help control the epidemic. We investigate the effect of the uptake rate and proportion of contacts recorded by the digital system on key model outputs: the effective reproduction number, the mean outbreak size after 30 days, and the probability of elimination.

Results

Effective manual contact tracing can reduce the effective reproduction number from 2.4 to around 1.5. The addition of a digital tracing system with a high uptake rate over 75% could further reduce the effective reproduction number to around 1.1. Fully automated digital tracing without manual contact tracing is predicted to be much less effective.

Conclusions

For digital tracing systems to make a significant contribution to the control of COVID-19, they need be designed in close conjunction with public health agencies to support and complement manual contact tracing by trained professionals.
Disease burden and clinical severity of the first pandemic wave of COVID-19 in Wuhan, China
Authors: Yang Juan , Chen Xinhua , Deng Xiaowei , Chen Zhiyuan , Gong Hui , Yan Han , Wu Qianhui , Shi Huilin , Lai Shengjie , Ajelli Marco , Viboud Cecile , Yu Hongjie
Published: September 2020

The pandemic of novel coronavirus disease 2019 (COVID-19) began in Wuhan, China, where a first wave of intense community transmission was cut short by interventions. Using multiple data source, we estimated the disease burden and clinical severity of COVID-19 by age in Wuhan from December 1, 2019 to March 31, 2020. We adjusted estimates for sensitivity of laboratory assays and accounted for prospective community screenings and healthcare seeking behaviors. Rates of symptomatic cases, medical consultations, hospitalizations and deaths were estimated at 796 (95%CI: 703-977), 489 (472-509), 370 (358-384), and 36.2 (35.0-37.3) per 100,000 persons, respectively. The COVID-19 outbreak in Wuhan had higher burden than the 2009 influenza pandemic or seasonal influenza, and that clinical severity was similar to that of the 1918 influenza pandemic. Our comparison puts the COVID-19 pandemic into context and could be helpful to guide intervention strategies and preparedness for the potential resurgence of COVID-19.
Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile
Authors: Law Jaclyn C. , Koh Wan Hon , Budylowski Patrick , Lin Jonah , Yue FengYun , Abe Kento T. , Rathod Bhavisha , Girard Melanie , Li Zhijie , Rini James M. , Mubareka Samira , McGeer Allison , Chan Adrienne K. , Gingras Anne-Claude , Watts Tania H. , Ostrowski Mario
Published: September 2020

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-γ to TNF-α ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-γg+ CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.
Integration of multi-omics data improves prediction of cervicovaginal microenvironment in cervical cancer
Authors: Bokulich Nicholas A. , Łaniewski Paweł , Chase Dana M. , Caporaso J. Gregory , Herbst-Kralovetz Melissa M.
Published: September 2020

Emerging evidence suggests that a complex interplay between human papillomavirus (HPV), microbiota, and the cervicovaginal microenvironment contribute to HPV persistence and carcinogenesis. Integration of multiple omics datasets is predicted to provide unique insight into HPV infection and cervical cancer progression. Cervicovaginal specimens were collected from a cohort (n=100) of Arizonan women with cervical cancer, cervical dysplasia, as well as HPV-positive and HPV-negative controls. Microbiome, immunoproteome and metabolome analyses were performed using 16S rRNA gene sequencing, multiplex cytometric bead arrays, and liquid chromatography-mass spectrometry, respectively. Multi-omics integration methods, including neural networks (mmvec) and Random Forest supervised learning, were utilized to explore potential interactions and develop predictive models. Our integrated bioinformatic analyses revealed that cancer biomarker concentrations were reliably predicted by Random Forest regressors trained on microbiome and metabolome features, suggesting close correspondence between the vaginal microbiome, metabolome, and genital inflammation involved in cervical carcinogenesis. Furthermore, we show that features of the microbiome and host microenvironment, including metabolites, microbial taxa, and immune biomarkers are predictive of genital inflammation status, but only weakly to moderately predictive of cervical cancer state. Different feature classes were important for prediction of different phenotypes. Lipids (e.g. sphingolipids and long-chain unsaturated fatty acids) were strong predictors of genital inflammation, whereas predictions of vaginal microbiota and vaginal pH relied mostly on alterations in amino acid metabolism. Finally, we identified key immune biomarkers associated with the vaginal microbiota composition and vaginal pH (MIF and TNFα), as well as genital inflammation (IL-6, IL-10, leptin and VEGF). Integration of multiple different microbiome “omics” data types resulted in modest increases in classifier performance over classifiers trained on the best performing individual omics data type. However, since the most predictive features cannot be known a priori, a multi-omics approach can still yield insights that might not be possible with a single data type. Additionally, integrating multiple omics datasets provided insight into different features of the cervicovaginal microenvironment and host response. Multi-omics is therefore likely to remain essential for realizing the advances promised by microbiome research.
Implementation and validation of a pooling strategy for a sustainable screening campaign for the presence of SARS-CoV-2
Authors: Cesselli Daniela , Bulfoni Michela , Marzinotto Stefania , Marcon Barbara , Cmet Sara , Cussigh Anna Rosa , Migotti Angelica , Martinella Romina , Pipan Corrado , Beltrami Antonio Paolo , Curcio Francesco
Published: September 2020

