bluuebunny/crossref_metadata_2025 huggingface dataset:
The neural and cognitive time course of intention reasoning: Electrophysiological evidence from ERPs
Authors: Jiang Qin , Wang Qi , Li Hong
Published: October 2020

Intention is a typical mental state in the theory of mind. However, to date, there have been theoretical debates on the conceptual structure of intention. The neural and cognitive time course of intention reasoning remains unclear. The present event-related potential (ERP) study had two purposes: first, to investigate the neural correlates of intention reasoning based on a differentiated conceptual structure distinguishing desire and intention; second, to investigate the neural basis of intention reasoning for different agents. Thus, we compared the neural activity elicited by intention reasoning for self and for others when the intention matched or mismatched the desire of the agent. The results revealed that three ERP components distinguished among different types of intention reasoning. A negative-going ERP deflection with right frontal distribution between 400 and 500 ms might reflect the cognitive conflict involved in intention reasoning, a right frontal late positive component might be associated with the categorisation of agents, and a centro-parietal late slow wave might indicate the conceptual mental operations associated with decoupling mechanisms in intention processing. These findings implied the neural and cognitive time course of intention reasoning and provided neural evidence for the differentiated conception of intention.
The fog of words: Assessing the problematic relationship between strategic narratives, (master) frames and ideology
Authors: Coticchia Fabrizio , Catanzaro Andrea
Published: October 2020

A growing body of the International Relations (IR) literature has started to pay attention to the concept of ‘strategic narratives’, stressing the role played by storylines in affecting public attitudes. However, the analytical differences between concepts like strategic narratives, master narratives, frames, framing and master frames have been rarely investigated through a comprehensive approach. Very different definitions and perspectives have been adopted in the IR scholarly debate and beyond, while few studies have identified how ideologies underlie frames and narratives. This article aims at filling this gap and makes two claims. First, the process of plot formation, their strategic dimension and the levels at which narratives operate are the special features that distinguish strategic narratives from all other concepts. Second, only by unpacking – from an interdisciplinary perspective – the complex relation between ideology and narratives can we understand the proper conceptual boundaries in the narrative literature. In sum, there are four levels of discourse to be considered: frame, strategic narrative, master narrative and ideology.
Flavonoids and Xanthones From the Genus Iris: Phytochemistry, Relationships with Flower Colors and Taxonomy, and Activities and Function
Authors: Iwashina Tsukasa , Mizuno Takayuki
Published: October 2020

The genus Iris consists of approximately 360 species and is distributed to Eurasia, North Africa, and North America. Belamcanda chinensis was incorporated into the genus Iris by APG III as Iris domestica. Iris species have also been cultivated as ornamentals since ancient times. Many flavonoids are isolated and identified from the flowers, leaves, and rhizomes. So far as we know, 6 anthocyanidins, 13 flavones, 20 flavonols, 20 C-glycosylflavones, 14 flavanones, 11 dihydroflavonols, 6 flavan and proanthocyanidins, and 85 isoflavonoids were reported as aglycones and glycosides. However, chalcones, dihydrochalcones, aurones, biflavonoids, and neoflavonoids are not found in the genus Iris. Fifteen xanthones that are related to flavonoids were also isolated from Iris species. In this review, we describe the flavonoids and xanthones that were isolated and characterized from Iris species. Moreover, their phytochemistry, contribution to the flower colors, relationships with taxonomy, and activities and functions are also discussed.
An Introduction to Research for Primary Dental Care Clinicians
Authors: Santini Ario , Eaton Kenneth A
Published: October 2020

This paper, the fourth in the series, will address the sixth of the ten stages of a research project suggested in the first paper. The ten suggested stages are:

1. The initial idea (asking a research question).

2. Searching the literature.

3. Refining the research question.

4. Planning the study.

5. Writing a protocol.

6. Obtaining ethical approval and funding.

7. Piloting the methodology and project management.

8. Collecting data.

9. Analysing the data.

10. Writing up and disseminating the results.

A previous paper1 has outlined the how to plan a research project. The next stage has two elements, which are to obtain ethical approval and to obtain funding. Each is the topic of a separate paper. This paper outlines the key areas within the topic and updates a previous publication, Ethical Considerations.2
Establishing the reference value for tibial tubercle-trochlear groove distance on MRI in Southern Chinese population and its correlation with age, sex, height, weight and size: A multi-centre study
Authors: Mo Kwun Man Cyrus , Cho Kwan Yin Francis , Au Ka Yan Alice , Lee Ka Yin Gregory , Cheng Hei Man Joyce
Published: October 2020

Objective:

The first objective of this study is to determine the reference Tibial Tubercle-Trochlear Groove (TT-TG) distance on MRI in Southern Chinese population. The second objective is to investigate the correlation between TT-TG distance and (i) age, (ii) sex, (iii) height, (iv) weight and (v) Body Mass Index (BMI) respectively.