Mass screening aimed at detecting, in asymptomatic subjects, the presence of SARS-CoV-2 is considered a strategic measure for the control of the present pandemic. It allows virus carriers to be identified and quarantined, thus preventing local spread and protecting vulnerable individuals. Although the screening strategy should be determined by the epidemiological situation, the size of the population that can be screened is indeed limited by the availability of resources. Here we present the implementation of an 8-sample pool strategy that relies on protocols, reagents and equipment currently used in clinical diagnostics. The method permitted to identify, with 100% sensitivity, specificity and accuracy, samples with low viral load, being the limit of detection of 11 viral copies extracted from the equivalent of 133μl of nasopharyngeal sample-pool. When the protocol has been applied, as a proof of principle, in a real population of 3592 consecutive nasopharyngeal swabs collected by healthcare providers in asymptomatic subjects, 20 positive pools were detected and in 100% of cases the positive specimens identified. Considering these performances, the 8-sample pool will allow, in populations with an expected positive rate of less than 1%, reducing costs by at least 80%, being a suitable method for a sustainable mass screening strategy in a population of asymptomatic subjects.
Does Clinical Nihilism affect the diagnostic approach for patients with undiagnosed adult coeliac disease? A UK Multicentre study
Authors: Blanshard RJ , Naylor G , Taylor MA , Penny HA , Mooney PD , Sanders DS
Published: September 2020

Background

Adult coeliac disease (CD) has delays in diagnosis but the reasons for this have not been explored.

Methods

Group 1) Time from primary care presentation to diagnostic endoscopy was prospectively quantified in 151 adult patients with a positive endomysial antibody test and compared with the diagnostic pathway of 92 adult patients with suspected inflammatory bowel disease (IBD). Group 2) Across 4 hospitals over a 3-month period, duodenal biopsy reports for suspected CD were reviewed (n=1423). Group 3) 50 gastroenterologists completed questionnaires concerning their viewpoints on CD.

Results

Group 1) Suspected coeliac patients waited significantly longer for diagnostic endoscopy following referral (48.5 [28-89] days) than suspected IBD patients (34.5 [18-70] days; p=0.003). Group 2) Of the 1423 patients that underwent diagnostic endoscopy for possible CD, 40.0% met the guidelines to take at least 4 biopsies. Diagnosis of CD was more likely if these guidelines were followed (10.1% vs 4.6% p<0.0001). 12.4% of newly diagnosed CD patients had at least 1 non-diagnostic gastroscopy in the 5 years prior to diagnosis. Group 3) 32.0% (16) of gastroenterologists failed to identify that CD has greater prevalence in adults than IBD. Moreover, 36.0% (18) of gastroenterologists felt that doctors were not required for the management of CD.

Conclusion

Prolonged waiting times for endoscopy and inadequacies in biopsy technique suggest clinical inertia towards CD. This is exemplified by the nihilistic approach to the condition demonstrated in our qualitative data. This is the first study to demonstrate clinical inertia towards CD.

Main messages

CD patients face greater delays at all wait intervals from referral to diagnostic endoscopy compared to inflammatory bowel disease (IBD) patients.

The majority of endoscopists do not follow guidelines for diagnostic endoscopy for CD. This reduced diagnosis rates by over 50%.

Questionnaire findings presented a nihilistic attitude towards CD alone and in comparison to IBD.

This is the first study to fully represent how clinical inertia towards CD directly leads to increased diagnostic delay and likely missed diagnoses.

What is already known on the subject

Diagnostic delay is a key issue facing modern management of coeliac disease (CD) whilst only 1 in 4 cases are estimated to be diagnosed.

Delayed diagnosis of CD is associated with an increased risk of complications from the disease and a worse quality of life.
Clinical, cerebrospinal fluid and neuroimaging findings in COVID-19 encephalopathy: a case series
Authors: Tuma Raphael , Guedes Bruno , Carra Rafael , Iepsen Bruno , Rodrigues Júlia , Camelo-Filho Antonio Edvan , Kubota Gabriel , Ferrari Maíra , Neto Adalberto Studart , Oku Mariana Hiromi Manoel , Terrim Sara , Lopes Cesar Castello Branco , Passos Neto Carlos E. B. , Fiorentino Matheus D. , Souza Julia C. C. , Baima José Pedro S. , Silva Tomás , Perissinotti Iago , Martin Maria da Graça M. , Gonçalves Marcia , Fortini Ida , Smid Jerusa , Adoni Tarso , Lucato Leandro , Nitrini Ricardo , Gomes Helio , Castro Luiz H
Published: September 2020

Objective

To describe the clinical, neurological, neuroimaging and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center.

Methods

We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020.

Results

Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2) or severe (3), p<0.001).

Conclusion

In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.
Quantifying respiratory tract deposition of airborne graphene nanoplatelets: The impact of plate-like shape and folded structure
Authors: Gao Hanchao , Hammer Tobias , Zhang Xiaole , He Weidong , Xu Guangbiao , Wang Jing
Published: September 2020

The booming development of commercial products containing graphene nanoplatelets (GNPs) triggers growing concerns over their release into the air. Precise prediction of human respiratory system deposition of airborne GNPs, especially in alveolar region, is very important for inhalation exposure assessment. In this study, the pulmonary deposition of airborne GNPs was predicted by the multiple-path particle dosimetry (MPPD) model with consideration of GNPs plate-like shape and folded structure effect. Different equivalent diameters of GNPs were derived and utilized to describe different deposition mechanisms in the MPPD model. Both of small GNPs (geometric lateral size dg < 0.1 μm) and large GNPs (dg > 10 μm) had high deposition fractions in human respiratory system. The total deposition fractions for 0.1 μm and 30 μm GNPs were 41.6% and 75.6%, respectively. Most of the small GNPs deposited in the alveolar region, while the large GNPs deposited in the head airways. The aerodynamic diameter of GNPs was much smaller than the geometric lateral dimension due to the nanoscale thickness. For GNPs with geometric lateral size of 30 μm, the aerodynamic diameter was 2.98 μm. The small aerodynamic diameter of plate-like GNPs enabled deposition in the alveolar region, and folded GNPs had higher alveolar deposition than planar GNPs. Heavy breathing led to higher GNPs deposition fraction in head airways and lower deposition fractions in the alveolar region than resting breathing. Our results reveal that large GNPs can have small enough aerodynamic diameters to be respirable and deposit beyond the ciliated airways. The plate-like morphology and folded structure of GNPs resulted in higher alveolar deposition compared to spherical particles.
The best bang for the bucks: rethinking global investment on biodiversity conservation
Authors: Fontúrbel Francisco E. , Cordero Sebastián , Castaño-Villa Gabriel J.
Published: September 2020

Biodiversity loss is a central issue in conservation biology, being protected areas the primary approach to stop biodiversity loss. However, education has been identified as an important factor in this regard. Based on a database of threatened species and socio-economic features for 138 countries, we tested whether more protected areas or more education investment are associated with a lower proportion of threatened species (for different groups of vertebrates and plants). We found that education investment was negatively associated with the proportion of threatened species in 2007 and 2017, as well as with their change rates. Conversely, the percentage of protected land was significant for reptiles, but show weak relationships with other groups. Our results suggest that only increasing protected areas will not stop or reduce biodiversity loss, as the context and people’s attitudes towards wildlife also play major roles here. Therefore, investing in education, in addition to protected areas, would have a positive effect missing to achieve effective species conservation actions worldwide.
Young chicks quickly lose their spontaneous preference to aggregate with females
Authors: Pallante Virginia , Rucco Daniele , Versace Elisabetta
Published: September 2020