Method:

Three hundred MRI knees performed in two different centres between August 2017 and October 2018 were included. All patients were prospectively recruited after MRI referral from Orthopaedics department. The TT-TG distances were measured by two radiologists independently. Measurement reliability was assessed using intraclass correlation coefficient (ICC). One sample t-test was used to compare the results between this study and other published studies. Spearman’s rank correlation coefficient was used to determine correlations between the TT-TG distance and age, sex, height, weight and BMI respectively.

Result:

There was no statistical significance between the mean of TT-TG distances from the two radiologists ( P-value = 0.32). The measurement reliability was excellent (ICC = 0.922 ± 0.02). The mean of averaged TT-TG distance was 8.32 ± 0.33 mm (range 2.01 to 17.48 mm). There were no statistical significant differences in means of TT-TG distance between laterality and gender. There were statistically significant correlations between (i) TT-TG distance and age ( p-value = 0.009), and (ii) TT-TG distance and height ( p-value = 0.014).

Conclusion:

The reference TT-TG distance on MRI in Southern Chinese population was 8.32 ± 0.33 mm. Statistically significant correlations were established between (i) TT-TG distance and age; and (ii) TT-TG distance and height.
Oyster Splint As an Adjuvant for Post-Traumatic Keloid on Cutaneous Upper Lip
Authors: Tengku Shaeran Tengku Aszraf , Ismail Suhaila
Published: October 2020

This article aims to share a simple method that can be adopted as part of treatment regimen of keloids. Two types of modified oyster splint was done and their usefulness is discussed. As an adjunct method, this device has shown to give a satisfactory result. Further investigation by clinical studies are invited.
Cerite: a new supergroup of minerals and cerite-(La) renamed ferricerite-(La)
Authors: Atencio Daniel , Azzi Andrezza de Almeida
Published: October 2020

The cerite supergroup is established and includes the cerite group (silicates) and merrillite group (phosphates). Cerite-group minerals are cerite-(Ce), ferricerite-(La), aluminocerite-(Ce) and taipingite-(Ce). The merrillite group is subdivided into two subgroups: merrillite (merrillite, ferromerrillite, keplerite and matyhite) and whitlockite (whitlockite, strontiowhitlockite, wopmayite and hedegaardite). Cerite-(La) has been renamed ferricerite-(La). The new nomenclature has been approved by the International Mineralogical Association Commission on New Minerals, Nomenclature and Classification.
Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit
Authors: Vaschetto Rosanna , Barone-Adesi Francesco , Racca Fabrizio , Pissaia Claudio , Maestrone Carlo , Colombo Davide , Olivieri Carlo , De Vita Nello , Santangelo Erminio , Scotti Lorenza , Castello Luigi , Cena Tiziana , Taverna Martina , Grillenzoni Luca , Moschella Maria Adele , Airoldi Gianluca , Borrè Silvio , Mojoli Francesco , Della Corte Francesco , Baggiani Marta , Baino Sara , Balbo Piero , Bazzano Simona , Bonato Valeria , Carbonati Sara , Crimaldi Federico , Daffara Veronica , De Col Luca , Maestrone Matteo , Malerba Mario , Moroni Federica , Perucca Raffaella , Pirisi Mario , Rondi Valentina , Rosalba Daniela , Vanni Letizia , Vigone Francesca , Navalesi Paolo , Cammarota Gianmaria
Published: October 2020

Aim

We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation.

Methods

In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality.

Results

The study included 537 patients with a median (interquartile range (IQR) age of 69 (60–76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1–8) days, while hospital length of stay was 16 (9–27) days. 60-day in-hospital mortality was 34% (95% CI 0.304–0.384%) overall, and 21% (95% CI 0.169–0.249%) and 73% (95% CI 0.648–0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345–0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008–0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010–1.184).

Conclusions

We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.
ICS-formoterol relieverversusICS and short-acting β2-agonist reliever in asthma: a systematic review and meta-analysis
Authors: Hatter Lee , Bruce Pepa , Braithwaite Irene , Holliday Mark , Fingleton James , Weatherall Mark , Beasley Richard
Published: October 2020

Background

The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β2-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation.