It is not clear when and how animals start to discriminate between male and female conspecifics and how this distinction drives their social behaviour. A recent study on pheasants found that one-week-old chicks (Phasianus colchicus) preferentially aggregated with same-sex peers and this trend became more pronounced through development, suggesting that sexual segregation increases during ontogeny. However, it remains unclear whether this ability depends on experience or develops spontaneously. Using a similar experimental protocol, we investigated whether sex discrimination is present at birth in domestic chickens (Gallus gallus) by testing the aggregation preferences of young chicks with clutch mates. We measured the amount of time spent close to male and female conspecifics in visually inexperienced chicks. Soon after hatching, both males and females preferentially aggregated with females. To clarify whether the experience with conspecifics modifies the initial preference for females we used an imprinting procedure. We exposed chicks to conspecifics of the same sex, different sex or both sexes for three days and then tested their preferences to aggregate with males or females. No sex preference was observed after three days of imprinting exposure. The disappearance of the initial sex preference shows that, although chicks can discriminate between conspecifics of different sex, sex segregation does not influence aggregation in the first week of life. We suggest that the absence of sexual assortment in the first week of age can enhance the social cohesion of the flock.
Human Olfactory Perception is Sensitive to Temporal Information within a Single Sniff
Authors: Wu Yuli , Chen Kepu , Zhao Kai , Zhou Wen
Published: September 2020

A sniff in humans typically lasts 1-2 seconds and is considered to produce a “snapshot” of the chemical environment that also sets the temporal resolution of olfactory perception. To examine whether the temporal order of events within a sniff influences the perceptual “snapshot”, we devised an apparatus that enabled us to phase-lock odor delivery to sniff onset and precisely manipulate onset asynchronies of odorants in humans. Psychophysical testing showed that participants were able to tell apart two odorants presented in the same or different order when the onset asynchrony was as low as 40 milliseconds. The performance improved with longer onset asynchronies and was not based on the molar ratio difference of the two odorants. Meanwhile, they were consistently at chance in reporting which odorant arrived first. These results provide behavioral evidence that human olfaction is sensitive to temporal patterns within a single sniff and indicate that timing of odor-evoked responses in relation to the sniff contributes to the perceived odor quality.
scMontage: Fast and Robust Gene Expression Similarity Search for Massive Single-cell Data
Authors: Mori Tomoya , Shinwari Naila , Fujibuchi Wataru
Published: September 2020

Single-cell RNA-seq (scRNA-seq) analysis is widely used to characterize cell types or detect heterogeneity of cell states at much higher resolutions than ever before. Here we introduce scMontage (https://scmontage.stemcellinformatics.org), a gene expression similarity search server dedicated to scRNA-seq data, which can rapidly compare a query with thousands of samples within a few seconds. The scMontage search is based on Spearman’s rank correlation coefficient and its robustness is ensured by introducing Fisher’s Z-transformation and Z-test. Furthermore, search results are linked to a human cell database SHOGoiN (http://shogoin.stemcellinformatics.org), which enable users to fast access to additional cell-type specific information. The scMontage is available not only as a web server but also as a stand-alone application for user’s own data, and thus it enhances the reliability and throughput of cell analysis and helps users gain new insights into their research.
Gonadectomy and blood sampling procedures in small size teleost models
Authors: Royan Muhammad Rahmad , Kanda Shinji , Kayo Daichi , Song Weiyi , Ge Wei , Weltzien Finn-Arne , Fontaine Romain
Published: September 2020

Sex steroids, produced by the gonads, play an essential role in the neuroendocrine control of reproduction in all vertebrates by providing feedback to the brain and pituitary. Sex steroids also play an important role in tissue plasticity by regulating cell proliferation in several tissues including the brain and the pituitary. Therefore, investigating the role of sex steroids and mechanisms by which they act is crucial to better understand both feedback mechanism and tissue plasticity. Teleost fish, which possess a higher degree of tissue plasticity and variations in reproduction strategies compared to mammals, appear to be useful models to investigate these questions. The removal of the main source of sex steroid production using gonadectomy together with blood sampling to measure steroid levels, have been well-established and fairly feasible in bigger fish and are powerful techniques to investigate the role and effects of sex steroids. However, small fish such as zebrafish and medaka, which are particularly good model organisms considering the well-developed genetic toolkit and the numerous protocols available to investigate their biology and physiology, raise challenges for applying such protocols due to their small size. Here, we demonstrate the step-by-step procedure of gonadectomy in both males and females followed by blood sampling in a small sized teleost model, the Japanese medaka (Oryzias latipes). The use of these procedures combined with the other advantages of using these small teleost models will greatly improve our understanding of feedback mechanisms in the neuroendocrine control of reproduction and tissue plasticity provided by sex steroids in vertebrates.