Methods

We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680).

Results

Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73–1.00; p=0.048) and reduced daily ICS dose (mean difference −177.3 μg, 95% CI −182.2–−172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09–0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84–1.36).

Conclusion

As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.
Susac syndrome (Retino-cochleo-cerebral vasculitis), the ophthalmologist in the role of the whistleblower
Authors: Papasavvas Ioannis , Teuchner Barbara , Herbort Carl Peter
Published: October 2020

Background/purpose

Susac syndrome is a rare microangiopathy of suspected autoimmune origin affecting arteries of the retina, the cochlea and the brain. The aim of the study was to give a review of the disease entity and determine the proportion of cases and their characteristics in a uveitis referral centre.

Patients and methods

Charts of patients with the diagnosis of Susac syndrome seen in the Uveitis Clinic of the Centre for Ophthalmic Specialised Care (COS), Lausanne, Switzerland were reviewed retrospectively to determine the frequency of such cases in a uveitis referral centre. Clinical symptoms and signs, functional data, imaging signs and evolution were analysed in the 3 COS cases and one case shared with the Uveitis Clinic of the Department of Ophthalmology, University of Innsbruck, Austria. Characteristic signs were searched possibly allowing a prompt diagnosis.

Results

During the period from 1994 to 2019 (24 years, 2045 patients), 3 charts with the diagnosis of Susac syndrome were found (0.15%). The whole collective, including the additional case, comprised three women aged 28, 32 and 63 at presentation and one man, aged 42. None of the 3 cases that were referred were diagnosed beforehand. The characteristic item found in all 4 cases was the abrupt arterial stop or segmental interruption of arteries and increased staining of arterial wall on angiography more clearly shown on indocyanine green angiography that can potentially be proposed as a crucial diagnostic element. All 4 cases responded to dual steroidal and non-steroidal immunosuppression. Under treatment, all four patients did not show any further evolution.

Conclusion

Susac syndrome is a multilocation arteritis of the head that can involve the eye, ear and brain often first diagnosed by the ophthalmologist. The diagnosis is rapidly reached in uveitis referral centres but seems to be missed otherwise, A helpful angiographic sign to be searched is an abrupt or segmental arterial stop and increased staining of the arterial wall more clearly seen on indocyanine green angiography. Patients often present first to the ophthalmologist who should be acting as a whistleblower to avoid severe involvement of the brain.
A novel cell permeability assay for macromolecules
Authors: Flores Bueso Yensi , Walker Sidney , Quinn Jennifer , Tangney Mark
Published: October 2020

Background

Many cell permeabilisation methods to mediate internalisation of various molecules to mammalian or bacterial cells have been developed. However, no size-specific permeability assay suitable for both cell types exists.

Results

We report the use of intrinsically biotinylated cell components as the target for reporter molecules for assessing permeabilisation. Due to its well-described biotin binding activity, we developed an assay using Streptavidin (SAv) as a molecular weight marker for assessing eukaryotic and prokaryotic cell internalisation, using flow cytometry as a readout. This concept was tested here as part of the development of host DNA depletion strategies for microbiome analysis of formalin-fixed (FF) samples. Host depletion (HD) strategies require differential cell permeabilisation, where mammalian cells but not bacterial cells are permeabilised, and are subsequently treated with a nuclease. Here, the internalisation of a SAv-conjugate was used as a reference for nucleases of similar dimensions. With this assay, it was possible to demonstrate that formalin fixation does not generate pores which allow the introduction of 60 KDa molecules in mammalian or bacterial membranes/envelopes. Among surfactants tested, Saponin derived from Quillaja bark showed the best selectivity for mammalian cell permeabilisation, which, when coupled with Benzonase nuclease, provided the best results for host DNA depletion, representing a new HD strategy for formalin fixed samples.

Conclusion

The assay presented provides researchers with a sensitive and accessible tool for discerning membrane/cell envelop permeability for different size macromolecules.
Correction to: Openness in the NHS: a secondary longitudinal analysis of national staff and patient surveys
Authors: McCarthy Imelda , Dawson Jeremy , Martin Graham
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Malaria and risk of lymphoid neoplasms and other cancer: a nationwide population-based cohort study
Authors: Wyss Katja , Granath Fredrik , Wångdahl Andreas , Djärv Therese , Fored Michael , Naucler Pontus , Färnert Anna
Published: October 2020

Background

Malaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa. No longitudinal studies have assessed the long-term risk of other lymphoma or cancer overall. Here, we investigated the risk of lymphoid neoplasms and other cancer after malaria.

Methods

We included 4125 patients diagnosed with malaria in Sweden in 1987–2015, identified either through the National Surveillance Database at the Public Health Agency of Sweden, the National Inpatient and Outpatient Register, or by reports from microbiology departments. A comparator cohort (N = 66,997) matched on sex, age and birth region was retrieved from the general population and an additional cohort with all individuals born in Sub-Saharan Africa registered in the Total Population Register in 1987–2015 (N = 171,756). Incident lymphomas and other cancers were identified through linkage with the Swedish Cancer Register. Hazard ratios (HRs) were assessed using Cox regression with attained age as the timescale.

Results

A total of 20 lymphoid neoplasms and 202 non-haematological cancers were identified among malaria patients during a mean follow-up of 13.3 and 13.7 years, respectively. The overall risk of lymphoid neoplasms was not significantly increased (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.79–1.94), neither did we find any association with all-site non-haematological cancer (HR 0.89, 95% CI 0.77–1.02). However, in the Sub-Saharan Africa cohort, we observed an increased risk of lymphoid neoplasms after malaria diagnosis (HR 2.39, 95% CI 1.06–5.40), but no difference in the risk of other cancer (HR 1.01, 95% CI 0.70–1.45). The association could not be explained by co-infection with HIV or chronic hepatitis B or C, since the risk estimate was largely unchanged after excluding patients with these comorbidities (HR 2.63, 95% CI 1.08–6.42). The risk became more pronounced when restricting analyses to only including non-Hodgkin and Hodgkin lymphomas (HR 3.49, 95% CI 1.42–8.56).

Conclusion

Individuals born in malaria-endemic areas and diagnosed with malaria in Sweden had an increased risk of lymphoid neoplasms, especially B cell lymphoma. There was no association with cancer overall nor did single malaria episodes confer an increased risk in travellers.
A new efficient method to detect genetic interactions for lung cancer GWAS
Authors: Luyapan Jennifer , Ji Xuemei , Li Siting , Xiao Xiangjun , Zhu Dakai , Duell Eric J. , Christiani David C. , Schabath Matthew B. , Arnold Susanne M. , Zienolddiny Shanbeh , Brunnström Hans , Melander Olle , Thornquist Mark D. , MacKenzie Todd A. , Amos Christopher I. , Gui Jiang
Published: October 2020

Background

Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset.

Methods

To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data.

Results

Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR 1.24, P = 3.15 × 10–15), as the top marker to predict age of lung cancer onset.

Conclusions

From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.
Towards remote healthcare monitoring using accessible IoT technology: state-of-the-art, insights and experimental design
Authors: Coulby G. , Clear A. , Jones O. , Young F. , Stuart S. , Godfrey A.
Published: October 2020

Healthcare studies are moving toward individualised measurement. There is need to move beyond supervised assessments in the laboratory/clinic. Longitudinal free-living assessment can provide a wealth of information on patient pathology and habitual behaviour, but cost and complexity of equipment have typically been a barrier. Lack of supervised conditions within free-living assessment means there is need to augment these studies with environmental analysis to provide context to individual measurements. This paper reviews low-cost and accessible Internet of Things (IoT) technologies with the aim of informing biomedical engineers of possibilities, workflows and limitations they present. In doing so, we evidence their use within healthcare research through literature and experimentation. As hardware becomes more affordable and feature rich, the cost of data magnifies. This can be limiting for biomedical engineers exploring low-cost solutions as data costs can make IoT approaches unscalable. IoT technologies can be exploited by biomedical engineers, but more research is needed before these technologies can become commonplace for clinicians and healthcare practitioners. It is hoped that the insights provided by this paper will better equip biomedical engineers to lead and monitor multi-disciplinary research investigations.
Development of prognosis model for colon cancer based on autophagy-related genes
Authors: Wang Xu , Xu Yuanmin , Li Ting , Chen Bo , Yang Wenqi
Published: October 2020

Background

Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied.

Methods

Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis.

Results

Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians.