The article describes a quick protocol to gonadectomize and sample blood from small teleost fish, using medaka (Oryzias latipes) as a model, to investigate the role of sex steroids in animal physiology.
Identification of Dysregulated Pathways and key genes in Human Retinal Angiogenesis using Microarray Metadata
Authors: Subramanian Umadevi , Devarajan Bharanidharan
Published: September 2020

Retinal angiogenesis is a common neovascularization mechanism that causes severe irreversible vision loss in the number of retinal diseases worldwide. Patients often do not respond to the current anti-angiogenic therapies and have a vision loss. Understanding the various angiogenic pathways and factors involved in the pathogenic mechanism is vital for disease management. In this study, to identify dysregulated angiogenic pathways and specific angiogenic factors involved in vision-threatening diseases namely proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP) and neovascular age-related macular degeneration (nAMD), we downloaded microarray metadata of samples and obtained the differentially expressed genes (DEGs) in all the disease and each disease samples compared to controls. Subsequently, we performed Gene Set Enrichment (GESA) analysis for pathways, a protein-protein interaction (PPI), and angiome network analysis using R and Cytoscape software. We identified highly enriched dysregulated pathways that were neuroactive ligand receptor interaction and cytokine-cytokine receptor interaction. The angiogenic–associated DEGs were predominately related to the cytokine-cytokine receptor interaction pathway, which we further confirmed with RNA-seq data of PDR samples. Together, our analysis of these data elucidated the molecular mechanisms of retinal angiogenesis and provided potential angiogenic targets for therapeutics.
Sensory stimulus evoked responses in layer 2/3 pyramidal neurons of the hind paw-related mouse primary somatosensory cortex
Authors: Bony Guillaume , Bhaskaran Arjun A , Le Corf Katy , Frick Andreas
Published: September 2020

The mouse primary somatosensory cortex (S1) processes tactile sensory information and is the largest neocortex area emphasizing the importance of this sensory modality for rodent behavior. Most of our knowledge regarding information processing in S1 stems from studies of the whisker-related barrel cortex (S1–BC), yet the processing of tactile inputs from the hind-paws is poorly understood. We usedin vivowhole-cell patch-clamp recordings from layer (L) 2/3 pyramidal neurons (PNs) of the S1 hind-paw (S1-HP) region of anaesthetized wild type (WT) mice to investigate their evoked sub- and supra-threshold activity, intrinsic properties, and spontaneous activity. Approximately 45% of these L2/3 PNs responded to brief contralateral HP stimulation in a subthreshold manner, ~5% fired action potentials, and ~50% of L2/3 PNs did not respond at all. The evoked subthreshold responses had long onset- (~23 ms) and peak-latencies (~61 ms). The majority (86%) of these L2/3 PNs responded to prolonged (stance-like) HP stimulation with both on- and off-responses. HP stimulation responsive L2/3 PNs had a greater intrinsic excitability compared to non-responsive ones, possibly reflecting differences in their physiological role. Similar to S1-BC, L2/3 PNs displayed up- and down-states, and low spontaneous firing rates (~0.1 Hz). Our findings support a sparse coding scheme of operation for S1–HP L2/3 PNs and highlight both differences and similarities with L2/3 PNs from other somatosensory cortex areas.

KEY POINTS

Responses of layer (L) 2/3 pyramidal neurons (PNs) of the primary somatosensory hind-paw cortex (S1-HP) to contralateral hind-paw stimulation reveal both differences and similarities compared to those of somatosensory neurons responding to other tactile (e.g. whiskers, forepaw, tongue) modalities.

Similar to whisker-related barrel cortex (S1-BC) and forepaw cortex (S1-FP) S1-HP L2/3 PNs show a low spontaneous firing rate and a sparse action potential coding of evoked activity.

In contrast to S1-BC, brief hind-paw stimulus evoked responses display a long latency in S1-HP neurons consistent with their different functional role.

The great majority of L 2/3 PNs respond to prolonged hind-paw stimulation with both on- and off-responses.

These results help us to better understand sensory information processing within layer 2/3 of the neocortex and the regional differences related to various tactile modalities.