Conclusion

The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.
Automated contouring and planning pipeline for hippocampal-avoidant whole-brain radiotherapy
Authors: Feng Christine H. , Cornell Mariel , Moore Kevin L. , Karunamuni Roshan , Seibert Tyler M.
Published: October 2020

Background

Whole-brain radiotherapy (WBRT) remains an important treatment for over 200,000 cancer patients in the United States annually. Hippocampal-avoidant WBRT (HA-WBRT) reduces neurocognitive toxicity compared to standard WBRT, but HA-WBRT contouring and planning are more complex and time-consuming than standard WBRT. We designed and evaluated a workflow using commercially available artificial intelligence tools for automated hippocampal segmentation and treatment planning to efficiently generate clinically acceptable HA-WBRT radiotherapy plans.

Methods

We retrospectively identified 100 consecutive adult patients treated for brain metastases outside the hippocampal region. Each patient’s T1 post-contrast brain MRI was processed using NeuroQuant, an FDA-approved software that provides segmentations of brain structures in less than 8 min.
Automated hippocampal segmentations were reviewed for accuracy, then converted to files compatible with a commercial treatment planning system, where hippocampal avoidance regions and planning target volumes (PTV) were generated. Other organs-at-risk (OARs) were previously contoured per clinical routine. A RapidPlan knowledge-based planning routine was applied for a prescription of 30 Gy in 10 fractions using volumetric modulated arc therapy (VMAT) delivery. Plans were evaluated based on NRG CC001 dose-volume objectives (Brown et al. in J Clin Oncol, 2020).

Results

Of the 100 cases, 99 (99%) had acceptable automated hippocampi segmentations without manual intervention. Knowledge-based planning was applied to all cases; the median processing time was 9 min 59 s (range 6:53–13:31). All plans met per-protocol dose-volume objectives for PTV per the NRG CC001 protocol. For comparison, only 65.5% of plans on NRG CC001 met PTV goals per protocol, with 26.1% within acceptable variation. In this study, 43 plans (43%) met OAR constraints, and the remaining 57 (57%) were within acceptable variation, compared to 42.5% and 48.3% on NRG CC001, respectively. No plans in this study had unacceptable dose to OARs, compared to 0.8% of manually generated plans from NRG CC001. 8.4% of plans from NRG CC001 were not scored or unable to be evaluated.

Conclusions

An automated pipeline harnessing the efficiency of commercially available artificial intelligence tools can generate clinically acceptable VMAT HA-WBRT plans with minimal manual intervention. This process could improve clinical efficiency for a treatment established to improve patient outcomes over standard WBRT.
COVID-19: a potential driver of immune-mediated breast cancer recurrence?
Authors: Francescangeli Federica , De Angelis Maria Laura , Zeuner Ann
Published: October 2020

Severe coronavirus disease 2019 (COVID-19) causes a hyperactivation of immune cells, resulting in lung inflammation. Recent studies showed that COVID-19 induces the production of factors previously implicated in the reawakening of dormant breast cancer cells such as neutrophil extracellular traps (NETs). The presence of NETs and of a pro-inflammatory microenvironment may therefore promote breast cancer reactivation, increasing the risk of pulmonary metastasis. Further studies will be required to confirm the link between COVID-19 and cancer recurrence. However, an increased awareness on the potential risks for breast cancer patients with COVID-19 may lead to improved treatment strategies to prevent metastatic relapse.
New insights into prediction of weak π–π complex association through proton-nuclear magnetic resonance analysis
Authors: Lin Chenyu , Skufca Joseph , Partch Richard E.
Published: October 2020

For analysis of weak π–π complexes proton-nuclear magnetic resonance (proton-NMR) simultaneously provides information of stacking configurations and association constants $$\left( K \right)$$

K

However, an apparent issue for this approach is inconsistent/impossible constant estimation which often leads to unreasonable interpretation for π–π complexation. Whether or not this proton-dependent constant variation could be attributed to simple experimental uncertainties or to more sophisticated additional unspecific shielding effects (AUS effects) was addressed by means of hypothesis tests using a robust bootstrap technique in this report. Our analysis shows the significance of AUS effects on such variation in constant estimation. A following study using numeric simulation further reveals the variation patterns induced by AUS effects and concludes that the largest $$K$$
K
among the obtained $$K$$
K
estimates of a complex is considered as the best estimate of $$K$$
K
due to minimum deviation from the true value of K and the multiple $$K$$
K
estimates of a π–π complex could provide preferable inferences for complex geometries.
No evidence for sylvatic cycles of chikungunya, dengue and Zika viruses in African green monkeys (Chlorocebus aethiops sabaeus) on St. Kitts, West Indies
Authors: Valentine Matthew John , Ciraola Brenda , Aliota Matthew Thomas , Vandenplas Michel , Marchi Silvia , Tenebray Bernard , Leparc-Goffart Isabelle , Gallagher Christa Ann , Beierschmitt Amy , Corey Tatiana , Dore Kerry McAuliffe , de Lamballerie Xavier , Wang Chengming , Murdock Courtney Cuin , Kelly Patrick John
Published: October 2020

Background

Dengue, chikungunya and Zika viruses (DENV, CHIKV and ZIKV) are transmitted in sylvatic transmission cycles between non-human primates and forest (sylvan) mosquitoes in Africa and Asia. It remains unclear if sylvatic cycles exist or could establish themselves elsewhere and contribute to the epidemiology of these diseases. The Caribbean island of St. Kitts has a large African green monkey (AGM) (Chlorocebus aethiops sabaeus) population and is therefore ideally suited to investigate sylvatic cycles.

Methods

We tested 858 AGM sera by ELISA and PRNT for virus-specific antibodies and collected and identified 9704 potential arbovirus vector mosquitoes. Mosquitoes were homogenized in 513 pools for testing by viral isolation in cell culture and by multiplex RT-qPCR after RNA extraction to detect the presence of DENV, CHIKV and ZIKVs. DNA was extracted from 122 visibly blood-fed individual mosquitoes and a polymorphic region of the hydroxymethylbilane synthase gene (HMBS) was amplified by PCR to determine if mosquitoes had fed on AGMs or humans.

Results

All of the AGMs were negative for DENV, CHIKV or ZIKV antibodies. However, one AGM did have evidence of an undifferentiatedFlavivirusinfection. Similarly, DENV, CHIKV and ZIKV were not detected in any of the mosquito pools by PCR or culture. AGMs were not the source of any of the mosquito blood meals.

Conclusion

Sylvatic cycles involving AGMs and DENV, CHIKV and ZIKV do not currently exist on St. Kitts.
Stool and sputum microbiome during quinolone prophylaxis of spontaneous bacterial peritonitis: an exploratory study
Authors: Mücke Marcus M. , Rüschenbaum Sabrina , Mayer Amelie , Mücke Victoria T. , Schwarzkopf Katharina M. , Zeuzem Stefan , Kehrmann Jan , Scholtysik René , Lange Christian M.
Published: October 2020

Introduction

Quinolone prophylaxis is recommended for patients with advanced cirrhosis at high risk of spontaneous bacterial peritonitis (SBP) or with prior SBP. Yet, the impact of long-term antibiotic prophylaxis on the microbiome of these patients is poorly characterized.

Methods

Patients with liver cirrhosis receiving long-term quinolone prophylaxis to prevent SBP were prospectively included and sputum and stool samples were obtained at baseline, 1, 4 and 12 weeks thereafter. Both bacterial DNA and RNA were assessed with 16S rRNA sequencing. Relative abundance, alpha and beta diversity were calculated and correlated with clinical outcome.

Results

Overall, 35 stool and 19 sputum samples were obtained from 11 patients. Two patients died (day 9 and 12) all others were followed for 180 days. Reduction of Shannon diversity and bacterial richness was insignificant after initiation of quinolone prophylaxis (p > 0.05). Gut microbiota were significantly different between patients (p < 0.001) but non-significantly altered between the different time points before and after initiation of antibiotic prophylaxis (p > 0.05). A high relative abundance ofEnterobacteriaceae> 20% during quinolone prophylaxis was found in three patients. Specific clinical scenarios (development of secondary infections during antibiotic prophylaxis or the detection of multidrug-resistantEnterobacteriaceae) characterized these patients. Sputum microbiota were not significantly altered in individuals during prophylaxis.

Conclusion

The present exploratory study with small sample size showed that inter-individual differences in diversity of gut microbiota were high at baseline, yet quinolone prophylaxis had only a moderate impact. High relative abundances ofEnterobacteriaceaeduring follow-up might indicate failure of or non-adherence to quinolone prophylaxis. However, our results may not be clinically significant given the limitations of the study and therefore future studies are needed to further investigate this phenomenon.
Performance characteristics of a quantitative PCR assay on repository stool specimens and smeared filter-paper cards
Authors: Tisdale Michele D. , Mitra Indrani , McCoy Andrea J. , Simons Mark P. , Reynolds Nathanael D. , Swierczewski Brett E. , Liu Jie , Houpt Eric R. , Fraser Jamie A. , Riddle Mark S. , Tribble David R. , Lalani Tahaniyat
Published: October 2020

Objective

Stool repositories are a valuable resource for retrospective analyses including quantitative PCR assays to distinguish between asymptomatic shedding and clinical disease. The suitability of archival specimens for this purpose is unclear and requires assessment. We conducted a pilot study to evaluate pathogen detection by TaqMan Array Card (TAC) in travelers’ diarrhea (TD) stool specimens stored for 1–13 years, as well as the impact of transporting specimens on Whatman FTA Elute cards (FTA Cards) on detection.

Results

The positive percent agreement (PPA) for TAC on stool vs. microbiologic testing was lower than our a priori PPA estimate of 80% for most pathogens: Shigella spp. (100% [95%CI 69–100%]), enterotoxigenic E coli (ETEC) (63% [95%CI 49–75%]), Campylobacter spp. (66% [95%CI 43–85%]) and Norovirus (37% [95%CI 16–61%]). Use of the FTA card resulted in a further reduction of PPA. Our findings suggest that archival specimens may lead to insensitive detection on quantitative PCR assays due to degradation of nucleic acid with prolonged storage, although our limited sample size precluded us from evaluating the impact of storage duration on nucleic acid yield. Additional studies are needed to understand the impact of storage duration on quantitative PCR data.
The impact of different suturing techniques for abdominal fascia closure on the Interleukin-6 expressions in Rattus norvegicus
Authors: Prima Heryu , Sofii Imam , Fauzi Aditya Rifqi , Dachlan Ishandono , Gunadi
Published: October 2020

Objective

Incisional hernia is a frequent complication of midline laparotomy. The suturing technique is an important determinant of the risk of developing an incisional hernia. Moreover, IL-6 has crucial roles in the wound-healing process. We aimed to compare the large stitch vs. small stitch technique for abdominal fascial closure on IL-6 expressions in rats.

Results

Twenty rats were used. The small stitch group received small tissue bites of 5 mm and the large stitch group received large bites of 10 mm. The incisions of fascia were closed by running sutures. Animals were euthanized on days 4 and 7. Histological sections of the tissue-embedded sutures were analyzed for IL-6 expressions. Two-way ANOVA showed that rats in the small stitch group had similar IL-6 expressions on days 4 and 7 to those in the large stitch group (p = 0.36). In conclusion, the IL-6 expressions are similar between the small and the large stitch groups, implying that different suturing techniques might not have an impact on the incisional hernia occurrence.
Gray matter covariations and core symptoms of autism: the EU-AIMS Longitudinal European Autism Project
Authors:   the EU-AIMS LEAP group, Mei Ting , Llera Alberto , Floris Dorothea L. , Forde Natalie J. , Tillmann Julian , Durston Sarah , Moessnang Carolin , Banaschewski Tobias , Holt Rosemary J. , Baron-Cohen Simon , Rausch Annika , Loth Eva , Dell’Acqua Flavio , Charman Tony , Murphy Declan G. M. , Ecker Christine , Beckmann Christian F. , Buitelaar Jan K.
Published: October 2020

Background

Voxel-based morphometry (VBM) studies in autism spectrum disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case–control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms.

Methods

We studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project. All participants’ VBM maps were decomposed into spatially independent components using independent component analysis. A generalized linear model (GLM) was used to examine case–control differences. Next, canonical correlation analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms.

Results

GLM analyses showed significant case–control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals.

Limitations

Only 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures.

Conclusions

Covaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.
Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice
Authors: Han Kyung Ah , Yoon Taek Han , Shin Jungsu , Um Ji Won , Ko Jaewon
Published: October 2020

Background

Recent progress in genomics has contributed to the identification of a large number of autism spectrum disorder (ASD) risk genes, many of which encode synaptic proteins. Our understanding of ASDs has advanced rapidly, partly owing to the development of numerous animal models. Extensive characterizations using a variety of behavioral batteries that analyze social behaviors have shown that a subset of engineered mice that model mutations in genes encoding Shanks, a family of excitatory postsynaptic scaffolding proteins, exhibit autism-like behaviors. Although these behavioral assays have been useful in identifying deficits in simple social behaviors, alterations in complex social behaviors remain largely untested.

Methods

Two syndromic ASD mouse models—Shank2 constitutive knockout [KO] mice and Shank3 constitutive KO mice—were examined for alterations in social dominance and social cooperative behaviors using tube tests and automated cooperation tests. Upon naïve and salient behavioral experience, expression levels of c-Fos were analyzed as a proxy for neural activity across diverse brain areas, including the medial prefrontal cortex (mPFC) and a number of subcortical structures.

Findings

As previously reported, Shank2 KO mice showed deficits in sociability, with intact social recognition memory, whereas Shank3 KO mice displayed no overt phenotypes. Strikingly, the two Shank KO mouse models exhibited diametrically opposed alterations in social dominance and cooperative behaviors. After a specific social behavioral experience, Shank mutant mice exhibited distinct changes in number of c-Fos+ neurons in the number of cortical and subcortical brain regions.

Conclusions

Our results underscore the heterogeneity of social behavioral alterations in different ASD mouse models and highlight the utility of testing complex social behaviors in validating neurodevelopmental and neuropsychiatric disorder models. In addition, neural activities at distinct brain regions are likely collectively involved in eliciting complex social behaviors, which are differentially altered in ASD mouse models.
Subspecialized radiological reporting reduces radiology report turnaround time
Authors: Zabel Andreas Otto Josef , Leschka Sebastian , Wildermuth Simon , Hodler Juerg , Dietrich Tobias Johannes
Published: October 2020

Objectives

The objective of this study was to compare the radiology report turnaround time (RTAT) between decentralized/modality-based and centralized/subspecialized radiological reporting at a multi-center radiology enterprise.

Methods

RTAT values for MRI, CT, and conventional radiography were compared between decentralized/modality-based (04 September 2017–22 December 2017) and centralized/subspecialized radiology (03 September 2018–21 December 2018) reporting grouped into three subspecializations (body radiology, musculoskeletal radiology, and neuroradiology) at eleven sites of a multi-center radiology enterprise. For the objective of this investigation, hospitals were defined as major and minor hospitals. The Mann-Whitney U test served for statistical analyses.

Results

Change of reporting system from decentralized/modality-based to centralized/subspecialized radiology resulted overall in a significant decrease of the RTAT: from 82 to 77 min for the first signature (p < 0.001), and 119 to 107 min and 295 to 238 min for the second signature (p < 0.001). Subgroup analyses demonstrate a significant decrease of the RTAT for MRI reports (e.g., second signature RTAT, 1051 to 401 min; p < 0.001) and conventional radiographs (e. g., second signature RTAT, 278 to 171 min; p < 0.001). The RTAT at major hospitals decreased from 288 to 245 min (second signature; p < 0.001) while the corresponding RTAT of minor hospitals decreased more remarkably, from 300 to 198 min (p < 0.001). However, the results were heterogenous; in some analyses, the RTAT even increased. The effect size analyses represent small effects.

Conclusions

Change of reporting system from decentralized/modality-based to centralized/subspecialized radiology was associated with a significant decreased RTAT. Specifically, the RTAT for MRI reports and conventional radiographs was significantly reduced. A pronounced RTAT decrease was observed at minor hospitals.
Acquired hemophilia A and plasma cell neoplasms: a case report and review of the literature
Authors: Jalowiec Katarzyna A. , Andres Martin , Taleghani Behrouz Mansouri , Musa Albulena , Dickenmann Martina , Angelillo-Scherrer Anne , Rovó Alicia , Kremer Hovinga Johanna A.
Published: October 2020

Background

Acquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare.

Case presentation

We describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered treatment of the plasma cell neoplasm necessary, and a VRD (bortezomib, lenalidomide, and dexamethasone) regimen was initiated. Due to multiple complications, VRD was reduced to VRD-lite after two cycles. After nine cycles of induction therapy and five cycles of consolidation therapy, the patient is in complete remission of his acquired hemophilia A and very good partial remission of the plasma cell neoplasm. We conducted a literature review to identify additional cases of this rare association and identified 15 other cases. Case descriptions, including the sequence of occurrence of acquired hemophilia A and plasma cell neoplasm , treatment, evolution, and outcome are presented.

Discussion and conclusions

Our case, together with 15 other cases described in the literature, underscore the possibility of plasma cell neoplasm as an underlying cause of acquired hemophilia A. Physicians should consider including protein electrophoresis, immunofixation, and analysis of free light chains in laboratory diagnostics when treating a patient with acquired hemophilia A. The occurrence of excessive and unexplained bleeding in patients diagnosed with plasma cell neoplasm should raise suspicion of secondary acquired hemophilia A and trigger the request for coagulation tests, particularly in patients treated with immunomodulatory drugs such as thalidomide or lenalidomide. Additionally, early intervention with immunoadsorption can be lifesaving in cases with high-titer factor VIII inhibitors, especially when surgical interventions are necessary.